WorldWideScience

Sample records for human carcinogen based

  1. Inter-laboratory study of human in vitro toxicogenomics-based tests as alternative methods for evaluating chemical carcinogenicity : a bioinformatics perspective

    NARCIS (Netherlands)

    Herwig, R; Gmuender, H; Corvi, Raffaella; Bloch, K.M.; Brandenburg, A.; Castell, J; Ceelen, L; Chesne, C; Doktorova, T Y; Jennen, D; Jennings, P; Limonciel, A; Lock, E A; McMorrow, T; Phrakonkham, P; Radford-Smith, G.; Slattery, C; Stierum, R; Vilardell, M; Wittenberger, T; Yildirimman, R; Ryan, M.; Rogiers, Vera; Kleinjans, Jos

    The assessment of the carcinogenic potential of chemicals with alternative, human-based in vitro systems has become a major goal of toxicogenomics. The central read-out of these assays is the transcriptome, and while many studies exist that explored the gene expression responses of such systems,

  2. Foetal exposure to food and environmental carcinogens in human beings.

    Science.gov (United States)

    Myöhänen, Kirsi; Vähäkangas, Kirsi

    2012-02-01

    Exposure to many different chemicals during pregnancy through maternal circulation is possible. Transplacental transfer of xenobiotics can be demonstrated using human placental perfusion. Also, placental perfusion can give information about the placental kinetics as well as metabolism and accumulation in the placenta because it retains the tissue structure and function. Although human placental perfusion has been used extensively to study the transplacental transfer of drugs, the information on food and environmental carcinogens is much more limited. This review deals with the foetal exposure to food and environmental carcinogens in human beings. In particular, human transplacental transfer of the food carcinogens such as acrylamide, glycidamide and nitrosodimethylamine are in focus. Because these carcinogens are genotoxic, the functional capacity of human placenta to induce DNA adduct formation or metabolize these above mentioned CYP2E1 substrates is of interest in this context. © 2011 The Authors. Basic & Clinical Pharmacology & Toxicology © 2011 Nordic Pharmacological Society.

  3. Biomonitoring human exposure to environmental carcinogenic chemicals

    DEFF Research Database (Denmark)

    Farmer, P.B.; Sepai, O.; Lawrence, R.

    1996-01-01

    for detecting carcinogen-induced damage to DNA and proteins, and subsequent biological effects. These methods were validated with the occupational exposures, which showed evidence of DNA and/or protein and/or chromosome damage in workers in a coke oven plant, garage workers exposed to diesel exhaust and workers...

  4. Environmental carcinogens in human target tissues in culture: Progress report

    International Nuclear Information System (INIS)

    Hsu, I.C.

    1987-01-01

    We have accumulated more experimental evidences that demonstrated the comparative approaches with human cells will allow us to predict human risk with good accuracy following exposure to toxic chemicals. We also synthesized several carcinogenic DNA adducts, i.e., the major benzo[a]pyrene DNA adduct, 0 6 -methyldeoxyguanosine, 7-methyl- deoxyguanosine and 2-methyl-deoxyguanosine to be used as standards for quantitating DNA adduct formation in carcinogen exposed cells. A simple synthetic method was developed for preparation of the major B[a]p DNA adduct with yields better than those reported. The main accomplishments related to the originally stated objectives are summarized. 8 refs., 2 figs., 1 tab

  5. Mycotoxins as human carcinogens-the IARC Monographs classification.

    Science.gov (United States)

    Ostry, Vladimir; Malir, Frantisek; Toman, Jakub; Grosse, Yann

    2017-02-01

    Humans are constantly exposed to mycotoxins (e.g. aflatoxins, ochratoxins), mainly via food intake of plant and animal origin. The health risks stemming from mycotoxins may result from their toxicity, in particular their carcinogenicity. In order to prevent these risks, the International Agency for Research on Cancer (IARC) in Lyon (France)-through its IARC Monographs programme-has performed the carcinogenic hazard assessment of some mycotoxins in humans, on the basis of epidemiological data, studies of cancer in experimental animals and mechanistic studies. The present article summarizes the carcinogenic hazard assessments of those mycotoxins, especially aflatoxins (aflatoxin B 1 , B 2 , G 1 , G 2 and M 1 ), fumonisins (fumonisin B 1 and B 2 ) and ochratoxin A (OTA). New information regarding the genotoxicity of OTA (formation of OTA-DNA adducts), the role of OTA in oxidative stress and the identification of epigenetic factors involved in OTA carcinogenesis-should they indeed provide strong evidence that OTA carcinogenicity is mediated by a mechanism that also operates in humans-could lead to the reclassification of OTA.

  6. IARC monographs: 40 years of evaluating carcinogenic hazards to humans.

    Science.gov (United States)

    Pearce, Neil; Blair, Aaron; Vineis, Paolo; Ahrens, Wolfgang; Andersen, Aage; Anto, Josep M; Armstrong, Bruce K; Baccarelli, Andrea A; Beland, Frederick A; Berrington, Amy; Bertazzi, Pier Alberto; Birnbaum, Linda S; Brownson, Ross C; Bucher, John R; Cantor, Kenneth P; Cardis, Elisabeth; Cherrie, John W; Christiani, David C; Cocco, Pierluigi; Coggon, David; Comba, Pietro; Demers, Paul A; Dement, John M; Douwes, Jeroen; Eisen, Ellen A; Engel, Lawrence S; Fenske, Richard A; Fleming, Lora E; Fletcher, Tony; Fontham, Elizabeth; Forastiere, Francesco; Frentzel-Beyme, Rainer; Fritschi, Lin; Gerin, Michel; Goldberg, Marcel; Grandjean, Philippe; Grimsrud, Tom K; Gustavsson, Per; Haines, Andy; Hartge, Patricia; Hansen, Johnni; Hauptmann, Michael; Heederik, Dick; Hemminki, Kari; Hemon, Denis; Hertz-Picciotto, Irva; Hoppin, Jane A; Huff, James; Jarvholm, Bengt; Kang, Daehee; Karagas, Margaret R; Kjaerheim, Kristina; Kjuus, Helge; Kogevinas, Manolis; Kriebel, David; Kristensen, Petter; Kromhout, Hans; Laden, Francine; Lebailly, Pierre; LeMasters, Grace; Lubin, Jay H; Lynch, Charles F; Lynge, Elsebeth; 't Mannetje, Andrea; McMichael, Anthony J; McLaughlin, John R; Marrett, Loraine; Martuzzi, Marco; Merchant, James A; Merler, Enzo; Merletti, Franco; Miller, Anthony; Mirer, Franklin E; Monson, Richard; Nordby, Karl-Cristian; Olshan, Andrew F; Parent, Marie-Elise; Perera, Frederica P; Perry, Melissa J; Pesatori, Angela Cecilia; Pirastu, Roberta; Porta, Miquel; Pukkala, Eero; Rice, Carol; Richardson, David B; Ritter, Leonard; Ritz, Beate; Ronckers, Cecile M; Rushton, Lesley; Rusiecki, Jennifer A; Rusyn, Ivan; Samet, Jonathan M; Sandler, Dale P; de Sanjose, Silvia; Schernhammer, Eva; Costantini, Adele Seniori; Seixas, Noah; Shy, Carl; Siemiatycki, Jack; Silverman, Debra T; Simonato, Lorenzo; Smith, Allan H; Smith, Martyn T; Spinelli, John J; Spitz, Margaret R; Stallones, Lorann; Stayner, Leslie T; Steenland, Kyle; Stenzel, Mark; Stewart, Bernard W; Stewart, Patricia A; Symanski, Elaine; Terracini, Benedetto; Tolbert, Paige E; Vainio, Harri; Vena, John; Vermeulen, Roel; Victora, Cesar G; Ward, Elizabeth M; Weinberg, Clarice R; Weisenburger, Dennis; Wesseling, Catharina; Weiderpass, Elisabete; Zahm, Shelia Hoar

    2015-06-01

    Recently, the International Agency for Research on Cancer (IARC) Programme for the Evaluation of Carcinogenic Risks to Humans has been criticized for several of its evaluations, and also for the approach used to perform these evaluations. Some critics have claimed that failures of IARC Working Groups to recognize study weaknesses and biases of Working Group members have led to inappropriate classification of a number of agents as carcinogenic to humans. The authors of this Commentary are scientists from various disciplines relevant to the identification and hazard evaluation of human carcinogens. We examined criticisms of the IARC classification process to determine the validity of these concerns. Here, we present the results of that examination, review the history of IARC evaluations, and describe how the IARC evaluations are performed. We concluded that these recent criticisms are unconvincing. The procedures employed by IARC to assemble Working Groups of scientists from the various disciplines and the techniques followed to review the literature and perform hazard assessment of various agents provide a balanced evaluation and an appropriate indication of the weight of the evidence. Some disagreement by individual scientists to some evaluations is not evidence of process failure. The review process has been modified over time and will undoubtedly be altered in the future to improve the process. Any process can in theory be improved, and we would support continued review and improvement of the IARC processes. This does not mean, however, that the current procedures are flawed. The IARC Monographs have made, and continue to make, major contributions to the scientific underpinning for societal actions to improve the public's health.

  7. Risk-based indicators of Canadians' exposures to environmental carcinogens.

    Science.gov (United States)

    Setton, Eleanor; Hystad, Perry; Poplawski, Karla; Cheasley, Roslyn; Cervantes-Larios, Alejandro; Keller, C Peter; Demers, Paul A

    2013-02-12

    Tools for estimating population exposures to environmental carcinogens are required to support evidence-based policies to reduce chronic exposures and associated cancers. Our objective was to develop indicators of population exposure to selected environmental carcinogens that can be easily updated over time, and allow comparisons and prioritization between different carcinogens and exposure pathways. We employed a risk assessment-based approach to produce screening-level estimates of lifetime excess cancer risk for selected substances listed as known carcinogens by the International Agency for Research on Cancer. Estimates of lifetime average daily intake were calculated using population characteristics combined with concentrations (circa 2006) in outdoor air, indoor air, dust, drinking water, and food and beverages from existing monitoring databases or comprehensive literature reviews. Intake estimates were then multiplied by cancer potency factors from Health Canada, the United States Environmental Protection Agency, and the California Office of Environmental Health Hazard Assessment to estimate lifetime excess cancer risks associated with each substance and exposure pathway. Lifetime excess cancer risks in excess of 1 per million people are identified as potential priorities for further attention. Based on data representing average conditions circa 2006, a total of 18 carcinogen-exposure pathways had potential lifetime excess cancer risks greater than 1 per million, based on varying data quality. Carcinogens with moderate to high data quality and lifetime excess cancer risk greater than 1 per million included benzene, 1,3-butadiene and radon in outdoor air; benzene and radon in indoor air; and arsenic and hexavalent chromium in drinking water. Important data gaps were identified for asbestos, hexavalent chromium and diesel exhaust in outdoor and indoor air, while little data were available to assess risk for substances in dust, food and beverages. The ability to

  8. IARC Monographs: 40 Years of Evaluating Carcinogenic Hazards to Humans

    Science.gov (United States)

    Blair, Aaron; Vineis, Paolo; Ahrens, Wolfgang; Andersen, Aage; Anto, Josep M.; Armstrong, Bruce K.; Baccarelli, Andrea A.; Beland, Frederick A.; Berrington, Amy; Bertazzi, Pier Alberto; Birnbaum, Linda S.; Brownson, Ross C.; Bucher, John R.; Cantor, Kenneth P.; Cardis, Elisabeth; Cherrie, John W.; Christiani, David C.; Cocco, Pierluigi; Coggon, David; Comba, Pietro; Demers, Paul A.; Dement, John M.; Douwes, Jeroen; Eisen, Ellen A.; Engel, Lawrence S.; Fenske, Richard A.; Fleming, Lora E.; Fletcher, Tony; Fontham, Elizabeth; Forastiere, Francesco; Frentzel-Beyme, Rainer; Fritschi, Lin; Gerin, Michel; Goldberg, Marcel; Grandjean, Philippe; Grimsrud, Tom K.; Gustavsson, Per; Haines, Andy; Hartge, Patricia; Hansen, Johnni; Hauptmann, Michael; Heederik, Dick; Hemminki, Kari; Hemon, Denis; Hertz-Picciotto, Irva; Hoppin, Jane A.; Huff, James; Jarvholm, Bengt; Kang, Daehee; Karagas, Margaret R.; Kjaerheim, Kristina; Kjuus, Helge; Kogevinas, Manolis; Kriebel, David; Kristensen, Petter; Kromhout, Hans; Laden, Francine; Lebailly, Pierre; LeMasters, Grace; Lubin, Jay H.; Lynch, Charles F.; Lynge, Elsebeth; ‘t Mannetje, Andrea; McMichael, Anthony J.; McLaughlin, John R.; Marrett, Loraine; Martuzzi, Marco; Merchant, James A.; Merler, Enzo; Merletti, Franco; Miller, Anthony; Mirer, Franklin E.; Monson, Richard; Nordby, Karl-Cristian; Olshan, Andrew F.; Parent, Marie-Elise; Perera, Frederica P.; Perry, Melissa J.; Pesatori, Angela Cecilia; Pirastu, Roberta; Porta, Miquel; Pukkala, Eero; Rice, Carol; Richardson, David B.; Ritter, Leonard; Ritz, Beate; Ronckers, Cecile M.; Rushton, Lesley; Rusiecki, Jennifer A.; Rusyn, Ivan; Samet, Jonathan M.; Sandler, Dale P.; de Sanjose, Silvia; Schernhammer, Eva; Costantini, Adele Seniori; Seixas, Noah; Shy, Carl; Siemiatycki, Jack; Silverman, Debra T.; Simonato, Lorenzo; Smith, Allan H.; Smith, Martyn T.; Spinelli, John J.; Spitz, Margaret R.; Stallones, Lorann; Stayner, Leslie T.; Steenland, Kyle; Stenzel, Mark; Stewart, Bernard W.; Stewart, Patricia A.; Symanski, Elaine; Terracini, Benedetto; Tolbert, Paige E.; Vainio, Harri; Vena, John; Vermeulen, Roel; Victora, Cesar G.; Ward, Elizabeth M.; Weinberg, Clarice R.; Weisenburger, Dennis; Wesseling, Catharina; Weiderpass, Elisabete; Zahm, Shelia Hoar

    2015-01-01

    Background: Recently, the International Agency for Research on Cancer (IARC) Programme for the Evaluation of Carcinogenic Risks to Humans has been criticized for several of its evaluations, and also for the approach used to perform these evaluations. Some critics have claimed that failures of IARC Working Groups to recognize study weaknesses and biases of Working Group members have led to inappropriate classification of a number of agents as carcinogenic to humans. Objectives: The authors of this Commentary are scientists from various disciplines relevant to the identification and hazard evaluation of human carcinogens. We examined criticisms of the IARC classification process to determine the validity of these concerns. Here, we present the results of that examination, review the history of IARC evaluations, and describe how the IARC evaluations are performed. Discussion: We concluded that these recent criticisms are unconvincing. The procedures employed by IARC to assemble Working Groups of scientists from the various disciplines and the techniques followed to review the literature and perform hazard assessment of various agents provide a balanced evaluation and an appropriate indication of the weight of the evidence. Some disagreement by individual scientists to some evaluations is not evidence of process failure. The review process has been modified over time and will undoubtedly be altered in the future to improve the process. Any process can in theory be improved, and we would support continued review and improvement of the IARC processes. This does not mean, however, that the current procedures are flawed. Conclusions: The IARC Monographs have made, and continue to make, major contributions to the scientific underpinning for societal actions to improve the public’s health. Citation: Pearce N, Blair A, Vineis P, Ahrens W, Andersen A, Anto JM, Armstrong BK, Baccarelli AA, Beland FA, Berrington A, Bertazzi PA, Birnbaum LS, Brownson RC, Bucher JR, Cantor KP

  9. Can creatine supplementation form carcinogenic heterocyclic amines in humans?

    Science.gov (United States)

    Pereira, Renato Tavares dos Santos; Dörr, Felipe Augusto; Pinto, Ernani; Solis, Marina Yazigi; Artioli, Guilherme Giannini; Fernandes, Alan Lins; Murai, Igor Hisashi; Dantas, Wagner Silva; Seguro, Antônio Carlos; Santinho, Mirela Aparecida Rodrigues; Roschel, Hamilton; Carpentier, Alain; Poortmans, Jacques Remi; Gualano, Bruno

    2015-01-01

    Abstract Creatine supplementation has been associated with increased cancer risk. In fact, there is evidence indicating that creatine and/or creatinine are important precursors of carcinogenic heterocyclic amines (HCAs). The present study aimed to investigate the acute and chronic effects of low- and high-dose creatine supplementation on the production of HCAs in healthy humans (i.e. 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (8-MeIQx),  2-amino-(1,6-dimethylfuro[3,2-e]imidazo[4,5-b])pyridine (IFP) and 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (4,8-DiMeIQx)). This was a non-counterbalanced single-blind crossover study divided into two phases, in which low- and high-dose creatine protocols were tested. After acute (1 day) and chronic supplementation (30 days), the HCAs PhIP, 8-MeIQx, IFP and 4,8-DiMeIQx were assessed through a newly developed HPLC–MS/MS method. Dietary HCA intake and blood and urinary creatinine were also evaluated. Out of 576 assessments performed (from 149 urine samples), only nine (3 from creatine and 6 from placebo) showed quantifiable levels of HCAs (8-MeIQx: n = 3; 4,8-DiMeIQx: n = 2; PhIP: n = 4). Individual analyses revealed that diet rather than creatine supplementation was the main responsible factor for HCA formation in these cases. This study provides compelling evidence that both low and high doses of creatine supplementation, given either acutely or chronically, did not cause increases in the carcinogenic HCAs PhIP, 8-MeIQx, IFP and 4,8-DiMeIQx in healthy subjects. These findings challenge the long-existing notion that creatine supplementation could potentially increase the risk of cancer by stimulating the formation of these mutagens. Key points There is a long-standing concern that creatine supplementation could be associated with cancer, possibly by facilitating the formation of carcinogenic heterocyclic amines (HCAs). This study provides compelling evidence

  10. Non-carcinogenic late effects of ionizing radiation; human data

    International Nuclear Information System (INIS)

    Beebe, G.W.

    1979-01-01

    The late effects of ionizing radiation may be somatic effect or potential effect, about which such informations as follows are required: teratogenesis the disturbances in growth and development, cataracts, infertility, cytogenetic aberration, and accelerated aging. Although much is known about the nature of the malformations produced by ionizing radiation, and about the vulnerability of human embryonal and fetal tissues during various stages of organogenesis, the quantitative information is uncertain and incomplete. The data on A-bomb survivors were flawed by confounding radiation dose with nutritional and other influences caused by the disasters created by war-time bombings. If the effects of radiation are real, they are quite small for the dose below 100 rad (kerma), are confined to the children of pre-pubertal age at the time of exposure, and are of much less consequence for low-LET radiation than for high. Radiation-induced lenticular changes are of graded severity, and as for cataracts, the threshold is in the range from 600 to 1,000 rad of low-LET radiation, and perhaps 75 to 100 rad for fast neutrons; the average latent period is 2 to 7 years. The estimate of the RBE for neutrons is in the range from 2 to 10, and dose-dependent. Ionizing radiation has important effects on fertility only at very high dose. The relationship of the quantitative aspects of the biologic significance of chromosomal aberration in somatic cells to dose may provide an interesting parallel to the carcinogenic effect. For neutrons, the dose-response curve appears to be linear, at least for stable aberration. (Yamashita, S.)

  11. Evaluating the mechanistic evidence and key data gaps in assessing the potential carcinogenicity of carbon nanotubes and nanofibers in humans

    NARCIS (Netherlands)

    Kuempel, Eileen D; Jaurand, Marie-Claude; Møller, Peter; Morimoto, Yasuo; Kobayashi, Norihiro; Pinkerton, Kent E; Sargent, Linda M; Vermeulen, Roel C H; Fubini, Bice; Kane, Agnes B

    2017-01-01

    In an evaluation of carbon nanotubes (CNTs) for the IARC Monograph 111, the Mechanisms Subgroup was tasked with assessing the strength of evidence on the potential carcinogenicity of CNTs in humans. The mechanistic evidence was considered to be not strong enough to alter the evaluations based on the

  12. The Food and Beverage Occurrence of Furfuryl Alcohol and Myrcene-Two Emerging Potential Human Carcinogens?

    Science.gov (United States)

    Okaru, Alex O; Lachenmeier, Dirk W

    2017-03-11

    For decades, compounds present in foods and beverages have been implicated in the etiology of human cancers. The World Health Organization (WHO) International Agency for Research on Cancer (IARC) continues to classify such agents regarding their potential carcinogenicity in humans based on new evidence from animal and human studies. Furfuryl alcohol and β-myrcene are potential human carcinogens due to be evaluated. The major source of furfuryl alcohol in foods is thermal processing and ageing of alcoholic beverages, while β-myrcene occurs naturally as a constituent of the essential oils of plants such as hops, lemongrass, and derived products. This study aimed to summarize the occurrence of furfuryl alcohol and β-myrcene in foods and beverages using literature review data. Additionally, results of furfuryl alcohol occurrence from our own nuclear magnetic resonance (NMR) analysis are included. The highest content of furfuryl alcohol was found in coffee beans (>100 mg/kg) and in some fish products (about 10 mg/kg), while among beverages, wines contained between 1 and 10 mg/L, with 8 mg/L in pineapple juice. The content of β-myrcene was highest in hops. In conclusion, the data about the occurrence of the two agents is currently judged as insufficient for exposure and risk assessment. The results of this study point out the food and beverage groups that may be considered for future monitoring of furfuryl alcohol and β-myrcene.

  13. The Food and Beverage Occurrence of Furfuryl Alcohol and Myrcene—Two Emerging Potential Human Carcinogens?

    Directory of Open Access Journals (Sweden)

    Alex O. Okaru

    2017-03-01

    Full Text Available For decades, compounds present in foods and beverages have been implicated in the etiology of human cancers. The World Health Organization (WHO International Agency for Research on Cancer (IARC continues to classify such agents regarding their potential carcinogenicity in humans based on new evidence from animal and human studies. Furfuryl alcohol and β-myrcene are potential human carcinogens due to be evaluated. The major source of furfuryl alcohol in foods is thermal processing and ageing of alcoholic beverages, while β-myrcene occurs naturally as a constituent of the essential oils of plants such as hops, lemongrass, and derived products. This study aimed to summarize the occurrence of furfuryl alcohol and β-myrcene in foods and beverages using literature review data. Additionally, results of furfuryl alcohol occurrence from our own nuclear magnetic resonance (NMR analysis are included. The highest content of furfuryl alcohol was found in coffee beans (>100 mg/kg and in some fish products (about 10 mg/kg, while among beverages, wines contained between 1 and 10 mg/L, with 8 mg/L in pineapple juice. The content of β-myrcene was highest in hops. In conclusion, the data about the occurrence of the two agents is currently judged as insufficient for exposure and risk assessment. The results of this study point out the food and beverage groups that may be considered for future monitoring of furfuryl alcohol and β-myrcene.

  14. Classification of weakly carcinogenic human papillomavirus types: addressing the limits of epidemiology at the borderline

    Directory of Open Access Journals (Sweden)

    Buonaguro Franco M

    2009-06-01

    Full Text Available Abstract Virtually all cases of cervical cancer are caused by persistent infections with a restricted set of human papillomaviruses (HPV. Some HPV types, like HPV16 and HPV18, are clear and powerful carcinogens. However, the categorization of the most weakly carcinogenic HPV types is extremely challenging. The decisions are important for screening test and vaccine development. This article describes for open discussion an approach recently taken by a World Health Organization International Agency for Research on Cancer (IARC Monographs Working Group to re-assess the carcinogenicity of different HPV types.

  15. On the International Agency for Research on Cancer classification of glyphosate as a probable human carcinogen.

    Science.gov (United States)

    Tarone, Robert E

    2018-01-01

    The recent classification by International Agency for Research on Cancer (IARC) of the herbicide glyphosate as a probable human carcinogen has generated considerable discussion. The classification is at variance with evaluations of the carcinogenic potential of glyphosate by several national and international regulatory bodies. The basis for the IARC classification is examined under the assumptions that the IARC criteria are reasonable and that the body of scientific studies determined by IARC staff to be relevant to the evaluation of glyphosate by the Monograph Working Group is sufficiently complete. It is shown that the classification of glyphosate as a probable human carcinogen was the result of a flawed and incomplete summary of the experimental evidence evaluated by the Working Group. Rational and effective cancer prevention activities depend on scientifically sound and unbiased assessments of the carcinogenic potential of suspected agents. Implications of the erroneous classification of glyphosate with respect to the IARC Monograph Working Group deliberative process are discussed.

  16. Carcinogenic Substances Naturrally Occuring in the Human Diet

    Directory of Open Access Journals (Sweden)

    Mogos Viorel T.

    2018-03-01

    Full Text Available Oncogenesis is a result of the combined action of numerous factors peculiar to the body and the environment (the latter are more effective. Among dietary factors directly implied in the occurrence of malignant tumors we can mention: food additives, contaminated food, polycyclic aromatic hydrocarbons, nitrosamines and some components which are naturally present in food. Moreover, food-related malignancies are a consequence of the increased consumption of fats, proteins, alcohol in parallel with decreases in the consumption of dietary fibers and some micronutrients. Carcinogenic substances naturally present in food are of a particular interest for both nutritionist’s and patient’s, usually not being perceived as being harmful.

  17. Epigenetic alterations induced by genotoxic occupational and environmental human chemical carcinogens: A systematic literature review

    Science.gov (United States)

    Chappell, Grace; Pogribny, Igor P.; Guyton, Kathryn Z.; Rusyn, Ivan

    2016-01-01

    Accumulating evidence suggests that epigenetic alterations play an important role in chemically-induced carcinogenesis. Although the epigenome and genome may be equally important in carcinogenicity, the genotoxicity of chemical agents and exposure-related transcriptomic responses have been more thoroughly studied and characterized. To better understand the evidence for epigenetic alterations of human carcinogens, and the potential association with genotoxic endpoints, we conducted a systematic review of published studies of genotoxic carcinogens that reported epigenetic endpoints. Specifically, we searched for publications reporting epigenetic effects for the 28 agents and occupations included in Monograph Volume 100F of the International Agency for the Research on Cancer (IARC) that were classified as “carcinogenic to humans” (Group 1) with strong evidence of genotoxic mechanisms of carcinogenesis. We identified a total of 158 studies that evaluated epigenetic alterations for 12 of these 28 carcinogenic agents and occupations (1,3-butadiene, 4-aminobiphenyl, aflatoxins, benzene, benzidine, benzo[a]pyrene, coke production, formaldehyde, occupational exposure as a painter, sulfur mustard, and vinyl chloride). Aberrant DNA methylation was most commonly studied, followed by altered expression of non-coding RNAs and histone changes (totaling 85, 59 and 25 studies, respectively). For 3 carcinogens (aflatoxins, benzene and benzo[a]pyrene), 10 or more studies reported epigenetic effects. However, epigenetic studies were sparse for the remaining 9 carcinogens; for 4 agents, only 1 or 2 published reports were identified. While further research is needed to better identify carcinogenesis-associated epigenetic perturbations for many potential carcinogens, published reports on specific epigenetic endpoints can be systematically identified and increasingly incorporated in cancer hazard assessments. PMID:27234561

  18. Circulating mitochondrial DNA as biomarker linking environmental chemical exposure to early preclinical lesions elevation of mtDNA in human serum after exposure to carcinogenic halo-alkane-based pesticides.

    Directory of Open Access Journals (Sweden)

    Lygia T Budnik

    Full Text Available There is a need for a panel of suitable biomarkers for detection of environmental chemical exposure leading to the initiation or progression of degenerative diseases or potentially, to cancer. As the peripheral blood may contain increased levels of circulating cell-free DNA in diseased individuals, we aimed to evaluate this DNA as effect biomarker recognizing vulnerability after exposure to environmental chemicals. We recruited 164 individuals presumably exposed to halo-alkane-based pesticides. Exposure evaluation was based on human biomonitoring analysis; as biomarker of exposure parent halo-methanes, -ethanes and their metabolites, as well as the hemoglobin-adducts methyl valine and hydroxyl ethyl valine in blood were used, complemented by expert evaluation of exposure and clinical intoxication symptoms as well as a questionnaire. Assessment showed exposures to halo alkanes in the concentration range being higher than non-cancer reference doses (RfD but (mostly lower than the occupational exposure limits. We quantified circulating DNA in serum from 86 individuals with confirmed exposure to off-gassing halo-alkane pesticides (in storage facilities or in home environment and 30 non-exposed controls, and found that exposure was significantly associated with elevated serum levels of circulating mitochondrial DNA (in size of 79 bp, mtDNA-79, p = 0.0001. The decreased integrity of mtDNA (mtDNA-230/mtDNA-79 in exposed individuals implicates apoptotic processes (p = 0.015. The relative amounts of mtDNA-79 in serum were positively associated with the lag-time after intoxication to these chemicals (r = 0.99, p<0.0001. Several months of post-exposure the specificity of this biomarker increased from 30% to 97% in patients with intoxication symptoms. Our findings indicate that mitochondrial DNA has a potential to serve as a biomarker recognizing vulnerable risk groups after exposure to toxic/carcinogenic chemicals.

  19. Gene discovery for the carcinogenic human liver fluke, Opisthorchis viverrini

    Directory of Open Access Journals (Sweden)

    Gasser Robin B

    2007-06-01

    Full Text Available Abstract Background Cholangiocarcinoma (CCA – cancer of the bile ducts – is associated with chronic infection with the liver fluke, Opisthorchis viverrini. Despite being the only eukaryote that is designated as a 'class I carcinogen' by the International Agency for Research on Cancer, little is known about its genome. Results Approximately 5,000 randomly selected cDNAs from the adult stage of O. viverrini were characterized and accounted for 1,932 contigs, representing ~14% of the entire transcriptome, and, presently, the largest sequence dataset for any species of liver fluke. Twenty percent of contigs were assigned GO classifications. Abundantly represented protein families included those involved in physiological functions that are essential to parasitism, such as anaerobic respiration, reproduction, detoxification, surface maintenance and feeding. GO assignments were well conserved in relation to other parasitic flukes, however, some categories were over-represented in O. viverrini, such as structural and motor proteins. An assessment of evolutionary relationships showed that O. viverrini was more similar to other parasitic (Clonorchis sinensis and Schistosoma japonicum than to free-living (Schmidtea mediterranea flatworms, and 105 sequences had close homologues in both parasitic species but not in S. mediterranea. A total of 164 O. viverrini contigs contained ORFs with signal sequences, many of which were platyhelminth-specific. Examples of convergent evolution between host and parasite secreted/membrane proteins were identified as were homologues of vaccine antigens from other helminths. Finally, ORFs representing secreted proteins with known roles in tumorigenesis were identified, and these might play roles in the pathogenesis of O. viverrini-induced CCA. Conclusion This gene discovery effort for O. viverrini should expedite molecular studies of cholangiocarcinogenesis and accelerate research focused on developing new interventions

  20. Carcinogen biomonitoring in human exposures and laboratory research: validation and application to human occupational exposures.

    Science.gov (United States)

    Talaska, Glenn; Maier, Andrew; Henn, Scott; Booth-Jones, Angela; Tsuneoka, Yutaka; Vermeulen, Roel; Schumann, Brenda L

    2002-08-05

    A multiple biomarker approach is required to integrate for metabolism, temporal response and exposure-response kinetics, biological relevance, and positive predictive value. Carcinogen DNA adduct analysis can be used in animal and in vitro studies to detect absorption permutations caused by mixture interactions, and to control metabolic variation when specific CYP450 genes (1A1 or 1A2) are knocked out. These enzymes are not critical to the metabolic activation of model Polycyclic Aromatic Compounds (PAC) and aromatic amines, respectively, as suggested by in vitro analysis. Several human studies have been carried out where multiple biomarkers have been measured. In a study of benzidine workers, the similarities in elimination kinetics between urinary metabolites and mutagenicity is likely responsible for a better correlation between these markers than to BZ-DNA adducts in exfoliated cells. In a study of rubber workers, the relationship between specific departments, urinary 1 HP and DNA adducts in exfoliated cells coincided with the historical urinary bladder cancer risk in these departments; the same relationship did not hold for urinary mutagenicity. In a study of automotive mechanics, biomarkers were used to monitor the effectiveness of exposure interventions. These data reinforce the notion that carcinogen biomarkers are useful to monitor exposure, but that a complementary approaches involving effect and perhaps susceptibility biomarkers is necessary to obtain the necessary information.

  1. Evaluating the mechanistic evidence and key data gaps in assessing the potential carcinogenicity of carbon nanotubes and nanofibers in humans

    DEFF Research Database (Denmark)

    Kuempel, Eileen D.; Jaurand, Marie-Claude; Møller, Peter

    2017-01-01

    In an evaluation of carbon nanotubes (CNTs) for the IARC Monograph 111, the Mechanisms Subgroup was tasked with assessing the strength of evidence on the potential carcinogenicity of CNTs in humans. The mechanistic evidence was considered to be not strong enough to alter the evaluations based...... on the animal data. In this paper, we provide an extended, in-depth examination of the in vivo and in vitro experimental studies according to current hypotheses on the carcinogenicity of inhaled particles and fibers. We cite additional studies of CNTs that were not available at the time of the IARC meeting...... in October 2014, and extend our evaluation to include carbon nanofibers (CNFs). Finally, we identify key data gaps and suggest research needs to reduce uncertainty. The focus of this review is on the cancer risk to workers exposed to airborne CNT or CNF during the production and use of these materials...

  2. The Weight of Evidence Does Not Support the Listing of Styrene as “Reasonably Anticipated to be a Human Carcinogen” in NTP's Twelfth Report on Carcinogens

    Science.gov (United States)

    Rhomberg, Lorenz R.; Goodman, Julie E.; Prueitt, Robyn L.

    2013-01-01

    Styrene was listed as “reasonably anticipated to be a human carcinogen” in the twelfth edition of the National Toxicology Program's Report on Carcinogens based on what we contend are erroneous findings of limited evidence of carcinogenicity in humans, sufficient evidence of carcinogenicity in experimental animals, and supporting mechanistic data. The epidemiology studies show no consistent increased incidence of, or mortality from, any type of cancer. In animal studies, increased incidence rates of mostly benign tumors have been observed only in certain strains of one species (mice) and at one tissue site (lung). The lack of concordance of tumor incidence and tumor type among animals (even within the same species) and humans indicates that there has been no particular cancer consistently observed among all available studies. The only plausible mechanism for styrene-induced carcinogenesis—a non-genotoxic mode of action that is specific to the mouse lung—is not relevant to humans. As a whole, the evidence does not support the characterization of styrene as “reasonably anticipated to be a human carcinogen,” and styrene should not be listed in the Report on Carcinogens. PMID:23335843

  3. Effects of alkylating carcinogens on human tumor cells in culture

    International Nuclear Information System (INIS)

    Goth-Goldstein, R.; Hughes, M.

    1987-01-01

    In Escherichia coli 3-methyladenine and 3-methylguanine have been identified as lethal lesions, since two types of alkylating agent-sensitive mutants were deficient in repair of either of these lesions. Similar alkylation-sensitive human cell lines exist. These are the tumor cell lines of the complex Mer - phenotype. All Mer - cells examined were hypersensitive to killing by MNNG and other alkylating agents, and failed to repair O 6 -methylguanine. The widely studied HeLa S3 cell line has the Mer + phenotype, but a Mer - variant (HeLa MR) has arisen. This offers the possibility to study Mer - and Mer + cells of otherwise similar genetic background. We are using these two variants to analyze the Mer - phenotype further. When HeLa S3 and HeLa MR were treated with a highly dose of MNNG, and the surviving population exposed to a second dose of MNNG 2-3 weeks later, HeLa S3 (Mer + ) cells were equally or even slightly more sensitive to a second exposure of MNNG, whereas the surviving HeLa MR (Mer - ) population was much more resistant to MNNG. 1 fig., 1 tab

  4. Effect of chemical mutagens and carcinogens on gene expression profiles in human TK6 cells.

    Directory of Open Access Journals (Sweden)

    Lode Godderis

    Full Text Available Characterization of toxicogenomic signatures of carcinogen exposure holds significant promise for mechanistic and predictive toxicology. In vitro transcriptomic studies allow the comparison of the response to chemicals with diverse mode of actions under controlled experimental conditions. We conducted an in vitro study in TK6 cells to characterize gene expression signatures of exposure to 15 genotoxic carcinogens frequently used in European industries. We also examined the dose-responsive changes in gene expression, and perturbation of biochemical pathways in response to these carcinogens. TK6 cells were exposed at 3 dose levels for 24 h with and without S9 human metabolic mix. Since S9 had an impact on gene expression (885 genes, we analyzed the gene expression data from cells cultures incubated with S9 and without S9 independently. The ribosome pathway was affected by all chemical-dose combinations. However in general, no similar gene expression was observed among carcinogens. Further, pathways, i.e. cell cycle, DNA repair mechanisms, RNA degradation, that were common within sets of chemical-dose combination were suggested by clustergram. Linear trends in dose-response of gene expression were observed for Trichloroethylene, Benz[a]anthracene, Epichlorohydrin, Benzene, and Hydroquinone. The significantly altered genes were involved in the regulation of (anti- apoptosis, maintenance of cell survival, tumor necrosis factor-related pathways and immune response, in agreement with several other studies. Similarly in S9+ cultures, Benz[a]pyrene, Styrene and Trichloroethylene each modified over 1000 genes at high concentrations. Our findings expand our understanding of the transcriptomic response to genotoxic carcinogens, revealing the alteration of diverse sets of genes and pathways involved in cellular homeostasis and cell cycle control.

  5. Cytotoxic and mutagenic effects of specific carcinogen-DNA adducts in diploid human fibroblasts

    International Nuclear Information System (INIS)

    McCormick, J.J.; Maher, V.M.

    1985-01-01

    A comparison of the cytotoxicity and mutagenicity of a series of carcinogens in normal diploid human fibroblasts and in cells deficient in one or more DNA repair processes has provided insight into the specific DNA adduct(s) responsible for these biological effects. The carcinogens tested include ultraviolet radiation; reactive derivatives of structurally related aromatic amides; metabolites of benzo(a)pyrene; the simple alkylating agents N-methyl-N'-nitro-N-nitrosoguanidine and N-ethyl-N-nitrosourea; and aflatoxin B 1 dichloride, a model for the reactive 2,3-epoxide of aflatoxin B 1 . Exponentially growing cells were exposed to agents and assayed for mutations and cell killing. Cells deficient in repair of particular DNA adducts or lesions proved more sensitive to the agent causing those lesions than did normally repairing cells. Many of the carcinogens were compared for their mutagenic and/or cytotoxic effect, not only as a function of dose administered, but also as a function of the initial number of adducts or photoproducts induced in DNA and the number remaining at critical times posttreatment. The results demonstrated a high correlation between the number of DNA lesions remaining unexcised at the time the DNA was replicated and frequency of mutations induced. Comparative studies of the frequency of UV-induced transformation of normal and repair-deficient cells showed this also to be true for transformation

  6. Environmental exposure to human carcinogens in teenagers and the association with DNA damage

    International Nuclear Information System (INIS)

    Franken, Carmen; Koppen, Gudrun; Lambrechts, Nathalie; Govarts, Eva; Bruckers, Liesbeth; Den Hond, Elly; Loots, Ilse; Nelen, Vera; Sioen, Isabelle; Nawrot, Tim S.; Baeyens, Willy; Van Larebeke, Nicolas; Boonen, Francis; Ooms, Daniëlla; Wevers, Mai; Jacobs, Griet; Covaci, Adrian; Schettgen, Thomas; Schoeters, Greet

    2017-01-01

    Background: We investigated whether human environmental exposure to chemicals that are labeled as (potential) carcinogens leads to increased (oxidative) damage to DNA in adolescents. Material and methods: Six hundred 14–15-year-old youngsters were recruited all over Flanders (Belgium) and in two areas with important industrial activities. DNA damage was assessed by alkaline and formamidopyrimidine DNA glycosylase (Fpg) modified comet assays in peripheral blood cells and analysis of urinary 8-hydroxydeoxyguanosine (8-OHdG) levels. Personal exposure to potentially carcinogenic compounds was measured in urine, namely: chromium, cadmium, nickel, 1-hydroxypyrene as a proxy for exposure to other carcinogenic polycyclic aromatic hydrocarbons (PAHs), t,t-muconic acid as a metabolite of benzene, 2,5-dichlorophenol (2,5-DCP), organophosphate pesticide metabolites, and di(2-ethylhexyl) phthalate (DEHP) metabolites. In blood, arsenic, polychlorinated biphenyl (PCB) congeners 118 and 156, hexachlorobenzene (HCB), dichlorodiphenyltrichloroethane (DDT) and perfluorooctanoic acid (PFOA) were analyzed. Levels of methylmercury (MeHg) were measured in hair. Multiple linear regression models were used to establish exposure-response relationships. Results: Biomarkers of exposure to PAHs and urinary chromium were associated with higher levels of both 8-OHdG in urine and DNA damage detected by the alkaline comet assay. Concentrations of 8-OHdG in urine increased in relation with increasing concentrations of urinary t,t-muconic acid, cadmium, nickel, 2,5-DCP, and DEHP metabolites. Increased concentrations of PFOA in blood were associated with higher levels of DNA damage measured by the alkaline comet assay, whereas DDT was associated in the same direction with the Fpg-modified comet assay. Inverse associations were observed between blood arsenic, hair MeHg, PCB 156 and HCB, and urinary 8-OHdG. The latter exposure biomarkers were also associated with higher fish intake. Urinary nickel

  7. Environmental exposure to human carcinogens in teenagers and the association with DNA damage

    Energy Technology Data Exchange (ETDEWEB)

    Franken, Carmen, E-mail: carmen.franken@vito.be [Flemish Institute for Technological Research (VITO), Mol (Belgium); Department of Biomedical Sciences, University of Antwerp, Antwerp (Belgium); Koppen, Gudrun; Lambrechts, Nathalie; Govarts, Eva [Flemish Institute for Technological Research (VITO), Mol (Belgium); Bruckers, Liesbeth [Interuniversity Institute for Biostatistics and Statistical Bioinformatics, Hasselt University, Hasselt (Belgium); Den Hond, Elly [Flemish Institute for Technological Research (VITO), Mol (Belgium); Loots, Ilse [Political and Social Sciences, University of Antwerp, Antwerp (Belgium); Nelen, Vera [Provincial Institute for Hygiene, Antwerp (Belgium); Sioen, Isabelle [Department of Public Health, Ghent University, Ghent (Belgium); Department of Food Safety and Food Quality, Ghent University, Ghent (Belgium); Nawrot, Tim S. [Centre for Environmental Sciences, Hasselt University, Diepenbeek (Belgium); Department of Public Health & Primary Care, Leuven University, Leuven (Belgium); Baeyens, Willy [Department of Analytical and Environmental Chemistry, Vrije Universiteit Brussel, Brussels (Belgium); Van Larebeke, Nicolas [Department of Analytical and Environmental Chemistry, Vrije Universiteit Brussel, Brussels (Belgium); Department of Radiotherapy and Experimental Cancerology, Ghent University, Ghent (Belgium); Boonen, Francis; Ooms, Daniëlla; Wevers, Mai; Jacobs, Griet [Flemish Institute for Technological Research (VITO), Mol (Belgium); Covaci, Adrian [Toxicological Centre, Department of Pharmaceutical Sciences, University of Antwerp, Antwerp (Belgium); Schettgen, Thomas [Department of Occupational and Social Medicine, RWTH Aachen University, Aachen (Germany); Schoeters, Greet [Flemish Institute for Technological Research (VITO), Mol (Belgium); Department of Biomedical Sciences, University of Antwerp, Antwerp (Belgium); University of Southern Denmark, Institute of Public Health, Department of Environmental Medicine, Odense (Denmark)

    2017-01-15

    Background: We investigated whether human environmental exposure to chemicals that are labeled as (potential) carcinogens leads to increased (oxidative) damage to DNA in adolescents. Material and methods: Six hundred 14–15-year-old youngsters were recruited all over Flanders (Belgium) and in two areas with important industrial activities. DNA damage was assessed by alkaline and formamidopyrimidine DNA glycosylase (Fpg) modified comet assays in peripheral blood cells and analysis of urinary 8-hydroxydeoxyguanosine (8-OHdG) levels. Personal exposure to potentially carcinogenic compounds was measured in urine, namely: chromium, cadmium, nickel, 1-hydroxypyrene as a proxy for exposure to other carcinogenic polycyclic aromatic hydrocarbons (PAHs), t,t-muconic acid as a metabolite of benzene, 2,5-dichlorophenol (2,5-DCP), organophosphate pesticide metabolites, and di(2-ethylhexyl) phthalate (DEHP) metabolites. In blood, arsenic, polychlorinated biphenyl (PCB) congeners 118 and 156, hexachlorobenzene (HCB), dichlorodiphenyltrichloroethane (DDT) and perfluorooctanoic acid (PFOA) were analyzed. Levels of methylmercury (MeHg) were measured in hair. Multiple linear regression models were used to establish exposure-response relationships. Results: Biomarkers of exposure to PAHs and urinary chromium were associated with higher levels of both 8-OHdG in urine and DNA damage detected by the alkaline comet assay. Concentrations of 8-OHdG in urine increased in relation with increasing concentrations of urinary t,t-muconic acid, cadmium, nickel, 2,5-DCP, and DEHP metabolites. Increased concentrations of PFOA in blood were associated with higher levels of DNA damage measured by the alkaline comet assay, whereas DDT was associated in the same direction with the Fpg-modified comet assay. Inverse associations were observed between blood arsenic, hair MeHg, PCB 156 and HCB, and urinary 8-OHdG. The latter exposure biomarkers were also associated with higher fish intake. Urinary nickel

  8. Human gastric cancer, Helicobacter pylori and bracken carcinogens: A connecting hypothesis.

    Science.gov (United States)

    Oliveros-Bastidas, Alberto; Calcagno-Pissarelli, María Pía; Naya, Marlene; Ávila-Núñez, Jorge Luis; Alonso-Amelot, Miguel E

    2016-03-01

    Long term infection of Helicobacter pylori (Hp) virulent strains is a key factor in the genesis of human gastric cancer, and so are certain dietary proinflammatory and genotoxic compounds. Carcinogenic bracken fern (Pteridium spp.) is one of these. Toxins from this plant are consumed as bracken culinary preparations, through milk and meat of bracken-exposed livestock, and drain waters from bracken swards. Bracken toxin ptaquiloside (PtQ), a suspected human carcinogen, elicits complex responses in animals leading to death. PtQ and Hp might cooperate in gastric pathologies. This paper presents an hypothesis on PtQ-Hp association leading to the enhancement of carcinogenesis in the human gastric environment that might explain the high gastric cancer incidence and death rates among Hp-infected people living in bracken zones at two levels: (1) The macroscopic scale comprising the flow of PtQ in the human diet. (2) the microscopic scale encompassing (A) gastric luminal medium; (B) gastric mucus structure and mucin degradation elicited by Hp; (C) bacterial pH gradient modification of the gastric mucosa that favors PtQ survival and its penetration into epithelial tissue; (D) combined PtQ/Hp effects on gastric immune and inflammatory responses; (E) PtQ-Hp complementary activity at selected cell signaling cascades and genome disturbance. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. The tobacco carcinogen NNK is stereoselectively reduced by human pancreatic microsomes and cytosols.

    Science.gov (United States)

    Trushin, Neil; Leder, Gerhard; El-Bayoumy, Karam; Hoffmann, Dietrich; Beger, Hans G; Henne-Bruns, Doris; Ramadani, Marco; Prokopczyk, Bogdan

    2008-07-01

    Cigarette smoking increases the risk of cancer of the pancreas. The tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is the only known environmental compound that induces pancreatic cancer in laboratory animals. Concentrations of NNK are significantly higher in the pancreatic juice of smokers than in that of nonsmokers. The chiral NNK metabolite, (R,S)-4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) is itself a potent pancreatic carcinogen in rats. The carcinogenicity of NNAL is related to its stereochemistry; (S)-NNAL is a more potent lung tumorigen in the A/J mouse than is (R)-NNAL. In this study, we determined the potential of the human pancreas to convert NNK into NNAL. Human pancreatic microsomes and cytosols were incubated with [5-(3)H]NNK, and the metabolic products were determined by high-performance liquid chromatography (HPLC). (S)-NNAL was the predominant isomer formed in all cytosolic incubations. In ten microsomal samples, NNAL was formed at an average rate of 3.8 +/- 1.6 pmol/mg/min; (R)-NNAL was the predominant isomer in this group. The average rate of NNAL formation in 18 other microsomal samples was significantly lower, 0.13 +/- 0.12 pmol/mg/min (p < 0.001); (S)-NNAL was the predominant isomer formed in this group. In human pancreatic tissues, there is intraindividual variability regarding the capacity for, and stereoselectivity of, carbonyl reduction of NNK.

  10. USING PROTEOMICS TO MONITOR PROTEIN EXPRESSION IN HUMAN CELLS EXPOSED TO CARCINOGENS

    Science.gov (United States)

    People are continuously exposed exogenously to varying amounts of chemicals that have been shown to have carcinogenic properties in experimental systems. It has been estimated that exposure to environmental chemical carcinogens in the environment may contribute significantly to t...

  11. Carcinogen derived biomarkers: applications in studies of human exposure to secondhand tobacco smoke

    OpenAIRE

    Hecht, S

    2004-01-01

    Objective: To review the literature on carcinogen derived biomarkers of exposure to secondhand tobacco smoke (SHS). These biomarkers are specifically related to known carcinogens in tobacco smoke and include urinary metabolites, DNA adducts, and blood protein adducts.

  12. Apple Flavonoids Suppress Carcinogen-Induced DNA Damage in Normal Human Bronchial Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Vazhappilly Cijo George

    2017-01-01

    Full Text Available Scope. Human neoplastic transformation due to DNA damage poses an increasing global healthcare concern. Maintaining genomic integrity is crucial for avoiding tumor initiation and progression. The present study aimed to investigate the efficacy of an apple flavonoid fraction (AF4 against various carcinogen-induced toxicity in normal human bronchial epithelial cells and its mechanism of DNA damage response and repair processes. Methods and Results. AF4-pretreated cells were exposed to nicotine-derived nitrosamine ketones (NNK, NNK acetate (NNK-Ae, methotrexate (MTX, and cisplatin to validate cytotoxicity, total reactive oxygen species, intracellular antioxidants, DNA fragmentation, and DNA tail damage. Furthermore, phosphorylated histone (γ-H2AX and proteins involved in DNA damage (ATM/ATR, Chk1, Chk2, and p53 and repair (DNA-PKcs and Ku80 mechanisms were evaluated by immunofluorescence and western blotting, respectively. The results revealed that AF4-pretreated cells showed lower cytotoxicity, total ROS generation, and DNA fragmentation along with consequent inhibition of DNA tail moment. An increased level of γ-H2AX and DNA damage proteins was observed in carcinogen-treated cells and that was significantly (p≤0.05 inhibited in AF4-pretreated cells, in an ATR-dependent manner. AF4 pretreatment also facilitated the phosphorylation of DNA-PKcs and thus initiation of repair mechanisms. Conclusion. Apple flavonoids can protect in vitro oxidative DNA damage and facilitate repair mechanisms.

  13. Role of DNA lesions and DNA repair in mutagenesis by carcinogens in diploid human fibroblasts

    International Nuclear Information System (INIS)

    Maher, V.M.; McCormick, J.J.

    1986-01-01

    The authors investigated the cytotoxicity, mutagenicity, and transforming activity of carcinogens and radiation in diploid human fibroblasts, using cells which differ in their DNA repair capacity. The results indicate that cell killing and induction of mutations are correlated with the number of specific lesions remaining unrepaired in the cells at a particular time posttreatment. DNA excision repair acts to eliminate potentially cytotoxic and mutagenic (and transforming) damage from DNA before these can be converted into permanent cellular effects. Normal human fibroblasts were derived from skin biopsies or circumcision material. Skin fibroblasts from xeroderma pigmentosum (XP) patients provided cells deficient in nucleotide excision repair of pyrimidine dimers or DNA adducts formed by bulky ring structures. Cytotoxicity was determined from loss of ability to form a colony. The genetic marker used was resistance to 6-thioguanine (TG). Transformation was measured by determining the frequency of anchorage-independent cells

  14. Prediction of rodent carcinogenic potential of naturally occurring chemicals in the human diet using high-throughput QSAR predictive modeling

    International Nuclear Information System (INIS)

    Valerio, Luis G.; Arvidson, Kirk B.; Chanderbhan, Ronald F.; Contrera, Joseph F.

    2007-01-01

    Consistent with the U.S. Food and Drug Administration (FDA) Critical Path Initiative, predictive toxicology software programs employing quantitative structure-activity relationship (QSAR) models are currently under evaluation for regulatory risk assessment and scientific decision support for highly sensitive endpoints such as carcinogenicity, mutagenicity and reproductive toxicity. At the FDA's Center for Food Safety and Applied Nutrition's Office of Food Additive Safety and the Center for Drug Evaluation and Research's Informatics and Computational Safety Analysis Staff (ICSAS), the use of computational SAR tools for both qualitative and quantitative risk assessment applications are being developed and evaluated. One tool of current interest is MDL-QSAR predictive discriminant analysis modeling of rodent carcinogenicity, which has been previously evaluated for pharmaceutical applications by the FDA ICSAS. The study described in this paper aims to evaluate the utility of this software to estimate the carcinogenic potential of small, organic, naturally occurring chemicals found in the human diet. In addition, a group of 19 known synthetic dietary constituents that were positive in rodent carcinogenicity studies served as a control group. In the test group of naturally occurring chemicals, 101 were found to be suitable for predictive modeling using this software's discriminant analysis modeling approach. Predictions performed on these compounds were compared to published experimental evidence of each compound's carcinogenic potential. Experimental evidence included relevant toxicological studies such as rodent cancer bioassays, rodent anti-carcinogenicity studies, genotoxic studies, and the presence of chemical structural alerts. Statistical indices of predictive performance were calculated to assess the utility of the predictive modeling method. Results revealed good predictive performance using this software's rodent carcinogenicity module of over 1200 chemicals

  15. Mechanism-Based Classification of PAH Mixtures to Predict Carcinogenic Potential.

    Science.gov (United States)

    Tilton, Susan C; Siddens, Lisbeth K; Krueger, Sharon K; Larkin, Andrew J; Löhr, Christiane V; Williams, David E; Baird, William M; Waters, Katrina M

    2015-07-01

    We have previously shown that relative potency factors and DNA adduct measurements are inadequate for predicting carcinogenicity of certain polycyclic aromatic hydrocarbons (PAHs) and PAH mixtures, particularly those that function through alternate pathways or exhibit greater promotional activity compared to benzo[a]pyrene (BaP). Therefore, we developed a pathway-based approach for classification of tumor outcome after dermal exposure to PAH/mixtures. FVB/N mice were exposed to dibenzo[def,p]chrysene (DBC), BaP, or environmental PAH mixtures (Mix 1-3) following a 2-stage initiation/promotion skin tumor protocol. Resulting tumor incidence could be categorized by carcinogenic potency as DBC > BaP = Mix2 = Mix3 > Mix1 = Control, based on statistical significance. Gene expression profiles measured in skin of mice collected 12 h post-initiation were compared with tumor outcome for identification of short-term bioactivity profiles. A Bayesian integration model was utilized to identify biological pathways predictive of PAH carcinogenic potential during initiation. Integration of probability matrices from four enriched pathways (P PAH mixtures. These data further provide a 'source-to-outcome' model that could be used to predict PAH interactions during tumorigenesis and provide an example of how mode-of-action-based risk assessment could be employed for environmental PAH mixtures. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  16. Human cytochrome P450 enzymes of importance for the bioactivation of methyleugenol to the proximate carcinogen 1′-hydroxymethyleugenol

    NARCIS (Netherlands)

    Jeurissen, S.M.F.; Bogaards, J.J.P.; Boersma, M.G.; Horst, J.P.F. ter; Awad, H.M.; Fiamegos, Y.C.; Beek, T.A. van; Alink, G.M.; Sudhölter, E.J.R.; Cnubben, N.H.P.; Rietjens, I.M.C.M.

    2006-01-01

    In vitro studies were performed to elucidate the human cytochrome P450 enzymes involved in the bioactivation of methyleugenol to its proximate carcinogen 1′-hydroxymethyleugenol. Incubations with Supersomes, expressing individual P450 enzymes to a high level, revealed that P450 1A2, 2A6, 2C9, 2C19,

  17. Changing the field of carcinogenicity testing of human pharmaceuticals by emphasizing mode of action

    NARCIS (Netherlands)

    Laan, J.W. van der; Duijndam, B.; Hoorn, T. van den; Woutersen, R.; Water, B. van de

    2017-01-01

    Lifetime testing for carcinogenicity of pharmaceuticals in rodents has been a controversial issue since the start of the International Conference on Harmonisation in 1990. Since 2010 the debate reached a new level following the proposal that a negative outcome of carcinogenicity studies can be

  18. The draft genome of the carcinogenic human liver fluke Clonorchis sinensis

    Science.gov (United States)

    2011-01-01

    Background Clonorchis sinensis is a carcinogenic human liver fluke that is widespread in Asian countries. Increasing infection rates of this neglected tropical disease are leading to negative economic and public health consequences in affected regions. Experimental and epidemiological studies have shown a strong association between the incidence of cholangiocarcinoma and the infection rate of C. sinensis. To aid research into this organism, we have sequenced its genome. Results We combined de novo sequencing with computational techniques to provide new information about the biology of this liver fluke. The assembled genome has a total size of 516 Mb with a scaffold N50 length of 42 kb. Approximately 16,000 reliable protein-coding gene models were predicted. Genes for the complete pathways for glycolysis, the Krebs cycle and fatty acid metabolism were found, but key genes involved in fatty acid biosynthesis are missing from the genome, reflecting the parasitic lifestyle of a liver fluke that receives lipids from the bile of its host. We also identified pathogenic molecules that may contribute to liver fluke-induced hepatobiliary diseases. Large proteins such as multifunctional secreted proteases and tegumental proteins were identified as potential targets for the development of drugs and vaccines. Conclusions This study provides valuable genomic information about the human liver fluke C. sinensis and adds to our knowledge on the biology of the parasite. The draft genome will serve as a platform to develop new strategies for parasite control. PMID:22023798

  19. Variability in DNA repair capacity in the human population and its relationship to carcinogenic risk

    International Nuclear Information System (INIS)

    Nuzzo, F.; Stefanini, M.; Giulotto, E.; Falaschi, A.

    1980-01-01

    Several inherited diseases, all characterized by a high incidence of tumours in the homozygous patients, show pronounced defects in DNA repair mechanisms, thus confirming the relationship between the repair process and mutation induction, and indicating clearly that a fraction of the population is certainly much more exposed to cancer that the bulk of the human population. The basic molecular defects in such diseases are summarized. The estimated heterozygote frequency in tumour predisposing syndromes is considered and possible identification of heterozygotes discussed. A procedure to reveal DNA repair capacity at the cellular level would perhaps identify the cancer-prone fraction of the population. A simple assay for measuring repair synthesis is outlined which can be used to determine whether a given substance or treatment elicits repair synthesis and is hence harmful to DNA and potentially mutagenic and/or carcinogenic. It can also be used to assess the capacity of an individual to respond to a known DNA damaging agent. (Auth./C.F.)

  20. Human health risk due to consumption of vegetables contaminated with carcinogenic polycyclic aromatic hydrocarbons

    Energy Technology Data Exchange (ETDEWEB)

    Khan, Sardar [Chinese Academy of Sciences, Xiamen (China). Inst. of Urban Environment; Peshawar Univ. (Pakistan). Dept. of Environmental Science; Cao, Qing [Chinese Academy of Sciences, Beijing (China). Research Center for Eco-Environemntal Sciences

    2012-02-15

    Polycyclic aromatic hydrocarbons (PAH) are persistent, toxic, and carcinogenic contaminants present in soil ecosystem globally. These pollutants are gradually accumulating in wastewater-irrigated soils and lead to the contamination of vegetables. Food chain contamination with PAH is considered as one of the major pathways for human exposure. This study was aimed to investigate the concentrations of PAH in soils and vegetables collected from wastewater-irrigated fields from metropolitan areas of Beijing, China. Origin of PAH, daily intake, and health risks of PAH through consumption of contaminated vegetables were studied. Soil samples were collected from the upper horizon (0-20 cm) of both wastewater-irrigated and reference sites and sieved (<2 mm mesh) and then followed by freeze-drying at -50 C and 123 {+-} 2 Pa. Standing vegetables were also collected from the same sites used for soil sampling and divided into roots and shoots, thoroughly washed with deionized water, and freeze-dried. PAH were extracted using the Soxhlet method with 200 mL DCM for 24 h, and the extracts were cleaned with silica adsorption chromatography prepared with silica gel, alumina, and capped with anhydrous sodium. The final concentrated extracts (soil and vegetable) were analyzed using gas chromatography-mass spectrometry (Agilent 6890). Bioaccumulation factors, daily intake of PAH, and carcinogenicity of PAH were calculated by different statistical equations. Results indicate that the soils and grown vegetables were contaminated with all possible carcinogenic PAH (declared by USEPA 2002) except indeno[1,2,3-c,d]pyrene. The highest concentration (242.9 {mu}g kg{sup -1}) was found for benzo(k)fluoranthene (BkF), while lowest (79.12 {mu}g kg{sup -1}) for benzo[a]pyrene (BaP). The emission sources of PAH were both pyrogenic and petrogenic in nature. However, the total concentrations of PAH were lower than the permissible limits set by different countries like Canada, Denmark and Germany

  1. Residues of carcinogenic animal drugs in food: difficulties in evaluation of human safety.

    Science.gov (United States)

    Somogyi, A

    1979-01-01

    The indisputable need to intensify animal production in order to provide an adequate food supply for the world population involves the use of substances that are highly potent pharmacologically and toxicologically. The history of regulatory action with regard to such additives is similar to that for other substances: first, no regulation; next, an over-reaction; and now decisions based on judicious evaluation of scientific facts. One factor that differentiates the chemicals used in animal production from other food additives is that both the parent compounds and their metabolites appear in edible products, posing problems both for the analytical detection and safety evaluation of such residues. It would be unrealistic to propose 'zero' tolerances for these additives, even if they are carcinogenic. The benefits gained from drugs that cure and prevent infections and parasitic diseases in food-producing animals, and the fact that analytical methods can now detect very small quantities make the presence of low levels of these substances in food unobjectionable.

  2. Animal carcinogenicity studies on radiofrequency fields related to mobile phones and base stations.

    Science.gov (United States)

    Dasenbrock, Clemens

    2005-09-01

    Since a report in 1997 on an increased lymphoma incidence in mice chronically exposed to a mobile phone radiofrequency signal, none of the subsequent long-term studies in rodents have confirmed these results. On the other hand, several of the follow-up co- and carcinogenicity studies are still underway or are presently being initiated. Most of the published long-term studies used 1 exposure level only and suffer from a poor dosimetry which does not consider the animal's growth. Additional points of criticism are a limited, in some cases, questionable histopathology and inadequate group sizes. Overall, if dealing with new chemicals or drugs, these studies would not be acceptable for registration with the responsible authorities. The major critical points are taken into consideration within the European co- and carcinogenicity projects (CEMFEC and PERFORM-A), which are in their final stages and in the US long-term studies in mice and rats which are about to be initiated. Nevertheless, the WHO evaluation for health risk assessment of long-term telephone use and base station exposure will start in late 2005.

  3. [The implementation of polymerase chain reaction technique: the real time to reveal and differentiate the viruses of human papilloma of high carcinogenic risk].

    Science.gov (United States)

    Andosova, L D; Kontorshchikova, K N; Blatova, O L; Kudel'kina, S Iu; Kuznetsova, I A; Belov, A V; Baĭkova, R A

    2011-07-01

    The polymerase chain reaction technique was applied in "real time" format to evaluate the occurrence rate and infection ratio of various genotypes of human papilloma of high carcinogenic risk in virus-positive women and contact persons. The examination sampling consisted of 738 women aged of 17-50 years. The examination results permitted to establish high percentage of infection of 546 patients (74%) by carcinogenic papilloma viruses. The analysis of detection rate of various genotypes of human papilloma of high carcinogenic risk established that the 56th and 16th types of high carcinogenic risk are revealed more often than others--in 33% and 15.4% correspondingly. In males, first place in occurrence rate is for those types of virus of human papilloma: the 56th n = 10 (33.3%), 16th n = 3 (10%), 45th n = 3 (10%), 51th n = 3 (10%). The rest of genotypes are detected in 3-7% cases.

  4. Polycyclic aromatic hydrocarbon-DNA adducts in cervix of women infected with carcinogenic human papillomavirus types: An immunohistochemistry study

    International Nuclear Information System (INIS)

    Pratt, M. Margaret; Sirajuddin, Paul; Poirier, Miriam C.; Schiffman, Mark; Glass, Andrew G.; Scott, David R.; Rush, Brenda B.; Olivero, Ofelia A.; Castle, Philip E.

    2007-01-01

    Among women infected with carcinogenic human papillomavirus (HPV), there is a two- to five-fold increased risk of cervical precancer and cancer in women who smoke compared to those who do not smoke. Because tobacco smoke contains carcinogenic polycyclic aromatic hydrocarbons (PAHs), it was of interest to examine human cervical tissue for PAH-DNA adduct formation. Here, we measured PAH-DNA adduct formation in cervical biopsies collected in follow-up among women who tested positive for carcinogenic HPV at baseline. A semi-quantitative immunohistochemistry (IHC) method using antiserum elicited against DNA modified with r7,t8-dihydroxy-t-9,10-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE) was used to measure nuclear PAH-DNA adduct formation. Cultured human cervical keratinocytes exposed to 0, 0.153, or 0.331 μM BPDE showed dose-dependent increases in r7,t8,t9-trihydroxy-c-10-(N 2 deoxyguanosyl)-7,8,9, 10-tetrahydro-benzo[a]pyrene (BPdG) adducts. For BPdG adduct analysis, paraffin-embedded keratinocytes were stained by IHC with analysis of nuclear color intensity by Automated Cellular Imaging System (ACIS) and, in parallel cultures, extracted DNA was assayed by quantitative BPDE-DNA chemiluminescence immunoassay (CIA). For paraffin-embedded samples from carcinogenic HPV-infected women, normal-appearing cervical squamous epithelium suitable for scoring was found in samples from 75 of the 114 individuals, including 29 cases of cervical precancer or cancer and 46 controls. With a lower limit of detection of 20 adducts/10 8 nucleotides, detectable PAH-DNA adduct values ranged from 25 to 191/10 8 nucleotides, with a median of 75/10 8 nucleotides. PAH-DNA adduct values above 150/10 8 nucleotides were found in eight samples, and in three samples adducts were non-detectable. There was no correlation between PAH-DNA adduct formation and either smoking or case status. Therefore, PAH-DNA adduct formation as measured by this methodology did not appear related to the increased risk

  5. Polycyclic aromatic hydrocarbon-DNA adducts in cervix of women infected with carcinogenic human papillomavirus types: An immunohistochemistry study

    Energy Technology Data Exchange (ETDEWEB)

    Pratt, M. Margaret [Carcinogen-DNA Interactions Section, LCBG, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD (United States)], E-mail: prattm@mail.nih.gov; Sirajuddin, Paul; Poirier, Miriam C. [Carcinogen-DNA Interactions Section, LCBG, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD (United States); Schiffman, Mark [Hormonal and Reproductive Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD (United States); Glass, Andrew G.; Scott, David R.; Rush, Brenda B. [Northwest Kaiser Permanente, Portland, OR (United States); Olivero, Ofelia A. [Carcinogen-DNA Interactions Section, LCBG, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD (United States); Castle, Philip E. [Hormonal and Reproductive Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD (United States)

    2007-11-01

    Among women infected with carcinogenic human papillomavirus (HPV), there is a two- to five-fold increased risk of cervical precancer and cancer in women who smoke compared to those who do not smoke. Because tobacco smoke contains carcinogenic polycyclic aromatic hydrocarbons (PAHs), it was of interest to examine human cervical tissue for PAH-DNA adduct formation. Here, we measured PAH-DNA adduct formation in cervical biopsies collected in follow-up among women who tested positive for carcinogenic HPV at baseline. A semi-quantitative immunohistochemistry (IHC) method using antiserum elicited against DNA modified with r7,t8-dihydroxy-t-9,10-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE) was used to measure nuclear PAH-DNA adduct formation. Cultured human cervical keratinocytes exposed to 0, 0.153, or 0.331 {mu}M BPDE showed dose-dependent increases in r7,t8,t9-trihydroxy-c-10-(N{sup 2}deoxyguanosyl)-7,8,9, 10-tetrahydro-benzo[a]pyrene (BPdG) adducts. For BPdG adduct analysis, paraffin-embedded keratinocytes were stained by IHC with analysis of nuclear color intensity by Automated Cellular Imaging System (ACIS) and, in parallel cultures, extracted DNA was assayed by quantitative BPDE-DNA chemiluminescence immunoassay (CIA). For paraffin-embedded samples from carcinogenic HPV-infected women, normal-appearing cervical squamous epithelium suitable for scoring was found in samples from 75 of the 114 individuals, including 29 cases of cervical precancer or cancer and 46 controls. With a lower limit of detection of 20 adducts/10{sup 8} nucleotides, detectable PAH-DNA adduct values ranged from 25 to 191/10{sup 8} nucleotides, with a median of 75/10{sup 8} nucleotides. PAH-DNA adduct values above 150/10{sup 8} nucleotides were found in eight samples, and in three samples adducts were non-detectable. There was no correlation between PAH-DNA adduct formation and either smoking or case status. Therefore, PAH-DNA adduct formation as measured by this methodology did not appear

  6. The carcinogenic risk of high dose total body irradiation in non-human primates

    International Nuclear Information System (INIS)

    Broerse, J.J.; Bartstra, R.W.; Bekkum, D.W. van; Hage, M.H. van der; Zurcher, C.; Zwieten, M.J. van; Hollander, C.F.

    2000-01-01

    High dose total body irradiation (TBI) in combination with chemotherapy, followed by rescue with bone marrow transplantation (BMT), is increasingly used for the treatment of haematological malignancies. With the increasing success of this treatment and its current introduction for treating refractory autoimmune diseases the risk of radiation carcinogenesis is of growing concern. Studies on turnout induction in non-human primates are of relevance in this context since the response of this species to radiation does not differ much from that in man. Since the early sixties, studies have been performed on acute effects in Rhesus monkeys and the protective action of bone marrow transplantation after irradiation with X-rays (average total body dose 6.8 Gy) and fission neutrons (average dose 3.4 Gy). Of those monkeys, which were irradiated and reconstituted with autologous bone marrow, 20 animals in the X-irradiated group and nine animals in the neutron group survived more than 3 years. A group of 21 non-irradiated Rhesus monkeys of a comparable age distribution served as controls. All animals were regularly screened for the occurrence of neoplasms. Complete necropsies were performed after natural death or euthanasia. At post-irradiation intervals of 4-21 years an appreciable number of tumours was observed. In the neutron irradiated group eight out of nine animals died with one or more malignant tumours. In the X-irradiated group this fraction was 10 out of 20. The tumours in the control group, in seven out of the 21 animals, appeared at much older a-e compared with those in the irradiated cohorts. The histogenesis of the tumours was diverse with a preponderance of renal carcinoma, sarcomas among which osteosarcormas, and malignant glomus tumours in the irradiated groups. When corrected for competing risks, the carcinogenic risk of TBI in the Rhesus monkeys is similar to that derived from the studies of the Japanese atomic bomb survivors. The increase of the risk by a

  7. Human cytochrome-P450 enzymes metabolize N-(2-methoxyphenyl)hydroxylamine, a metabolite of the carcinogens o-anisidine and o-nitroanisole, thereby dictating its genotoxicity.

    Science.gov (United States)

    Naiman, Karel; Martínková, Markéta; Schmeiser, Heinz H; Frei, Eva; Stiborová, Marie

    2011-12-24

    N-(2-Methoxyphenyl)hydroxylamine is a component in the human metabolism of two industrial and environmental pollutants and bladder carcinogens, viz. 2-methoxyaniline (o-anisidine) and 2-methoxynitrobenzene (o-nitroanisole), and it is responsible for their genotoxicity. Besides its capability to form three deoxyguanosine adducts in DNA, N-(2-methoxyphenyl)-hydroxylamine is also further metabolized by hepatic microsomal enzymes. To investigate its metabolism by human hepatic microsomes and to identify the major microsomal enzymes involved in this process are the aims of this study. N-(2-Methoxyphenyl)hydroxylamine is metabolized by human hepatic microsomes predominantly to o-anisidine, one of the parent carcinogens from which N-(2-methoxyphenyl)hydroxylamine is formed, while o-aminophenol and two N-(2-methoxyphenyl)hydroxylamine metabolites, whose exact structures have not been identified as yet, are minor products. Selective inhibitors of microsomal CYPs, NADPH:CYP reductase and NADH:cytochrome-b(5) reductase were used to characterize human liver microsomal enzymes reducing N-(2-methoxyphenyl)hydroxylamine to o-anisidine. Based on these studies, we attribute the main activity for this metabolic step in human liver to CYP3A4, 2E1 and 2C (more than 90%). The enzymes CYP2D6 and 2A6 also partake in this N-(2-methoxyphenyl)hydroxylamine metabolism in human liver, but only to ∼6%. Among the human recombinant CYP enzymes tested in this study, human CYP2E1, followed by CYP3A4, 1A2, 2B6 and 2D6, were the most efficient enzymes metabolizing N-(2-methoxyphenyl)hydroxylamine to o-anisidine. The results found in this study indicate that genotoxicity of N-(2-methoxyphenyl)hydroxylamine is dictated by its spontaneous decomposition to nitrenium/carbenium ions generating DNA adducts, and by its susceptibility to metabolism by CYP enzymes. Copyright © 2011 Elsevier B.V. All rights reserved.

  8. Chemical Carcinogen (Hydrazine et al.) Induced Carcinogenesis of Human Diploid Cells in Vitro

    Science.gov (United States)

    1982-09-07

    untreated cell popula- pared from the stock solutions in complete growth tions were seeded onto CES in vitro. The CES medium (CIM). Thee solutions were added...time from induction pared to metastases IFig. IBl. We want to imply to neoplasia of 6 to 10 wk instead of 1 to 1.5 yr. that these chemical carcinogen...This definition was used because the pathologist was ds:b celular invasion Into CE,, an organ culture, In vitro. Thw two Interpretations am not

  9. The carcinogenic air pollutant 3-nitrobenzanthrone induces GC to TA transversion mutations in human p53 sequences.

    Science.gov (United States)

    vom Brocke, Jochen; Krais, Annette; Whibley, Catherine; Hollstein, Monica C; Schmeiser, Heinz H

    2009-01-01

    3-Nitrobenzanthrone (3-NBA) is a potent mutagen and a suspected human carcinogen present in particulate matter of diesel exhaust and ambient air pollution. Employing an assay with human p53 knock-in (Hupki) murine embryonic fibroblasts (HUFs), we examined p53 mutations induced by 3-NBA and its active metabolite, N-hydroxy-3-aminobenzanthrone (N-OH-3-ABA). Twenty-nine immortalized cultures (cell lines) from 89 HUF primary cultures exposed at passage 1 for 5 days to 2 microM 3-NBA harboured 22 different mutations in the human DNA-binding domain sequence of the Hupki p53 tumour suppressor gene. The most frequently observed mutation was GC to TA transversion (46%), corroborating previous mutation studies with 3-NBA, and consistent with the presence of persistent 3-NBA-guanosine adducts found in DNA of exposed rodents. Six of the transversions found solely in 3-NBA-treated HUFs have not been detected thus far in untreated HUFs, but have been found repeatedly in human lung tumours. (32)P-post-labelling adduct analysis of DNA from HUF cells treated with 2 microM 3-NBA for 5 days showed a pattern similar to that found in vivo, indicating the metabolic competence of HUF cells to metabolize 3-NBA to electrophilic intermediates. Total DNA binding was 160 +/- 56 per 10(7) normal nucleotides with N(2)-guanosine being the major adduct. In contrast, identical treatment with N-OH-3-ABA resulted in a 100-fold lower level of specific DNA adducts and no carcinogen-specific mutation pattern in the Hupki assay. This indicates that the level of DNA adduct formation by the mutagen is critical to obtain specific mutation spectra in the assay. Our results are consistent with previous experiments in Muta Mouse and are compatible with the possibility that diesel exhaust exposure contributes to mutation load in humans and to lung cancer risk.

  10. A Web-based Simulator for Sample Size and Power Estimation in Animal Carcinogenicity Studies

    Directory of Open Access Journals (Sweden)

    Hojin Moon

    2002-12-01

    Full Text Available A Web-based statistical tool for sample size and power estimation in animal carcinogenicity studies is presented in this paper. It can be used to provide a design with sufficient power for detecting a dose-related trend in the occurrence of a tumor of interest when competing risks are present. The tumors of interest typically are occult tumors for which the time to tumor onset is not directly observable. It is applicable to rodent tumorigenicity assays that have either a single terminal sacrifice or multiple (interval sacrifices. The design is achieved by varying sample size per group, number of sacrifices, number of sacrificed animals at each interval, if any, and scheduled time points for sacrifice. Monte Carlo simulation is carried out in this tool to simulate experiments of rodent bioassays because no closed-form solution is available. It takes design parameters for sample size and power estimation as inputs through the World Wide Web. The core program is written in C and executed in the background. It communicates with the Web front end via a Component Object Model interface passing an Extensible Markup Language string. The proposed statistical tool is illustrated with an animal study in lung cancer prevention research.

  11. Carcinogenic polycyclic aromatic hydrocarbons in umbilical cord blood of human neonates from Guiyu, China

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Yongyong; Huo, Xia [Analytic Cytology Laboratory and the Key Immunopathology Laboratory of Guangdong Province, Shantou University Medical College, Shantou (China); Wu, Kusheng [Analytic Cytology Laboratory and the Key Immunopathology Laboratory of Guangdong Province, Shantou University Medical College, Shantou (China); Department of Preventive Medicine, Shantou University Medical College, Shantou (China); Liu, Junxiao; Zhang, Yuling [Analytic Cytology Laboratory and the Key Immunopathology Laboratory of Guangdong Province, Shantou University Medical College, Shantou (China); Xu, Xijin, E-mail: xuxj@stu.edu.cn [Analytic Cytology Laboratory and the Key Immunopathology Laboratory of Guangdong Province, Shantou University Medical College, Shantou (China); Department of Cell Biology and Genetics, Shantou University Medical College, Shantou (China)

    2012-06-15

    Unregulated electronic-waste recycling results in serious environmental pollution of polycyclic aromatic hydrocarbons (PAHs) in Guiyu, China. We evaluated the body burden of seven carcinogenic PAHs and potential health risks for neonates. Umbilical cord blood (UCB) samples were collected from Guiyu (n = 103), and the control area of Chaonan (n = 80), China. PAHs in UCB were determined by gas chromatography/mass spectrometry. The median N-Ary-Summation 7c-PAH concentration was 108.05 ppb in UCB samples from Guiyu, vs. 79.36 ppb in samples from Chaonan. Residence in Guiyu and longer cooking time of food during the gestation period were significant factors contributing to the N-Ary-Summation 7c-PAH level. Benzo[a]anthracene (BaA), chrysene (Chr), and benzo[a]pyrene (BaP) were found to correlate with reduced neonatal height and gestational age. Infants experiencing adverse birth outcomes, on the whole, displayed higher BaA, Chr, and BaP levels compared to those with normal outcomes. We conclude that maternal PAH exposure results in fetal accumulation of toxic PAHs, and that such prenatal exposure correlates with adverse effects on neonatal health.

  12. What advice to give when ELF is classified as a possible human carcinogen

    International Nuclear Information System (INIS)

    Repacholi, M.

    2002-01-01

    In 1996, the World Health Organization (WHO) established the International Electromagnetic Fields (EMF) Project to address the health issues associated with exposure to EMF. This Project is intended to provide independent scientific assessment of health effects from exposure to EMF (0-300 GHz); identify gaps in knowledge requiring further research in order to improve health risk assessments; encourage focused, high quality research; and conduct formal WHO/IARC/ICNIRP health risk assessments after key research has been completed. The International EMF Project is currently reviewing research results and conducting risk assessments of exposure to static and extremely low frequency (ELF) electric and magnetic fields. WHO will be conducting an evaluation of all health effects from ELF field exposure during 2002-3. This paper summarizes what is known about ELF exposure on childhood leukaemia, what the IARC classification means and how some national authorities have responded. In addition, WHO recommendations are given to provide guidance to national authorities wanting to protect their populations against EMF exposure. Whenever electricity is conducted through transmission lines, distribution lines or is used in appliances, both electric and magnetic fields exist close to the lines or appliances. The power frequency used is 50 or 60 Hz. Use of electric power has become part of everyday life. However, questions have been raised as to whether these and other ELF fields are carcinogenic or can produce any other effects on health

  13. Assessment of possible carcinogenicity of oxyfluorfen to humans using mode of action analysis of rodent liver effects.

    Science.gov (United States)

    Stagg, Nicola J; LeBaron, Matthew J; Eisenbrandt, David L; Gollapudi, B Bhaskar; Klaunig, James E

    2012-08-01

    Oxyfluorfen is a herbicide that is not genotoxic and produces liver toxicity in rodents, following repeated administration at high dose levels. Lifetime rodent feeding studies reported in 1977 with low-purity oxyfluorfen (85%) showed no increase in any tumor type in rats (800 ppm, high dose) and only a marginally increased incidence of hepatocellular tumors in male CD-1 mice at the highest dose (200 ppm). To evaluate the potential carcinogenicity of the currently registered oxyfluorfen (> 98% purity), we conducted a series of short-term liver mode of action (MOA) toxicology studies in male CD-1 mice administered dietary doses of 0, 40, 200, 800, and 1600 ppm for durations of 3, 7, 10, or 28 days. MOA endpoints examined included liver weight, histopathology, cell proliferation, nuclear receptor-mediated gene expression, and other peroxisome proliferator-specific endpoints and their reversibility. Minimal liver effects were observed in mice administered doses at or below 200 ppm for up to 28 days. Increased liver weight, single-cell necrosis, cell proliferation, and peroxisomal acyl-CoA oxidase (ACO) were observed at 800 ppm after 28 days, but there was no increase in peroxisomes. Expression of Cyp2b10 and Cyp4a10 transcripts, markers of constitutive androstane receptor and peroxisome proliferator activated receptor α nuclear receptor activation, respectively, were increased at 800 and 1600 ppm after 3 or 10 days. Collectively, these data along with the negative genotoxicity demonstrate that oxyfluorfen (> 98% purity) has the potential to induce mouse liver tumors through a nongenotoxic, mitogenic MOA with a clear threshold and is not predicted to be carcinogenic in humans at relevant exposure levels.

  14. Carcinogenic compounds in alcoholic beverages: an update.

    Science.gov (United States)

    Pflaum, Tabea; Hausler, Thomas; Baumung, Claudia; Ackermann, Svenja; Kuballa, Thomas; Rehm, Jürgen; Lachenmeier, Dirk W

    2016-10-01

    The consumption of alcoholic beverages has been classified as carcinogenic to humans by the International Agency for Research on Cancer (IARC) since 1988. More recently, in 2010, ethanol as the major constituent of alcoholic beverages and its metabolite acetaldehyde were also classified as carcinogenic to humans. Alcoholic beverages as multi-component mixtures may additionally contain further known or suspected human carcinogens as constituent or contaminant. This review will discuss the occurrence and toxicology of eighteen carcinogenic compounds (acetaldehyde, acrylamide, aflatoxins, arsenic, benzene, cadmium, ethanol, ethyl carbamate, formaldehyde, furan, glyphosate, lead, 3-MCPD, 4-methylimidazole, N-nitrosodimethylamine, pulegone, ochratoxin A, safrole) occurring in alcoholic beverages as identified based on monograph reviews by the IARC. For most of the compounds of alcoholic beverages, quantitative risk assessment provided evidence for only a very low risk (such as margins of exposure above 10,000). The highest risk was found for ethanol, which may reach exposures in ranges known to increase the cancer risk even at moderate drinking (margin of exposure around 1). Other constituents that could pose a risk to the drinker were inorganic lead, arsenic, acetaldehyde, cadmium and ethyl carbamate, for most of which mitigation by good manufacturing practices is possible. Nevertheless, due to the major effect of ethanol, the cancer burden due to alcohol consumption can only be reduced by reducing alcohol consumption in general or by lowering the alcoholic strength of beverages.

  15. Food derived carcinogenic amnoimidazoazaarenes

    DEFF Research Database (Denmark)

    Frandsen, Henrik

    Carcinogenic aminoimidazoazaarenes are formed during cooking of meat and fish. Important factors for the formation of these compounds are meat type, cooking temperature and time. The compounds are genotoxic in bacterial and mammalian cells. In animal feeding studies the compounds tested so far were...... of the exocyclic amino group. Estimations of human cancer risk have indicated that ingestion of food containing aminoimidazoazaarenes are of importance....

  16. Carcinogenicity of Human Papillomavirus (HPV) Types in HIV-Positive Women: A Meta-Analysis From HPV Infection to Cervical Cancer

    OpenAIRE

    Clifford, Gary M.; Tully, Stephen; Franceschi, Silvia

    2017-01-01

    Abstract Background. Data on the relative carcinogenic potential of human papillomavirus (HPV) types among women infected with human immunodeficiency virus (HIV) (WHIV) are needed to inform prevention programs for this population. Methods. A systematic literature review and meta-analysis of high-risk HPV-type distribution in 19883 HIV-positive women was performed. The women, from 86 studies worldwide, included 11739 with normal cytological findings; 1784 with atypical squamous cells of undete...

  17. Blood proteins as carcinogen dosimeters

    International Nuclear Information System (INIS)

    Tannenbaum, S.R.; Skipper, P.L.

    1986-01-01

    The problem of quantifying exposure to genotoxins in a given individual represents a formidable challenge. In this paper methods which rely on the covalent binding of carcinogens and their metabolites to blood proteins are described. That carcinogens interact with proteins as well as with DNA has been established, although whether protein-carcinogen adducts can result in genetic damage has not been established. It has been shown, however, that the amount of a protein carcinogen adduct formed may be used as a quantitative measure of exposure to a carcinogen. Such a measure presumably is reflective of the absorption, metabolism, and excretion of the compound in an exposed individual. Protein adduction may reflect exposure in a time-frame of weeks to months. Thus, protein adduct measurement is a form of human chemical dosimetry. Hemoglobin and albumin are promising candidates for such dosimeters. Hemoglobin has a lifetime of about 120 days in humans; thus, circulating levels of carcinogen-modified hemoglobin will reflect the level of carcinogen exposure during a period of nearly four months. It also possesses some metabolic competence, particularly, the ability to oxidize aromatic hydroxylamines to nitroso compounds which react quite efficiently with sulfhydryl groups. Albumin has a half-life of 20 to 25 days in man. This protein does not possess metabolic capacity other than, perhaps, some esterase activity. In contrast to hemoglobin, though, it is not protected by the erythrocyte membrane and might be the target for a greater number of carcinogens. It is present and is synthesized in the same cells in which the reactive metabolic intermediates of carcinogens are mostly formed - the hepatocytes. Also, albumin has a number of high-affinity binding sites for a broad spectrum of xenobiotics and endobiotics. 25 refs., 1 tab

  18. Trichloroethylene: Mechanistic, epidemiologic and other supporting evidence of carcinogenic hazard.

    Science.gov (United States)

    Rusyn, Ivan; Chiu, Weihsueh A; Lash, Lawrence H; Kromhout, Hans; Hansen, Johnni; Guyton, Kathryn Z

    2014-01-01

    The chlorinated solvent trichloroethylene (TCE) is a ubiquitous environmental pollutant. The carcinogenic hazard of TCE was the subject of a 2012 evaluation by a Working Group of the International Agency for Research on Cancer (IARC). Information on exposures, relevant data from epidemiologic studies, bioassays in experimental animals, and toxicity and mechanism of action studies was used to conclude that TCE is carcinogenic to humans (Group 1). This article summarizes the key evidence forming the scientific bases for the IARC classification. Exposure to TCE from environmental sources (including hazardous waste sites and contaminated water) is common throughout the world. While workplace use of TCE has been declining, occupational exposures remain of concern, especially in developing countries. The strongest human evidence is from studies of occupational TCE exposure and kidney cancer. Positive, although less consistent, associations were reported for liver cancer and non-Hodgkin lymphoma. TCE is carcinogenic at multiple sites in multiple species and strains of experimental animals. The mechanistic evidence includes extensive data on the toxicokinetics and genotoxicity of TCE and its metabolites. Together, available evidence provided a cohesive database supporting the human cancer hazard of TCE, particularly in the kidney. For other target sites of carcinogenicity, mechanistic and other data were found to be more limited. Important sources of susceptibility to TCE toxicity and carcinogenicity were also reviewed by the Working Group. In all, consideration of the multiple evidence streams presented herein informed the IARC conclusions regarding the carcinogenicity of TCE. © 2013.

  19. Human bronchus-mediated mutagenesis of mammalian cells by carcinogenic polycyclic aromatic hydrocarbon

    DEFF Research Database (Denmark)

    Hsu, Ih Chang; Stoner, Gary D.; Autrup, Herman

    1978-01-01

    Cultured human bronchial explants activated benzo[alpha]pyrene (BzaP) into electrophilic metabolites that bind to DNA in bronchial epithelial cells. Promutagenic and mutagenic metabolites of BzaP were also released into the culture medium. An increase in mutation frequency for ouabain resistance ...

  20. Chemical Carcinogen-Induced Changes in tRNA Metabolism in Human Cells.

    Science.gov (United States)

    1981-11-01

    the resolution and quantitation of modified ucleosides in the urine of cancer patients would not be particularly useful for the cell culture studies...Comparison of nucleic acid catabolism by normal human fibroblasts and fibroblasts transformed with methylazoxymethyl alcohol ( MAMA ),an activated...catabolite in long-term, pulse-chase experiments. However, the kinetics of catabolism differed, in that only the MAMA -transformed cells had generated

  1. Chromium carcinogenicity: California strategies.

    Science.gov (United States)

    Alexeeff, G V; Satin, K; Painter, P; Zeise, L; Popejoy, C; Murchison, G

    1989-10-01

    Hexavalent chromium was identified by California as a toxic air contaminant (TAC) in January 1986. The California Department of Health Services (CDHS) concurred with the findings of the International Agency for Research on Cancer that there is sufficient evidence to demonstrate the carcinogenicity of chromium in both animals and humans. CDHS did not find any compelling evidence demonstrating the existence of a threshold with respect to chromium carcinogenesis. Experimental data was judged inadequate to assess potential human reproductive risks from ambient exposures. Other health effects were not expected to occur at ambient levels. The theoretically increased lifetime carcinogenic risk from a continuous lifetime exposure to hexavalent chromium fell within the range 12-146 cancer cases per nanogram hexavalent chromium per cubic meter of air per million people exposed, depending on the potency estimate used. The primary sources found to contribute significantly to the risk of exposure were chrome platers, chromic acid anodizing facilities and cooling towers utilizing hexavalent chromium as a corrosion inhibitor. Evaluation of genotoxicity data, animal studies and epidemiological studies indicates that further consideration should be given to the potential carcinogenicity of hexavalent chromium via the oral route.

  2. Nitrites and nitrates in the human diet: Carcinogens or beneficial hypotensive agents?

    Science.gov (United States)

    Butler, Anthony

    2015-06-05

    The presence of nitrite in the human diet was thought to constitute a hazard as secondary nitrosamines are known to cause gastric cancers. Recent publications on the physiology of serum nitrite have been consulted. Nitrite is added to some foodstuffs as an antibotulinum agent. The epidemiological evidence that nitrite causes gastric ulcers is weak. On the other hand, evidence that the presence of nitrite in serum lowers blood pressure is strong. This allows us to explain why a Tang dynasty treatment for angina, given in a Dunhuang medical manuscript, can be successful. The presence of nitrite in food is free of danger and a diet high in nitrate is beneficial to the health. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  3. Laser diagnostics of native cervix dabs with human papilloma virus in high carcinogenic risk

    Science.gov (United States)

    Peresunko, O. P.; Karpenko, Ju. G.; Burkovets, D. N.; Ivashko, P. V.; Nikorych, A. V.; Yermolenko, S. B.; Gruia, Ion; Gruia, M. J.

    2015-11-01

    The results of experimental studies of coordinate distributions of Mueller matrix elements of the following types of cervical scraping tissue are presented: rate- low-grade - highly differentiated dysplasia (CIN1-CIN3) - adenocarcinoma of high, medium and low levels of differentiation (G1-G3). The rationale for the choice of statistical points 1-4 orders polarized coherent radiation field, transformed as a result of interaction with the oncologic modified biological layers "epithelium-stroma" as a quantitative criterion of polarimetric optical differentiation state of human biological tissues are shown here. The analysis of the obtained Mueller matrix elements and statistical correlation methods, the systematized by types studied tissues is accomplished. The results of research images of Mueller matrix elements m34 for this type of pathology as low-grade dysplasia (CIN2), the results of its statistical and correlation analysis are presented.

  4. DNA repair in human cells exposed to combinations of carcinogenic agents

    International Nuclear Information System (INIS)

    Setlow, R.B.; Ahmed, F.E.

    1980-01-01

    Normal human and XP 2 fibroblasts were treated with uv plus uv-mimetic chemicals. The uv dose used was sufficient to saturate the uv excision repair system. Excision repair after combined treatments was estimated by unscheduled DNA synthesis, BrdUrd photolysis, and the loss of sites sensitive to a uv specific endonuclease. Since the repair of damage from uv and its mimetics is coordinately controlled we expected that there would be similar rate-limiting steps in the repair of uv and chemical damage and that after a combined treatment the total amount of repair would be the same as from uv or the chemicals separately. The expectation was not fulfilled. In normal cells repair after a combined treatment was additive whereas in XP cells repair after a combined treatment was usually less than after either agent separately. The chemicals tested were AAAF, DMBA-epoxide, 4NQO, and ICR-170

  5. Carcinogen-DNA interaction study by base sequence footprinting. Final report, July 1, 1983-June 30, 1986

    International Nuclear Information System (INIS)

    Bases, R.

    1986-01-01

    Our previous studies on acetylaminofluorene (AAF) modified DNA demonstrated three kinds of structural changes in DNA of defined base sequence. For example, adduct formation by N-Aco-AAF was found at each guanine. We studied the interaction of IgG specific for AAF guanosine in an in vitro system using AAF modified phi X-174 rf DNA. We had expected to find protection against DNAase I digestion. Instead, when the DNA was immunobound to an inert matrix via the IgG, DNAase I digestion was enhanced 20 fold without changing the base sequence pattern of digestion. DNAase I hypersensitive sites are a necessary but not a sufficient condition for transcription. Moreover, some hypersensitive sites are stably propagated, independent of the continued presence of the inducer. Stability of these hypersensitive sites in the absence of their inducer suggests that they can be propagated. It appeared likely that distortion of DNA by a carcinogen adduct such as AAF, and the interaction of this modified DNA with a specific protein such as IgG or cellular proteins might inappropriately enhance the transcription of specific genes. That hypothesis will be tested; surprisingly, little is known about the early action of carcinogens on expression of specific genes. 34 refs., 2 figs., 1 tab

  6. Interpretation of the margin of exposure for genotoxic carcinogens - elicitation of expert knowledge about the form of the dose response curve at human relevant exposures.

    Science.gov (United States)

    Boobis, Alan; Flari, Villie; Gosling, John Paul; Hart, Andy; Craig, Peter; Rushton, Lesley; Idahosa-Taylor, Ehi

    2013-07-01

    The general approach to risk assessment of genotoxic carcinogens has been to advise reduction of exposure to "as low as reasonably achievable/practicable" (ALARA/P). However, whilst this remains the preferred risk management option, it does not provide guidance on the urgency or extent of risk management actions necessary. To address this, the "Margin of Exposure" (MOE) approach has been proposed. The MOE is the ratio between the point of departure for carcinogenesis and estimated human exposure. However, interpretation of the MOE requires implicit or explicit consideration of the shape of the dose-response curve at human relevant exposures. In a structured elicitation exercise, we captured expert opinion on available scientific evidence for low dose-response relationships for genotoxic carcinogens. This allowed assessment of: available evidence for the nature of dose-response relationships at human relevant exposures; the generality of judgments about such dose-response relationships; uncertainties affecting judgments on the nature of such dose-response relationships; and whether this last should differ for different classes of genotoxic carcinogens. Elicitation results reflected the variability in experts' views on the form of the dose-response curve for low dose exposure and major sources of uncertainty affecting the assumption of a linear relationship. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Gene expression changes induced by estrogen and selective estrogen receptor modulators in primary-cultured human endometrial cells: signals that distinguish the human carcinogen tamoxifen

    International Nuclear Information System (INIS)

    Pole, Jessica C.M.; Gold, Leslie I.; Orton, Terry; Huby, Russell; Carmichael, Paul L.

    2005-01-01

    Tamoxifen has long been the endocrine treatment of choice for women with breast cancer and is now employed for prophylactic use in women at high risk from breast cancer. Other selective estrogen receptor modulators (SERMs), such as raloxifene, mimic some of tamoxifen's beneficial effects and, like tamoxifen, exhibit a complex mixture of organ-specific estrogen agonist and antagonistic properties. However, accompanying the positive effects of tamoxifen has been the emergence of evidence for an increased risk of endometrial cancer associated with its use. A more complete understanding of the mechanism(s) of SERM carcinogenicity and endometrial effects is therefore required. We have sought to compare and characterise the transcript profile of tamoxifen, raloxifene and the agonist estradiol in human endometrial cells. Using primary cultures of human endometria, to best emulate the in vivo responses in a manageable in vitro system, we have shown 230 significant changes in gene expression for epithelial cultures and 83 in stromal cultures, either specific to 17β-estradiol, tamoxifen or raloxifene, or changed across more than one of the treatments. Considering the transcriptome as a whole, the endometrial responses to raloxifene or tamoxifen were more similar than either drug was to 17β-estradiol. Treatment of endometrial cultures with tamoxifen resulted in the largest number of gene changes relative to control cultures and a high proportion of genes associated with regulation of gene transcription, cell-cycle control and signal transduction. Tamoxifen-specific changes that might point towards mechanisms for its proliferative response in the endometrium included changes in retinoblastoma and c-myc binding proteins, the APCL, dihydrofolate reductase (DHFR) and E2F1 genes and other transcription factors. Tamoxifen was also found to give rise to the highest number of gene expression changes common to those that characterise malignant endometria. It is anticipated that this

  8. Two azole fungicides (carcinogenic triadimefon and non-carcinogenic myclobutanil) exhibit different hepatic cytochrome P450 activities in medaka fish

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Chun-Hung [Department of Agricultural Chemistry, National Taiwan University, Taipei, Taiwan (China); Chou, Pei-Hsin [Department of Environmental Engineering, National Cheng-Kung University, Tainan, Taiwan (China); Chen, Pei-Jen, E-mail: chenpj@ntu.edu.tw [Department of Agricultural Chemistry, National Taiwan University, Taipei, Taiwan (China)

    2014-07-30

    Highlights: • We assess ecotoxicological impact of azole fungicides in the aquatic environment. • Carcinogenic and non-carcinogenic azoles show different CYP activities in medaka. • We compare azole-induced CYP expression and carcinogenesis between fish and rodents. • Liver CYP-enzyme induction is a key event in conazole-induced tumorigenesis. • We suggest toxicity evaluation methods for azole fungicides using medaka fish. - Abstract: Conazoles are a class of imidazole- or triazole-containing drugs commonly used as fungicides in agriculture and medicine. The broad application of azole drugs has led to the contamination of surface aquifers receiving the effluent of municipal or hospital wastewater or agricultural runoff. Several triazoles are rodent carcinogens; azole pollution is a concern to environmental safety and human health. However, the carcinogenic mechanisms associated with cytochrome P450 enzymes (CYPs) of conazoles remain unclear. We exposed adult medaka fish (Oryzias latipes) to continuous aqueous solutions of carcinogenic triadimefon and non-carcinogenic myclobutanil for 7 to 20 days at sub-lethal or environmentally relevant concentrations and assessed hepatic CYP activity and gene expression associated with CYP-mediated toxicity. Both triadimefon and myclobutanil induced hepatic CYP3A activity, but only triadimefon enhanced CYP1A activity. The gene expression of cyp3a38, cyp3a40, pregnane x receptor (pxr), cyp26b, retinoid acid receptor γ1 (rarγ1) and p53 was higher with triadimefon than myclobutanil. As well, yeast-based reporter gene assay revealed that 4 tested conazoles were weak agonists of aryl hydrocarbon receptor (AhR). We reveal differential CYP gene expression with carcinogenic and non-carcinogenic conazoles in a lower vertebrate, medaka fish. Liver CYP-enzyme induction may be a key event in conazole-induced tumorigenesis. This information is essential to evaluate the potential threat of conazoles to human health and fish

  9. Two azole fungicides (carcinogenic triadimefon and non-carcinogenic myclobutanil) exhibit different hepatic cytochrome P450 activities in medaka fish

    International Nuclear Information System (INIS)

    Lin, Chun-Hung; Chou, Pei-Hsin; Chen, Pei-Jen

    2014-01-01

    Highlights: • We assess ecotoxicological impact of azole fungicides in the aquatic environment. • Carcinogenic and non-carcinogenic azoles show different CYP activities in medaka. • We compare azole-induced CYP expression and carcinogenesis between fish and rodents. • Liver CYP-enzyme induction is a key event in conazole-induced tumorigenesis. • We suggest toxicity evaluation methods for azole fungicides using medaka fish. - Abstract: Conazoles are a class of imidazole- or triazole-containing drugs commonly used as fungicides in agriculture and medicine. The broad application of azole drugs has led to the contamination of surface aquifers receiving the effluent of municipal or hospital wastewater or agricultural runoff. Several triazoles are rodent carcinogens; azole pollution is a concern to environmental safety and human health. However, the carcinogenic mechanisms associated with cytochrome P450 enzymes (CYPs) of conazoles remain unclear. We exposed adult medaka fish (Oryzias latipes) to continuous aqueous solutions of carcinogenic triadimefon and non-carcinogenic myclobutanil for 7 to 20 days at sub-lethal or environmentally relevant concentrations and assessed hepatic CYP activity and gene expression associated with CYP-mediated toxicity. Both triadimefon and myclobutanil induced hepatic CYP3A activity, but only triadimefon enhanced CYP1A activity. The gene expression of cyp3a38, cyp3a40, pregnane x receptor (pxr), cyp26b, retinoid acid receptor γ1 (rarγ1) and p53 was higher with triadimefon than myclobutanil. As well, yeast-based reporter gene assay revealed that 4 tested conazoles were weak agonists of aryl hydrocarbon receptor (AhR). We reveal differential CYP gene expression with carcinogenic and non-carcinogenic conazoles in a lower vertebrate, medaka fish. Liver CYP-enzyme induction may be a key event in conazole-induced tumorigenesis. This information is essential to evaluate the potential threat of conazoles to human health and fish

  10. Vaccinia virus, herpes simplex virus, and carcinogens induce DNA amplification in a human cell line and support replication of a helpervirus dependent parvovirus

    International Nuclear Information System (INIS)

    Schlehofer, J.R.; Ehrbar, M.; zur Hausen, H.

    1986-01-01

    The SV40-transformed human kidney cell line, NB-E, amplifies integrated as well as episomal SV40 DNA upon treatment with chemical (DMBA) or physical (uv irradiation) carcinogens (initiators) as well as after infection with herpes simplex virus (HSV) type 1 or with vaccinia virus. In addition it is shown that vaccinia virus induces SV40 DNA amplification also in the SV40-transformed Chinese hamster embryo cell line, CO631. These findings demonstrate that human cells similar to Chinese hamster cells amplify integrated DNA sequences after treatment with carcinogens or infection with specific viruses. Furthermore, a poxvirus--vaccinia virus--similar to herpes group viruses induces DNA amplification. As reported for other systems, the vaccinia virus-induced DNA amplification in NB-E cells is inhibited by coinfection with adeno-associated virus (AAV) type 5. This is in line with previous studies on inhibition of carcinogen- or HSV-induced DNA amplification in CO631 cells. The experiments also demonstrate that vaccinia virus, in addition to herpes and adenoviruses acts as a helper virus for replication and structural antigen synthesis of AAV-5 in NB-E cells

  11. Risk Assessment Approaches for Carcinogenic Food Contaminants

    OpenAIRE

    Gillespie, Zoe; Pulido, Olga; Vavasour, Elizabeth

    2011-01-01

    Health Canada has identified the need for a standardized department-wide approach for the risk assessment of carcinogens in foods (e.g., pesticides, food chemical contaminants, veterinary therapeutics). A standardized approach would better facilitate and inform risk management strategies for the control of human exposure to food sources of carcinogens. Within the post- market regulatory context, directly DNA-reactive carcinogens are of most concern because any exposure is theoretically assume...

  12. Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells

    International Nuclear Information System (INIS)

    Stueckle, Todd A.; Lu, Yongju; Davis, Mary E.; Wang, Liying; Jiang, Bing-Hua; Holaskova, Ida; Schafer, Rosana; Barnett, John B.; Rojanasakul, Yon

    2012-01-01

    Chronic arsenic exposure remains a human health risk; however a clear mode of action to understand gene signaling-driven arsenic carcinogenesis is currently lacking. This study chronically exposed human lung epithelial BEAS-2B cells to low-dose arsenic trioxide to elucidate cancer promoting gene signaling networks associated with arsenic-transformed (B-As) cells. Following a 6 month exposure, exposed cells were assessed for enhanced cell proliferation, colony formation, invasion ability and in vivo tumor formation compared to control cell lines. Collected mRNA was subjected to whole genome expression microarray profiling followed by in silico Ingenuity Pathway Analysis (IPA) to identify lung carcinogenesis modes of action. B-As cells displayed significant increases in proliferation, colony formation and invasion ability compared to BEAS-2B cells. B-As injections into nude mice resulted in development of primary and secondary metastatic tumors. Arsenic exposure resulted in widespread up-regulation of genes associated with mitochondrial metabolism and increased reactive oxygen species protection suggesting mitochondrial dysfunction. Carcinogenic initiation via reactive oxygen species and epigenetic mechanisms was further supported by altered DNA repair, histone, and ROS-sensitive signaling. NF-κB, MAPK and NCOR1 signaling disrupted PPARα/δ-mediated lipid homeostasis. A ‘pro-cancer’ gene signaling network identified increased survival, proliferation, inflammation, metabolism, anti-apoptosis and mobility signaling. IPA-ranked signaling networks identified altered p21, EF1α, Akt, MAPK, and NF-κB signaling networks promoting genetic disorder, altered cell cycle, cancer and changes in nucleic acid and energy metabolism. In conclusion, transformed B-As cells with their whole genome expression profile provide an in vitro arsenic model for future lung cancer signaling research and data for chronic arsenic exposure risk assessment. Highlights: ► Chronic As 2 O 3

  13. Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Stueckle, Todd A., E-mail: tstueckle@hsc.wvu.edu [Department of Basic Pharmaceutical Sciences, West Virginia University, Morgantown, WV 26506 (United States); Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505 (United States); Lu, Yongju, E-mail: yongju6@hotmail.com [Department of Basic Pharmaceutical Sciences, West Virginia University, Morgantown, WV 26506 (United States); Davis, Mary E., E-mail: mdavis@wvu.edu [Department of Physiology, West Virginia University, Morgantown, WV 26506 (United States); Wang, Liying, E-mail: lmw6@cdc.gov [Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505 (United States); Jiang, Bing-Hua, E-mail: bhjiang@jefferson.edu [Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107 (United States); Holaskova, Ida, E-mail: iholaskova@hsc.wvu.edu [Department of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, WV 26506 (United States); Schafer, Rosana, E-mail: rschafer@hsc.wvu.edu [Department of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, WV 26506 (United States); Barnett, John B., E-mail: jbarnett@hsc.wvu.edu [Department of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, WV 26506 (United States); Rojanasakul, Yon, E-mail: yrojan@hsc.wvu.edu [Department of Basic Pharmaceutical Sciences, West Virginia University, Morgantown, WV 26506 (United States)

    2012-06-01

    Chronic arsenic exposure remains a human health risk; however a clear mode of action to understand gene signaling-driven arsenic carcinogenesis is currently lacking. This study chronically exposed human lung epithelial BEAS-2B cells to low-dose arsenic trioxide to elucidate cancer promoting gene signaling networks associated with arsenic-transformed (B-As) cells. Following a 6 month exposure, exposed cells were assessed for enhanced cell proliferation, colony formation, invasion ability and in vivo tumor formation compared to control cell lines. Collected mRNA was subjected to whole genome expression microarray profiling followed by in silico Ingenuity Pathway Analysis (IPA) to identify lung carcinogenesis modes of action. B-As cells displayed significant increases in proliferation, colony formation and invasion ability compared to BEAS-2B cells. B-As injections into nude mice resulted in development of primary and secondary metastatic tumors. Arsenic exposure resulted in widespread up-regulation of genes associated with mitochondrial metabolism and increased reactive oxygen species protection suggesting mitochondrial dysfunction. Carcinogenic initiation via reactive oxygen species and epigenetic mechanisms was further supported by altered DNA repair, histone, and ROS-sensitive signaling. NF-κB, MAPK and NCOR1 signaling disrupted PPARα/δ-mediated lipid homeostasis. A ‘pro-cancer’ gene signaling network identified increased survival, proliferation, inflammation, metabolism, anti-apoptosis and mobility signaling. IPA-ranked signaling networks identified altered p21, EF1α, Akt, MAPK, and NF-κB signaling networks promoting genetic disorder, altered cell cycle, cancer and changes in nucleic acid and energy metabolism. In conclusion, transformed B-As cells with their whole genome expression profile provide an in vitro arsenic model for future lung cancer signaling research and data for chronic arsenic exposure risk assessment. Highlights: ► Chronic As{sub 2}O

  14. Report on carcinogens monograph on 1-bromopropane.

    Science.gov (United States)

    2013-09-01

    The National Toxicology Program conducted a cancer evaluation on 1 bromopropane for possible listing in the Report on Carcinogens (RoC). The cancer evaluation is captured in the RoC monograph, which was peer reviewed in a public forum. The monograph consists of two components: (Part 1) the cancer evaluation, which reviews the relevant scientific information, assesses its quality, applies the RoC listing criteria to the scientific information, and provides the NTP recommendation for listing status for 1 bromopropane in the RoC, and (Part 2) the substance profile proposed for the RoC, containing the NTP's listing status recommendation, a summary of the scientific evidence considered key to reaching that decision, and data on properties, use, production, exposure, and Federal regulations and guidelines to reduce exposure to 1-bromopropane. This monograph provides an assessment of the available scientific information on 1 bromopropane, including human exposure and properties, disposition and toxicokinetics, cancer studies in experimental animals, and studies of mechanisms and other related effects, including relevant toxicological effects, genetic toxicology, and mechanisms of carcinogenicity. From this assessment, the NTP recommended that 1 bromopropane be listed as reasonably anticipated to be a human carcinogen in the RoC based on sufficient evidence from studies in experimental animals, which found inhalation exposure to 1-bromopropane caused skin tumors in male rats, large intestine tumors in female and male rats, and lung tumors in female mice. Also noted was that 1 bromopropane, either directly or via reactive metabolites, caused molecular alterations that typically are associated with carcinogenesis, including genotoxicity, oxidative stress, and glutathione depletion. These alterations, observed in mainly in vitro and toxicity studies in rodents, are relevant to possible mechanisms of human carcinogenicity and support the relevance of the cancer studies in

  15. Environmental exposure to carcinogens in northwestern Cameroon ...

    African Journals Online (AJOL)

    African Health Sciences ... Humans can prevent themselves from a number of workplace and environmental carcinogens. ... Methods: A structured questionnaire was used to collect information on carcinogen exposure in the workplace and environment through trained field staff from volunteers after gaining informed ...

  16. The history, genotoxicity, and carcinogenicity of carbon-based fuels and their emissions. Part 3: diesel and gasoline.

    Science.gov (United States)

    Claxton, Larry D

    2015-01-01

    Within this review the genotoxicity of diesel and gasoline fuels and emissions is placed in an historical context. New technologies have changed the composition of transportation methods considerably, reducing emissions of many of the components of health concern. The similarity of modern diesel and gasoline fuels and emissions to other carbonaceous fuels and emissions is striking. Recently an International Agency for Research on Cancer (IARC) Working Group concluded that there was sufficient evidence in humans for the carcinogenicity of diesel exhaust (Group 1). In addition, the Working Group found that diesel exhaust has "a positive association (limited evidence) with an increased risk of bladder cancer." Like most other carbonaceous fuel emissions, diesel and gasoline exhausts contain toxic levels of respirable particles (PM gasoline emissions has declined in certain regions over time because of changes in engine design, the development of better aftertreatment devices (e.g., catalysts), increased fuel economy, changes in the fuels and additives used, and greater regulation. Additional research and better exposure assessments are needed so that decision makers and the public can decide to what extent diesel and gasoline engines should be replaced. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Inter-laboratory comparison of turkey in ovo carcinogenicity assessment (IOCA) of hepatocarcinogens.

    Science.gov (United States)

    Enzmann, H; Brunnemann, K; Iatropoulos, M; Shpyleva, S; Lukyanova, N; Todor, I; Moore, M; Spicher, K; Chekhun, V; Tsuda, H; Williams, G

    2013-09-01

    In three independent laboratories carcinogens (diethylnitrosamine, DEN, 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone, NNK) and non-carcinogens (N-nitrosoproline, nicotine) were evaluated in turkey eggs for in ovo carcinogenicity assessment (IOCA). Compounds were injected into aseptic fertilized eggs. After incubation for 24 days, foci of altered hepatocytes (FAH), some with a pseudoglandular structure and/or signs of compression of the surrounding tissue were observed in the fetal liver. All laboratories were able to distinguish unequivocally the hepatocarcinogen-exposed groups from those exposed to non-carcinogens or the vehicle controls, based on the pre-specified evaluation parameters: tumor-like lesions, pseudoglandular areas and FAH. In addition to focal changes, only the carcinogens induced hepatocellular karyomegaly. Lower doses of the carcinogens, which did not induce FAH, were sufficient to induce hepatocellular karyomegaly. After exposure to 4 mg DEN, gall bladder agenesis was observed in all fetuses. The IOCA may be a valuable tool for early investigative studies on carcinogenicity and since it does not use rodents may complement chronic rat or mouse bioassays. Test substances that are positive in both rodents and fertilized turkey eggs are most probably trans-species carcinogens with particular significance for humans. The good concordance observed among the three laboratories demonstrates that the IOCA is a reliable and robust method. Copyright © 2012 Elsevier GmbH. All rights reserved.

  18. Risk assessment of carcinogens in food

    International Nuclear Information System (INIS)

    Barlow, Susan; Schlatter, Josef

    2010-01-01

    Approaches for the risk assessment of carcinogens in food have evolved as scientific knowledge has advanced. Early methods allowed little more than hazard identification and an indication of carcinogenic potency. Evaluation of the modes of action of carcinogens and their broad division into genotoxic and epigenetic (non-genotoxic, non-DNA reactive) carcinogens have played an increasing role in determining the approach followed and provide possibilities for more detailed risk characterisation, including provision of quantitative estimates of risk. Reliance on experimental animal data for the majority of risk assessments and the fact that human exposures to dietary carcinogens are often orders of magnitude below doses used in experimental studies has provided a fertile ground for discussion and diverging views on the most appropriate way to offer risk assessment advice. Approaches used by national and international bodies differ, with some offering numerical estimates of potential risks to human health, while others express considerable reservations about the validity of quantitative approaches requiring extrapolation of dose-response data below the observed range and instead offer qualitative advice. Recognising that qualitative advice alone does not provide risk managers with information on which to prioritise the need for risk management actions, a 'margin of exposure' approach for substances that are both genotoxic and carcinogenic has been developed, which is now being used by the World Health Organization and the European Food Safety Authority. This review describes the evolution of risk assessment advice on carcinogens and discusses examples of ways in which carcinogens in food have been assessed in Europe.

  19. Risk assessment of carcinogens in food.

    Science.gov (United States)

    Barlow, Susan; Schlatter, Josef

    2010-03-01

    Approaches for the risk assessment of carcinogens in food have evolved as scientific knowledge has advanced. Early methods allowed little more than hazard identification and an indication of carcinogenic potency. Evaluation of the modes of action of carcinogens and their broad division into genotoxic and epigenetic (non-genotoxic, non-DNA reactive) carcinogens have played an increasing role in determining the approach followed and provide possibilities for more detailed risk characterisation, including provision of quantitative estimates of risk. Reliance on experimental animal data for the majority of risk assessments and the fact that human exposures to dietary carcinogens are often orders of magnitude below doses used in experimental studies has provided a fertile ground for discussion and diverging views on the most appropriate way to offer risk assessment advice. Approaches used by national and international bodies differ, with some offering numerical estimates of potential risks to human health, while others express considerable reservations about the validity of quantitative approaches requiring extrapolation of dose-response data below the observed range and instead offer qualitative advice. Recognising that qualitative advice alone does not provide risk managers with information on which to prioritise the need for risk management actions, a "margin of exposure" approach for substances that are both genotoxic and carcinogenic has been developed, which is now being used by the World Health Organization and the European Food Safety Authority. This review describes the evolution of risk assessment advice on carcinogens and discusses examples of ways in which carcinogens in food have been assessed in Europe.

  20. trans-11 18:1 Vaccenic Acid (TVA Has a Direct Anti-Carcinogenic Effect on MCF-7 Human Mammary Adenocarcinoma Cells

    Directory of Open Access Journals (Sweden)

    Ji-Na Lim

    2014-02-01

    Full Text Available Trans vaccenic acid (TVA; trans-11 18:1 is a positional and geometric isomer of oleic acid and it is the predominant trans isomer found in ruminant fats. TVA can be converted into cis-9, trans-11 conjugated linoleic acid (c9, t11-CLA, a CLA isomer that has many beneficial effects, by stearoyl CoA desaturase 1 (SCD1 in the mammary gland. The health benefits associated with CLA are well documented, but it is unclear whether trans fatty acids (TFAs from ruminant products have healthy effects. Therefore, the effects of TVA on the proliferation of MCF-7 human breast adenocarcinoma cells and MCF-10A human breast epithelial cells were investigated in the present study. Results showed that TVA inhibited the proliferation of MCF-7 cells but not MCF-10A cells by down-regulating the expression of Bcl-2 as well as procaspase-9. In addition, the suppressive effect of TVA was confirmed in SCD1-depleted MCF-7 cells. Our results suggested that TVA exerts a direct anti-carcinogenic effect on MCF-7 cells. These findings provided a better understanding of the research on the anti-carcinogenic effects of TVA and this may facilitate the manufacture of TVA/c9, t11-CLA fortified ruminant products.

  1. Report on carcinogens monograph on cumene.

    Science.gov (United States)

    2013-09-01

    The National Toxicology Program conducted a cancer evaluation on cumene for possible listing in the Report on Carcinogens (RoC). The cancer evaluation is captured in the RoC monograph, which was peer reviewed in a public forum. The monograph consists of two components: (Part 1) the cancer evaluation, which reviews the relevant scientific information, assesses its quality, applies the RoC listing criteria to the scientific information, and provides the NTP recommendation for listing status for cumene in the RoC, and (Part 2) the substance profile proposed for the RoC, containing the NTP's listing status recommendation, a summary of the scientific evidence considered key to reaching that decision, and data on properties, use, production, exposure, and Federal regulations and guidelines to reduce exposure to cumene. This monograph provides an assessment of the available scientific information on cumene, including human exposure and properties, disposition and toxicokinetics, cancer studies in experimental animals, and studies of mechanisms and other related effects, including relevant toxicological effects, genetic toxicology, and mechanisms of carcinogenicity. From this assessment, the NTP recommended that cumene be listed as reasonably anticipated to be a human carcinogen in the RoC based on sufficient evidence from studies in experimental animals, which found that cumene exposure caused lung tumors in male and female mice and liver tumors in female mice. Several proposed mechanisms of carcinogenesis support the relevance to humans of the lung and liver tumors observed in experimental animals. Specifically, there is evidence that humans and experimental animals metabolize cumene through similar metabolic pathways. In addition, mutations of the K-ras oncogene and p53 tumor-suppressor gene observed in cumene-induced lung tumors in mice, along with altered expression of many other genes, resemble molecular alterations found in human lung and other cancers.

  2. [QUANTITATIVE DNA EVALUATION OF THE HIGH CARCINOGENIC RISK OF HUMAN PAPILLOMA VIRUSES AND HUMAN HERPES VIRUSES IN MALES WITH FERTILITY DISORDERS].

    Science.gov (United States)

    Evdokimov, V V; Naumenko, V A; Tulenev, Yu A; Kurilo, L F; Kovalyk, V P; Sorokina, T M; Lebedeva, A L; Gomberg, M A; Kushch, A A

    2016-01-01

    Infertility is an actual medical and social problem. In 50% of couples it is associated with the male factor and in more than 50% of cases the etiology of the infertility remains insufficiently understood. The goal of this work was to study the prevalence and to perform quantitative analysis of the human herpes viruses (HHV) and high carcinogenic risk papilloma viruses (HR HPV) in males with infertility, as well as to assess the impact of these infections on sperm parameters. Ejaculate samples obtained from 196 males fall into 3 groups. Group 1 included men with the infertility of unknown etiology (n = 112); group 2, patients who had female partners with the history of spontaneous abortion (n = 63); group 3 (control), healthy men (n = 21). HHV and HR HPV DNA in the ejaculates were detected in a total of 42/196 (21.4%) males: in 31 and 11 patients in groups 1 and 2, respectively (p > 0.05) and in none of healthy males. HHV were detected in 24/42; HR HPV, in 18/42 males (p > 0.05) without significant difference between the groups. Among HR HPV genotypes of the clade A9 in ejaculate were more frequent (14/18, p = 0.04). Comparative analysis of the sperm parameters showed that in the ejaculates of the infected patients sperm motility as well as the number of morphologically normal cells were significantly reduced compared with the healthy men. The quantification of the viral DNA revealed that in 31% of the male ejaculates the viral load was high: > 3 Ig10/100000 cells. Conclusion. The detection of HHV and HR HPV in the ejaculate is associated with male infertility. Quantification of the viral DNA in the ejaculate is a useful indicator for monitoring viral infections in infertility and for decision to start therapy.

  3. Non-covalent interactions of the carcinogen (+)-anti-BPDE with exon 1 of the human K-ras proto-oncogene

    Science.gov (United States)

    Rodriguez, Jorge H.; Deligkaris, Christos

    2013-03-01

    Investigating the complementary, but different, effects of physical (non-covalent) and chemical (covalent) mutagen-DNA and carcinogen-DNA interactions is important for understanding possible mechanisms of development and prevention of mutagenesis and carcinogenesis. A highly mutagenic and carcinogenic metabolite of the polycyclic aromatic hydrocarbon benzo[ α]pyrene, namely (+)-anti-BPDE, is known to undergo both physical and chemical complexation with DNA. The major covalent adduct, a promutagenic, is known to be an external (+)-trans-anti-BPDE-N2-dGuanosine configuration whose origins are not fully understood. Thus, it is desirable to study the mechanisms of external non-covalent BPDE-DNA binding and their possible relationships to external covalent trans adduct formation. We present a detailed codon-by-codon computational study of the non-covalent interactions of (+)-anti-BPDE with DNA which explains and correctly predicts preferential (+)-anti-BPDE binding at minor groove guanosines. Due to its relevance to carcinogenesis, the interaction of (+)-anti-BPDE with exon 1 of the human K-ras gene has been studied in detail. Present address: Department of Physics, Drury University

  4. Hexavalent chromium, a lung carcinogen, confers resistance to thermal stress and interferes with heat shock protein expression in human bronchial epithelial cells.

    Science.gov (United States)

    Abreu, Patrícia L; Cunha-Oliveira, Teresa; Ferreira, Leonardo M R; Urbano, Ana M

    2018-03-16

    Exposure to hexavalent chromium [Cr(VI)], a lung carcinogen, triggers several types of cellular stresses, namely oxidative, genotoxic and proteotoxic stresses. Given the evolutionary character of carcinogenesis, it is tempting to speculate that cells that survive the stresses produced by this carcinogen become more resistant to subsequent stresses, namely those encountered during neoplastic transformation. To test this hypothesis, we determined whether pre-incubation with Cr(VI) increased the resistance of human bronchial epithelial cells (BEAS-2B cells) to the antiproliferative action of acute thermal shock, used here as a model for stress. In line with the proposed hypothesis, it was observed that, at mildly cytotoxic concentrations, Cr(VI) attenuated the antiproliferative effects of both cold and heat shock. Mechanistically, Cr(VI) interfered with the expression of two components of the stress response pathway: heat shock proteins Hsp72 and Hsp90α. Specifically, Cr(VI) significantly depleted the mRNA levels of the former and the protein levels of the latter. Significantly, these two proteins are members of heat shock protein (Hsp) families (Hsp70 and Hsp90, respectively) that have been implicated in carcinogenesis. Thus, our results confirm and extend previous studies showing the capacity of Cr(VI) to interfere with the expression of stress response components.

  5. Approaches to the risk assessment of genotoxic carcinogens in food: a critical appraisal.

    Science.gov (United States)

    O'Brien, J; Renwick, A G; Constable, A; Dybing, E; Müller, D J G; Schlatter, J; Slob, W; Tueting, W; van Benthem, J; Williams, G M; Wolfreys, A

    2006-10-01

    The present paper examines the particular difficulties presented by low levels of food-borne DNA-reactive genotoxic carcinogens, some of which may be difficult to eliminate completely from the diet, and proposes a structured approach for the evaluation of such compounds. While the ALARA approach is widely applicable to all substances in food that are both carcinogenic and genotoxic, it does not take carcinogenic potency into account and, therefore, does not permit prioritisation based on potential risk or concern. In the absence of carcinogenicity dose-response data, an assessment based on comparison with an appropriate threshold of toxicological concern may be possible. When carcinogenicity data from animal bioassays are available, a useful analysis is achieved by the calculation of margins of exposure (MOEs), which can be used to compare animal potency data with human exposure scenarios. Two reference points on the dose-response relationship that can be used for MOE calculation were examined; the T25 value, which is derived from linear extrapolation, and the BMDL10, which is derived from mathematical modelling of the dose-response data. The above approaches were applied to selected food-borne genotoxic carcinogens. The proposed approach is applicable to all substances in food that are DNA-reactive genotoxic carcinogens and enables the formulation of appropriate semi-quantitative advice to risk managers.

  6. Evaluation of carcinogenic potential of the herbicide glyphosate, drawing on tumor incidence data from fourteen chronic/carcinogenicity rodent studies.

    Science.gov (United States)

    Greim, Helmut; Saltmiras, David; Mostert, Volker; Strupp, Christian

    2015-03-01

    Abstract Glyphosate, an herbicidal derivative of the amino acid glycine, was introduced to agriculture in the 1970s. Glyphosate targets and blocks a plant metabolic pathway not found in animals, the shikimate pathway, required for the synthesis of aromatic amino acids in plants. After almost forty years of commercial use, and multiple regulatory approvals including toxicology evaluations, literature reviews, and numerous human health risk assessments, the clear and consistent conclusions are that glyphosate is of low toxicological concern, and no concerns exist with respect to glyphosate use and cancer in humans. This manuscript discusses the basis for these conclusions. Most toxicological studies informing regulatory evaluations are of commercial interest and are proprietary in nature. Given the widespread attention to this molecule, the authors gained access to carcinogenicity data submitted to regulatory agencies and present overviews of each study, followed by a weight of evidence evaluation of tumor incidence data. Fourteen carcinogenicity studies (nine rat and five mouse) are evaluated for their individual reliability, and select neoplasms are identified for further evaluation across the data base. The original tumor incidence data from study reports are presented in the online data supplement. There was no evidence of a carcinogenic effect related to glyphosate treatment. The lack of a plausible mechanism, along with published epidemiology studies, which fail to demonstrate clear, statistically significant, unbiased and non-confounded associations between glyphosate and cancer of any single etiology, and a compelling weight of evidence, support the conclusion that glyphosate does not present concern with respect to carcinogenic potential in humans.

  7. Identification of Radiation Effects on Carcinogenic Food Estimated by Ames Test

    International Nuclear Information System (INIS)

    Afifi, M.; Eid, I.; El - Nagdy, M.; Zaher, R.; Abd El-Karem, H.; Abd EL Karim, A.

    2016-01-01

    A major concern in studies related to carcinogenesis is the exposure to the exogenous carcinogens that may occur in food in both natural and polluted human environments. The purpose of the present study is to examine some of food products by Ames test to find out if food products carcinogenic then expose food to gamma radiation to find out the effect of radiation on it as a treatment. In this study, the food samples were examined by Ames test (Salmonella typhimurium mutagenicity test) to find out that a food product could be carcinogenic or highly mutated. Testing of chemicals for mutagenicity is based on the knowledge that a substance which is mutagenic in the bacterium is more likely than not to be a carcinogen in laboratory animals, and thus , by extension, present a risk of cancer to humans. After that food products that showed mutagenicity exposed to gamma radiation at different doses to examine the effect of gamma radiation on food products. This study represent γ radiation effect on carcinogenic food by using Ames test in the following steps: Detect food by Ames test using Salmonella typhimurium strains in which the colony count /plate for each food sample will show if food is slightly mutated or highly mutated or carcinogenic. If food is highly mutated or carcinogenic with high number of colonies /plate, then the carcinogenic food or highly mutated food exposed to different doses of radiation The applied doses in this study were 0, 2.5, 5, and 10 (KGy). Detect the radiation effect on food samples by Ames test after irradiation. The study shows that mutated and carcinogenic food products estimated by Ames test could be treated by irradiation

  8. Use of early phenotypic in vivo markers to assess human relevance of an unusual rodent non-genotoxic carcinogen in vitro

    International Nuclear Information System (INIS)

    Boess, Franziska; Lenz, Barbara; Funk, Juergen; Niederhauser, Urs; Bassett, Simon; Zhang, Jitao David; Singer, Thomas; Roth, Adrian B.

    2017-01-01

    Highlights: • RG3487 induced foci of altered hepatocytes and subsequent liver tumors in rats. • Early phenotypic markers preceding foci appearance in rats were identified. • These early foci markers could be recapitulated in cellular rat liver models. • A species comparison using rat, mouse and dog liver cell models qualified the approach. • In vitro human data support non-human-relevance for RG3487 induced foci formation. - Abstract: Foci of altered hepatocytes (FAH) are considered putative, pre-neoplastic lesions that can occur spontaneously in aging rodents, but can also be induced by chemicals or drugs. Progression of FAH to hepatocellular neoplasms has been reported repeatedly but increases in foci in rodents do not necessarily lead to tumors in carcinogenicity studies and the relevance for humans often remains unclear. Here we present the case of RG3487, a molecule which induced FAH and, later on, tumors in rats. Because the molecule was negative in genotoxicity assays it was classified as a non-genotoxic carcinogen. In order to assess the potential for liver tumor formation in humans, we analyzed treatment-induced changes in vivo to establish a possible mode of action (MoA). In vivo and in vitro gene expression analysis revealed that nuclear receptor signaling was unlikely to be the relevant MoA and no other known mechanism could be established. We therefore took an approach comparing phenotypic markers, including mRNA changes, proliferation and glycogen accumulation, in vitro using cells of different species to assess the human relevance of this finding. Since the alterations observed in rats were not seen in the liver of mice or dogs in vivo, we could validate the relevance of the cell models chosen by use of hepatocytes from these species in vitro. This ultimately allowed for a cross-species comparison, which suggested that the formation of FAH and liver tumors was rat specific and unlikely to translate to human. Our work showed that phenotypic

  9. A call to expand regulation to all carcinogenic fibrous minerals

    Science.gov (United States)

    Baumann, F.; Steele, I.; Ambrosi, J.; Carbone, M.

    2013-05-01

    The regulatory term "asbestos" groups only the six fibrous minerals that were commercially used among approximately 400. The carcinogenicity of these six regulated minerals has been largely demonstrated and is related to fiber structure, fiber length/diameter ratio, and bio-persistence. From a public perception, the generic term "asbestos" refers to the fibrous minerals that cause asbestosis, mesothelioma and other cancers. However, other non-regulated fibrous minerals are potentially as dangerous as the regulatory asbestos because they share similar physical and chemical properties, epidemiological studies have demonstrated their relationship with asbestos-related diseases, and both in vitro and in vivo experiments have established the toxicity of these minerals. For example, the non-regulated asbestiform winchite and richterite minerals that contaminated the vermiculite mined from Libby, Montana, (USA) were associated with mesothelioma, lung cancer and asbestosis observed among the area's residents and miners. Many other examples of non-regulated carcinogenic fibrous minerals include, but are not limited to, antigorite, arfvedsonite, balangeroite, carlosturanite, erionite, fluoro-edenite, hornblende, mordenite, palygorskite, and sepiolite. To propose a regulatory definition that would provide protection from all carcinogenic fibers, we have conducted an interdisciplinary literature review to compare the characteristics of "asbestos" and of non-regulated mineral fibers that relate to carcinogenicity. We specifically studied two non-regulated fibrous minerals that are associated with asbestos-related diseases: the serpentine antigorite and the zeolite erionite. Both examples underscore the problem of regulation based on commercial, rather than scientific principles: 1) the occurrence of fibrous antigorite in materials used to pave roads has been correlated with high mesothelioma rates in New Caledonia. Antigorite was also the cause of asbestosis in Poland, and in

  10. Long-term estrogen exposure promotes carcinogen bioactivation, induces persistent changes in gene expression, and enhances the tumorigenicity of MCF-7 human breast cancer cells

    International Nuclear Information System (INIS)

    Spink, Barbara C.; Bennett, James A.; Pentecost, Brian T.; Lostritto, Nicole; Englert, Neal A.; Benn, Geoffrey K.; Goodenough, Angela K.; Turesky, Robert J.; Spink, David C.

    2009-01-01

    The cumulative exposure to estrogens is an important determinant in the risk of breast cancer, yet the full range of mechanisms involving estrogens in the genesis and progression of breast cancer remains a subject of debate. Interactions of estrogens and environmental toxicants have received attention as putative factors contributing to carcinogenesis. Mechanistic studies have demonstrated interactions between estrogen receptor α (ERα) and the aryl hydrocarbon receptor (AhR), with consequences on the genes that they regulate. Many studies of ERα and AhR-mediated effects and crosstalk between them have focused on the initial molecular events. In this study, we investigated ERα- and AhR-mediated effects in long-term estrogen exposed (LTEE) MCF-7 human breast cancer cells, which were obtained by continuous culturing for at least 12 weeks in medium supplemented with 1 nM of 17β-estradiol (E 2 ). With these LTEE cells and with parallel control cells cultured without E 2 supplementation, we performed an extensive study of cytochrome P450 (CYP) induction, carcinogen bioactivation, global gene expression, and tumorigenicity in immunocompromised mice. We found that LTEE cells, in comparison with control cells, had higher levels of AhR mRNA and protein, greater responsiveness for AhR-regulated CYP1A1 and CYP1B1 induction, a 6-fold higher initial level of benzo(a)pyrene-DNA adducts as determined by liquid chromatography tandem mass spectrometry, marked differences in the expression of numerous genes, and a higher rate of E 2 -dependent tumor growth as xenografts. These studies indicate that LTEE causes adaptive responses in MCF-7 cells, which may reflect processes that contribute to the overall carcinogenic effect of E 2 .

  11. Expression profile of human cells in culture exposed to glycidamide, a reactive metabolite of the heat-induced food carcinogen acrylamide

    International Nuclear Information System (INIS)

    Clement, Flurina C.; Dip, Ramiro; Naegeli, Hanspeter

    2007-01-01

    Recent findings of acrylamide in many common foods have sparked renewed interest in assessing human health hazards and the long-term risk associated with exposure to vinyl compounds. Acrylamide is tumorigenic at high doses in rodents and has been classified as a probable human carcinogen. However, cancer risk projections in the population remain problematic because the molecular pathogenesis of acrylamide at the low level of dietary uptake is not understood. In particular, the question of whether specific transcriptional responses may amplify or mitigate the known genotoxicity of acrylamide has never been examined. Here, we used high-density DNA microarrays and PCR validations to assess genome-wide messenger profiles induced by glycidamide, the more reactive metabolite of acrylamide. The expression changes resulting from glycidamide treatment of human epithelial cells are characterized by the induction of detoxification enzymes, several members of the glutathione system and antioxidant factors. Low-dose experiments indicate that the up-regulation of epoxide hydrolase 1 represents the most sensitive transcriptional biomarker of glycidamide exposure. At higher concentrations, glycidamide induces typical markers of tumor progression such as steroid hormone activators, positive regulators of nuclear factor-κB, growth stimulators and apoptosis inhibitors. Concomitantly, growth suppressors and cell adhesion molecules are down-regulated. The main implication of these findings for risk assessment is that low concentrations of glycidamide elicit cytoprotective reactions whereas transcriptional signatures associated with tumor progression may be expected only at doses that exceed the range of ordinary dietary exposures

  12. [THE COMPARATIVE ANALYSIS OF RESULTS OF DETECTION OF CARCINOGENIC TYPES OF HUMAN PAPILLOMA VIRUS BY QUALITATIVE AND QUANTITATIVE TESTS].

    Science.gov (United States)

    Kuzmenko, E T; Labigina, A V; Leshenko, O Ya; Rusanov, D N; Kuzmenko, V V; Fedko, L P; Pak, I P

    2015-05-01

    The analysis of results of screening (n = 3208; sexually active citizen aged from 18 to 59 years) was carried out to detect oncogene types of human papilloma virus in using qualitative (1150 females and 720 males) and quantitative (polymerase chain reaction in real-time (843 females and 115 males) techniques. The human papilloma virus of high oncogene type was detected in 65% and 68.4% of females and in 48.6% and 53% of males correspondingly. Among 12 types of human papilloma virus the most frequently diagnosed was human papilloma virus 16 independently of gender of examined and technique of analysis. In females, under application of qualitative tests rate of human papilloma virus 16 made up to 18.3% (n = 280) and under application of quantitative tests Rte of human papilloma virus made up to 14.9% (n = 126; p ≤ 0.05). Under examination of males using qualitative tests rate of human papilloma virus 16 made up to 8.3% (n = 60) and under application of qualitative tests made up to 12.2% (n = 14; p ≥ 0.05). Under application of qualitative tests rate of detection on the rest ofoncogene types of human papilloma virus varied in females from 3.4% to 8.4% and in males from 1.8% to 5.9%. Under application of qualitative tests to females rate of human papilloma virus with high viral load made up to 68.4%, with medium viral load - 2.85% (n = 24) and with low viral load -0.24% (n = 2). Under application of quantitative tests in males rate of detection of types of human papilloma virus made up to 53% and at that in all high viral load was established. In females, the most of oncogene types of human papilloma virus (except for 31, 39, 59) are detected significantly more often than in males.

  13. A Review of the Carcinogenic Potential of Bisphenol A

    Science.gov (United States)

    Seachrist, Darcie D; Bonk, Kristen W.; Ho, Shuk-Mei; Prins, Gail S.; Soto, Ana M.; Keri, Ruth A.

    2015-01-01

    The estrogenic properties of bisphenol A (BPA), a ubiquitous synthetic monomer that can leach into the food and water supply, have prompted considerable research into exposure-associated health risks in humans. Endocrine-disrupting properties of BPA suggest it may impact developmental plasticity during early life, predisposing individuals to disease at doses below the oral reference dose (RfD) established by the Environmental Protection Agency in 1982. Herein, we review the current in vivo literature evaluating the carcinogenic properties of BPA. We conclude that there is substantial evidence from rodent studies indicating that early-life BPA exposures below the RfD lead to increased susceptibility to mammary and prostate cancer. Based on the definitions of “carcinogen” put forth by the International Agency for Research on Cancer and the National Toxicology Program, we propose that BPA may be reasonably anticipated to be a human carcinogen in the breast and prostate due to its tumor promoting properties. PMID:26493093

  14. Auto-catalysed progression of aneuploidy explains the Hayflick limit of cultured cells, carcinogen-induced tumours in mice, and the age distribution of human cancer.

    Science.gov (United States)

    Rasnick, D

    2000-06-15

    Evidence continues to accumulate that aneuploidy, an imbalance in the number of chromosomes, is responsible for the characteristic phenotypes of cancer, including the abnormal cellular size and morphology of cancer cells, the appearance of tumour-associated antigens, as well as the high levels of membrane-bound and secreted proteins responsible for invasiveness and loss of contact inhibition. Aneuploidy has also been demonstrated to be the self-perpetuating source of the karyotypic instability of cancer cells. Here it is shown that the auto-catalysed progression of aneuploidy explains the kinetics of the finite lifetime of diploid cells in culture, the time course of the appearance of papillomas and carcinomas in benzo[a]pyrene-treated mice, and the age-dependence of human cancers. Modelling studies indicate that the ease of spontaneous transformation of mouse cells in culture may be due to a chaotic progression of aneuploidy. Conversely, the strong preference towards senescence and resistance to transformation of human cells in culture may be the result of a non-chaotic progression of aneuploidy. Finally, a method is proposed for quantifying the aneuploidogenic potencies of carcinogens.

  15. [The identification of viruses of human papilloma of high carcinogenic risk and evaluation of physical status of viral DNA using technique of polymerase-chain reaction under affection of cervical epithelium].

    Science.gov (United States)

    Viazovaia, A A; Kuevda, D A; Trofimova, O B; Shipulina, O Iu; Ershov, V A; Lialina, L V; Narvskaia, O V

    2013-08-01

    The DNA of virus of human papilloma of high carcinogenic risk was detected in 116 cervical samples. At that, the morphological symptoms of background processes are detected in 19 samples, CIN 1 in 9, CIN 2 in 23, CIN 3 in 54 (and out of them carcinoma in situ in 13), epidermoid cancer (squamous cell carcinoma) in 11 cases. The viral load of human papilloma of high carcinogenic risk in all samples of DNA exceeded threshold of clinical value (3 lg copies of DNA of human papilloma/105 cells). The genetic typing of human papilloma of high carcinogenic risk revealed the dominance of human papilloma of type 16 in 49.7%, type 33 in 15.3%, type 31 in 12.3% and type 45 in 5.5%. In women with background processes in cervix of the uterus DNA of human papilloma type 16 was detected more often in episome form. In case of dysplastic alterations of epithelium and cervical cancer DNA of human papilloma type 16 is detected in mixt form with different degree of integration into cell genome.

  16. How many food additives are rodent carcinogens?

    Science.gov (United States)

    Johnson, F M

    2002-01-01

    One generally assumes that chemical agents added to foods are reasonably free of risks to human health, and practically everyone consumes some additives in his or her food daily throughout life. In the United States, the 1958 Food Additives Amendment to the Federal Food, Drug and Cosmetic Act of 1938 requires food manufacturers to demonstrate the safety of food additives to the Food and Drug Administration (FDA). The Amendment contains a provision that prohibits approval of an additive if it is found to cause cancer in humans or animals. In the present study, data from the National Toxicology Program rodent bioassay (NTPRB) were used to identify a sample of approximately 50 rodent-tested additives and other chemicals added to food that had been evaluated independently of the FDA/food industry. Surprisingly, the sample shows more than 40% of these food chemicals to be carcinogenic in one or more rodent groups. If this percentage is extrapolated to all substances added to food in the United States, it would imply that more than 1000 of such substances are potential rodent carcinogens. The NTP and FDA test guidelines use similar, though not necessarily identical, rodent test procedures, including near lifetime exposures to the maximum tolerated dose. The FDA specifies that test chemicals should be administered by the oral route. However, the oral route includes three methods of delivering chemicals, that is, mixed in the food or water or delivered by stomach tube (gavage). The NTP data show only 1 of 18 food chemicals mixed in the food are rodent carcinogens, but 16 of 23 gavage-administered food chemicals are carcinogenic to rodents. The distribution suggests that among orally delivered chemicals, those administered in the feed will more likely prove to be noncarcinogens than chemicals given by gavage. The rodent data also reveal that effects may vary according to dose and genotype, as well as by route of administration, to further complicate extrapolation to humans

  17. Carcinogen-Induced Hepatic Tumors in KLF6+/- Mice Recapitulate Aggressive Human Hepatocellular Carcinoma Associated with p53 Pathway Deregulation

    NARCIS (Netherlands)

    Tarocchi, Mirko; Hannivoort, Rebekka; Hoshida, Yujin; Lee, Ursula E.; Vetter, Diana; Narla, Goutham; Villanueva, Augusto; Oren, Moshe; Llovet, Josep M.; Friedman, Scott L.

    Inactivation of KLF6 is common in hepatocellular carcinoma (HCC) associated with hepatitis C virus (HCV) infection, thereby abrogating its normal antiproliferative activity in liver cells. The aim of the study was to evaluate the impact of KLF6 depletion on human HCC and experimental

  18. Research toward the development of a biologically based dose response assessment for inorganic arsenic carcinogenicity: A progress report

    International Nuclear Information System (INIS)

    Clewell, Harvey J.; Thomas, Russell S.; Gentry, P. Robinan; Crump, Kenny S.; Kenyon, Elaina M.; El-Masri, Hisham A.; Yager, Janice W.

    2007-01-01

    Cancer risk assessments for inorganic arsenic have been based on human epidemiological data, assuming a linear dose response below the range of observation of tumors. Part of the reason for the continued use of the linear approach in arsenic risk assessments is the lack of an adequate biologically based dose response (BBDR) model that could provide a quantitative basis for an alternative nonlinear approach. This paper describes elements of an ongoing collaborative research effort between the CIIT Centers for Health Research, the U.S. Environmental Protection Agency, ENVIRON International, and EPRI to develop BBDR modeling approaches that could be used to inform a nonlinear cancer dose response assessment for inorganic arsenic. These efforts are focused on: (1) the refinement of physiologically based pharmacokinetic (PBPK) models of the kinetics of inorganic arsenic and its metabolites in the mouse and human; (2) the investigation of mathematical solutions for multi-stage cancer models involving multiple pathways of cell transformation; (3) the review and evaluation of the literature on the dose response for the genomic effects of arsenic; and (4) the collection of data on the dose response for genomic changes in the urinary bladder (a human target tissue for arsenic carcinogenesis) associated with in vivo drinking water exposures in the mouse as well as in vitro exposures of both mouse and human cells. An approach is proposed for conducting a biologically based margin of exposure risk assessment for inorganic arsenic using the in vitro dose response for the expression of genes associated with the obligatory precursor events for arsenic tumorigenesis

  19. The environmental carcinogen 3-nitrobenzanthrone and its main metabolite 3-aminobenzanthrone enhance formation of reactive oxygen intermediates in human A549 lung epithelial cells

    International Nuclear Information System (INIS)

    Hansen, Tanja; Seidel, Albrecht; Borlak, Juergen

    2007-01-01

    The environmental contaminant 3-nitrobenzanthrone (3-NBA) is highly mutagenic and a suspected human carcinogen. We aimed to evaluate whether 3-NBA is able to deregulate critical steps in cell cycle control and apoptosis in human lung epithelial A549 cells. Increased intracellular Ca 2+ and caspase activities were detected upon 3-NBA exposure. As shown by cell cycle analysis, an increased number of S-phase cells was observed after 24 h of treatment with 3-NBA. Furthermore, 3-NBA was shown to inhibit cell proliferation when added to subconfluent cell cultures. The main metabolite of 3-NBA, 3-ABA, induced statistically significant increases in tail moment as judged by alkaline comet assay. The potential of 3-NBA and 3-ABA to enhance the production of reactive oxygen species (ROS) was demonstrated by flow cytometry using 2',7'-dichlorofluorescein-diacetate (DCFH-DA). The enzyme inhibitors allopurinol, dicumarol, resveratrol and SKF525A were used to assess the impact of metabolic conversion on 3-NBA-mediated ROS production. Resveratrol decreased dichlorofluorescein (DCF) fluorescence by 50%, suggesting a role for CYP1A1 in 3-NBA-mediated ROS production. Mitochondrial ROS production was significantly attenuated (20% reduction) by addition of rotenone (complex I inhibition) and thenoyltrifluoroacetone (TTFA, complex II inhibition). Taken together, the results of the present study provide evidence for a genotoxic potential of 3-ABA in human epithelial lung cells. Moreover, both compounds lead to increased intracellular ROS and create an environment favorable to DNA damage and the promotion of cancer

  20. Predictive Models for Carcinogenicity and Mutagenicity ...

    Science.gov (United States)

    Mutagenicity and carcinogenicity are endpoints of major environmental and regulatory concern. These endpoints are also important targets for development of alternative methods for screening and prediction due to the large number of chemicals of potential concern and the tremendous cost (in time, money, animals) of rodent carcinogenicity bioassays. Both mutagenicity and carcinogenicity involve complex, cellular processes that are only partially understood. Advances in technologies and generation of new data will permit a much deeper understanding. In silico methods for predicting mutagenicity and rodent carcinogenicity based on chemical structural features, along with current mutagenicity and carcinogenicity data sets, have performed well for local prediction (i.e., within specific chemical classes), but are less successful for global prediction (i.e., for a broad range of chemicals). The predictivity of in silico methods can be improved by improving the quality of the data base and endpoints used for modelling. In particular, in vitro assays for clastogenicity need to be improved to reduce false positives (relative to rodent carcinogenicity) and to detect compounds that do not interact directly with DNA or have epigenetic activities. New assays emerging to complement or replace some of the standard assays include VitotoxTM, GreenScreenGC, and RadarScreen. The needs of industry and regulators to assess thousands of compounds necessitate the development of high-t

  1. The history, genotoxicity, and carcinogenicity of carbon-based fuels and their emissions. Part 2: solid fuels.

    Science.gov (United States)

    Claxton, Larry D

    2014-01-01

    The combustion of solid fuels (like wood, animal dung, and coal) usually involves elevated temperatures and altered pressures and genotoxicants (e.g., PAHs) are likely to form. These substances are carcinogenic in experimental animals, and epidemiological studies implicate these fuels (especially their emissions) as carcinogens in man. Globally, ∼50% of all households and ∼90% of all rural households use solid fuels for cooking or heating and these fuels often are burnt in simple stoves with very incomplete combustion. Exposed women and children often exhibit low birth weight, increased infant and perinatal mortality, head and neck cancer, and lung cancer although few studies have measured exposure directly. Today, households that cannot meet the expense of fuels like kerosene, liquefied petroleum gas, and electricity resort to collecting wood, agricultural residue, and animal dung to use as household fuels. In the more developed countries, solid fuels are often used for electric power generation providing more than half of the electricity generated in the United States. The world's coal reserves, which equal approximately one exagram, equal ∼1 trillion barrels of crude oil (comparable to all the world's known oil reserves) and could last for 600 years. Studies show that the PAHs that are identified in solid fuel emissions react with NO2 to form direct-acting mutagens. In summary, many of the measured genotoxicants found in both the indoor and electricity-generating combustors are the same; therefore, the severity of the health effects vary with exposure and with the health status of the exposed population. Copyright © 2014. Published by Elsevier B.V.

  2. Dietary Carcinogens and Anticarcinogens.

    Science.gov (United States)

    Ames, Bruce N.

    1983-01-01

    Describes 16 mutagens/carcinogens found in plant food and coffee as well as several anticarcinogens also found in such food. Speculates on relevant biochemical mechanisms, particularly the role of oxygen radicals and their inhibitors in the fat/cancer relationship, promotion, anticarcinogenesis, and aging. (JN)

  3. Frequency of twelve carcinogenic human papilloma virus types among women from the South Backa region, Vojvodina, Serbia.

    Science.gov (United States)

    Kovacevic, Gordana; Nikolic, Natasa; Jovanovic-Galovic, Aleksandra; Hrnjakovic-Cvjetkovic, Iv; Vuleta, Dusan; Patic, Aleksandra; Radovanov, Jelena; Milosevic, Vesna

    2016-01-05

    The aim of this study was to determine the presence and age distribution of different oncogenic human papilloma virus (HPV) types in women in the South Backa region and its relationship to Pap results. In a group of 1087 women with normal and abnormal cytology, the commercial HR HPV Real-TM kit (Sacace Biotechnologies, Italy) was used. Overall, 50.5% of the women were HPV positive. The presence of HPV types 18, 31, 51, and 58 was significantly influenced by age, while the presence of HPV types 16 and 45 was significantly influenced by cervical cytology. Results of the LSD test show a wide spectrum of high risk HPV among women with normal cytology and women with a low grade cervical lesion rate (atypical squamous cell of undetermined significance (ASCUS) and low grade squamous intraepithelial lesions (LSIL). The most prevalent HPV types found were 16, 31, 51, 18, and 52. In the HSIL group the most prevalent HPV types were 16 and 45. The reported results provide new data on the circulation of oncogenic HPV genotypes and frequency of multiple infections among women in Vojvodina and suggest that a prophylactic vaccine against HPV 16 and 18 has the potential to prevent approximately half of the high-grade lesions.

  4. Epigenetic factors in cancer risk: effect of chemical carcinogens on global DNA methylation pattern in human TK6 cells.

    Directory of Open Access Journals (Sweden)

    Ali M Tabish

    Full Text Available In the current study, we assessed the global DNA methylation changes in human lymphoblastoid (TK6 cells in vitro in response to 5 direct and 10 indirect-acting genotoxic agents. TK6 cells were exposed to the selected agents for 24 h in the presence and/or absence of S9 metabolic mix. Liquid chromatography-mass spectrometry was used for quantitative profiling of 5-methyl-2'-deoxycytidine. The effect of exposure on 5-methyl-2'-deoxycytidine between control and exposed cultures was assessed by applying the marginal model with correlated residuals on % global DNA methylation data. We reported the induction of global DNA hypomethylation in TK6 cells in response to S9 metabolic mix, under the current experimental settings. Benzene, hydroquinone, styrene, carbon tetrachloride and trichloroethylene induced global DNA hypomethylation in TK6 cells. Furthermore, we showed that dose did not have an effect on global DNA methylation in TK6 cells. In conclusion we report changes in global DNA methylation as an early event in response to agents traditionally considered as genotoxic.

  5. The history, genotoxicity and carcinogenicity of carbon-based fuels and their emissions: part 4 - alternative fuels.

    Science.gov (United States)

    Claxton, Larry D

    2015-01-01

    Much progress has been made in reducing the pollutants emitted from various combustors (including diesel engines and power plants) by the use of alternative fuels; however, much more progress is needed. Not only must researchers improve fuels and combustors, but also there is a need to improve the toxicology testing and analytical chemistry methods associated with these complex mixtures. Emissions from many alternative carbonaceous fuels are mutagenic and carcinogenic. Depending on their source and derivation, alternative carbonaceous fuels before combustion may or may not be genotoxic; however, in order to know their genotoxicity, appropriate chemical analysis and/or bioassay must be performed. Newly developed fuels and combustors must be tested to determine if they provide a public health advantage over existing technologies - including what tradeoffs can be expected (e.g., decreasing levels of PAHs versus increasing levels of NOx and possibly nitroarenes in ambient air). Another need is to improve exposure estimations which presently are a weak link in doing risk analyses. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Flavonoids targeting of IκB phosphorylation abrogates carcinogen-induced MMP-9 and COX-2 expression in human brain endothelial cells

    Directory of Open Access Journals (Sweden)

    Tahanian E

    2011-05-01

    Full Text Available Elizabeth Tahanian¹, Luis Arguello Sanchez¹, Tze Chieh Shiao², René Roy², Borhane Annabi¹¹Centre de Recherche BioMED, ²Centre de Recherche PharmaQAM, Département de chimie, Université du Québec à Montréal, QC, CanadaAbstract: Brain endothelial cells play an essential role as structural and functional components of the blood–brain barrier (BBB. Increased BBB breakdown and brain injury are associated with neuroinflammation and are thought to trigger mechanisms involving matrix metalloproteinase upregulation. Emerging evidence also indicates that cyclooxygenase (COX inhibition limits BBB disruption, but the mechanisms linking metalloproteinase to COX remain unknown. In this study, we sought to investigate the nuclear factor-kappa B (NF-κB signaling pathway, a common pathway in both the regulation of matrix metalloproteinase-9 (MMP-9 and COX-2 expression, and the inhibitory properties of several chemopreventive flavonoids. Human brain microvascular endothelial cells were treated with a combination of phorbol 12-myristate 13-acetate (PMA, a carcinogen documented to increase MMP-9 and COX-2 through NF-κB, and several naturally occurring flavonoids. Among the molecules tested, we found that fisetin, apigenin, and luteolin specifically and dose-dependently antagonized PMA-induced COX-2 and MMP-9 gene and protein expressions as assessed by qRT-PCR, immunoblotting, and zymography respectively. We further demonstrate that flavonoids impact on IκK-mediated phosphorylation activity as demonstrated by the inhibition of PMA-induced IκB phosphorylation levels. Our results suggest that BBB disruption during neuroinflammation could be pharmacologically reduced by a specific class of flavonoids acting as NF-κB signal transduction inhibitors.Keywords: blood–brain barrier, flavonoids, neuroinflammation, NF-κB signal transduction inhibitors

  7. Carcinogen risk assessment

    International Nuclear Information System (INIS)

    Hazelwoold, R.N.

    1987-01-01

    This article describes the methods by which risk factors for carcinogenic hazards are determined and the limitations inherent in the process. From statistical and epidemiological studies, the major identifiable factors related to cancer in the United States were determined to be cigarette smoking, diet, reproductive and sexual behavior, infections, ultraviolet and ionizing radiation, and alcohol consumption. The incidence of lung cancer due to air pollutants was estimated to be less than 2%. Research needs were discussed

  8. Smoking out carcinogens

    OpenAIRE

    Baines, David; Griffiths, Huw; Parker, Jane

    2016-01-01

    Smoked foods are becoming increasingly popular and are being produced by large and small food operations, artisan producers, chefs and consumers themselves. Epidemiological studies conducted over a number of decades have linked the consumption of smoked foods with various cancers and these findings have been supported by animal testing. Smoke contains a group of dangerous carcinogens that are responsible for lung cancer in cigarette smokers and implicated as causative agents for colorectal an...

  9. Carcinogenicity and mutagenicity of chromium.

    Science.gov (United States)

    Léonard, A; Lauwerys, R R

    1980-11-01

    Occupational exposure represents the main source of human contamination by chromium. For non-occupationally exposed people the major environmental exposure to chromium occurs as a consequence of its presence in food. Chromium must be considered as an essential element. Its deficiency impairs glucose metabolism. Trivalent chromium salts are poorly absorbed through the gastro-intestinal and respiratory tracts because they do not cross membranes easily. Hexavalent chromium can be absorbed by the oral and pulmonary routes and probably also through the skin. After its absorption, hexavalent chromium is rapidly reduced to the trivalent form which is probably the only form to be found in biological material. Epidemiological studies have shown that some chromium salts (mainly the slightly soluble hexavalent salts) are carcinogens. Lung cancers have, indeed, often been reported among workers in chromate-producing industry and, to a lesser extent, in workers from the chrome-pigment industry. The first attempts to produce cancers in experimental animals by inhalation or parenteral introduction gave negative or equivocal results but, from 1960, positive results have been obtained with various chromium compounds. As for the carcinogenic activity, the mutagenicity of chromium has mainly been found with hexavalent salts. In the majority of assay systems used, trivalent chromium appears inactive. It can be considered as evident, however, that the ultimate mutagen which binds to the genetic material is the trivalent form produced intracellularly from hexavalent chromium, the apparent lack of activity of the trivalent form being due to its poor cellular uptake.

  10. Respiratory carcinogenicity assessment of soluble nickel compounds.

    Science.gov (United States)

    Oller, Adriana R

    2002-10-01

    The many chemical forms of nickel differ in physicochemical properties and biological effects. Health assessments for each main category of nickel species are needed. The carcinogenicity assessment of water-soluble nickel compounds has proven particularly difficult. Epidemiologic evidence indicates an association between inhalation exposures to nickel refinery dust containing soluble nickel compounds and increased risk of respiratory cancers. However, the nature of this association is unclear because of limitations of the exposure data, inconsistent results across cohorts, and the presence of mixed exposures to water-insoluble nickel compounds and other confounders that are known or suspected carcinogens. Moreover, well-conducted animal inhalation studies, where exposures were solely to soluble nickel, failed to demonstrate a carcinogenic potential. Similar negative results were seen in animal oral studies. A model exists that relates respiratory carcinogenic potential to the bioavailability of nickel ion at nuclear sites within respiratory target cells. This model helps reconcile human, animal, and mechanistic data for soluble nickel compounds. For inhalation exposures, the predicted lack of bioavailability of nickel ion at target sites suggests that water-soluble nickel compounds, by themselves, will not be complete human carcinogens. However, if inhaled at concentrations high enough to induce chronic lung inflammation, these compounds may enhance carcinogenic risks associated with inhalation exposure to other substances. Overall, the weight of evidence indicates that inhalation exposure to soluble nickel alone will not cause cancer; moreover, if exposures are kept below levels that cause chronic respiratory toxicity, any possible tumor-enhancing effects (particularly in smokers) would be avoided.

  11. Identification of molecular candidates and interaction networks via integrative toxicogenomic analysis in a human cell line following low-dose exposure to the carcinogenic metals cadmium and nickel.

    Science.gov (United States)

    Kwon, Jee Young; Weon, Jong-Il; Koedrith, Preeyaporn; Park, Kang-Sik; Kim, Im Soon; Seo, Young Rok

    2013-09-01

    Cadmium and nickel have been classified as carcinogenic to humans by the World Health Organization's International Agency for Research on Cancer. Given their prevalence in the environment, the fact that cadmium and nickel may cause diseases including cancer even at low doses is a cause for concern. However, the exact mechanisms underlying the toxicological effects induced by low-dose exposure to cadmium and nickel remain to be elucidated. Furthermore, it has recently been recognized that integrative analysis of DNA, mRNA and proteins is required to discover biomarkers and signaling networks relevant to human toxicant exposure. In the present study, we examined the deleterious effects of chronic low-dose exposure of either cadmium or nickel on global profiling of DNA copy number variation, mRNA and proteins. Array comparative genomic hybridization, gene expression microarray and functional proteomics were conducted, and a bioinformatics tool, which predicted signaling pathways, was applied to integrate data for each heavy metal separately and together. We found distinctive signaling networks associated with subchronic low-dose exposure to cadmium and nickel, and identified pathways common to both. ACTB, HSP90AA1, HSPA5 and HSPA8, which are key mediators of pathways related to apoptosis, proliferation and neoplastic processes, were key mediators of the same pathways in low-dose nickel and cadmium exposure in particular. CASP-associated signaling pathways involving CASP3, CASP7 and CASP9 were observed in cadmium-exposed cells. We found that HSP90AA1, one of the main modulators, interacted with HIF1A, AR and BCL2 in nickel-exposed cells. Interestingly, we found that HSP90AA1 was involved in the BCL2-associated apoptotic pathway in the nickel-only data, whereas this gene interacted with several genes functioning in CASP-associated apoptotic signaling in the cadmium-only data. Additionally, JUN and FASN were main modulators in nickel-responsive signaling pathways. Our

  12. Carcinogenicity of Human Papillomavirus (HPV) Types in HIV-Positive Women: A Meta-Analysis From HPV Infection to Cervical Cancer

    Science.gov (United States)

    Tully, Stephen; Franceschi, Silvia

    2017-01-01

    Abstract Background. Data on the relative carcinogenic potential of human papillomavirus (HPV) types among women infected with human immunodeficiency virus (HIV) (WHIV) are needed to inform prevention programs for this population. Methods. A systematic literature review and meta-analysis of high-risk HPV-type distribution in 19883 HIV-positive women was performed. The women, from 86 studies worldwide, included 11739 with normal cytological findings; 1784 with atypical squamous cells of undetermined significance (ASCUS); 2173 with low-grade and 1282 with high-grade squamous intraepithelial lesions (HSILs) diagnosed cytologically; 1198 with cervical intraepithelial neoplasia grade 1 (CIN1), 456 with CIN2, and 455 with CIN3 diagnosed histologically; and 796 with invasive cervical cancers (ICCs). A large proportion of WHIV, and almost all with ICCs, were from Africa. Results. In Africa, HPV 16 accounted for 13% of HPV-positive WHIV with normal cytological findings, but this proportion increased through ASCUS, low-grade squamous intraepithelial lesions, CIN1, and CIN2 (18%–25%), up to 41%–47% for CIN3 and ICCs. Only HPV 16, HPV 18, and HPV 45 accounted for a greater proportion of HPV infections in ICCs compared with normal cytological findings (ICC:normal ratios, 3.68, 2.47, and 2.55, respectively). Other high-risk types accounted for important proportions of low- and/or high-grade lesions, but their contribution dropped in ICCs, with ICC:normal ratios in Africa ranging from 0.79 for HPV 33 down to 0.38 for HPV 56. Findings for HPV 16 and HPV 18 in Europe/North America, Asia, and Latin America were compatible with those from Africa. Conclusions. HPV 16 and HPV 18 in particular, but also HPV 45, at least in Africa, warrant special attention in WHIV. Broad consistency of findings with those in HIV-uninfected population would suggest that the risk stratification offered by partial HPV genotyping tests also have relevance for HIV-positive women. PMID:28199532

  13. A Low-Cost Wheat Bran Medium for Biodegradation of the Benzidine-Based Carcinogenic Dye Trypan Blue Using a Microbial Consortium

    Directory of Open Access Journals (Sweden)

    Harshad Lade

    2015-03-01

    Full Text Available Environmental release of benzidine-based dyes is a matter of health concern. Here, a microbial consortium was enriched from textile dye contaminated soils and investigated for biodegradation of the carcinogenic benzidine-based dye Trypan Blue using wheat bran (WB as growth medium. The PCR-DGGE analysis of enriched microbial consortium revealed the presence of 15 different bacteria. Decolorization studies suggested that the microbial consortium has high metabolic activity towards Trypan Blue as complete removal of 50 mg∙L−1 dye was observed within 24 h at 30 ± 0.2 °C and pH 7. Significant reduction in TOC (64% and COD (88% of dye decolorized broths confirmed mineralization. Induction in azoreductase (500%, NADH-DCIP reductase (264% and laccase (275% proved enzymatic decolorization of dye. HPLC analysis of dye decolorized products showed the formation of six metabolites while the FTIR spectrum indicated removal of diazo bonds at 1612.30 and 1581.34 cm−1. The proposed dye degradation pathway based on GC-MS and enzyme analysis suggested the formation of two low molecular weight intermediates. Phytotoxicity and acute toxicity studies revealed the less toxic nature of the dye degradation products. These results provide experimental evidence for the utilization of agricultural waste as a novel low-cost growth medium for biodegradation of benzidine-based dyes, and suggested the potential of the microbial consortium in detoxification.

  14. Immunologic methods for monitoring carcinogen exposure

    Science.gov (United States)

    Santella, Regina M.; Perera, Frederica P.; Zhang, Yu J.; Chen, Chen J.; Young, Tie L.

    1993-03-01

    Immunologic methods have been developed for monitoring human exposure to environmental and occupational carcinogens. These methods involve the development of monoclonal and polyclonal antisera which specifically recognize the carcinogens themselves or their DNA or protein adducts. Antisera recognizing the DNA adducts of several polycyclic aromatic hydrocarbon diol epoxides have been used in competitive enzyme-linked immunosorbent assays to monitor adducts in tissue or blood samples. Elevated levels of DNA adducts have been seen in mononuclear cells of smokers and in total white blood cells of foundry and coke oven workers. Environmental exposure to PAH has been measured in individuals living in a highly polluted region of Poland. Antisera recognizing PAH-DNA adducts have also been used in immunohistochemical studies to monitor adducts in specific cells of biopsy samples. The DNA adducts of aflatoxin B1 have been monitored in liver tissue of hepatocellular carcinoma patients in Taiwan. Detectable adducts were seen in 50 - 70% of the patients suggesting that dietary exposure to this carcinogen may be a risk factor for cancer induction. Thus, immunoassays for monitoring exposure to carcinogens are an important tool in epidemiologic studies.

  15. Risk estimation for carcinogens based on epidemiological data: A structured approach, illustrated by an example on chromium

    NARCIS (Netherlands)

    Goldbohm, R.A.; Tielemans, E.L.J.P.; Heederik, D.; Rubingh, C.M.; Dekkers, S.; Willems, M.I.; Dinant Kroese, E.

    2006-01-01

    It is generally recognized that human, epidemiological data, if available, are preferred as the starting point for quantitative risk analysis above the use of data from animal studies. Although methods to obtain proper risk estimates from epidemiological data are available, several impediments

  16. Physiologically-based pharmacokinetic modelling of immune, reproductive and carcinogenic effects from contaminant exposure in polar bears (Ursus maritimus) across the Arctic.

    Science.gov (United States)

    Dietz, Rune; Gustavson, Kim; Sonne, Christian; Desforges, Jean-Pierre; Rigét, Frank F; Pavlova, Viola; McKinney, Melissa A; Letcher, Robert J

    2015-07-01

    Polar bears (Ursus maritimus) consume large quantities of seal blubber and other high trophic marine mammals and consequently have some of the highest tissue concentrations of organohalogen contaminants (OHCs) among Arctic biota. In the present paper we carried out a risk quotient (RQ) evaluation on OHC-exposed polar bears harvested from 1999 to 2008 and from 11 circumpolar subpopulations spanning from Alaska to Svalbard in order to evaluate the risk of OHC-mediated reproductive effects (embryotoxicity, teratogenicity), immunotoxicity and carcinogenicity (genotoxicity). This RQ evaluation was based on the Critical Body Residue (CBR) concept and a Physiologically-Based Pharmacokinetic Modelling (PBPK) approach using OHC concentrations measured in polar bear adipose or liver tissue. The range of OHC concentrations within polar bear populations were as follows for adipose, sum polychlorinated biphenyls ∑PCBs (1797-10,537 ng/g lw), sum methylsulphone-PCB ∑MeSO2-PCBs (110-672 ng/g lw), sum chlordanes ∑CHLs (765-3477 ng/g lw), α-hexachlorocyclohexane α-HCH (8.5-91.3 ng/g lw), β-hexachlorocyclohexane β-HCH (65.5-542 ng/g lw), sum chlorbenzenes ∑ClBzs (145-304 ng/g lw), dichlorodiphenyltrichloroethane ∑DDTs (31.5-206 ng/g lw), dieldrin (69-249 ng/g lw), polybrominated diphenyl ethers ∑PBDEs (4.6-78.4 ng/g lw). For liver, the perfluorooctanesulfonic acid (PFOS) concentrations ranged from 231-2792 ng/g ww. The total additive RQ from all OHCs ranged from 4.3 in Alaska to 28.6 in East Greenland bears for effects on reproduction, immune health and carcinogenicity, highlighting the important result that the toxic effect threshold (i.e. RQ>1) was exceeded for all polar bear populations assessed. PCBs were the main contributors for all three effect categories, contributing from 70.6% to 94.3% of the total risk and a RQ between 3.8-22.5. ∑MeSO2-PCBs were the second highest effect contributor for reproductive and immunological effects (0.17polar bears. We therefore

  17. Determination and risk assessment of naturally occurring genotoxic and carcinogenic alkenylbenzenes in nutmeg-based plant food supplements

    NARCIS (Netherlands)

    Al-Malahmeh, Amer J.; Alajlouni, Abdul; Ning, Jia; Wesseling, Sebas; Vervoort, Jacques; Rietjens, Ivonne M.C.M.

    2017-01-01

    A risk assessment of nutmeg-based plant food supplements (PFS) containing different alkenylbenzenes was performed based on the alkenylbenzene levels quantified in a series of PFS collected via the online market. The estimated daily intake (EDI) of the alkenylbenzenes amounted to 0.3 to 312μg kg-1

  18. Environmental carcinogenic agents and cancer prevention. Risk assessment and management

    International Nuclear Information System (INIS)

    Tsugane, Shoichiro

    2013-01-01

    Many agents in our environment have been established as being carcinogenic, and in most cases, the carcinogenic properties of these agents were identified because of high-dose occupational or accidental exposure. Risk characterization, taking into account the dose-response relationship, and exposure assessment are essential for risk assessment and subsequent cancer prevention. Based on scientific risk assessment, risk management should be conducted practically by considering the economic, social, political, and other technical issues and by balancing the risks and benefits. Asbestos and environmental tobacco smoke are typical examples of established carcinogenic agents in the general environment, contributing to low-dose exposure. Further epidemiological studies are required to investigate the carcinogenicity of low-dose exposure to known carcinogenic agents such as arsenic and cadmium through dietary intake, radiation via medical and natural exposure, and air pollution due to diesel exhaust. In contrast, occupational chemical exposure to 1,2-dichloropropane and/or dichloromethane, whose carcinogenicity had not been established, was suggested to cause cholangiocarcinoma among workers involved in offset color proof-printing only after a rare situation of high-dose exposure was unveiled. Continuous monitoring of unusual cancer occurrences in target populations such as workers in occupational and regional settings as well as exposure reduction to suspected carcinogenic agents to levels as low as reasonably achievable is essential for reducing the risk of cancer due to environmental carcinogens. (author)

  19. Identification and monitoring of non-radiological carcinogens

    Energy Technology Data Exchange (ETDEWEB)

    Chuaqui, C A; Petkau, A; Greenstock, C L; Brown, C P [Atomic Energy of Canada Ltd., Pinawa, MB (Canada). Whiteshell Labs.

    1995-09-01

    This study examines the feasibility of identifying and monitoring occupational exposures to non-radiological carcinogens in the workplace at Canadian nuclear establishments (Whiteshell Laboratories, Pickering Nuclear Generating Station, Cameco Limited and Canadian General Electric Company Limited). Recent epidemiological studies recommended that potential confounding factors of a non-radiological nature be identified and analyzed, particularly non-radiological carcinogens that may be present in the workplace at nuclear facilities. The feasibility of identifying and measuring occupational exposures to non-radiological carcinogens in Canadian nuclear facilities is examined. Also, the report describes the problem of chemical carcinogens and the mechanisms involved in chemical carcinogenesis; the epidemiology related to the problem, followed by a description of the analytical aspects of detection, monitoring and analysis of carcinogens, as well as a discussion on the regulatory aspects and the regulations in place; and the findings, recommendations and concluding remarks of this study. Several problem areas became apparent as the study proceeded. For example, the classification of a chemical as a human carcinogen is a difficult problem, as is its adequate monitoring and analysis. This situation reflects, in turn, the regulatory aspects in the workplace. A list of chemical carcinogens used industrially at the four Canadian nuclear facilities has been identified. The list includes arsenic, asbestos, benzene, cadmium, beryllium, nickel, polychlorinated biphenyls, lead and trichloroethylene. Several recommendations are made in relation to the need for practical and efficient monitoring methods for chemical carcinogens, the definition of radiation and chemical dose equivalencies, and the classification of human chemical carcinogens, as well as their disposal. (author). 122 refs., 8 tabs., 6 figs.

  20. Identification and monitoring of non-radiological carcinogens

    International Nuclear Information System (INIS)

    Chuaqui, C.A.; Petkau, A.; Greenstock, C.L.; Brown, C.P.

    1995-09-01

    This study examines the feasibility of identifying and monitoring occupational exposures to non-radiological carcinogens in the workplace at Canadian nuclear establishments (Whiteshell Laboratories, Pickering Nuclear Generating Station, Cameco Limited and Canadian General Electric Company Limited). Recent epidemiological studies recommended that potential confounding factors of a non-radiological nature be identified and analyzed, particularly non-radiological carcinogens that may be present in the workplace at nuclear facilities. The feasibility of identifying and measuring occupational exposures to non-radiological carcinogens in Canadian nuclear facilities is examined. Also, the report describes the problem of chemical carcinogens and the mechanisms involved in chemical carcinogenesis; the epidemiology related to the problem, followed by a description of the analytical aspects of detection, monitoring and analysis of carcinogens, as well as a discussion on the regulatory aspects and the regulations in place; and the findings, recommendations and concluding remarks of this study. Several problem areas became apparent as the study proceeded. For example, the classification of a chemical as a human carcinogen is a difficult problem, as is its adequate monitoring and analysis. This situation reflects, in turn, the regulatory aspects in the workplace. A list of chemical carcinogens used industrially at the four Canadian nuclear facilities has been identified. The list includes arsenic, asbestos, benzene, cadmium, beryllium, nickel, polychlorinated biphenyls, lead and trichloroethylene. Several recommendations are made in relation to the need for practical and efficient monitoring methods for chemical carcinogens, the definition of radiation and chemical dose equivalencies, and the classification of human chemical carcinogens, as well as their disposal. (author). 122 refs., 8 tabs., 6 figs

  1. Application of the key characteristics of carcinogens in cancer hazard identification

    Science.gov (United States)

    Guyton, Kathryn Z; Rusyn, Ivan; Chiu, Weihsueh A; Corpet, Denis E; van den Berg, Martin; Ross, Matthew K; Christiani, David C; Beland, Frederick A; Smith, Martyn T

    2018-01-01

    Abstract Smith et al. (Env. Health Perspect. 124: 713, 2016) identified 10 key characteristics (KCs), one or more of which are commonly exhibited by established human carcinogens. The KCs reflect the properties of a cancer-causing agent, such as ‘is genotoxic,’ ‘is immunosuppressive’ or ‘modulates receptor-mediated effects,’ and are distinct from the hallmarks of cancer, which are the properties of tumors. To assess feasibility and limitations of applying the KCs to diverse agents, methods and results of mechanistic data evaluations were compiled from eight recent IARC Monograph meetings. A systematic search, screening and evaluation procedure identified a broad literature encompassing multiple KCs for most (12/16) IARC Group 1 or 2A carcinogens identified in these meetings. Five carcinogens are genotoxic and induce oxidative stress, of which pentachlorophenol, hydrazine and malathion also showed additional KCs. Four others, including welding fumes, are immunosuppressive. The overall evaluation was upgraded to Group 2A based on mechanistic data for only two agents, tetrabromobisphenol A and tetrachloroazobenzene. Both carcinogens modulate receptor-mediated effects in combination with other KCs. Fewer studies were identified for Group 2B or 3 agents, with the vast majority (17/18) showing only one or no KCs. Thus, an objective approach to identify and evaluate mechanistic studies pertinent to cancer revealed strong evidence for multiple KCs for most Group 1 or 2A carcinogens but also identified opportunities for improvement. Further development and mapping of toxicological and biomarker endpoints and pathways relevant to the KCs can advance the systematic search and evaluation of mechanistic data in carcinogen hazard identification. PMID:29562322

  2. Human Microdosing with Carcinogenic Polycyclic Aromatic Hydrocarbons: In Vivo Pharmacokinetics of Dibenzo[ def,p ]chrysene and Metabolites by UPLC Accelerator Mass Spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Madeen, Erin P.; Ognibene, Ted J.; Corley, Richard A.; McQuistan, Tammie J.; Henderson, Marilyn C.; Baird, William M.; Bench, Graham; Turteltaub, Ken W.; Williams, David E.

    2016-10-17

    Metabolism is a key health risk factor following exposures to pro-carcinogenic polycyclic aromatic hydrocarbons (PAHs) such as dibenzo[def,p]chrysene (DBC), an IARC classified 2A probable human carcinogen. Human exposure to PAHs occurs primarily from the diet in non-smokers. However, little data is available on the metabolism and pharmacokinetics in humans of high molecular weight PAHs (≥4 aromatic rings), including DBC. We previously determined the pharmacokinetics of DBC in human volunteers orally administered a micro-dose (29 ng; 5 nCi) of [14C]-DBC by accelerator mass spectrometry (AMS) analysis of total [14C] in plasma and urine. In the current study, we utilized a novel “moving wire” interface between ultra-performance liquid chromatography (UPLC) and AMS to detect and quantify parent DBC and its major metabolites. The major [14C] product identified in plasma was unmetabolized [14C]-DBC itself, (Cmax= 18.5 ± 15.9 fg/mL, Tmax= 2.1 ± 1.0 h), whereas the major metabolite was identified as [14C]-(+/-)-DBC-11,12-diol (Cmax= 2.5 ± 1.3 fg/mL, Tmax= 1.8 h). Several minor species of [14C]-DBC metabolites were also detected for which no reference standards were available. Free and conjugated metabolites were detected in urine with [14C]-(+/-)-DBC-11,12,13,14-tetraol isomers identified as the major metabolites, 56.3% of which were conjugated (Cmax= 35.8 ± 23.0 pg/pool, Tmax= 6-12 h pool). [14C]-DBC-11,12-diol, of which 97.5% was conjugated, was also identified in urine (Cmax= 29.4 ± 11.6 pg/pool, Tmax= 6-12 h pool). Parent [14C]-DBC was not detected in urine. This is the first dataset to assess metabolite profiles and associated pharmacokinetics of a carcinogenic PAH in human volunteers at an environmentally relevant dose, providing the data necessary for translation of high dose animal models to humans for translation of environmental health risk assessment.

  3. An estimation of the carcinogenic risk associated with the intake of multiple relevant carcinogens found in meat and charcuterie products.

    Science.gov (United States)

    Hernández, Ángel Rodríguez; Boada, Luis D; Almeida-González, Maira; Mendoza, Zenaida; Ruiz-Suárez, Norberto; Valeron, Pilar F; Camacho, María; Zumbado, Manuel; Henríquez-Hernández, Luis A; Luzardo, Octavio P

    2015-05-01

    Numerous epidemiological studies have demonstrated a link between excessive meat consumption and the incidence of various cancers, especially colorectal cancer, and it has been suggested that environmental carcinogens present in meat might be related to the increased risk of cancer associated with this food. However, there are no studies evaluating the carcinogenic potential of meat in relation to its content of carcinogens. Our purpose was to emphasize the relevance of environmental carcinogens existing in meat as a determinant of the association between cancer and meat consumption. Because within Europe, Spain shows high consumption of meat and charcuterie, we performed this study focusing on Spanish population. Based on the preferences of consumers we acquired 100 samples of meat and charcuterie that reflect the variety available in the European market. We quantified in these samples the concentration of 33 chemicals with calculated carcinogenic potential (PAHs, organochlorine pesticides, and dioxin-like PCBs). The carcinogenic risk of these contaminants was assessed for each food using a risk ratio based on the current consumption of meat and charcuterie and the maximum tolerable intake of these foods depending on the level of contamination by the carcinogens they contain. Our results indicate that the current consumption of beef, pork, lamb, chicken, and "chorizo", represents a relevant carcinogenic risk for consumers (carcinogenic risk quotient between 1.33 and 13.98). In order to reduce carcinogenic risk, the study population should halve the monthly consumption of these foods, and also not to surpass the number of 5 servings of beef/pork/chicken (considered together). Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Carcinogenicity of soil extracts

    Energy Technology Data Exchange (ETDEWEB)

    Shcherbak, N P

    1970-01-01

    A total of 270 3-mo-old mice, hybrids of the C57BL and CBA strains which are highly susceptible to carcinogens, were painted on the skin (2-3 admin./week) with 3-4 drops of (1) a concentrated benzene extract of soil taken near a petroleum refinery with a 3,4 benzpyrene (BP) content of 0.22%; (2) a 0.22% soln of pure BP in benzene; (3) a concentrated benzene extract of soil taken from an old residential area of Moscow (BP content 0.0004%); (4) a 0.0004% BP soln in benzene; and (5) pure benzene. Only mice in the first 2 groups developed tumors. In group (1), 8 mice had papillomas, 46 had skin cancer, 1 had a sarcoma and 2 had plasmocytomas. In group (2) all 60 animals had skin cancer. Lung metastases were present at autopsy in 5 mice in group (1) and in 10 mice in group (2); in some cases, these tumors were multiple. Lymph node metastases were found in 6 mice in group (1) and in 10 mice in group (2). Tumors developed more slowly in group (1) than in group (2).

  5. Determination and risk assessment of naturally occurring genotoxic and carcinogenic alkenylbenzenes in nutmeg-based plant food supplements.

    Science.gov (United States)

    Al-Malahmeh, Amer J; Alajlouni, Abdalmajeed M; Ning, Jia; Wesseling, Sebastiaan; Vervoort, Jacques; Rietjens, Ivonne M C M

    2017-10-01

    A risk assessment of nutmeg-based plant food supplements (PFS) containing different alkenylbenzenes was performed based on the alkenylbenzene levels quantified in a series of PFS collected via the online market. The estimated daily intake (EDI) of the alkenylbenzenes amounted to 0.3 to 312 μg kg -1 body weight (bw) for individual alkenylbenzenes, to 1.5 to 631 μg kg -1 bw when adding up the alkenylbenzene levels assuming equal potency, and to 0.4 to 295 μg kg -1 bw when expressed in safrole equivalents using toxic equivalency factors (TEFs). The margin of exposure approach (MOE) was used to evaluate the potential risks. Independent of the method used for the intake estimate, the MOE values obtained were generally lower than 10000 indicating a priority for risk management. When taking into account that PFS may be used for shorter periods of time and using Haber's rule to correct for shorter than lifetime exposure it was shown that limiting exposure to only 1 or 2 weeks would result in MOE values that would be, with the presently determined levels of alkenylbenzenes and proposed uses of the PFS, of low priority for risk management (MOE > 10000). It is concluded that the results of the present paper reveal that nutmeg-based PFS consumption following recommendations for daily intake especially for longer periods of time raise a concern. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  6. Oxidative Stress in the Carcinogenicity of Chemical Carcinogens

    International Nuclear Information System (INIS)

    Kakehashi, Anna; Wei, Min; Fukushima, Shoji; Wanibuchi, Hideki

    2013-01-01

    This review highlights several in vivo studies utilizing non-genotoxic and genotoxic chemical carcinogens, and the mechanisms of their high and low dose carcinogenicities with respect to formation of oxidative stress. Here, we survey the examples and discuss possible mechanisms of hormetic effects with cytochrome P 450 inducers, such as phenobarbital, α-benzene hexachloride and 1,1-bis(p-chlorophenyl)-2,2,2-trichloroethane. Epigenetic processes differentially can be affected by agents that impinge on oxidative DNA damage, repair, apoptosis, cell proliferation, intracellular communication and cell signaling. Non-genotoxic carcinogens may target nuclear receptors and induce post-translational modifications at the protein level, thereby impacting on the stability or activity of key regulatory proteins, including oncoproteins and tumor suppressor proteins. We further discuss role of oxidative stress focusing on the low dose carcinogenicities of several genotoxic carcinogens such as a hepatocarcinogen contained in seared fish and meat, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline, arsenic and its metabolites, and the kidney carcinogen potassium bromate

  7. Oxidative Stress in the Carcinogenicity of Chemical Carcinogens

    Energy Technology Data Exchange (ETDEWEB)

    Kakehashi, Anna; Wei, Min [Department of Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-Ku, Osaka 545-8585 (Japan); Fukushima, Shoji [Japan Bioassay Research Center, Japan Industrial Safety and Health Association, 2445 Hirasawa, Hadano, Kanagawa 257-0015 (Japan); Wanibuchi, Hideki, E-mail: wani@med.osaka-cu.ac.jp [Department of Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-Ku, Osaka 545-8585 (Japan)

    2013-10-28

    This review highlights several in vivo studies utilizing non-genotoxic and genotoxic chemical carcinogens, and the mechanisms of their high and low dose carcinogenicities with respect to formation of oxidative stress. Here, we survey the examples and discuss possible mechanisms of hormetic effects with cytochrome P{sub 450} inducers, such as phenobarbital, α-benzene hexachloride and 1,1-bis(p-chlorophenyl)-2,2,2-trichloroethane. Epigenetic processes differentially can be affected by agents that impinge on oxidative DNA damage, repair, apoptosis, cell proliferation, intracellular communication and cell signaling. Non-genotoxic carcinogens may target nuclear receptors and induce post-translational modifications at the protein level, thereby impacting on the stability or activity of key regulatory proteins, including oncoproteins and tumor suppressor proteins. We further discuss role of oxidative stress focusing on the low dose carcinogenicities of several genotoxic carcinogens such as a hepatocarcinogen contained in seared fish and meat, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline, arsenic and its metabolites, and the kidney carcinogen potassium bromate.

  8. Oxidative Stress in the Carcinogenicity of Chemical Carcinogens

    Directory of Open Access Journals (Sweden)

    Hideki Wanibuchi

    2013-10-01

    Full Text Available This review highlights several in vivo studies utilizing non-genotoxic and genotoxic chemical carcinogens, and the mechanisms of their high and low dose carcinogenicities with respect to formation of oxidative stress. Here, we survey the examples and discuss possible mechanisms of hormetic effects with cytochrome P450 inducers, such as phenobarbital, a-benzene hexachloride and 1,1-bis(p-chlorophenyl-2,2,2-trichloroethane. Epigenetic processes differentially can be affected by agents that impinge on oxidative DNA damage, repair, apoptosis, cell proliferation, intracellular communication and cell signaling. Non-genotoxic carcinogens may target nuclear receptors and induce post-translational modifications at the protein level, thereby impacting on the stability or activity of key regulatory proteins, including oncoproteins and tumor suppressor proteins. We further discuss role of oxidative stress focusing on the low dose carcinogenicities of several genotoxic carcinogens such as a hepatocarcinogen contained in seared fish and meat, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline, arsenic and its metabolites, and the kidney carcinogen potassium bromate.

  9. METABOLISM, GENOTOXICITY, AND CARCINOGENICITY OF COMFREY

    Science.gov (United States)

    Mei, Nan; Guo, Lei; Fu, Peter P.; Fuscoe, James C.; Luan, Yang; Chen, Tao

    2018-01-01

    Comfrey has been consumed by humans as a vegetable and a tea and used as an herbal medicine for more than 2000 years. Comfrey, however, produces hepatotoxicity in livestock and humans and carcinogenicity in experimental animals. Comfrey contains as many as 14 pyrrolizidine alkaloids (PA), including 7-acetylintermedine, 7-acetyllycopsamine, echimidine, intermedine, lasiocarpine, lycopsamine, myoscorpine, symlandine, symphytine, and symviridine. The mechanisms underlying comfrey-induced genotoxicity and carcinogenicity are still not fully understood. The available evidence suggests that the active metabolites of PA in comfrey interact with DNA in liver endothelial cells and hepatocytes, resulting in DNA damage, mutation induction, and cancer development. Genotoxicities attributed to comfrey and riddelliine (a representative genotoxic PA and a proven rodent mutagen and carcinogen) are discussed in this review. Both of these compounds induced similar profiles of 6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP)-derived DNA adducts and similar mutation spectra. Further, the two agents share common mechanisms of drug metabolism and carcinogenesis. Overall, comfrey is mutagenic in liver, and PA contained in comfrey appear to be responsible for comfrey-induced toxicity and tumor induction. PMID:21170807

  10. Metabolism, genotoxicity, and carcinogenicity of comfrey.

    Science.gov (United States)

    Mei, Nan; Guo, Lei; Fu, Peter P; Fuscoe, James C; Luan, Yang; Chen, Tao

    2010-10-01

    Comfrey has been consumed by humans as a vegetable and a tea and used as an herbal medicine for more than 2000 years. Comfrey, however, produces hepatotoxicity in livestock and humans and carcinogenicity in experimental animals. Comfrey contains as many as 14 pyrrolizidine alkaloids (PA), including 7-acetylintermedine, 7-acetyllycopsamine, echimidine, intermedine, lasiocarpine, lycopsamine, myoscorpine, symlandine, symphytine, and symviridine. The mechanisms underlying comfrey-induced genotoxicity and carcinogenicity are still not fully understood. The available evidence suggests that the active metabolites of PA in comfrey interact with DNA in liver endothelial cells and hepatocytes, resulting in DNA damage, mutation induction, and cancer development. Genotoxicities attributed to comfrey and riddelliine (a representative genotoxic PA and a proven rodent mutagen and carcinogen) are discussed in this review. Both of these compounds induced similar profiles of 6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP)-derived DNA adducts and similar mutation spectra. Further, the two agents share common mechanisms of drug metabolism and carcinogenesis. Overall, comfrey is mutagenic in liver, and PA contained in comfrey appear to be responsible for comfrey-induced toxicity and tumor induction.

  11. Carcinogen-DNA interaction study by base sequence footprinting. Progress report, July 1, 1985-January 21, 1986

    International Nuclear Information System (INIS)

    Bases, R.

    1986-01-01

    Acetyl-aminofluorene (AAF) modified plasmid pSV 2 CAT is being studied to learn how the adducts influence expression of chloramphenicol acetyltransferase (CAT) genes. phi X-174 RF DNA exhibits specific base sequence abnormalities induced by the formation of AAF adducts. The DNAase I sensitive state of AAF modified DNA sequences could presumably lead to enhanced expression of genes since it is a well-known characteristic of active or potentially active derepressed genes. DNAase I hypersensitive sites are necessary but not sufficient for transcription. We observed enhanced expression of CAT genes in CV-1 cells after transfection with modified plasmids, using electroporation to introduce the plasmids into the cells. 34 refs., 2 figs

  12. An analysis of pharmaceutical experience with decades of rat carcinogenicity testing: support for a proposal to modify current regulatory guidelines.

    Science.gov (United States)

    Sistare, Frank D; Morton, Daniel; Alden, Carl; Christensen, Joel; Keller, Douglas; Jonghe, Sandra De; Storer, Richard D; Reddy, M Vijayaraj; Kraynak, Andrew; Trela, Bruce; Bienvenu, Jean-Guy; Bjurström, Sivert; Bosmans, Vanessa; Brewster, David; Colman, Karyn; Dominick, Mark; Evans, John; Hailey, James R; Kinter, Lewis; Liu, Matt; Mahrt, Charles; Marien, Dirk; Myer, James; Perry, Richard; Potenta, Daniel; Roth, Arthur; Sherratt, Philip; Singer, Thomas; Slim, Rabih; Soper, Keith; Fransson-Steen, Ronny; Stoltz, James; Turner, Oliver; Turnquist, Susan; van Heerden, Marjolein; Woicke, Jochen; DeGeorge, Joseph J

    2011-06-01

    Data collected from 182 marketed and nonmarketed pharmaceuticals demonstrate that there is little value gained in conducting a rat two-year carcinogenicity study for compounds that lack: (1) histopathologic risk factors for rat neoplasia in chronic toxicology studies, (2) evidence of hormonal perturbation, and (3) positive genetic toxicology results. Using a single positive result among these three criteria as a test for outcome in the two-year study, fifty-two of sixty-six rat tumorigens were correctly identified, yielding 79% test sensitivity. When all three criteria were negative, sixty-two of seventy-six pharmaceuticals (82%) were correctly predicted to be rat noncarcinogens. The fourteen rat false negatives had two-year study findings of questionable human relevance. Applying these criteria to eighty-six additional chemicals identified by the International Agency for Research on Cancer as likely human carcinogens and to drugs withdrawn from the market for carcinogenicity concerns confirmed their sensitivity for predicting rat carcinogenicity outcome. These analyses support a proposal to refine regulatory criteria for conducting a two-year rat study to be based on assessment of histopathologic findings from a rat six-month study, evidence of hormonal perturbation, genetic toxicology results, and the findings of a six-month transgenic mouse carcinogenicity study. This proposed decision paradigm has the potential to eliminate over 40% of rat two-year testing on new pharmaceuticals without compromise to patient safety.

  13. ABCG2/BCRP decreases the transfer of a food-born chemical carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in perfused term human placenta

    International Nuclear Information System (INIS)

    Myllynen, Paeivi; Kummu, Maria; Kangas, Tiina; Ilves, Mika; Immonen, Elina; Rysae, Jaana; Pirilae, Rauna; Lastumaeki, Anni; Vaehaekangas, Kirsi H.

    2008-01-01

    We have studied the role of ATP binding cassette (ABC) transporters in fetal exposure to carcinogens using 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) a known substrate for ABC transporters as a model compound. In perfusion of human term placenta, transfer of 14 C-PhIP (2 μM) through the placenta resulted in fetal-to-maternal concentration ratio (FM ratio) of 0.72 ± 0.09 at 6 h. The specific ABCG2 inhibitor KO143 increased the transfer of 14 C-PhIP from maternal to fetal circulation (FM ratio 0.90 ± 0.08 at 6 h, p 14 C-PhIP (R = - 0.81, p 14 C-PhIP in perfused human placenta. Also, PhIP may modify ABC transporter expression in choriocarinoma cells

  14. Identifying occupational carcinogens: an update from the IARC Monographs.

    Science.gov (United States)

    Loomis, Dana; Guha, Neela; Hall, Amy L; Straif, Kurt

    2018-05-16

    The recognition of occupational carcinogens is important for primary prevention, compensation and surveillance of exposed workers, as well as identifying causes of cancer in the general population. This study updates previously published lists of known occupational carcinogens while providing additional information on cancer type, exposure scenarios and routes, and discussing trends in the identification of carcinogens over time. Data were extracted from International Agency for Research on Cancer (IARC) Monographs covering the years 1971-2017, using specific criteria to ensure occupational relevance and provide high confidence in the causality of observed exposure-disease associations. Selected agents were substances, mixtures or types of radiation classified in IARC Group 1 with 'sufficient evidence of carcinogenicity' in humans from studies of exposed workers and evidence of occupational exposure documented in the pertinent monograph. The number of known occupational carcinogens has increased over time: 47 agents were identified as known occupational carcinogens in 2017 compared with 28 in 2004. These estimates are conservative and likely underestimate the number of carcinogenic agents present in workplaces. Exposure to these agents causes a wide range of cancers; cancers of the lung and other respiratory sites, followed by skin, account for the largest proportion. The dominant routes of exposure are inhalation and dermal contact. Important progress has been made in identifying occupational carcinogens; nevertheless, there is an ongoing need for research on the causes of work-related cancer. Most workplace exposures have not been evaluated for their carcinogenic potential due to inadequate epidemiologic evidence and a paucity of quantitative exposure data. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  15. Recent developments in carcinogenic risk assessment

    International Nuclear Information System (INIS)

    Krewski, D.; Murdoch, D.; Withey, J.R.

    1989-01-01

    In this paper, recent developments in the quantitative assessment of carcinogenic risks based on toxicological and epidemiological data are reviewed. In particular, model-free approaches to low-dose risk assessment which involve only the assumption of low-dose linearity are considered. Measures of carcinogenic potency which avoid the need to extrapolate to low doses are also described. The allometric bases for converting risk estimates between species are then discussed. Pharmacokinetic models for determining the dose delivered to the target tissue are examined, and the implications of using such models in extrapolating between doses, of exposure, and species are examined. The application of these concepts in chemical and radiation carcinogenesis is illustrated by means of brief case studies of methylene chloride and Rn. Biologically motivated cancer models based on the initiation-promotion-progression theory of carcinogenesis are discussed and compared with the classical multistage model. The estimation of risks with time-dependent exposure patterns is considered, and conditions under which the use of a time-weighted average dose is appropriate are identified. Finally, the estimation of carcinogenic risks posed by exposure to complex mixtures is explored. 92 references

  16. Prediction of Chemical Carcinogenicity in Rodents from in vitro Genetic Toxicity Assays

    Science.gov (United States)

    Tennant, Raymond W.; Margolin, Barry H.; Shelby, Michael D.; Zeiger, Errol; Haseman, Joseph K.; Spalding, Judson; Caspary, William; Resnick, Michael; Stasiewicz, Stanley; Anderson, Beth; Minor, Robert

    1987-05-01

    carcinogenicity and the four in vitro STTs to attempt to confirm the current findings. The standard against which the performance of STTs is measured has changed dramatically in the past decade. The high levels of concordance published in the early 1970s were accurate at the time. Nearly all known carcinogens tested were genotoxic, and there was little experimental evidence on which to base a judgment of noncarcinogenicity which, taken together, restricted assessment of test performances with noncarcinogens. With the increasing availability of results from NCI and NTP 2-year carcinogenicity studies in rodents, higher frequencies of nongenotoxic carcinogens and genotoxic noncarcinogens have been observed; this has resulted in the reduced concordance of the STT results with carcinogenicity results. It is clear that even with a battery of assays, not all rodent carcinogens are in vitro mutagens nor are all in vitro mutagens rodent carcinogens. If current in vitro STTs are expected to replace long-term rodent studies for the identification of chemical carcinogens, then that expectation should be abandoned. STTs do, however, continue to offer an economical, rapid, and dependable means to detect genotoxic chemicals. There is a range of applications in which STTs have been used successfully, from the identification of mutagenic fractions in complex mixtures such as cooked meat (32, 33) or air pollutants (34) to the early identification of genetic toxicity in the development of new chemical products (35). Requirements for the use of STT have not been consistent in both the national and international regulatory agencies. This is evident in the variety of testing requirements (8) and the different impacts that positive test results have on the registration or further testing requirements of chemicals. Consensus on these matters is not likely to occur in the near future, but agreement should be possible in certain areas. For instance, any time a new test or strategy is proposed, it is

  17. Assessment of respiratory carcinogenicity associated with exposure to metallic nickel: a review.

    Science.gov (United States)

    Sivulka, Donna J

    2005-11-01

    Human studies prior to 1990 have shown an association between respiratory cancer and exposure to some nickel compounds, but not to metallic nickel. Numerous reviews have examined the nature of the association between nickel compounds and respiratory cancer, but little has been published on metallic nickel. This paper reviews the animal and human cancer-related data on metallic nickel to determine whether the conclusions regarding metallic nickel reached a decade ago still apply. Based upon past and current human studies, metallic nickel appears to show little evidence of carcinogenicity when present at the same or higher concentrations than those seen in current workplace environments. By comparison, animal studies currently available have shown mixed results. A number of studies have shown evidence of carcinogenicity in animals exposed to nickel powders via injection, but other studies have shown no or inconsistent results in animals exposed via inhalation or intratracheal instillation. Further studies in animals via inhalation and humans would be helpful in elucidating the respiratory carcinogenic potential of metallic nickel.

  18. Tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) induces cell proliferation in normal human bronchial epithelial cells through NFκB activation and cyclin D1 up-regulation

    International Nuclear Information System (INIS)

    Ho, Y.-S.; Chen, Chien-Ho; Wang, Y.-J.; Pestell, Richard G.; Albanese, Chris; Chen, R.-J.; Chang, M.-C.; Jeng, J.-H.; Lin, S.-Y.; Liang, Y.-C.; Tseng, H.; Lee, W.-S.; Lin, J.-K.; Chu, J.-S.; Chen, L.-C.; Lee, C.-H.; Tso, W.-L.; Lai, Y.-C.; Wu, C.-H.

    2005-01-01

    Cigarette smoke contains several carcinogens known to initiate and promote tumorigenesis as well as metastasis. Nicotine is one of the major components of the cigarette smoke and the 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a tobacco-specific carcinogen. Here, we demonstrated that NNK stimulated cell proliferation in normal human bronchial epithelial cells (NHBE) and small airway epithelial cells (SAEC). Cells exposed to NNK resulted in an increase in the level of cyclin D1 protein (as early as 3-6 h). Increased phosphorylation of the Rb Ser 795 was detected at 6-15 h after NNK treatment and thereby promoted cells entering into the S phase (at 15-21 h). The increased cyclin D1 protein level was induced through activation of the transcription factor, nuclear factor kB (NFκB), in the NHBE cells. Treatment of the NHBE cells with PD98059, an ERK1/2 (extracellular signal-regulated protein kinase)-specific inhibitor, specifically suppressed the NNK-induced IκBα phosphorylation at position 32 of the serine residue, suggesting that the ERK1/2 kinase was involved in the IκBα phosphorylation induced by NFκB activation. To determine whether the NNK-induced NFκB activation and cyclin D1 induction were also observed in vivo, A/J mice were treated with NNK (9.1 mg) for 20 weeks and the results showed a significant induction of cyclin D1 and NFκB translocation determined by immunoblotting analyses. We further demonstrated that the nicotine acetylcholine receptor (nAchR), which contains the α3-subunit, was the major target mediating NNK-induced cyclin D1 expression in the NHBE cells. In summary, our findings demonstrate for the first time that NNK could stimulate normal human bronchial cell proliferation through activation of the NFκB, which in turn up-regulated the cyclin D1 expression

  19. Is ionizing radiation regulated more stringently than chemical carcinogens

    International Nuclear Information System (INIS)

    Travis, C.C.; Pack, S.R.; Hattemer-Frey, H.A.

    1989-01-01

    It is widely believed that United States government agencies regulate exposure to ionizing radiation more stringently than exposure to chemical carcinogens. It is difficult to verify this perception, however, because chemical carcinogens and ionizing radiation are regulated using vastly different strategies. Chemical carcinogens are generally regulated individually. Regulators consider the risk of exposure to one chemical rather than the cumulative radiation exposure from all sources. Moreover, standards for chemical carcinogens are generally set in terms of quantities released or resultant environmental concentrations, while standards for ionizing radiation are set in terms of dose to the human body. Since chemicals and ionizing radiation cannot be compared on the basis of equal dose to the exposed individual, standards regulating chemicals and ionizing radiation cannot be compared directly. It is feasible, however, to compare the two sets of standards on the basis of equal risk to the exposed individual, assuming that standards for chemicals and ionizing radiation are equivalent if estimated risk levels are equitable. This paper compares risk levels associated with current standards for ionizing radiation and chemical carcinogens. The authors do not attempt to determine whether either type of risk is regulated too stringently or not stringently enough but endeavor only to ascertain if ionizing radiation is actually regulated more strictly than chemical carcinogens

  20. Carcinogenicity of methyl-tertiary butyl ether in gasoline.

    Science.gov (United States)

    Mehlman, Myron A

    2002-12-01

    Methyl tertiary butyl ether (MTBE) was added to gasoline on a nationwide scale in 1992 without prior testing of adverse, toxic, or carcinogenic effects. Since that time, numerous reports have appeared describing adverse health effects of individuals exposed to MTBE, both from inhalation of fumes in the workplace and while pumping gasoline. Leakage of MTBE, a highly water-soluble compound, from underground storage tanks has led to contamination of the water supply in many areas of the United States. Legislation has been passed by many states to prohibit the addition of MTBE to gasoline. The addition of MTBE to gasoline has not accomplished its stated goal of decreasing air pollution, and it has posed serious health risks to a large portion of the population, particularly the elderly and those with respiratory problems, asthma, and skin sensitivity. Reports of animal studies of carcinogenicity of MTBE began to appear in the 1990s, prior to the widespread introduction of MTBE into gasoline. These reports were largely ignored. In ensuing years, further studies have shown that MTBE causes various types of malignant tumors in mice and rats. The National Toxicology Program (NTP) Board of Scientific Counselors' Report on Carcinogens Subcommittee met in December 1998 to consider listing MTBE as "reasonably anticipated to be a human carcinogen." In spite of recommendations from Dr. Bailer, the primary reviewer, and other scientists on the committee, the motion to list MTBE in the report was defeated by a six to five vote, with one abstention. On the basis of animal studies, it is widely accepted that if a chemical is carcinogenic in appropriate laboratory animal test systems, it must be treated as though it were carcinogenic in humans. In the face of compelling evidence, NTP Committee members who voted not to list MTBE as "reasonably anticipated to be a human carcinogen" did a disservice to the general public; this action may cause needless exposure of many to health risks

  1. Evaluation of the carcinogenic risks at the influence of POPs.

    Science.gov (United States)

    Nazhmetdinova, Aiman; Kassymbayev, Adlet; Chalginbayeva, Altinay

    2017-12-20

    Kazakhstan is included in the list of environmentally vulnerable countries and Kyzylorda oblast in particular. This is due to its geographical, spatial and temporal and socioeconomic features. As part of the program "Integrated approaches in the management of public health in the Aral region", we have carried out an expertise on many samples of natural environments and products. Samples were selected in accordance with sampling procedures according to regulatory documents by specialists of the Pesticide Toxicology Laboratory. It is accredited by the State Standard of the Republic of Kazakhstan, for compliance with ST RK ISO/IEC 17025-2007 "General requirements for the competence of test and calibration laboratories". Gas chromatograph was used for the determination of residues of organochlorine pesticides. For the determination of dioxins, polychlorinated biphenyl was conducted on the gas chromatomass spectrometer with quadruple detector produce by Agilent Company, USA. To assess the risk, we carried out the mathematical calculations according to the risk of chemicals polluting (No P 2.1.10.1920-04, Russia). Calculation of the carcinogenic risk was carried out with the use of data on the size of the exposure and meanings of carcinogenic potential factors (slope factor and unit risk). The evaluation of persistent organic pollutants (POPs), based on the previous results of the research concerning water, soil and food products, was held in five population settlements in Kyzylorda oblast villages: Ayteke bi, Zhalagash, Zhosaly, Shieli and Aralsk town. Pollution with the POPs in the environmental objects by means of exposition and evaluation of the carcinogenic risk to human health is confirmed by the data of the statistical reporting about some morbidity in Kyzylorda oblast, such as skin diseases and subcutaneous tissue, endocrine system diseases, pregnancy complications etc. The received levels of carcinogenic risks, which were first carried out in the Republic of

  2. Physiologically based pharmacokinetic rat model for methyl tertiary-butyl ether; comparison of selected dose metrics following various MTBE exposure scenarios used for toxicity and carcinogenicity evaluation

    International Nuclear Information System (INIS)

    Borghoff, Susan J.; Parkinson, Horace; Leavens, Teresa L.

    2010-01-01

    There are a number of cancer and toxicity studies that have been carried out to assess hazard from methyl tertiary-butyl ether (MTBE) exposure via inhalation and oral administration. MTBE has been detected in surface as well as ground water supplies which emphasized the need to assess the risk from exposure via drinking water contamination. This model can now be used to evaluate route-to-route extrapolation issues concerning MTBE exposures but also as a means of comparing potential dose metrics that may provide insight to differences in biological responses observed in rats following different routes of MTBE exposure. Recently an updated rat physiologically based pharmacokinetic (PBPK) model was published that relied on a description of MTBE and its metabolite tertiary-butyl alcohol (TBA) binding to α2u-globulin, a male rat-specific protein. This model was used to predict concentrations of MTBE and TBA in the kidney, a target tissue in the male rat. The objective of this study was to use this model to evaluate the dosimetry of MTBE and TBA in rats following different exposure scenarios, used to evaluate the toxicity and carcinogenicity of MTBE, and compare various dose metrics under these different conditions. Model simulations suggested that although inhalation and drinking water exposures show a similar pattern of MTBE and TBA exposure in the blood and kidney (i.e. concentration-time profiles), the total blood and kidney levels following exposure of MTBE to 7.5 mg/ml MTBE in the drinking water for 90 days is in the same range as administration of an oral dose of 1000 mg/kg MTBE. Evaluation of the dose metrics also supports that a high oral bolus dose (i.e. 1000 mg/kg MTBE) results in a greater percentage of the dose exhaled as MTBE with a lower percent metabolized to TBA as compared to dose of MTBE that is delivered over a longer period of time as in the case of drinking water.

  3. Micropropagation effect on the anti-carcinogenic activitiy of polyphenolics from Mexican oregano (Poliomintha glabrescens Gray) in human colon cancer cells HT-29.

    Science.gov (United States)

    García-Pérez, Enrique; Noratto, Giuliana D; García-Lara, Silverio; Gutiérrez-Uribe, Janet A; Mertens-Talcott, Susanne U

    2013-06-01

    Phenolic extracts obtained from spices are known to have anti-carcinogenic activities but little is known about the effect of micropropagation on these beneficial effects. The main objective of this study was to evaluate the cytotoxic activity of flavonoid-enriched extracts (FEE) from the leaves of wild (WT), in vitro (IN), and ex vitro (EX) grown oregano plants in colon cancer cells HT-29 and the non-cancer cells CCD-18Co. Cell proliferation of HT-29 cells was reduced to 50 % by WT, IN, and EX at concentrations of 4.01, 1.32, and 4.84 mg of gallic acid equivalents (GAE)/L, respectively. In contrast, in CCD-18Co cells, higher concentrations were required for the same cytotoxic effect. At 6 mg GAE/L, WT and IN reduced the production of reactive oxygen species (ROS) of lipopolysaccharides (LPS)-stimulated control cells to 59.89 and 59.43 %, respectively, and EX to 73.89 %. The mRNA of Caspase-3 was increased 1.53-fold when cells were treated with 4 mg GAE/L of IN extract, and tumor necrosis factor receptor superfamily, member 6 (FAS), and BCL2-associated X protein (BAX) mRNA increased 2.55 and 1.53 fold, respectively. Results on protein expression corroborated the apoptotic effects with a significant decrease of B-cell lymphoma 2 (BCL2) expression for all treatments but more remarkable for EX that also showed the most intense signal of BAX. Overall, FEE extracts derived from micropropagation had increased pro-apoptotic effects, however extracts from the in vitro plants produced more efficacy at the transcriptional level while extracts from the ex vitro plant were superior at the traductional level.

  4. Glyphosate rodent carcinogenicity bioassay expert panel review.

    Science.gov (United States)

    Williams, Gary M; Berry, Colin; Burns, Michele; de Camargo, Joao Lauro Viana; Greim, Helmut

    2016-09-01

    Glyphosate has been rigorously and extensively tested for carcinogenicity by administration to mice (five studies) and to rats (nine studies). Most authorities have concluded that the evidence does not indicate a cancer risk to humans. The International Agency for Research on Cancer (IARC), however, evaluated some of the available data and concluded that glyphosate probably is carcinogenic to humans. The expert panel convened by Intertek assessed the findings used by IARC, as well as the full body of evidence and found the following: (1) the renal neoplastic effects in males of one mouse study are not associated with glyphosate exposure, because they lack statistical significance, strength, consistency, specificity, lack a dose-response pattern, plausibility, and coherence; (2) the strength of association of liver hemangiosarcomas in a different mouse study is absent, lacking consistency, and a dose-response effect and having in high dose males only a significant incidence increase which is within the historical control range; (3) pancreatic islet-cell adenomas (non-significant incidence increase), in two studies of male SD rats did not progress to carcinomas and lacked a dose-response pattern (the highest incidence is in the low dose followed by the high dose); (4) in one of two studies, a non-significant positive trend in the incidence of hepatocellular adenomas in male rats did not lead to progression to carcinomas; (5) in one of two studies, the non-significant positive trend in the incidence of thyroid C-cell adenomas in female rats was not present and there was no progression of adenomas to carcinomas at the end of the study. Application of criteria for causality considerations to the above mentioned tumor types and given the overall weight-of-evidence (WoE), the expert panel concluded that glyphosate is not a carcinogen in laboratory animals.

  5. Aryl hydrocarbon receptor activation and CYP1A induction by cooked food-derived carcinogenic heterocyclic amines in human HepG2 cell lines.

    Science.gov (United States)

    Sekimoto, Masashi; Sumi, Haruna; Hosaka, Takuomi; Umemura, Takashi; Nishikawa, Akiyoshi; Degawa, Masakuni

    2016-11-01

    The ability of nine cooked food-derived heterocyclic aromatic amines (HCAs), such as 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1), 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), 2-amino-6-methylpyrido[12-a:3',2'-d]imidazole (Glu-P-1), 2-amino-pyrido[12-a:3',2'-d]imidazole hydrochloride (Glu-P-2), 2-amino-9H-pyrido[2,3-b]indole (AαC), 2-amino-3-methyl-9H-pyrido[2,3-b]indole (MeAαC), 2-amino-3-methylimidazo[4,5-f]quinolone (IQ), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-1-methyl-6-phenyl-1H-imidazo[4,5-b]pyridine (PhIP), to activate human aryl hydrocarbon receptor (hAhR) was examined using a HepG2-A10 cell line, which has previously established from human hepatocarcinoma-derived HepG2 cells for use in hAhR-based luciferase reporter gene assays. Trp-P-1, Trp-P-2, AαC, MeAαC, IQ and MeIQx showed a definite ability to induce not only luciferase (hAhR activation) in HepG2-A10 cells but also cytochrome P450 (CYP)1A1/1A2 mRNAs in HepG2 cells, while such the ability of Glu-P-1, Glu-P-2, and PhIP was very low. In addition, all the HCAs examined, especially MeAαC and MeIQx, had a definite capacity for inhibiting the activity of ethoxyresorfin O-deethylase (CYP1As, especially CYP1A1). The present findings demonstrate that all the HCAs examined have the ability to activate hAhR and its target genes, and further confirm that these HCAs become good substrates for human CYP1A subfamily enzyme(s). Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. A review of the carcinogenic potential of glyphosate by four independent expert panels and comparison to the IARC assessment.

    Science.gov (United States)

    Williams, Gary M; Aardema, Marilyn; Acquavella, John; Berry, Sir Colin; Brusick, David; Burns, Michele M; de Camargo, Joao Lauro Viana; Garabrant, David; Greim, Helmut A; Kier, Larry D; Kirkland, David J; Marsh, Gary; Solomon, Keith R; Sorahan, Tom; Roberts, Ashley; Weed, Douglas L

    2016-09-01

    The International Agency for Research on Cancer (IARC) published a monograph in 2015 concluding that glyphosate is "probably carcinogenic to humans" (Group 2A) based on limited evidence in humans and sufficient evidence in experimental animals. It was also concluded that there was strong evidence of genotoxicity and oxidative stress. Four Expert Panels have been convened for the purpose of conducting a detailed critique of the evidence in light of IARC's assessment and to review all relevant information pertaining to glyphosate exposure, animal carcinogenicity, genotoxicity, and epidemiologic studies. Two of the Panels (animal bioassay and genetic toxicology) also provided a critique of the IARC position with respect to conclusions made in these areas. The incidences of neoplasms in the animal bioassays were found not to be associated with glyphosate exposure on the basis that they lacked statistical strength, were inconsistent across studies, lacked dose-response relationships, were not associated with preneoplasia, and/or were not plausible from a mechanistic perspective. The overall weight of evidence from the genetic toxicology data supports a conclusion that glyphosate (including GBFs and AMPA) does not pose a genotoxic hazard and therefore, should not be considered support for the classification of glyphosate as a genotoxic carcinogen. The assessment of the epidemiological data found that the data do not support a causal relationship between glyphosate exposure and non-Hodgkin's lymphoma while the data were judged to be too sparse to assess a potential relationship between glyphosate exposure and multiple myeloma. As a result, following the review of the totality of the evidence, the Panels concluded that the data do not support IARC's conclusion that glyphosate is a "probable human carcinogen" and, consistent with previous regulatory assessments, further concluded that glyphosate is unlikely to pose a carcinogenic risk to humans.

  7. Carcinogen-induced damage to DNA

    International Nuclear Information System (INIS)

    Strauss, B.; Altamirano, M.; Bose, K.; Sklar, R.; Tatsumi, K.

    1979-01-01

    Human cells respond to carcinogen-induced damage in their DNA in at least two ways. The first response, excision repair, proceeds by at least three variations, depending on the nature of the damage. Nucleotide excision results in relatively large repair patches but few free DNA breaks, since the endonuclease step is limiting. Apurinic repair is characterized by the appearance of numerous breaks in the DNA and by short repair patches. The pathways behave as though they function independently. Lymphoic cells derived from a xeroderma pigmentosum complementation group C patient are deficient in their ability to perform nucleotide excision and also to excise 6 methoxyguanine adducts, but they are apurinic repair competent. Organisms may bypass damage in their DNA. Lymphoblastoid cells, including those derived from xeroderma pigmentosum treated with 3 H-anti-BPDE, can replicate their DNA at low doses of carcinogen. Unexcised 3 H is found in the light or parental strand of the resulting hybrid DNA when replication occurs in medium with BrdUrd. This observation indicates a bypass reaction occurring by a mechanism involving branch migration at DNA growing points. Branch migration in DNA preparations have been observed, but the evidence is that most occurs in BrdUrd-containing DNA during cell lysis. The measurement of the bifilarly substituted DNA resulting from branch migration is a convenient method of estimating the proportion of new synthesis remaining in the vicinity of the DNA growing point. Treatment with carcinogens or caffeine results in accumulation of DNA growing points accompanied by the synthesis of shortened pieces of daughter DNA

  8. Electrochemical methods for monitoring of environmental carcinogens.

    Science.gov (United States)

    Barek, J; Cvacka, J; Muck, A; Quaiserová, V; Zima, J

    2001-04-01

    The use of modern electroanalytical techniques, namely differential pulse polarography, differential pulse voltammetry on hanging mercury drop electrode or carbon paste electrode, adsorptive stripping voltammetry and high performance liquid chromatography with electrochemical detection for the determination of trace amounts of carcinogenic N-nitroso compounds, azo compounds, heterocyclic compounds, nitrated polycyclic aromatic hydrocarbons and aromatic and heterocyclic amines is discussed. Scope and limitations of these methods are described and some practical applications based on their combination with liquid-liquid or solid phase extraction are given.

  9. Potential carcinogenicity predicted by computational toxicity evaluation of thiophosphate pesticides using QSTR/QSCarciAR model.

    Science.gov (United States)

    Petrescu, Alina-Maria; Ilia, Gheorghe

    2017-07-01

    This study presents in silico prediction of toxic activities and carcinogenicity, represented by the potential carcinogenicity DSSTox/DBS, based on vector regression with a new Kernel activity, and correlating the predicted toxicity values through a QSAR model, namely: QSTR/QSCarciAR (quantitative structure toxicity relationship/quantitative structure carcinogenicity-activity relationship) described by 2D, 3D descriptors and biological descriptors. The results showed a connection between carcinogenicity (compared to the structure of a compound) and toxicity, as a basis for future studies on this subject, but each prediction is based on structurally similar compounds and the reactivation of the substructures of these compounds.

  10. Comparative risk assessment of carcinogens in alcoholic beverages using the margin of exposure approach.

    Science.gov (United States)

    Lachenmeier, Dirk W; Przybylski, Maria C; Rehm, Jürgen

    2012-09-15

    Alcoholic beverages have been classified as carcinogenic to humans. As alcoholic beverages are multicomponent mixtures containing several carcinogenic compounds, a quantitative approach is necessary to compare the risks. Fifteen known and suspected human carcinogens (acetaldehyde, acrylamide, aflatoxins, arsenic, benzene, cadmium, ethanol, ethyl carbamate, formaldehyde, furan, lead, 4-methylimidazole, N-nitrosodimethylamine, ochratoxin A and safrole) occurring in alcoholic beverages were identified based on monograph reviews by the International Agency for Research on Cancer. The margin of exposure (MOE) approach was used for comparative risk assessment. MOE compares a toxicological threshold with the exposure. MOEs above 10,000 are judged as low priority for risk management action. MOEs were calculated for different drinking scenarios (low risk and heavy drinking) and different levels of contamination for four beverage groups (beer, wine, spirits and unrecorded alcohol). The lowest MOEs were found for ethanol (3.1 for low risk and 0.8 for heavy drinking). Inorganic lead and arsenic have average MOEs between 10 and 300, followed by acetaldehyde, cadmium and ethyl carbamate between 1,000 and 10,000. All other compounds had average MOEs above 10,000 independent of beverage type. Ethanol was identified as the most important carcinogen in alcoholic beverages, with clear dose response. Some other compounds (lead, arsenic, ethyl carbamate, acetaldehyde) may pose risks below thresholds normally tolerated for food contaminants, but from a cost-effectiveness point of view, the focus should be on reducing alcohol consumption in general rather than on mitigative measures for some contaminants that contribute only to a limited extent (if at all) to the total health risk. Copyright © 2012 UICC.

  11. Prevalence of occupational exposure to carcinogens among workers of Arabic, Chinese and Vietnamese ancestry in Australia.

    Science.gov (United States)

    Boyle, Terry; Carey, Renee N; Glass, Deborah C; Peters, Susan; Fritschi, Lin; Reid, Alison

    2015-09-01

    Although job-related diseases result in more deaths per year than job-related injuries, most research concerning ethnic minority workers has concerned accidents and injuries rather than disease-causing exposures such as carcinogens. We conducted a telephone-based cross-sectional survey to estimate the prevalence of occupational exposure to carcinogens among a sample of ethnic minority workers in Australia, and compared their exposure prevalence to that of a sample of the general Australian-born working population ('Australian workers'). One-third of the ethnic minority workers were exposed to at least one carcinogen at work. The likelihood of exposure to carcinogens was not significantly different from that of Australian workers, although the likelihood of exposure to individual carcinogens varied by ethnicity. Knowing the prevalence of exposure to carcinogens in the workplace in different ethnic groups will allow better targeted and informed occupational health and safety measures to be implemented where necessary. © 2015 Wiley Periodicals, Inc.

  12. Transformation of human fibroblasts by ionizing radiation, a chemical carcinogen, or simian virus 40 correlates with an increase in susceptibility to the autonomous parvoviruses H-1 virus and minute virus of mice

    International Nuclear Information System (INIS)

    Cornelis, J.J.; Becquart, P.; Duponchel, N.; Salome, N.; Avalosse, B.L.; Namba, M.; Rommelaere, J.

    1988-01-01

    Morphologically altered and established human fibroblasts, obtained either by 60 Co gamma irradiation, treatment with the carcinogen 4-nitroquinoline 1-oxide, or simian virus 40 (SV40) infection, were compared with their normal finite-life parental strains for susceptibility to the autonomous parvoviruses H-1 virus and the prototype strain of minute virus of mice (MVMp). All transformed cells suffered greater virus-induced killing than their untransformed progenitors. The cytotoxic effect of H-1 virus was more severe than that of MVMp. Moreover, the level of viral DNA replication was much (10- to 85-fold) enhanced in the transformants compared with their untransformed parent cells. Thus, in this system, cell transformation appears to correlate with an increase in both DNA amplification and cytotoxicity of the parvoviruses. However, the accumulation of parvovirus DNA in the transformants was not always accompanied by the production of infectious virus. Like in vitro-transformed fibroblasts, a fibrosarcoma-derived cell line was sensitive to the killing effect of both H-1 virus and MVMp and amplified viral DNA to high extents. The results indicate that oncogenic transformation can be included among cellular states which modulate permissiveness to parvoviruses under defined growth conditions

  13. NAD(P)H:quinone oxidoreductase expression in Cyp1a-knockout and CYP1A-humanized mouse lines and its effect on bioactivation of the carcinogen aristolochic acid I

    Energy Technology Data Exchange (ETDEWEB)

    Levova, Katerina; Moserova, Michaela [Department of Biochemistry, Faculty of Science, Charles University, Prague (Czech Republic); Nebert, Daniel W. [Department of Environmental Health, University of Cincinnati Medical Center, Cincinnati (United States); Phillips, David H. [Analytical and Environmental Sciences Division, MRC-HPA Centre for Environment and Health, King' s College London, London (United Kingdom); Frei, Eva [Division of Preventive Oncology, National Center for Tumor Diseases, German Cancer Research Center (DKFZ), Heidelberg (Germany); Schmeiser, Heinz H. [Research Group Genetic Alterations in Carcinogenesis, German Cancer Research Center (DKFZ), Heidelberg (Germany); Arlt, Volker M. [Analytical and Environmental Sciences Division, MRC-HPA Centre for Environment and Health, King' s College London, London (United Kingdom); Stiborova, Marie, E-mail: stiborov@natur.cuni.cz [Department of Biochemistry, Faculty of Science, Charles University, Prague (Czech Republic)

    2012-12-15

    Aristolochic acid causes a specific nephropathy (AAN), Balkan endemic nephropathy, and urothelial malignancies. Using Western blotting suitable to determine protein expression, we investigated in several transgenic mouse lines expression of NAD(P)H:quinone oxidoreductase (NQO1)—the most efficient cytosolic enzyme that reductively activates aristolochic acid I (AAI). The mouse tissues used were from previous studies [Arlt et al., Chem. Res. Toxicol. 24 (2011) 1710; Stiborova et al., Toxicol. Sci. 125 (2012) 345], in which the role of microsomal cytochrome P450 (CYP) enzymes in AAI metabolism in vivo had been determined. We found that NQO1 levels in liver, kidney and lung of Cyp1a1(−/−), Cyp1a2(−/−) and Cyp1a1/1a2(−/−) knockout mouse lines, as well as in two CYP1A-humanized mouse lines harboring functional human CYP1A1 and CYP1A2 and lacking the mouse Cyp1a1/1a2 orthologs, differed from NQO1 levels in wild-type mice. NQO1 protein and enzymic activity were induced in hepatic and renal cytosolic fractions isolated from AAI-pretreated mice, compared with those in untreated mice. Furthermore, this increase in hepatic NQO1 enzyme activity was associated with bioactivation of AAI and elevated AAI-DNA adduct levels in ex vivo incubations of cytosolic fractions with DNA and AAI. In conclusion, AAI appears to increase its own metabolic activation by inducing NQO1, thereby enhancing its own genotoxic potential. Highlights: ► NAD(P)H:quinone oxidoreductase expression in Cyp1a knockout and humanized CYP1A mice ► Reductive activation of the nephrotoxic and carcinogenic aristolochic acid I (AAI) ► NAD(P)H:quinone oxidoreductase is induced in mice treated with AAI. ► Induced hepatic enzyme activity resulted in elevated AAI-DNA adduct levels.

  14. NAD(P)H:quinone oxidoreductase expression in Cyp1a-knockout and CYP1A-humanized mouse lines and its effect on bioactivation of the carcinogen aristolochic acid I

    International Nuclear Information System (INIS)

    Levova, Katerina; Moserova, Michaela; Nebert, Daniel W.; Phillips, David H.; Frei, Eva; Schmeiser, Heinz H.; Arlt, Volker M.; Stiborova, Marie

    2012-01-01

    Aristolochic acid causes a specific nephropathy (AAN), Balkan endemic nephropathy, and urothelial malignancies. Using Western blotting suitable to determine protein expression, we investigated in several transgenic mouse lines expression of NAD(P)H:quinone oxidoreductase (NQO1)—the most efficient cytosolic enzyme that reductively activates aristolochic acid I (AAI). The mouse tissues used were from previous studies [Arlt et al., Chem. Res. Toxicol. 24 (2011) 1710; Stiborova et al., Toxicol. Sci. 125 (2012) 345], in which the role of microsomal cytochrome P450 (CYP) enzymes in AAI metabolism in vivo had been determined. We found that NQO1 levels in liver, kidney and lung of Cyp1a1(−/−), Cyp1a2(−/−) and Cyp1a1/1a2(−/−) knockout mouse lines, as well as in two CYP1A-humanized mouse lines harboring functional human CYP1A1 and CYP1A2 and lacking the mouse Cyp1a1/1a2 orthologs, differed from NQO1 levels in wild-type mice. NQO1 protein and enzymic activity were induced in hepatic and renal cytosolic fractions isolated from AAI-pretreated mice, compared with those in untreated mice. Furthermore, this increase in hepatic NQO1 enzyme activity was associated with bioactivation of AAI and elevated AAI-DNA adduct levels in ex vivo incubations of cytosolic fractions with DNA and AAI. In conclusion, AAI appears to increase its own metabolic activation by inducing NQO1, thereby enhancing its own genotoxic potential. Highlights: ► NAD(P)H:quinone oxidoreductase expression in Cyp1a knockout and humanized CYP1A mice ► Reductive activation of the nephrotoxic and carcinogenic aristolochic acid I (AAI) ► NAD(P)H:quinone oxidoreductase is induced in mice treated with AAI. ► Induced hepatic enzyme activity resulted in elevated AAI-DNA adduct levels.

  15. A proposed framework for consistent regulation of public exposures to radionuclides and other carcinogens

    International Nuclear Information System (INIS)

    Kocher, D.C.; Hoffman, F.O.

    1991-01-01

    This paper discusses a proposed framework for consistent regulation of carcinogenic risks to the public based on establishing de manifestis (i.e., unacceptable) and de minimis (i.e., trivial) lifetime risks from exposure to any carcinogens at levels of about 10 -1 --10 -3 and 10 -4 --10 -6 , respectively, and reduction of risks above de minimis levels as low as reasonably achievable (ALARA). We then discuss certain differences in the way risks from exposure to radionuclides and other carcinogens currently are regulated or assessed which would need to be considered in implementing the proposed regulatory framework for all carcinogens

  16. The influence of thresholds on the risk assessment of carcinogens in food.

    Science.gov (United States)

    Pratt, Iona; Barlow, Susan; Kleiner, Juliane; Larsen, John Christian

    2009-08-01

    The risks from exposure to chemical contaminants in food must be scientifically assessed, in order to safeguard the health of consumers. Risk assessment of chemical contaminants that are both genotoxic and carcinogenic presents particular difficulties, since the effects of such substances are normally regarded as being without a threshold. No safe level can therefore be defined, and this has implications for both risk management and risk communication. Risk management of these substances in food has traditionally involved application of the ALARA (As Low as Reasonably Achievable) principle, however ALARA does not enable risk managers to assess the urgency and extent of the risk reduction measures needed. A more refined approach is needed, and several such approaches have been developed. Low-dose linear extrapolation from animal carcinogenicity studies or epidemiological studies to estimate risks for humans at low exposure levels has been applied by a number of regulatory bodies, while more recently the Margin of Exposure (MOE) approach has been applied by both the European Food Safety Authority and the Joint FAO/WHO Expert Committee on Food Additives. A further approach is the Threshold of Toxicological Concern (TTC), which establishes exposure thresholds for chemicals present in food, dependent on structure. Recent experimental evidence that genotoxic responses may be thresholded has significant implications for the risk assessment of chemicals that are both genotoxic and carcinogenic. In relation to existing approaches such as linear extrapolation, MOE and TTC, the existence of a threshold reduces the uncertainties inherent in such methodology and improves confidence in the risk assessment. However, for the foreseeable future, regulatory decisions based on the concept of thresholds for genotoxic carcinogens are likely to be taken case-by-case, based on convincing data on the Mode of Action indicating that the rate limiting variable for the development of cancer

  17. Oncogenic human papillomavirus genital infection in southern Iranian women: population-based study versus clinic-based data

    Directory of Open Access Journals (Sweden)

    Eghbali Seyed

    2012-09-01

    Full Text Available Abstract Background Epidemiological studies on genital human papilloma viruses infection (HPVs in general population are crucial for the implementation of health policy guidelines for developing the strategies to prevent the primary and secondary cervical cancer. In different parts of Iran, there is a lack of population-based studies to determine the prevalence of HPV in the general population. The aim of this population-based study is to compare the prevalence rate of genital HPV infection among reproductive women with our previous clinic-based data, which showed a prevalence rate of 5% in women in southern Iran. Results Using general primers for all genotypes of HPV, of 799 randomly selected women, five (0.63%, 95% CI 0.23-1.55% tested positive for HPV DNA. Overall, seven different HPV genotypes were detected: six types (16, 18, 31, 33, 51 and 56 were carcinogenic, or “high risk genotypes” and one genotype (HPV-66 was “probably carcinogenic.” Conclusions In a population-based study, the prevalence of HPV infection among southern Iranian women was lower than that observed worldwide. However, our gynaecological clinic-based study on the prevalence of HPV infection showed results comparable with other studies in the Middle East and Persian Gulf countries. Since gynaecological clinic-based data may generally overestimate HPV prevalence, estimates of prevalence according to clinic-based data should be adjusted downward by the population-based survey estimates.

  18. Metabolism of benzo(a)pyrene, N-nitrosomethylamine, and N-nitrosopyrrolidine and identification of the major carcinogen-DNA adducts formed in cultured human esophagus

    DEFF Research Database (Denmark)

    Harris, Curtis C.; Autrup, Herman; Stoner, Gary D.

    1979-01-01

    The wide variation in the world-wide incidence of esophageal carcinoma suggests that environmental agents including chemicals cause this cancer. Since the interaction between chemical procarcinogens and human esophagus has not been studied previously, we examined the metabolic fate of benzo......(a)pyrene (BP), N-nitrosodimethylamine (DMN), and A/-nitrosopyrrolidine in cultured nontumorous esophagus from two patients with and six patients without esophageal carcinoma. Esophageal explants were cultured in a chemically defined medium for 7 days prior to adding [3H]BP (1.5 JUM),[14C]DMN (100 /IM), or [14C...

  19. Risk assessment of DNA-reactive carcinogens in food.

    Science.gov (United States)

    Jeffrey, A M; Williams, G M

    2005-09-01

    Risk assessment of DNA-reactive carcinogens in food requires knowledge of the extent of DNA damage in the target organ which results from the competition between DNA adduct formation and repair. Estimates of DNA adduct levels can be made by direct measurement or indirectly as a consequence of their presence, for example, by tumor formation in animal models or exposed populations epidemiologically. Food-borne DNA-reactive carcinogens are present from a variety of sources. They are generally not intrinsically DNA-reactive but require bioactivation to DNA-reactive metabolites a process which may be modulated by the compound itself or the presence of other xenobiotics. A single DNA reactant may form several distinct DNA adducts each undergoing different rates of repair. Some DNA reactants may be photochemically activated or produce reactive oxygen species and thus indirect oxidative DNA damage. The levels of DNA adducts arising from exposures influenced by variations in the doses, the frequency with which an individual is exposed, and rates of DNA repair for specific adducts. Each adduct has a characteristic efficiency with which it induces mutations. Based on experience with the well-studied DNA-reactive food carcinogen aflatoxin B(1) (AFB(1)), a limit of 20 ppb or approximately 30 microg/day has been set and is considered a tolerable daily intake (TDI). Since AFB(1) is considered a potent carcinogen, doses of carcinogens is made.

  20. Carcinogenicity of multi-walled carbon nanotubes: challenging issue on hazard assessment.

    Science.gov (United States)

    Fukushima, Shoji; Kasai, Tatsuya; Umeda, Yumi; Ohnishi, Makoto; Sasaki, Toshiaki; Matsumoto, Michiharu

    2018-01-25

    This report reviews the carcinogenicity of multi-walled carbon nanotubes (MWCNTs) in experimental animals, concentrating on MWNT-7, a straight fibrous MWCNT. MWCNTs were administered to mice and rats by intraperitoneal injection, intrascrotal injection, subcutaneous injection, intratracheal instillation and inhalation. Intraperitoneal injection of MWNT-7 induced peritoneal mesothelioma in mice and rats. Intrascrotal injection induced peritoneal mesothelioma in rats. Intratracheal instillation of MWCNT-N (another straight fibrous MWCNT) induced both lung carcinoma and pleural mesothelioma in rats. In the whole body inhalation studies, in mice MWNT-7 promoted methylcholanthrene-initiated lung carcinogenesis. In rats, inhalation of MWNT-7 induced lung carcinoma and lung burdens of MWNT-7 increased with increasing concentration of airborne MWNT-7 and increasing duration of exposure. Straight, fibrous MWCNTs exerted carcinogenicity in experimental animals. Phagocytosis of MWCNT fibers by macrophages was very likely to be a principle factor in MWCNT lung carcinogenesis. Using no-observed-adverse-effect level-based approach, we calculated that the occupational exposure limit (OEL) of MWNT-7 for cancer protection is 0.15 μg/m 3 for a human worker. Further studies on the effects of the shape and size of MWCNT fibers and mode of action on the carcinogenicity are required.

  1. Understanding arsenic carcinogenicity by the use of animal models

    International Nuclear Information System (INIS)

    Wanibuchi, Hideki; Salim, Elsayed I.; Kinoshita, Anna; Shen Jun; Wei Min; Morimura, Keiichirou; Yoshida, Kaoru; Kuroda, Koichi; Endo, Ginji; Fukushima, Shoji

    2004-01-01

    Although numerous epidemiological studies have indicated that human arsenic exposure is associated with increased incidences of bladder, liver, skin, and lung cancers, limited attempts have been made to understand mechanisms of carcinogenicity using animal models. Dimethylarsinic acid (DMA), an organic arsenic compound, is a major metabolite of ingested inorganic arsenics in mammals. Recent in vitro studies have proven DMA to be a potent clastogenic agent, capable of inducing DNA damage including double strand breaks and cross-link formation. In our attempts to clarify DMA carcinogenicity, we have recently shown carcinogenic effects of DMA and its related metabolites using various experimental protocols in rats and mice: (1) a multi-organ promotion bioassay in rats; (2) a two-stage promotion bioassay by DMA of rat urinary bladder and liver carcinogenesis; (3) a 2-year carcinogenicity test of DMA in rats; (4) studies on the effects of DMA on lung carcinogenesis in rats; (5) promotion of skin carcinogenesis by DMA in keratin (K6)/ornithine decarboxylase (ODC) transgenic mice; (6) carcinogenicity of DMA in p53(+/-) knockout and Mmh/8-OXOG-DNA glycolase (OGG1) mutant mice; (7) promoting effects of DMA and related organic arsenicals in rat liver; (8) promoting effects of DMA and related organic arsenicals in a rat multi-organ carcinogenesis test; and (9) 2-year carcinogenicity tests of monomethylarsonic acid (MMA) and trimethylarsine oxide (TMAO) in rats. The results revealed that the adverse effects of arsenic occurred either by promoting and initiating carcinogenesis. These data, as covered in the present review, suggest that several mechanisms may be involved in arsenic carcinogenesis

  2. [Effect of fruit and vegetable juices on the changes in the production of carcinogenic N-nitroso compounds in human gastric juice].

    Science.gov (United States)

    Ilńitskiĭ, A P; Iurchenko, V A

    1993-01-01

    The study was made of the effect of apple, grapefruit, orange and beet juices on in vitro formation of N-nitrosodimethylamine (NDMA) from sodium nitrite and amidopirin in human gastric juice (GJ). Experimental samples of GJ from outpatients attending the outpatient department of the AMS Cancer Research Center were used. The patients had various forms of gastritis and gastric cancer. It was found that fruit and beet juices may inhibit or enhance NDMA formation depending on the GJ composition, pH in particular. In acid medium (pH-1.3-3.4) there was a trend to inhibition of NDMA synthesis, while in neutral and alkaline (pH = 7.4-8.5) medium NDMA synthesis is activated. Practical implications of the findings are discussed.

  3. ABCG2/BCRP decreases the transfer of a food-born chemical carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in perfused term human placenta.

    Science.gov (United States)

    Myllynen, Päivi; Kummu, Maria; Kangas, Tiina; Ilves, Mika; Immonen, Elina; Rysä, Jaana; Pirilä, Rauna; Lastumäki, Anni; Vähäkangas, Kirsi H

    2008-10-15

    We have studied the role of ATP binding cassette (ABC) transporters in fetal exposure to carcinogens using 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) a known substrate for ABC transporters as a model compound. In perfusion of human term placenta, transfer of (14)C-PhIP (2 microM) through the placenta resulted in fetal-to-maternal concentration ratio (FM ratio) of 0.72+/-0.09 at 6 h. The specific ABCG2 inhibitor KO143 increased the transfer of (14)C-PhIP from maternal to fetal circulation (FM ratio 0.90+/-0.08 at 6 h, p<0.05) while the ABCC1/ABCC2 inhibitor probenecid had no effect (FM ratio at 6 h 0.75+/-0.10, p=0.84). There was a negative correlation between the expression of ABCG2 protein in perfused tissue and the FM ratio of (14)C-PhIP (R=-0.81, p<0.01) at the end of the perfusion. The expression of ABCC2 protein did not correlate with FM ratio of PhIP (R: -0.11, p=0.76). In addition, PhIP induced the expression of ABC transporters in BeWo cells at mRNA level. In conclusion, our data indicates that ABCG2 decreases placental transfer of (14)C-PhIP in perfused human placenta. Also, PhIP may modify ABC transporter expression in choriocarcinoma cells.

  4. Mutagenic and carcinogenic structural alerts and their mechanisms of action.

    Science.gov (United States)

    Plošnik, Alja; Vračko, Marjan; Dolenc, Marija Sollner

    2016-09-01

    Knowing the mutagenic and carcinogenic properties of chemicals is very important for their hazard (and risk) assessment. One of the crucial events that trigger genotoxic and sometimes carcinogenic effects is the forming of adducts between chemical compounds and nucleic acids and histones. This review takes a look at the mechanisms related to specific functional groups (structural alerts or toxicophores) that may trigger genotoxic or epigenetic effects in the cells. We present up-to-date information about defined structural alerts with their mechanisms and the software based on this knowledge (QSAR models and classification schemes).

  5. Dehydropyrrolizidine Alkaloid Toxicity, Cytotoxicity, and Carcinogenicity

    Directory of Open Access Journals (Sweden)

    Bryan L. Stegelmeier

    2016-11-01

    Full Text Available Dehydropyrrolizidine alkaloid (DHPA-producing plants have a worldwide distribution amongst flowering plants and commonly cause poisoning of livestock, wildlife, and humans. Previous work has produced considerable understanding of DHPA metabolism, toxicity, species susceptibility, conditions, and routes of exposure, and pathogenesis of acute poisoning. Intoxication is generally caused by contaminated grains, feed, flour, and breads that result in acute, high-dose, short-duration poisoning. Acute poisoning produces hepatic necrosis that is usually confirmed histologically, epidemiologically, and chemically. Less is known about chronic poisoning that may result when plant populations are sporadic, used as tisanes or herbal preparations, or when DHPAs contaminate milk, honey, pollen, or other animal-derived products. Such subclinical exposures may contribute to the development of chronic disease in humans or may be cumulative and probably slowly progress until liver failure. Recent work using rodent models suggest increased neoplastic incidence even with very low DHPA doses of short durations. These concerns have moved some governments to prohibit or limit human exposure to DHPAs. The purpose of this review is to summarize some recent DHPA research, including in vitro and in vivo DHPA toxicity and carcinogenicity reports, and the implications of these findings with respect to diagnosis and prognosis for human and animal health.

  6. On the issue of higher human sensitivity to carcinogenic substances in early childhood; Zur Frage einer hoeheren Empfindlichkeit von Kindern gegenueber krebserzeugenden Stoffen

    Energy Technology Data Exchange (ETDEWEB)

    Schneider, K [comp.

    1998-09-01

    Age-dependent carcinogenesis in humans has been proven with high probability for a number of substances investigated within one or several model systems. Sometimes, very high tumor incidence after short exposure time was observed. Extreme differences were found in some models. (A) Vinyl chloride, Maltoni et al.,1981: 6000 ppm, hepatic angiosarcoma incidence: - Exposure for 4 weeks, from day 1: 40.5 %, - exposure for 4 weeks, from week 13: 0%, - exposure for 52 weeks, from week 13: 22%. Hepatoma incidence: - Exposure for 4 weeks, from day 1: 47.6%, exposure for 4 weeks, from week 13: 0%, exposure for 52 weeks, from week 13: 1.7%. (B) Diethyl nitrosamine, Dyroff et al., 1986: (DEN + phenobarbital), hepatic carcinoma after exposure of rats for 6 weeks: - as from 4 weeks of age: 100% incidence, - as from 8 weeks of age: 0% incidence. (C) Benzopyrene, Vesselinovitch et al., 1975: Hepatic tumor incidence after single, parenteral administration to rats: - at day 1: males: 81%, females: 18%, - at day 42: males: 9%, females: 0%. As is shown by the study on vinyl chloride by Maltoni et al., the same exposure concentration may lead to higher tumor incidence in young animals after short exposure times than it does in long-term experiments with adult animals. Genetic toxicity was detected for all substances, except for saccharin. So it can be assumed that the mechanism of carcinogenesis has an essential influence on the age-dependence. This conclusion agrees well with mechanistic approaches. (orig./CB) [German] Fuer eine Reihe von Schadstoffen ist eine Altersabhaengigkeit der Kanzerogenese mit hoher Wahrscheinlichkeit in einem oder mehreren Modellsystemen gezeigt worden. Dabei wurden zum Teil bereits nach kurzer Expositionszeit sehr hohe Tumorausbeuten erzielt. Extreme Unterschiede wurden in folgenden Modellen beobachtet. (A) Vinylchlorid, Maltoni et al., 1981: 6000 ppm, Inzidenz Leberangiosarkome: - Exposition ueber 4 Wochen ab Tag 1: 40,5%, - Exposition ueber 4 Wochen ab 13

  7. The use of dose-response data in a margin of exposure approach to carcinogenic risk assessment for genotoxic chemicals in food.

    Science.gov (United States)

    Benford, Diane J

    2016-05-01

    Genotoxic substances are generally not permitted for deliberate use in food production. However, an appreciable number of known or suspected genotoxic substances occur unavoidably in food, e.g. from natural occurrence, environmental contamination and generation during cooking and processing. Over the past decade a margin of exposure (MOE) approach has increasingly been used in assessing the exposure to substances in food that are genotoxic and carcinogenic. The MOE is defined as a reference point on the dose-response curve (e.g. a benchmark dose lower confidences limit derived from a rodent carcinogenicity study) divided by the estimated human intake. A small MOE indicates a higher concern than a very large MOE. Whilst the MOE cannot be directly equated to risk, it supports prioritisation of substances for further research or for possible regulatory action, and provides a basis for communicating to the public. So far, the MOE approach has been confined to substances for which carcinogenicity data are available. In the absence of carcinogenicity data, evidence of genotoxicity is used only in hazard identification. The challenge to the genetic toxicology community is to develop approaches for characterising risk to human health based on data from genotoxicity studies. In order to achieve wide acceptance, it would be important to further address the issues that have been discussed in the context of dose-response modelling of carcinogenicity data in order to assign levels of concern to particular MOE values, and also whether it is possible to make generic conclusions on how potency in genotoxicity assays relates to carcinogenic potency. © Crown copyright 2015.

  8. Carcinogenicity assessment of water-soluble nickel compounds.

    Science.gov (United States)

    Goodman, Julie E; Prueitt, Robyn L; Dodge, David G; Thakali, Sagar

    2009-01-01

    IARC is reassessing the human carcinogenicity of nickel compounds in 2009. To address the inconsistencies among results from studies of water-soluble nickel compounds, we conducted a weight-of-evidence analysis of the relevant epidemiological, toxicological, and carcinogenic mode-of-action data. We found the epidemiological evidence to be limited, in that some, but not all, data suggest that exposure to soluble nickel compounds leads to increased cancer risk in the presence of certain forms of insoluble nickel. Although there is no evidence that soluble nickel acts as a complete carcinogen in animals, there is limited evidence that suggests it may act as a tumor promoter. The mode-of-action data suggest that soluble nickel compounds will not be able to cause genotoxic effects in vivo because they cannot deliver sufficient nickel ions to nuclear sites of target cells. Although the mode-of-action data suggest several possible non-genotoxic effects of the nickel ion, it is unclear whether soluble nickel compounds can elicit these effects in vivo or whether these effects, if elicited, would result in tumor promotion. The mode-of-action data equally support soluble nickel as a promoter or as not being a causal factor in carcinogenesis at all. The weight of evidence does not indicate that soluble nickel compounds are complete carcinogens, and there is only limited evidence that they could act as tumor promoters.

  9. Biological bases of human musicality.

    Science.gov (United States)

    Perrone-Capano, Carla; Volpicelli, Floriana; di Porzio, Umberto

    2017-04-01

    Music is a universal language, present in all human societies. It pervades the lives of most human beings and can recall memories and feelings of the past, can exert positive effects on our mood, can be strongly evocative and ignite intense emotions, and can establish or strengthen social bonds. In this review, we summarize the research and recent progress on the origins and neural substrates of human musicality as well as the changes in brain plasticity elicited by listening or performing music. Indeed, music improves performance in a number of cognitive tasks and may have beneficial effects on diseased brains. The emerging picture begins to unravel how and why particular brain circuits are affected by music. Numerous studies show that music affects emotions and mood, as it is strongly associated with the brain's reward system. We can therefore assume that an in-depth study of the relationship between music and the brain may help to shed light on how the mind works and how the emotions arise and may improve the methods of music-based rehabilitation for people with neurological disorders. However, many facets of the mind-music connection still remain to be explored and enlightened.

  10. Environmental exposure to carcinogens in northwestern Cameroon

    African Journals Online (AJOL)

    EB

    2013-09-03

    Sep 3, 2013 ... Twenty-nine (69.0%) [95% CI: 47.0 – 75.0] participants could smell the carcinogenic chemicals they use. Thirty. (71.4%) [95% CI: 65.0 – 77.0] participants had been instructed in the use of protective equipment against carcinogens. Participants used preventive devices like hand gloves, laboratory coats, ...

  11. Biomonitoring human exposure to environmental carcinogenic chemicals

    DEFF Research Database (Denmark)

    Farmer, P.B.; Sepai, O.; Lawrence, R.

    1996-01-01

    A coordinated study was carried out on the development, evaluation and application of biomonitoring procedures for populations exposed to environmental genotoxic pollutants. The procedures used involved both direct measurement of DNA or protein damage (adducts) and assessment of second biological...... spectrometry). The measurement of adducts was focused on those from genotoxicants that result from petrochemical combustion or processing, e.g. low-molecular-weight alkylating agents, PAHs and compounds that cause oxidative DNA damage. Cytogenetic analysis of lymphocytes was undertaken (micronuclei, chromosome...... aberrations and sister chromatid exchanges) and mutation frequency was estimated at a number of loci including the hprt gene and genes involving in cancer development. Blood and urine samples from individuals exposed to urban pollution were collected. Populations exposed through occupational or medical...

  12. Mammalian cell transformation: Mechanisms of carcinogenesis and assays for carcinogens

    International Nuclear Information System (INIS)

    Barrett, J.C.; Tennant, R.W.

    1985-01-01

    This book contains nine sections, each consisting of several papers. The section titles are: Molecular Changes in Cell Transformation; Differentiation, Growth Control, and Cell Transformation; Mutagenesis and Cell Transformation; Tumor Promotion and Cell Transformation; Mechanisms of Transformation of Human Fibroblasts; Mechanisms of Transformation of Epithelial Cells; Mechanisms of C 3 H 10T12 Cell Transformation; Mechanisms of Radiation-Induced Cell Transformation; and Use of Cell Transformation Assays for Carcinogen Testing

  13. Carcinogenic activity of polycyclic hydrocarbons on man and animals

    Energy Technology Data Exchange (ETDEWEB)

    Shabad, L M

    1976-03-01

    Basic facts are reported on the carcinogenic activity of polycyclic aromatic hydrocarbons (PAH) towards humans and animals. Benzyprene (BP) is taken as a standard indicator for PAH. Studies of the distribution of BP in atmosphere, hydrosphere, in soil, in plants, and in animals led to an understanding of the accumulation and breakdown of this chemical. On this basis, safety limits were set as a prophylactic measure.

  14. Ethanol potentiates the genotoxicity of the food-derived mammary carcinogen PhIP in human estrogen receptor-positive mammary cells: mechanistic support for lifestyle factors (cooked red meat and ethanol) associated with mammary cancer.

    Science.gov (United States)

    Malik, Durr-E-Shahwar; David, Rhiannon M; Gooderham, Nigel J

    2018-04-01

    Consumption of cooked/processed meat and ethanol are lifestyle risk factors in the aetiology of breast cancer. Cooking meat generates heterocyclic amines such as 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Epidemiology, mechanistic and animal studies indicate that PhIP is a mammary carcinogen that could be causally linked to breast cancer incidence; PhIP is DNA damaging, mutagenic and oestrogenic. PhIP toxicity involves cytochrome P450 (CYP1 family)-mediated metabolic activation to DNA-damaging species, and transcriptional responses through Aryl hydrocarbon receptor (AhR) and estrogen-receptor-α (ER-α). Ethanol consumption is a modifiable lifestyle factor strongly associated with breast cancer risk. Ethanol toxicity involves alcohol dehydrogenase metabolism to reactive acetaldehyde, and is also a substrate for CYP2E1, which when uncoupled generates reactive oxygen species (ROS) and DNA damage. Here, using human mammary cells that differ in estrogen-receptor status, we explore genotoxicity of PhIP and ethanol and mechanisms behind this toxicity. Treatment with PhIP (10 -7 -10 -4 M) significantly induced genotoxicity (micronuclei formation) preferentially in ER-α positive human mammary cell lines (MCF-7, ER-α+) compared to MDA-MB-231 (ER-α-) cells. PhIP-induced CYP1A2 in both cell lines but CYP1B1 was selectively induced in ER-α(+) cells. ER-α inhibition in MCF-7 cells attenuated PhIP-mediated micronuclei formation and CYP1B1 induction. PhIP-induced CYP2E1 and ROS via ER-α-STAT-3 pathway, but only in ER-α (+) MCF-7 cells. Importantly, simultaneous treatments of physiological concentrations ethanol (10 -3 -10 -1 M) with PhIP (10 -7 -10 -4 M) increased oxidative stress and genotoxicity in MCF-7 cells, compared to the individual chemicals. Collectively, these data offer a mechanistic basis for the increased risk of breast cancer associated with dietary cooked meat and ethanol lifestyle choices.

  15. Hexavalent chrome: threshold concept for carcinogenicity.

    Science.gov (United States)

    Jones, R E

    1990-03-01

    Certain hexavalent chromium (Cr6+) compounds when administered via inhalation at high doses have the potential to induce lung tumors in humans and experimental animals. Trivalent chromium (Cr3+) is an essential human and animal nutrient at levels of 50 to 200 micrograms/day. Recent data have shown that the human body is able to reduce Cr6+ to Cr3+. This reduction occurs in bodily fluids such as gastric juice, epithelial lining fluid of the respiratory tract, blood, and other fluids. Secondary reduction occurs at the cellular level by the cytosol, mitochondria, and microsomes. Thus, at low levels of exposure hexavalent chromium ions are reduced before the 6+ ions can interact with DNA unless the dose is sufficient to overwhelm the body's reduction capacity. This paper summarizes the available data concerning the reducing ability of the body and formulates the steps in the mechanism of cancer induction. These steps include: (1) only certain Cr6+ compounds have the capacity to interact with cellular components; (2) Cr6+ is reduced by body fluids and excess Cr6+ enters the cell (Cr3+ is poorly absorbed across membranes); (3) cellular organelles and the cytoplasm reduce Cr6+ to Cr3+; (4) excess Cr6+ can enter the nucleus; (5) Cr6+ reduction through 5+ and 4+ to 3+ has a potential to interact with the DNA molecule; and (6) if unrepaired, this DNA damage can lead to cancer induction. On the basis of current evidence Cr6+ has a threshold for carcinogenic potential in humans that is greater than the current TLV.

  16. Risk assessment of DNA-reactive carcinogens in food

    International Nuclear Information System (INIS)

    Jeffrey, A.M.; Williams, G.M.

    2005-01-01

    Risk assessment of DNA-reactive carcinogens in food requires knowledge of the extent of DNA damage in the target organ which results from the competition between DNA adduct formation and repair. Estimates of DNA adduct levels can be made by direct measurement or indirectly as a consequence of their presence, for example, by tumor formation in animal models or exposed populations epidemiologically. Food-borne DNA-reactive carcinogens are present from a variety of sources. They are generally not intrinsically DNA-reactive but require bioactivation to DNA-reactive metabolites a process which may be modulated by the compound itself or the presence of other xenobiotics. A single DNA reactant may form several distinct DNA adducts each undergoing different rates of repair. Some DNA reactants may be photochemically activated or produce reactive oxygen species and thus indirect oxidative DNA damage. The levels of DNA adducts arising from exposures influenced by variations in the doses, the frequency with which an individual is exposed, and rates of DNA repair for specific adducts. Each adduct has a characteristic efficiency with which it induces mutations. Based on experience with the well-studied DNA-reactive food carcinogen aflatoxin B 1 (AFB 1 ), a limit of 20 ppb or ∼30 μg/day has been set and is considered a tolerable daily intake (TDI). Since AFB 1 is considered a potent carcinogen, doses of 32 P-postlabeling or the use of surrogates such as hemoglobin adducts, together with approaches to evaluate the results. A discussion of approaches to estimating possible threshold effects for DNA-reactive carcinogens is made

  17. Chemical-based risk assessment and in vitro models of human health effects induced by organic pollutants in soils from the Olona valley

    Energy Technology Data Exchange (ETDEWEB)

    Baderna, Diego, E-mail: diego.baderna@marionegri.it; Colombo, Andrea; Amodei, Giorgia; Cantù, Stefano; Teoldi, Federico; Cambria, Felice; Rotella, Giuseppe; Natolino, Fabrizio; Lodi, Marco; Benfenati, Emilio

    2013-10-01

    Risk assessment of soils is usually based on chemical measurements and assuming accidental soil ingestion and evaluating induced toxic and carcinogenic effects. Recently biological tools have been coupled to chemical-based risk assessment since they integrate the biological effects of all xenobiotics in soils. We employed integrated monitoring of soils based on chemical analyses, risk assessment and in vitro models in the highly urbanized semirural area of the Olona Valley in northern Italy. Chemical characterization of the soils indicated low levels of toxic and carcinogenic pollutants such as PAHs, PCDD/Fs, PCBs and HCB and human risk assessment did not give any significant alerts. HepG2 and BALB/c 3T3 cells were used as a model for the human liver and as a tool for the evaluation of carcinogenic potential. Cells were treated with soil extractable organic matters (EOMs) and the MTS assay, LDH release and morphological transformation were selected as endpoints for toxicity and carcinogenicity. Soil EOMs induced dose-dependent inhibition of cell growth at low doses and cytotoxicity after exposure to higher doses. This might be the result of block of cell cycle progression to repair DNA damage caused by oxidative stress; if this DNA damage cannot be repaired, cells die. No significant inductions of foci were recorded after exposure to EOMs. These results indicate that, although the extracts contain compounds with proven carcinogenic potential, the levels of these pollutants in the analyzed soils were too low to induce carcinogenesis in our experimental conditions. In this proposed case study, HepG2 cells were found an appropriate tool to assess the potential harm caused by the ingestion of contaminated soil as they were able to detect differences in the toxicity of soil EOMs. Moreover, the cell transformation assay strengthened the combined approach giving useful information on carcinogenic potential of mixtures. Highlights: • A combined approach for risk

  18. Systematic network assessment of the carcinogenic activities of cadmium

    International Nuclear Information System (INIS)

    Chen, Peizhan; Duan, Xiaohua; Li, Mian; Huang, Chao; Li, Jingquan; Chu, Ruiai; Ying, Hao; Song, Haiyun; Jia, Xudong; Ba, Qian; Wang, Hui

    2016-01-01

    Cadmium has been defined as type I carcinogen for humans, but the underlying mechanisms of its carcinogenic activity and its influence on protein-protein interactions in cells are not fully elucidated. The aim of the current study was to evaluate, systematically, the carcinogenic activity of cadmium with systems biology approaches. From a literature search of 209 studies that performed with cellular models, 208 proteins influenced by cadmium exposure were identified. All of these were assessed by Western blotting and were recognized as key nodes in network analyses. The protein-protein functional interaction networks were constructed with NetBox software and visualized with Cytoscape software. These cadmium-rewired genes were used to construct a scale-free, highly connected biological protein interaction network with 850 nodes and 8770 edges. Of the network, nine key modules were identified and 60 key signaling pathways, including the estrogen, RAS, PI3K-Akt, NF-κB, HIF-1α, Jak-STAT, and TGF-β signaling pathways, were significantly enriched. With breast cancer, colorectal and prostate cancer cellular models, we validated the key node genes in the network that had been previously reported or inferred form the network by Western blotting methods, including STAT3, JNK, p38, SMAD2/3, P65, AKT1, and HIF-1α. These results suggested the established network was robust and provided a systematic view of the carcinogenic activities of cadmium in human. - Highlights: • A cadmium-influenced network with 850 nodes and 8770 edges was established. • The cadmium-rewired gene network was scale-free and highly connected. • Nine modules were identified, and 60 key signaling pathways related to cadmium-induced carcinogenesis were found. • Key mediators in the network were validated in multiple cellular models.

  19. Systematic network assessment of the carcinogenic activities of cadmium

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Peizhan; Duan, Xiaohua; Li, Mian; Huang, Chao [Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai (China); Li, Jingquan; Chu, Ruiai; Ying, Hao; Song, Haiyun [Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai (China); Key Laboratory of Food Safety Risk Assessment, Ministry of Health, Beijing (China); Jia, Xudong [Key Laboratory of Food Safety Risk Assessment, Ministry of Health, Beijing (China); Ba, Qian, E-mail: qba@sibs.ac.cn [Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai (China); Key Laboratory of Food Safety Risk Assessment, Ministry of Health, Beijing (China); Wang, Hui, E-mail: huiwang@sibs.ac.cn [Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai (China); Key Laboratory of Food Safety Risk Assessment, Ministry of Health, Beijing (China); School of Life Science and Technology, ShanghaiTech University, Shanghai (China)

    2016-11-01

    Cadmium has been defined as type I carcinogen for humans, but the underlying mechanisms of its carcinogenic activity and its influence on protein-protein interactions in cells are not fully elucidated. The aim of the current study was to evaluate, systematically, the carcinogenic activity of cadmium with systems biology approaches. From a literature search of 209 studies that performed with cellular models, 208 proteins influenced by cadmium exposure were identified. All of these were assessed by Western blotting and were recognized as key nodes in network analyses. The protein-protein functional interaction networks were constructed with NetBox software and visualized with Cytoscape software. These cadmium-rewired genes were used to construct a scale-free, highly connected biological protein interaction network with 850 nodes and 8770 edges. Of the network, nine key modules were identified and 60 key signaling pathways, including the estrogen, RAS, PI3K-Akt, NF-κB, HIF-1α, Jak-STAT, and TGF-β signaling pathways, were significantly enriched. With breast cancer, colorectal and prostate cancer cellular models, we validated the key node genes in the network that had been previously reported or inferred form the network by Western blotting methods, including STAT3, JNK, p38, SMAD2/3, P65, AKT1, and HIF-1α. These results suggested the established network was robust and provided a systematic view of the carcinogenic activities of cadmium in human. - Highlights: • A cadmium-influenced network with 850 nodes and 8770 edges was established. • The cadmium-rewired gene network was scale-free and highly connected. • Nine modules were identified, and 60 key signaling pathways related to cadmium-induced carcinogenesis were found. • Key mediators in the network were validated in multiple cellular models.

  20. INTEGRATION OF QSAR AND SAR METHODS FOR THE MECHANISTIC INTERPRETATION OF PREDICTIVE MODELS FOR CARCINOGENICITY

    Directory of Open Access Journals (Sweden)

    Natalja Fjodorova

    2012-07-01

    Full Text Available The knowledge-based Toxtree expert system (SAR approach was integrated with the statistically based counter propagation artificial neural network (CP ANN model (QSAR approach to contribute to a better mechanistic understanding of a carcinogenicity model for non-congeneric chemicals using Dragon descriptors and carcinogenic potency for rats as a response. The transparency of the CP ANN algorithm was demonstrated using intrinsic mapping technique specifically Kohonen maps. Chemical structures were represented by Dragon descriptors that express the structural and electronic features of molecules such as their shape and electronic surrounding related to reactivity of molecules. It was illustrated how the descriptors are correlated with particular structural alerts (SAs for carcinogenicity with recognized mechanistic link to carcinogenic activity. Moreover, the Kohonen mapping technique enables one to examine the separation of carcinogens and non-carcinogens (for rats within a family of chemicals with a particular SA for carcinogenicity. The mechanistic interpretation of models is important for the evaluation of safety of chemicals.

  1. Biomarkers of carcinogen exposure and early effects.

    OpenAIRE

    2006-01-01

    The purpose of this review is to summarise the current situation regarding the types and uses of biomarkers of exposure and effect for the main classes of food-derived genotoxic carcinogens, and to consider some aspects of the intercomparison between these biomarkers. The biomarkers of exposure and early effects of carcinogens that have been most extensively developed are those for genotoxic agents and for compounds that generate hydroxyl radicals and other reactive radical species, and it is...

  2. Mutagenic and carcinogenic properties of drinking water

    International Nuclear Information System (INIS)

    Kool, H.J.; van Kreijl, C.F.; Hrubec, J.

    1985-01-01

    In this chapter results of oxidation treatments with chlorine, ozone, chlorine dioxide, and ultraviolet (UV), with respect to their effects on activity (Ames test) in drinking water supplies are reviewed. In addition, the authors present the preliminary results of a pilot plant study on the effects of chlorine and chlorine dioxide on mutagenicity. Furthermore, results of several carcinogenicity studies performed with organic drinking water concentrates are discussed in relation to the results of a Dutch carcinogenicity study with mutagenic drinking water concentrates

  3. A review of biosensing techniques for detection of trace carcinogen contamination in food products.

    Science.gov (United States)

    Li, Zhanming; Yu, Yue; Li, Zhiliang; Wu, Tao

    2015-04-01

    Carcinogen contaminations in the food chain, for example heavy metal ions, pesticides, acrylamide, and mycotoxins, have caused serious health problems. A major objective of food-safety research is the identification and prevention of exposure to these carcinogens, because of their impossible-to-reverse tumorigenic effects. However, carcinogen detection is difficult because of their trace-level presence in food. Thus, reliable and accurate separation and determination methods are essential to protect food safety and human health. This paper summarizes the state of the art in separation and determination methods for analyzing carcinogen contamination, especially the advances in biosensing methods. Furthermore, the application of promising technology including nanomaterials, imprinted polymers, and microdevices is detailed. Challenges and perspectives are also discussed.

  4. Groundwater contamination by polycyclic aromatic hydrocarbon due to diesel spill from a telecom base station in a Nigerian City: assessment of human health risk exposure.

    Science.gov (United States)

    Ugochukwu, Uzochukwu Cornelius; Ochonogor, Alfred

    2018-03-26

    Diesel pollution of groundwater poses great threat to public health, mainly as a result of the constituent polycyclic aromatic hydrocarbons (PAHs). In this study, the human health risk exposure to polycyclic aromatic hydrocarbons (PAHs) in diesel contaminated groundwater used by several families at Ring Road, Jos, Nigeria (as caused by diesel spill from a telecom base station) was assessed. Prior to the groundwater being treated, the residents were using the water after scooping off the visible diesel sheen for purposes of cooking, washing, and bathing. Until this study, it is not clear whether the groundwater contamination had resulted in sub-chronic exposure of the residents using the water to polycyclic aromatic hydrocarbons (PAHs) to the extent of the PAHs posing a health risk. The diesel contaminated groundwater and uncontaminated nearby groundwater (control) were collected and analyzed for PAHs using gas chromatography-mass spectrometry (GC-MS). The dosage of the dermal and oral ingestion entry routes of PAHs was determined. The estimation of the non-carcinogenic health risk was via hazard quotients (HQ) and the associated hazard index (HI), while the estimation of the carcinogenic health risk was via lifetime cancer risks (LCR) and the associated risk index (RI). Obtained results indicate that the exposure of the residents to the PAHs may have made them susceptible to the risk of non-carcinogenic health effects of benzo(a)pyrene and the carcinogenic health effects of benzo(a)anthracene and benzo(a)pyrene.

  5. Nuclear DNA synthesis rate and labelling index: effects of carcinogenic and non-carcinogenic chemicals on its behaviour in the organism of growing CBA mice

    International Nuclear Information System (INIS)

    Amlacher, E.; Rudolph, C.

    1978-01-01

    Well known bioassays have been compared with the author's thymidine incorporation-screening system and other assays based on biochemical quantification of DNA synthesis as a possibility of identification of carcinogens. The partial inhibition of the whole DNA synthesis in a proliferating cell population after treatment with toxic and carcinogenic chemicals is an early common response especially in hepatectomized animal, livers caused by the effects of those substances. However, by quantitative evaluation of the nuclear DNA synthesis rate as a basic parameter, using autoradiographs of kidney and liver of juvenile growing CBA mice, it is possible to differentiate carcinogenic from non-carcinogenic chemicals by means of silver grain counting after 3 H-TdR incorporation. On the contrary, the whole DNA synthesis, expressed by the 3 H-labelling index (in per cent) of kidney and liver, did not permit such a differentiation in the experimental arrangement used. It could be demonstrated that carcinogenic compounds of different chemical classes partially inhibit the nuclear DNA synthesis rate significantly over a period of more than 24 hours. The tested non-carcinogenic compounds did not show this suppressive effect on the nuclear DNA synthesis rate. (author)

  6. Abnormal regulation of DNA replication and increased lethality in ataxia telangiectasia cells exposed to carcinogenic agents

    International Nuclear Information System (INIS)

    Jaspers, N.G.; de Wit, J.; Regulski, M.R.; Bootsma, D.

    1982-01-01

    The effect of different carcinogenic agents on the rate of semiconservative DNA replication in normal and ataxia telangiectasis (AT) cells was investigated. The rate of DNA synthesis in all AT cell strains tested was depressed to a significantly lesser extent than in normal cells after exposure to X-rays under oxia or hypoxia or to bleomycin, agents to which AT cells are hypersensitive. In contrast, inhibition of DNA replication in normal human and AT cells was similar after treatment with some DNA-methylating agents or mitomycin C. Colony-forming ability of AT cells treated with these agents was not different from normal cells. Treatment with 4-nitroquinoline 1-oxide elicited a variable response in both AT and normal cell strains. In some strains, including those shown to be hypersensitive to the drug by other workers, the inhibition of DNA synthesis was more pronounced than in other cell strains, but no significant difference between AT and normal cells could be detected. The rejoining of DNA strand breaks induced by X-rays, measured by DNA elution techniques, occurred within l2 hr after treatment and could not be correlated with the difference in DNA synthesis inhibition in AT and normal cells. After low doses of X-rays, AT cells rejoined single-strand breaks slightly more slowly than did normal cells. The rate of DNA replication in X-irradiation AT and normal cells was not affected by nicotinamide, an inhibitor of poly(adenosine diphosphate ribose) synthesis. These data indicate that the diminished inhibition of DNA replication in carcinogen-treated AT cells (a) is a general characteristic of all AT cell strains, (b) correlates with AT cellular hypersensitivity, (c) is not directly caused by the bulk of the DNA strand breaks produced by carcinogenic agents, and (d) is not based on differences in the induction of poly(adenosine diphosphate ribose) synthesis between X-irradiated AT and normal cells

  7. Impact of DNA repair on the dose-response of colorectal cancer formation induced by dietary carcinogens.

    Science.gov (United States)

    Fahrer, Jörg; Kaina, Bernd

    2017-08-01

    Colorectal cancer (CRC) is one of the most frequently diagnosed cancers, which is causally linked to dietary habits, notably the intake of processed and red meat. Processed and red meat contain dietary carcinogens, including heterocyclic aromatic amines (HCAs) and N-nitroso compounds (NOC). NOC are agents that induce various N-methylated DNA adducts and O 6 -methylguanine (O 6 -MeG), which are removed by base excision repair (BER) and O 6 -methylguanine-DNA methyltransferase (MGMT), respectively. HCAs such as the highly mutagenic 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) cause bulky DNA adducts, which are removed from DNA by nucleotide excision repair (NER). Both O 6 -MeG and HCA-induced DNA adducts are linked to the occurrence of KRAS and APC mutations in colorectal tumors of rodents and humans, thereby driving CRC initiation and progression. In this review, we focus on DNA repair pathways removing DNA lesions induced by NOC and HCA and assess their role in protecting against mutagenicity and carcinogenicity in the large intestine. We further discuss the impact of DNA repair on the dose-response relationship in colorectal carcinogenesis in view of recent studies, demonstrating the existence of 'no effect' point of departures (PoDs), i.e. thresholds for genotoxicity and carcinogenicity. The available data support the threshold concept for NOC with DNA repair being causally involved. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Carcinogenicity of chromium and chemoprevention: a brief update

    Directory of Open Access Journals (Sweden)

    Wang Y

    2017-08-01

    Full Text Available Yafei Wang,1,* Hong Su,1,* Yuanliang Gu,1 Xin Song,1 Jinshun Zhao1,2 1Department of Preventative Medicine, Zhejiang Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, People’s Republic of China; 2Toxicology and Molecular Biology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV, USA *These authors contributed equally to this work Abstract: Chromium has two main valence states: hexavalent chromium (Cr[VI] and trivalent chromium (Cr[III]. Cr(VI, a well-established human carcinogen, can enter cells by way of a sulfate/phosphate anion-transport system, and then be reduced to lower-valence intermediates consisting of pentavalent chromium (Cr[V], tetravalent chromium (Cr[IV] or Cr(III via cellular reductants. These intermediates may directly or indirectly result in DNA damage or DNA–protein cross-links. Although Cr(III complexes cannot pass easily through cell membranes, they have the ability to accumulate around cells to induce cell-surface morphological alteration and result in cell-membrane lipid injuries via disruption of cellular functions and integrity, and finally to cause DNA damage. In recent years, more research, including in vitro, in vivo, and epidemiological studies, has been conducted to evaluate the genotoxicity/carcinogenicity induced by Cr(VI and/or Cr(III compounds. At the same time, various therapeutic agents, especially antioxidants, have been explored through in vitro and in vivo studies for preventing chromium-induced genotoxicity/carcinogenesis. This review aims to provide a brief update on the carcinogenicity of Cr(VI and Cr(III and chemoprevention with different antioxidants. Keywords: hexavalent chromium, Cr(VI, trivalent chromium, Cr(III, genotoxicity, carcinogenicity, chemoprevention, antioxidant 

  9. Ptaquiloside, the major carcinogen of bracken fern, in the pooled raw milk of healthy sheep and goats: an underestimated, global concern of food safety.

    Science.gov (United States)

    Virgilio, Antonella; Sinisi, Annamaria; Russo, Valeria; Gerardo, Salvatore; Santoro, Adriano; Galeone, Aldo; Taglialatela-Scafati, Orazio; Roperto, Franco

    2015-05-20

    Bracken fern (Pteridium aquilinum) is a worldwide plant containing toxic substances, which represent an important chemical hazard for animals, including humans. Ptaquiloside, 1, a norsesquiterpenoid glucoside, is the major carcinogen of bracken detected in the food chain, particularly in the milk from farm animals. To date, ptaquiloside has been shown in the milk of cows feeding on a diet containing bracken fern. This is the first study that shows the systematic detection of ptaquiloside, 1, and reports its direct quantitation in pooled raw milk of healthy sheep and goats grazing on bracken. Ptaquiloside, 1, was detected by a sensitive method based on the chemical conversion of ptaquiloside, 1, into bromopterosine, 4, following gas chromatography-mass spectrometry (GC-MS) analysis. The presence of ptaquiloside, 1, possibly carcinogenic to humans, in the milk of healthy animals is an unknown potential health risk, thus representing a harmful and potential global concern of food safety.

  10. Studies on carcinogenic effect of tritiated water

    International Nuclear Information System (INIS)

    Zou Shuai; Wang Hui; Li Maohe; Lin Suqin

    1994-09-01

    Studies on carcinogenic effect of tritiated water is introduced in two parts. The first part is an in vitro study in which CHL-1 cells were exposed to tritiated water (9.25 x 10 5 ∼ 3.5 x 10 6 Bq/ml) for 24 ∼ 96 h and the accumulated dose was from 0.055 to 0.88 Gy. In order to estimate RBE of tritium for malignant transformation in CHL-1 cells, the induction of malignant transformation in CHL-1 cells by exposure to gamma rays of 137 Cs was tested. Based on the transformation rates, the RBE of tritium for malignant transformation in CHL-1 cells was estimated to be 1.6. The second part is an in vivo study. In the study, rats were fed with tritiated water (2.22 x 10 5 and 1.11 x 10 5 Bq/ml) for 1.5 a. Rats in control group were fed with tap water. Results showed that in the statistics, the differences in the total tumor incidence and malignant tumor incidence between high and low dose rate groups and control groups were remarkably significant

  11. Transplacental carcinogenicity of inorganic arsenic in the drinking water: induction of hepatic, ovarian, pulmonary, and adrenal tumors in mice

    International Nuclear Information System (INIS)

    Waalkes, Michael P.; Ward, Jerrold M.; Liu Jie; Diwan, Bhalchandra A.

    2003-01-01

    Arsenic is a known human carcinogen, but development of rodent models of inorganic arsenic carcinogenesis has been problematic. Since gestation is often a period of high sensitivity to chemical carcinogenesis, we performed a transplacental carcinogenicity study in mice using inorganic arsenic. Groups (n=10) of pregnant C3H mice were given drinking water containing sodium arsenite (NaAsO 2 ) at 0 (control), 42.5, and 85 ppm arsenite ad libitum from day 8 to 18 of gestation. These doses were well tolerated and body weights of the dams during gestation and of the offspring subsequent to birth were not reduced. Dams were allowed to give birth, and offspring were weaned at 4 weeks and then put into separate gender-based groups (n=25) according to maternal exposure level. The offspring received no additional arsenic treatment. The study lasted 74 weeks in males and 90 weeks in females. A complete necropsy was performed on all mice and tissues were examined by light microscopy in a blind fashion. In male offspring, there was a marked increase in hepatocellular carcinoma incidence in a dose- related fashion (control, 12%; 42.5 ppm, 38%; 85 ppm, 61%) and in liver tumor multiplicity (tumors per liver; 5.6-fold over control at 85 ppm). In males, there was also a dose-related increase in adrenal tumor incidence and multiplicity. In female offspring, dose-related increases occurred in ovarian tumor incidence (control, 8%; 42.5 ppm, 26%; 85 ppm, 38%) and lung carcinoma incidence (control, 0%; 42.5 ppm, 4%; 85 ppm, 21%). Arsenic exposure also increased the incidence of proliferative lesions of the uterus and oviduct. These results demonstrate that oral inorganic arsenic exposure, as a single agent, can induce tumor formation in rodents and establishes inorganic arsenic as a complete transplacental carcinogen in mice. The development of this rodent model of inorganic arsenic carcinogenesis has important implications in defining the mechanism of action for this common environmental

  12. The multitude and diversity of environmental carcinogens

    International Nuclear Information System (INIS)

    Belpomme, D.; Irigaray, P.; Hardell, L.; Clapp, R.; Montagnier, L.; Epstein, S.; Sasco, A.J.

    2007-01-01

    We have recently proposed that lifestyle-related factors, screening and aging cannot fully account for the present overall growing incidence of cancer. In order to propose the concept that in addition to lifestyle related factors, exogenous environmental factors may play a more important role in carcinogenesis than it is expected, and may therefore account for the growing incidence of cancer, we overview herein environmental factors, rated as certainly or potentially carcinogenic by the International Agency for Research on Cancer (IARC). We thus analyze the carcinogenic effect of microorganisms (including viruses), radiations (including radioactivity, UV and pulsed electromagnetic fields) and xenochemicals. Chemicals related to environmental pollution appear to be of critical importance, since they can induce occupational cancers as well as other cancers. Of major concerns are: outdoor air pollution by carbon particles associated with polycyclic aromatic hydrocarbons; indoor air pollution by environmental tobacco smoke, formaldehyde and volatile organic compounds such as benzene and 1,3 butadiene, which may particularly affect children, and food pollution by food additives and by carcinogenic contaminants such as nitrates, pesticides, dioxins and other organochlorines. In addition, carcinogenic metals and metalloids, pharmaceutical medicines and cosmetics may be involved. Although the risk fraction attributable to environmental factors is still unknown, this long list of carcinogenic and especially mutagenic factors supports our working hypothesis according to which numerous cancers may in fact be caused by the recent modification of our environment

  13. Carcinogen susceptibility is regulated by genome architecture and predicts cancer mutagenesis.

    Science.gov (United States)

    García-Nieto, Pablo E; Schwartz, Erin K; King, Devin A; Paulsen, Jonas; Collas, Philippe; Herrera, Rafael E; Morrison, Ashby J

    2017-10-02

    The development of many sporadic cancers is directly initiated by carcinogen exposure. Carcinogens induce malignancies by creating DNA lesions (i.e., adducts) that can result in mutations if left unrepaired. Despite this knowledge, there has been remarkably little investigation into the regulation of susceptibility to acquire DNA lesions. In this study, we present the first quantitative human genome-wide map of DNA lesions induced by ultraviolet (UV) radiation, the ubiquitous carcinogen in sunlight that causes skin cancer. Remarkably, the pattern of carcinogen susceptibility across the genome of primary cells significantly reflects mutation frequency in malignant melanoma. Surprisingly, DNase-accessible euchromatin is protected from UV, while lamina-associated heterochromatin at the nuclear periphery is vulnerable. Many cancer driver genes have an intrinsic increase in carcinogen susceptibility, including the BRAF oncogene that has the highest mutation frequency in melanoma. These findings provide a genome-wide snapshot of DNA injuries at the earliest stage of carcinogenesis. Furthermore, they identify carcinogen susceptibility as an origin of genome instability that is regulated by nuclear architecture and mirrors mutagenesis in cancer. © 2017 The Authors.

  14. Heterocyclic amines: Mutagens/carcinogens produced during cooking of meat and fish.

    Science.gov (United States)

    Sugimura, Takashi; Wakabayashi, Keiji; Nakagama, Hitoshi; Nagao, Minako

    2004-04-01

    Research leading to the discovery of a series of mutagenic and carcinogenic heterocyclic amines (HCAs) was inspired by the idea that smoke produced during cooking of food, especially meat or fish, might be carcinogenic. More than ten kinds of HCAs, actually produced by cooking or heating of meat or fish, have now been isolated and their structures determined, most being previously unregistered compounds. They are highly mutagenic towards Salmonella typhimurium in the presence of S9 mix and are also mutagenic in vitro and in vivo toward mammalian cells. HCAs have now been chemically synthesized in quantity and subjected to long-term animal testing. When HCAs were fed in the diet, rodents developed cancers in many organs, including the colon, breast and prostate, and one HCA produced hepatomas in monkeys. The lesions exhibited alteration in genes including Apc, beta-catenin and Ha-ras, and these changes provide clues to the induction mechanisms. The HCAs are oxidized to hydroxyamino derivatives by cytochrome P450s, and further converted to ester forms by acetyltransferase and sulfotransferase. Eventually, they produce DNA adducts through the formation of N-C bonds at guanine bases. There are HCA-sensitive and resistant strains of rodents and a search for the responsible genes is now under way. While the content of HCAs in dishes consumed in ordinary life is low and not sufficient in itself to explain human cancer, the coexistence of many other mutagens/carcinogens of either autobiotic or xenobiotic type and the possibility that HCAs induce genomic instability and heightened sensitivity to tumor promoters suggest that avoidance of exposure to HCAs or reduction of HCAs' biological effects as far as possible are to be highly recommended. Usage of microwave ovens for cooking and supplementation of the diet, for example with soy-isoflavones, which have been found to suppress the occurrence of HCA-induced breast cancers, should be encouraged. Advice to the general public

  15. Keishibukuryogan is not carcinogenic in Sprague-Dawley rats

    OpenAIRE

    Kanitani, Masanao; Nishimura, Nobuo; Edamoto, Hiroshi; Kase, Yoshio

    2016-01-01

    Keishibukuryogan is a traditional Japanese medicine widely administered to patients with menopausal symptoms. Because humans use it on a long-term basis, we believed that a carcinogenicity study was warranted. We orally administered keishibukuryogan (TJ-25) extract powder to 6-week-old Sprague-Dawley rats [Crl:CD(SD)], which were divided into four dosage groups-0 (water for injection), 100, 500 and 2,500 mg/kg/day for 24 months. We found that TJ-25 did not affect the survival rate of either s...

  16. Concentrations of environmental organic contaminants in meat and meat products and human dietary exposure: A review.

    Science.gov (United States)

    Domingo, José L

    2017-09-01

    Meat and meat products is one of the most relevant food groups in an important number of human diets. Recently, the IARC, based on results of a number of epidemiological studies, classified the consumptions of red meat and processed meat as "probably carcinogenic to humans" and as "carcinogenic to humans", respectively. It was suggested that the substances responsible of the potential carcinogenicity would be mainly generated during meat processing, such as curing and smoking, or when meat is heated at high temperatures. However, the exposure to environmental pollutants through meat consumption was not discussed. The purpose of the present paper was to review recent studies reporting the concentrations of PCDD/Fs, DL-PCBs and PAHs in meat and meat products, as well as the human exposure to these pollutants through the diet. It is concluded that the health risks derived from exposure to carcinogenic environmental contaminants must be considered in the context of each specific diet, which besides meat and meat products, includes other foodstuffs containing also chemical pollutants, some of them with carcinogenic potential. Anyhow, meat and meat products are not the main food group responsible of the dietary exposure to carcinogenic (or probably carcinogenic) environmental organic pollutants. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Genotoxicity and potential carcinogenicity of cyanobacterial toxins - a review.

    Science.gov (United States)

    Zegura, Bojana; Straser, Alja; Filipič, Metka

    2011-01-01

    The occurrence of cyanobacterial blooms has increased significantly in many regions of the world in the last century due to water eutrophication. These blooms are hazardous to humans, animals, and plants due to the production of cyanotoxins, which can be classified in five different groups: hepatotoxins, neurotoxins, cytotoxins, dermatotoxins, and irritant toxins (lipopolysaccharides). There is evidence that certain cyanobacterial toxins are genotoxic and carcinogenic; however, the mechanisms of their potential carcinogenicity are not well understood. The most frequently occurring and widespread cyanotoxins in brackish and freshwater blooms are the cyclic heptapeptides, i.e., microcystins (MCs), and the pentapeptides, i.e., nodularins (NODs). The main mechanism associated with potential carcinogenic activity of MCs and NOD is the inhibition of protein phosphatases, which leads to the hyperphosphorylation of cellular proteins, which is considered to be associated with their tumor-promoting activity. Apart from this, MCs and NOD induce increased formation of reactive oxygen species and, consequently, oxidative DNA damage. There is also evidence that MCs and NOD induce micronuclei, and NOD was shown to have aneugenic activity. Both cyanotoxins interfere with DNA damage repair pathways, which, along with DNA damage, is an important factor involved in the carcinogenicity of these agents. Furthermore, these toxins increase the expression of TNF-α and early-response genes, including proto-oncogenes, genes involved in the response to DNA damage, cell cycle arrest, and apoptosis. Rodent studies indicate that MCs and NOD are tumor promotors, whereas NOD is thought to have also tumor-initiating activity. Another cyanobacterial toxin, cylindrospermopsin (CYN), which has been neglected for a long time, is lately being increasingly found in the freshwater environment. The principal mechanism of its toxicity is the irreversible inhibition of protein synthesis. It is pro

  18. Nano-TiO₂--feasibility and challenges for human health risk assessment based on open literature.

    Science.gov (United States)

    Christensen, Frans M; Johnston, Helinor J; Stone, Vicki; Aitken, Robert J; Hankin, Steve; Peters, Sheona; Aschberger, Karin

    2011-06-01

    This study aims at investigating feasibility and challenges associated with conducting a human health risk assessment for nano-titanium-dioxide (nano-TiO₂) based on the open literature by following an approach similar to a classical regulatory risk assessment. Gaps in the available data set, both in relation to exposures and hazard, do not allow reaching any definite conclusions that could be used for regulatory decision-making. Results show that repeated inhalation in the workplace and possibly consumer inhalation may cause risks. Also short-term inhalation following spray applications may cause risks. Main future work should focus on generating occupational and consumer inhalation exposure data, as well as toxicity data on absorption following inhalation, repeated dermal contact, and contact with damaged skin. Also relevant seems further information on possible neurotoxicity and genotoxicity/carcinogenicity, as well as establishing a No Observed Adverse Effect Level (NOAEL) for acute inhalation of nano-TiO₂.

  19. Dietary Carcinogens and Breast Cancer.

    Science.gov (United States)

    1997-07-01

    detected by autoradiography on X-ray film with intensifying screens at - 70 0C. Using this TLC separation system, we have observed one abundant adduct...report in Science, published earlier this year, showed that resveratrol (a phytochemical found in many plant species) inhibited both cyclooxygenase I...the dietary phytochemical resveratrol significantly inhibits PhIP-DNA adduct formation in primary cultures of human mammary epithelial cells. From

  20. SHORT COMMUNICATION CARCINOGENIC POTENCY OF ...

    African Journals Online (AJOL)

    humans comes primarily from occupational studies of workers following inhalation ... Rats given 50 or 150 mg/kg per day of benzo(a)pyrene orally for four days showed ... exposed by inhalation to 7.7 mg/m3 of benzo(a)pyrene dust for 2 h/day, five days .... and the toxic effects of different compounds in a mixture are additive.

  1. Toxic Potential of Carcinogenic Polycyclic Aromatic Hydrocarbons ...

    African Journals Online (AJOL)

    Toxic Potential of Carcinogenic Polycyclic Aromatic Hydrocarbons (cPAHs) and Heavy Metal in Crude Oil from Gokana Area, Rivers State, Nigeria. ... Considerable caution should be applied in exploration, exposure and distribution of the crude oil through protected and well maintained pipelines to avoid the possible ...

  2. Mutagens and carcinogens in foods. Epidemiologic review.

    OpenAIRE

    Hislop, T. G.

    1993-01-01

    Evidence that diet contributes to the development of cancer is strengthening. This paper examines mutagens and carcinogens, such as naturally occurring substances, products of cooking and food processing, intentional and unintentional additives, and contaminants, found in foods. Such substances are present in minute quantities in the diets of average Canadians. Indication of health risk is largely limited to experimental laboratory evidence.

  3. Mutagens and carcinogens in foods. Epidemiologic review.

    Science.gov (United States)

    Hislop, T. G.

    1993-01-01

    Evidence that diet contributes to the development of cancer is strengthening. This paper examines mutagens and carcinogens, such as naturally occurring substances, products of cooking and food processing, intentional and unintentional additives, and contaminants, found in foods. Such substances are present in minute quantities in the diets of average Canadians. Indication of health risk is largely limited to experimental laboratory evidence. PMID:8499796

  4. Determination of carcinogenic polycyclic aromatic hydrocarbons in ...

    African Journals Online (AJOL)

    Determination of carcinogenic polycyclic aromatic hydrocarbons in air samples in Irbid, north Jordan. A Al-Gawadreh Sat, M.B. Gasim, A.R. Hassan, A Azid. Abstract. Air samples were collected at an urban site and a rural (BERQESH) site during February (2017) until March (2017) to determine concentrations of polycyclic ...

  5. Carcinogenic effects of radiation-introduction

    International Nuclear Information System (INIS)

    Setlow, R.B.

    1976-01-01

    The weight of experimental evidence reviewed indicates that UV damage to DNA, probably pyrimidine dimers, is the best molecular candidate for the initiating damage that leads to skin cancer. It is postulated that the carcinogenic action spectrum should be similar to the DNA action spectrum filtered through the upper layer of skin

  6. Effect of DNA type on response of DNA biosensor for carcinogens

    Science.gov (United States)

    Sani, Nor Diyana bt. Md.; Heng, Lee Yook; Surif, Salmijah; Lazim, Azwani Mat

    2013-11-01

    Carcinogens are cancer causing chemicals that can bind to DNA and cause damage to the DNA. These chemicals are available everywhere including in water, air, soil and food. Therefore, a sensor that can detect the presence of these chemicals will be a very useful tool. Since carcinogens bind to DNA, DNA can be used as the biological element in a biosensor. This study has utilized different types of DNA in a biosensor for carcinogen detection. The DNAs include double stranded calf thymus DNA, single stranded calf thymus DNA and guanine rich single stranded DNA. The modified SPE was exposed to a carcinogen followed by interaction with methylene blue which acts as the electroactive indicator. The SPE was then analysed using differential pulse voltammetry (DPV). Optimization studies were conducted for MB concentration and accumulation time, DNA concentration, as well as effect of buffer concentration, buffer pH and ionic strength. The performance of the biosensor was tested on a group 1 carcinogen, formaldehyde. The results indicated that the usage of guanine rich single stranded DNA also gives higher response as carcinogens prefer to bind with guanine compared to other bases.

  7. MGMT: key node in the battle against genotoxicity, carcinogenicity and apoptosis induced by alkylating agents.

    Science.gov (United States)

    Kaina, Bernd; Christmann, Markus; Naumann, Steffen; Roos, Wynand P

    2007-08-01

    O(6)-methylguanine-DNA methyltransferase (MGMT) plays a crucial role in the defense against alkylating agents that generate, among other lesions, O(6)-alkylguanine in DNA (collectively termed O(6)-alkylating agents [O(6)AA]). The defense is highly important, since O(6)AA are common environmental carcinogens, are formed endogenously during normal cellular metabolism and possibly inflammation, and are being used in cancer therapy. O(6)AA induced DNA damage is subject to repair, which is executed by MGMT, AlkB homologous proteins (ABH) and base excision repair (BER). Although this review focuses on MGMT, the mechanism of repair by ABH and BER will also be discussed. Experimental systems, in which MGMT has been modulated, revealed that O(6)-methylguanine (O(6)MeG) and O(6)-chloroethylguanine are major mutagenic, carcinogenic, recombinogenic, clastogenic and killing lesions. O(6)MeG-induced clastogenicity and cell death require MutS alpha-dependent mismatch repair (MMR), whereas O(6)-chloroethylguanine-induced killing occurs independently of MMR. Extensive DNA replication is required for O(6)MeG to provoke cytotoxicity. In MGMT depleted cells, O(6)MeG induces apoptosis almost exclusively, barely any necrosis, which is presumably due to the remarkable ability of secondarily formed DNA double-strand breaks (DSBs) to trigger apoptosis via ATM/ATR, Chk1, Chk2, p53 and p73. Depending on the cellular background, O(6)MeG activates both the death receptor and the mitochondrial apoptotic pathway. The inter-individual expression of MGMT in human lymphocytes is highly variable. Given the key role of MGMT in cellular defense, determination of MGMT activity could be useful for assessing a patient's drug sensitivity. MGMT is expressed at highly variable amounts in human tumors. In gliomas, a correlation was found between MGMT activity, MGMT promoter methylation and response to O(6)AA. Although the human MGMT gene is inducible by glucocorticoids and genotoxins such as radiation and

  8. EPA's evaluation of the carcinogenic potential of glyphosate

    Science.gov (United States)

    Recently, several international agencies have evaluated the carcinogenic potential of glyphosate. In March 2015, the International Agency for Research on Cancer (IARC), a subdivision of the World Health Organization (WHO), determined that glyphosate was a probable carcinogen (gro...

  9. Encryption Technology based on Human Biometrics

    Directory of Open Access Journals (Sweden)

    Wei Yang

    2017-08-01

    Full Text Available The research progress of encryption technologies based on human biometrics is reviewed in this paper.The technologies that utilize human biometrics to make information encryption and identity authentication,and the technologies which combine biometrics encryption with optical encryption methods are introduced in detail.The advantages and disadvantages of these encryption systems are discussed,and the obstacles in practical applications are pointed out.Finally,the prospect of the new encryption technologies that are based on human biometrics are predicted.

  10. [Risk assessment of carcinogenic and non-carcinogenic effects in the use of food].

    Science.gov (United States)

    Frolova, O A; Karpova, M V

    2012-01-01

    Application of methodology for assessing the risk of diseases associated with consumption of contaminated foods, is aimed at predicting possible changes in the future and helps to create a framework for the prevention of negative effects on public health. The purpose of the study is assessment of health risks formed under the influence of chemical contaminants that pollute the food. Exponential average daily dose of receipt of chemicals in the body, non-carcinogenic and carcinogenic risks were calculated.

  11. Detection of carcinogen-DNA adducts by radioimmunoassay

    International Nuclear Information System (INIS)

    Poirier, M.C.; Yuspa, S.H.; Weinstein, I.B.; Blobstein, S.

    1977-01-01

    Covalent binding of carcinogen to nucleic acids is believed to be an essential component of the carcinogenic process, so it is desirable to have highly sensitive and specific methods for detecting such adducts in cells and tissues exposed to known and suspected carcinogens. A radioimmunoassay is here described capable of detecting nanogram amounts of DNA adducts resulting from the covalent binding of the carcinogen N-2-acetylaminofluorene and its activated N-acetoxy derivative. (author)

  12. Use of the modified Ames test as an indicator of the carcinogenicity of residual aromatic extracts

    Energy Technology Data Exchange (ETDEWEB)

    Boogaard, P.; Hedelin, A.; Riley, A.; Rushton, E.; Vaissiere, M.; Minsavage, G.; Rohde, A.; Dalbey, W.

    2013-01-15

    Existing data demonstrate that residual aromatic extracts (RAEs) can be either carcinogenic or non-carcinogenic. CONCAWE had previously concluded that 'Although limited data available indicate that some RAEs are weakly carcinogenic, it is not possible to provide a general recommendation. Classify on a case-by-case basis' (CONCAWE 2005). Therefore CONCAWE's Health/Toxicology Subgroup (H/TSG) has developed a proposal for the use of the modified Ames test as a short-term predictive screening tool for decisions on the classification of RAEs for carcinogenicity. The relationship between RAE chemistry and carcinogenic potential is not as well understood as it is for some other categories of substances, e.g. Other Lubricant Base Oils (OLBO). However, a correlation has been found between the results of the skin carcinogenicity bioassay and the mutagenicity index (MI) obtained from the modified Ames test. Data supporting this correlation are summarised in this report. The H/TSG confirmed that the modified Ames test can be used as a predictive screening tool and that a cut-off value can be established to make a distinction between carcinogenic and non-carcinogenic products. RAEs with a MI > 0.4 demonstrated carcinogenic potential upon dermal application to mouse skin with chronic exposure. RAEs with a MI > 0.4 did not demonstrate a carcinogenic potential. To justify the use of the modified Ames test with RAEs, additional analysis of the repeatability of the test with RAEs was required. With this objective, CONCAWE sponsored a round robin study with different samples of RAEs from member companies, at three different laboratories. The repeatability demonstrated in the round robin study with RAEs support the proposed use of the modified Ames test. As part of the tools available for use by member companies, the H/TSG proposed a standard operating procedure (SOP) (included as an Appendix to this report) on the conduct of the modified Ames test with RAEs. The H

  13. Repair of DNA treated with lambda-irradiation and chemical carcinogens. Progress report, 1984-1985

    International Nuclear Information System (INIS)

    Goldthwait, D.A.

    1985-01-01

    Research progress is reported in the following areas: (1) DNA repair in HeLa cells; (2) a search for human transposable elements; (3) the effect of radiation and carcinogens on the activation of LTR sequences; and (4) studies on oncogenes of central nervous system tumors

  14. 78 FR 57868 - Nominations to the Report on Carcinogens; Request for Information

    Science.gov (United States)

    2013-09-20

    ... Carcinogens (ORoC) requests information on 20 substances, mixtures, and exposure circumstances (collectively... for the following topics: (1) data on current production, use patterns, and human exposure; (2... (CAS No. 108-10-1) Nickel nanoparticles Nitro polycyclic aromatic hydrocarbons (PAH) as a class...

  15. On the carcinogenic polycyclic aromatic hydrocarbon benzo(a)pyrene in volcano exhausts.

    Science.gov (United States)

    Ilnitsky, A P; Belitsky, G A; Shabad, L M

    1976-05-01

    The content of benzo(a)pyrene in the juvenile ashes of the volcano Tyatya (Kunashir Island, Kuriles) and in the soil, vegetation and volcanic mud collected near volcanos in Kamchatka was studied. It was concluded that volcanic activity does not play a large role in forming the background level of this carcinogen in the human environment.

  16. Capturing Labile Sulfenamide and Sulfinamide Serum Albumin Adducts of Carcinogenic Arylamines by Chemical Oxidation

    Science.gov (United States)

    Peng, Lijuan; Turesky, Robert J.

    2013-01-01

    Aromatic amines and heterocyclic aromatic amines (HAAs) are a class of structurally related carcinogens that are formed during the combustion of tobacco or during the high temperature cooking of meats. These procarcinogens undergo metabolic activation by N-oxidation of the exocyclic amine group to produce N-hydroxylated metabolites, which are critical intermediates implicated in toxicity and DNA damage. The arylhydroxylamines and their oxidized arylnitroso derivatives can also react with cysteine (Cys) residues of glutathione or proteins to form, respectively, sulfenamide and sulfinamide adducts. However, sulfur-nitrogen linked adducted proteins are often difficult to detect because they are unstable and undergo hydrolysis during proteolytic digestion. Synthetic N-oxidized intermediates of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a carcinogenic HAA produced in cooked meats, and 4-aminobiphenyl, a carcinogenic aromatic amine present in tobacco smoke were reacted with human serum albumin (SA) and formed labile sulfenamide or sulfinamide adducts at the Cys34 residue. Oxidation of the carcinogen-modified SA with m-chloroperoxybenzoic acid (m-CPBA) produced the arylsulfonamide adducts, which were stable to heat and the chemical reduction conditions employed to denature SA. The sulfonamide adducts of PhIP and 4-ABP were identified, by liquid chromatography/mass spectrometry, in proteolytic digests of denatured SA. Thus, selective oxidation of arylamine-modified SA produces stable arylsulfonamide-SA adducts, which may serve as biomarkers of these tobacco and dietary carcinogens. PMID:23240913

  17. Developments in assessing carcinogenic risks from radiation

    International Nuclear Information System (INIS)

    Beebe, G.W.

    1984-01-01

    The papers in this volume have ranged widely over theoretical, experimental, and epidemiologic topics relating to radiation carcinogenesis. The multistage character of carcinogenesis, emphasis on the ease with which the initial event occurs in contrast to the infrequency of carcinogenic expression, the role of cell repair, and factors that may influence expression were major themes of the theoretical and experimental papers. The elegance of the cell transformation tool was illustrated in reviews of experimental work dealing with the exposure and environmental variables that influence radiation-induced transformation, among them the intracellular environment. Arguments were advanced for the view that more than one cell must be affected by radiation if a critical event is to occur. The relative congruence of carcinogens and clastogens was noted, and the suggestion made that the rules governing the induction of chromosomal aberrations by ionizing may apply to radiation carcinogenesis as well

  18. Dose-response relationships for carcinogens: a review

    International Nuclear Information System (INIS)

    Zeise, L.; Wilson, R.; Crouch, E.A.C.

    1987-01-01

    The authors review the experimental evidence for various shapes of dose-response relationships for carcinogens and summarize those experiments that give the most information on relatively low doses. A brief review of some models is given to illustrate the shapes of dose-response curve expected from them. Their major interest is in the use of dose-response relationships to estimate risks to humans at low doses, and so they pay special attention to experimentally observed and theoretically expected nonlinearities. There are few experimental examples of nonlinear dose-response relations in humans, but this may simply be due to the limitations in the data. The several examples in rodents, even though for high dose data, suggest that nonlinearity is common. In some cases such nonlinearities may be rationalized on the basis of the pharmacokinetics of the test compound or its metabolites

  19. Electrochemical sensing carcinogens in beverages

    CERN Document Server

    Zia, Asif Iqbal

    2016-01-01

    This book describes a robust, low-cost electrochemical sensing system that is able to detect hormones and phthalates – the most ubiquitous endocrine disruptor compounds – in beverages and is sufficiently flexible to be readily coupled with any existing chemical or biochemical sensing system. A novel type of silicon substrate-based smart interdigital transducer, developed using MEMS semiconductor fabrication technology, is employed in conjunction with electrochemical impedance spectroscopy to allow real-time detection and analysis. Furthermore, the presented interdigital capacitive sensor design offers a sufficient penetration depth of the fringing electric field to permit bulk sample testing. The authors address all aspects of the development of the system and fully explain its benefits. The book will be of wide interest to engineers, scientists, and researchers working in the fields of physical electrochemistry and biochemistry at the undergraduate, postgraduate, and research levels. It will also be high...

  20. RADON AND CARCINOGENIC RISK IN MOSCOW

    Directory of Open Access Journals (Sweden)

    S. M. Golovanev

    2015-01-01

    Full Text Available Objective: comparative evaluation of carcinogenic risk inMoscowfrom radon in indoor and atmospheric pollutants.Materials and methods: the lung cancer incidence in Moscow; radiation-hygienic passport of the territory; .U.S. EPA estimated average age at all and radon induced deaths, years of life lost; Report of UNSCEAR 2006 and WHO handbook on indoor radon, 2009. Trend analysis of incidence; evaluation of the excess relative risk; assessment of ratio radon-induced population risk and published values оf total population carcinogenic risk from chemical carcinogens.Results: it is shown that the 304 cases of lung cancer per year (1. 85 10-3 on average from 2006 to 2011 (21280diseases for 70 years in addition to background level induced by radon; the differences in average trends of all lungcancer incidence in the districts can exceed 25%.Conclusion. The potential of risk reduction by measures of mitigation radon concentration exceeds 5 times the cost efficiency to reduce emissions from vehicles and can reduce cancer incidence, on average 236 cases per year; population risk 16520 cases over 70 years or save not less than 2832 person-years of life per year. The annual effect of reducing losses from not-survival of 12 years as a result of radon-induced lung cancer deaths exceeds 14160000 dollars. The evaluating of the carcinogenic risk from radon in accordance with the definition of population risk increases the predictive evaluation of the effectiveness of preventive measures more than twice.

  1. Respiratory carcinogenicity assessment of soluble nickel compounds.

    OpenAIRE

    Oller, Adriana R

    2002-01-01

    The many chemical forms of nickel differ in physicochemical properties and biological effects. Health assessments for each main category of nickel species are needed. The carcinogenicity assessment of water-soluble nickel compounds has proven particularly difficult. Epidemiologic evidence indicates an association between inhalation exposures to nickel refinery dust containing soluble nickel compounds and increased risk of respiratory cancers. However, the nature of this association is unclear...

  2. Inconsistency... or why differentiate, where prevention is concerned, between radioactive substances and carcinogenic chemicals

    International Nuclear Information System (INIS)

    Choquet, R.; Vinit, J.

    1982-01-01

    Radiotracers, low-activity unsealed radioactive sources, and certain chemical products belong to the list of substances and agents known to promote cancers in humans. The dangers of radiotracers and carcinogenic chemicals being very similar, or even identical, it is inadmissible that preventive measures have not been equally developed and are not viewed in the same way in our country. It should be noted that the International Labour Bureau has long since included radioactive products in the list of carcinogenic substances and agents and treated preventive measures as a whole by proceeding in this way it would be easier to account for the possible combined effects of ionising radiations and chemical molecules. After a review of some facts about cancer the present situation is examined with regard to statutory measures applied on the one hand to radioelements and on the other to chemicals recognised as carcinogenic by international organisations. Proposals are made to remedy this illogical situation [fr

  3. Average Gait Differential Image Based Human Recognition

    Directory of Open Access Journals (Sweden)

    Jinyan Chen

    2014-01-01

    Full Text Available The difference between adjacent frames of human walking contains useful information for human gait identification. Based on the previous idea a silhouettes difference based human gait recognition method named as average gait differential image (AGDI is proposed in this paper. The AGDI is generated by the accumulation of the silhouettes difference between adjacent frames. The advantage of this method lies in that as a feature image it can preserve both the kinetic and static information of walking. Comparing to gait energy image (GEI, AGDI is more fit to representation the variation of silhouettes during walking. Two-dimensional principal component analysis (2DPCA is used to extract features from the AGDI. Experiments on CASIA dataset show that AGDI has better identification and verification performance than GEI. Comparing to PCA, 2DPCA is a more efficient and less memory storage consumption feature extraction method in gait based recognition.

  4. Molecular basis of carcinogenicity of tungsten alloy particles

    Energy Technology Data Exchange (ETDEWEB)

    Harris, Robert M.; Williams, Tim D.; Waring, Rosemary H.; Hodges, Nikolas J., E-mail: n.hodges@bham.ac.uk

    2015-03-15

    The tungsten alloy of 91% tungsten, 6% nickel and 3% cobalt (WNC 91–6–3) induces rhabdomyosarcoma when implanted into a rat thigh muscle. To investigate whether this effect is species-specific human HSkMc primary muscle cells were exposed to WNC 91–6–3 particles and responses were compared with those from a rat skeletal muscle cell line (L6-C11). Toxicity was assessed by the adenylate kinase assay and microscopy, DNA damage by the Comet assay. Caspase 3 enzyme activity was measured and oligonucleotide microarrays were used for transcriptional profiling. WNC 91–6–3 particles caused toxicity in cells adjacent to the particles and also increased DNA strand breaks. Inhibition of caspase 3 by WNC 91–6–3 occurred in rat but not in human cells. In both rat and human cells, the transcriptional response to WNC 91–6–3 showed repression of transcripts encoding muscle-specific proteins with induction of glycolysis, hypoxia, stress responses and transcripts associated with DNA damage and cell death. In human cells, genes encoding metallothioneins were also induced, together with genes related to angiogenesis, dysregulation of apoptosis and proliferation consistent with pre-neoplastic changes. An alloy containing iron, WNF 97–2–1, which is non-carcinogenic in vivo in rats, did not show these transcriptional changes in vitro in either species while the corresponding cobalt-containing alloy, WNC 97–2–1 elicited similar responses to WNC 91–6–3. Tungsten alloys containing both nickel and cobalt therefore have the potential to be carcinogenic in man and in vitro assays coupled with transcriptomics can be used to identify alloys, which may lead to tumour formation, by dysregulation of biochemical processes. - Highlights: • Use of transcriptomics to identify likely carcinogenic tungsten alloys in vitro • Cobalt containing alloys cause oxidative stress, DNA-damage and perturb apoptosis. • Presence of cobalt causes changes in gene expression

  5. Carcinogen specific dosimetry model for passive smokers of various ages

    International Nuclear Information System (INIS)

    Robinson, Risa J.

    2005-01-01

    Studies indicate that being exposed to second hand smoke increases the chance of developing lung cancer. Understanding the deposition of carcinogenic particles present in second hand smoke is necessary to understand the development of specific histologic type cancers. In this study, a deposition model is presented for subjects of various ages exposed to sidestream smoke. The model included particle dynamics of coagulation, hygroscopic growth, charge and cloud behavior. Concentrations were varied from the maximum measured indoor concentrations (10 6 particles/cm 3 ) to what would be expected from wisps of smoke (10 8 particles/cm 3 ). Model results agreed well with experimental data taken from human subject deposition measurements (four studies). The model results were used to determine the dose intensity (dose per unit airway surface area) of Benzo[a]pyrene (BaP) in the respiratory tract for subjects of various ages. Model predictions for BaP surface concentration on the airway walls paralleled incident rates of tumors by location in the upper tracheobronchial region. Mass deposition efficiency was found to be larger for younger subjects, consistent with diffusion being the predominant mechanism for this particle size range. However, the actual dose intensity of BaP was found to be smaller for children than adults. This occurred due to the predominant effect of the smaller initial inhaled mass for children resulting from smaller tidal volumes. The resulting model is a useful tool to predict carcinogen specific particle deposition

  6. Carcinogenic action of polycyclic hydrocarbons in animals and man

    Energy Technology Data Exchange (ETDEWEB)

    Shabad, L M

    1976-01-01

    Polycyclic hydrocarbons are universally present in the atmosphere, soil, lakes and streams, vegetation, and human and animal tissues, the concentrations varying with distance from the sources (heating systems, industrial plants, automobile highways and airports, petroleum refineries, etc.). The most potent of the carcinogens is benz(a)pyrene whose presence in an object, as shown by studies done in the author's laboratory, is an indication that other polycyclic hydrocarbons are also present. These studies also demonstrated that while benz(a)pyrene may accumulate in soil with seasonal fluctuations, it can also be destroyed by certain microorganisms. Other experiments showed that benz(a)pyrene and other such compounds can be destroyed in tissue culture as well as in vivo (e.g., benz(a)pyrene given to cows with fodder was found in their milk but not in meat after they were slaughtered). It is suggested that maximum permissible concentrations be set for benz(a)pyrene in air and water to minimize its potential carcinogenic effects.

  7. Detection of genotoxic and non-genotoxic carcinogens in Xpc−/−p53+/− mice

    International Nuclear Information System (INIS)

    Melis, Joost P.M.; Speksnijder, Ewoud N.; Kuiper, Raoul V.; Salvatori, Daniela C.F.; Schaap, Mirjam M.; Maas, Saskia; Robinson, Joke; Verhoef, Aart; Benthem, Jan van; Luijten, Mirjam; Steeg, Harry van

    2013-01-01

    An accurate assessment of the carcinogenic potential of chemicals and pharmaceutical drugs is essential to protect humans and the environment. Therefore, substances are extensively tested before they are marketed to the public. Currently, the rodent two-year bioassay is still routinely used to assess the carcinogenic potential of substances. However, over time it has become clear that this assay yields false positive results and also has several economic and ethical drawbacks including the use of large numbers of animals, the long duration, and the high cost. The need for a suitable alternative assay is therefore high. Previously, we have proposed the Xpa*p53 mouse model as a very suitable alternative to the two-year bioassay. We now show that the Xpc*p53 mouse model preserves all the beneficial traits of the Xpa*p53 model for sub-chronic carcinogen identification and can identify both genotoxic and non-genotoxic carcinogens. Moreover, Xpc*p53 mice appear to be more responsive than Xpa*p53 mice towards several genotoxic and non-genotoxic carcinogens. Furthermore, Xpc*p53 mice are far less sensitive than Xpa*p53 mice for the toxic activity of DNA damaging agents and as such clearly respond in a similar way as wild type mice do. These advantageous traits of the Xpc*p53 model make it a better alternative for in vivo carcinogen testing than Xpa*p53. This pilot study suggests that Xpc*p53 mice are suited for routine sub-chronic testing of both genotoxic and non-genotoxic carcinogens and as such represent a suitable alternative to possibly replace the murine life time cancer bioassay. Highlights: ► The Xpc*p53 mouse model is able to identify genotoxic and non-genotoxic carcinogens. ► Time, animals and cost can be significantly reduced compared to the 2-year bioassay. ► Xpc*p53 mice are more advantageous for carcinogen identification than Xpa*p53 mice. ► Xpc*p53 mice exhibit a wild type response upon exposure to genotoxicants.

  8. Human body contour data based activity recognition.

    Science.gov (United States)

    Myagmarbayar, Nergui; Yuki, Yoshida; Imamoglu, Nevrez; Gonzalez, Jose; Otake, Mihoko; Yu, Wenwei

    2013-01-01

    This research work is aimed to develop autonomous bio-monitoring mobile robots, which are capable of tracking and measuring patients' motions, recognizing the patients' behavior based on observation data, and providing calling for medical personnel in emergency situations in home environment. The robots to be developed will bring about cost-effective, safe and easier at-home rehabilitation to most motor-function impaired patients (MIPs). In our previous research, a full framework was established towards this research goal. In this research, we aimed at improving the human activity recognition by using contour data of the tracked human subject extracted from the depth images as the signal source, instead of the lower limb joint angle data used in the previous research, which are more likely to be affected by the motion of the robot and human subjects. Several geometric parameters, such as, the ratio of height to weight of the tracked human subject, and distance (pixels) between centroid points of upper and lower parts of human body, were calculated from the contour data, and used as the features for the activity recognition. A Hidden Markov Model (HMM) is employed to classify different human activities from the features. Experimental results showed that the human activity recognition could be achieved with a high correct rate.

  9. Robotics-based synthesis of human motion

    KAUST Repository

    Khatib, O.; Demircan, E.; De Sapio, V.; Sentis, L.; Besier, T.; Delp, S.

    2009-01-01

    The synthesis of human motion is a complex procedure that involves accurate reconstruction of movement sequences, modeling of musculoskeletal kinematics, dynamics and actuation, and characterization of reliable performance criteria. Many of these processes have much in common with the problems found in robotics research. Task-based methods used in robotics may be leveraged to provide novel musculoskeletal modeling methods and physiologically accurate performance predictions. In this paper, we present (i) a new method for the real-time reconstruction of human motion trajectories using direct marker tracking, (ii) a task-driven muscular effort minimization criterion and (iii) new human performance metrics for dynamic characterization of athletic skills. Dynamic motion reconstruction is achieved through the control of a simulated human model to follow the captured marker trajectories in real-time. The operational space control and real-time simulation provide human dynamics at any configuration of the performance. A new criteria of muscular effort minimization has been introduced to analyze human static postures. Extensive motion capture experiments were conducted to validate the new minimization criterion. Finally, new human performance metrics were introduced to study in details an athletic skill. These metrics include the effort expenditure and the feasible set of operational space accelerations during the performance of the skill. The dynamic characterization takes into account skeletal kinematics as well as muscle routing kinematics and force generating capacities. The developments draw upon an advanced musculoskeletal modeling platform and a task-oriented framework for the effective integration of biomechanics and robotics methods.

  10. Robotics-based synthesis of human motion

    KAUST Repository

    Khatib, O.

    2009-05-01

    The synthesis of human motion is a complex procedure that involves accurate reconstruction of movement sequences, modeling of musculoskeletal kinematics, dynamics and actuation, and characterization of reliable performance criteria. Many of these processes have much in common with the problems found in robotics research. Task-based methods used in robotics may be leveraged to provide novel musculoskeletal modeling methods and physiologically accurate performance predictions. In this paper, we present (i) a new method for the real-time reconstruction of human motion trajectories using direct marker tracking, (ii) a task-driven muscular effort minimization criterion and (iii) new human performance metrics for dynamic characterization of athletic skills. Dynamic motion reconstruction is achieved through the control of a simulated human model to follow the captured marker trajectories in real-time. The operational space control and real-time simulation provide human dynamics at any configuration of the performance. A new criteria of muscular effort minimization has been introduced to analyze human static postures. Extensive motion capture experiments were conducted to validate the new minimization criterion. Finally, new human performance metrics were introduced to study in details an athletic skill. These metrics include the effort expenditure and the feasible set of operational space accelerations during the performance of the skill. The dynamic characterization takes into account skeletal kinematics as well as muscle routing kinematics and force generating capacities. The developments draw upon an advanced musculoskeletal modeling platform and a task-oriented framework for the effective integration of biomechanics and robotics methods.

  11. Nanostructural point-contact sensors for diagnostics of carcinogenic strains of Helicobacter pylori

    Directory of Open Access Journals (Sweden)

    Г. В. Камарчук

    2017-12-01

    a specially developed technique. The sensor response curves were recorded by a measuring complex and original software designed by the authors. Results: A set of 350 active-type TCNQ-based sensors was studied under the influence of a mixture of breath gases. Gas-sensitive sensors based on TCNQ compounds are characterized by a complex response curve with two extrema. Since the temporal variation in electrical conductivity of the sensor correlates well with the dependence of its resistance on the energy of the adsorbed components of the gas mixture, the resulting response curves of point-contact sensors can be called spectral profiles of a complex gas mixture. It is possible to differentiate among the various states of human body caused by the H. pylori bacterium by using spectral profiles of the gas exhaled by different patients. As a result, the developed sensors were shown to be an effective tool for analyzing breath gas exhaled in real time mode. They demonstrated a high sensitivity and selectivity to the products of activity of different H. pylori strains. Conclusions: It was shown that the products of metabolism of carcinogenic H. pylori strains had a dominant influence on electrical conductivity of the sensor and thus shaped the behavior of the features on sensor response curves. As a result, it is possible to differentiate H. pylori strains with respect to their carcinogenic potential using point-contact sensors based on TCNQ compounds. Thus, an effective portable tool was created in this work for the first time to develop innovative screening technologies for non-invasive diagnosis of human body conditions characterized by gastroduodenal pathology and to distinguish carcinogenic strains of H. pylori from tolerant ones.

  12. Development of a two-dimensional high-performance liquid chromatography system coupled with on-line reduction as a new efficient analytical method of 3-nitrobenzanthrone, a potential human carcinogen.

    Science.gov (United States)

    Hasei, Tomohiro; Nakanishi, Haruka; Toda, Yumiko; Watanabe, Tetsushi

    2012-08-31

    3-Nitrobenzanthrone (3-NBA) is an extremely strong mutagen and carcinogen in rats inducing squamous cell carcinoma and adenocarcinoma. We developed a new sensitive analytical method, a two-dimensional HPLC system coupled with on-line reduction, to quantify non-fluorescent 3-NBA as fluorescent 3-aminobenzanthrone (3-ABA). The two-dimensional HPLC system consisted of reversed-phase HPLC and normal-phase HPLC, which were connected with a switch valve. 3-NBA was purified by reversed-phase HPLC and reduced to 3-ABA with a catalyst column, packed with alumina coated with platinum, in ethanol. An alcoholic solvent is necessary for reduction of 3-NBA, but 3-ABA is not fluorescent in the alcoholic solvent. Therefore, 3-ABA was separated from alcohol and impurities by normal-phase HPLC and detected with a fluorescence detector. Extracts from surface soil, airborne particles, classified airborne particles, and incinerator dust were applied to the two-dimensional HPLC system after clean-up with a silica gel column. 3-NBA, detected as 3-ABA, in the extracts was found as a single peak on the chromatograms without any interfering peaks. 3-NBA was detected in 4 incinerator dust samples (n=5). When classified airborne particles, that is, those 7.0 μm in size, were applied to the two-dimensional HPLC system after purified using a silica gel column, 3-NBA was detected in those particles with particle sizes NBA in airborne particles and the detection of 3-NBA in incinerator dust. Copyright © 2012 Elsevier B.V. All rights reserved.

  13. In vitro screening of inhibition of PPAR-γ activity as a first step in identification of potential breast carcinogens

    DEFF Research Database (Denmark)

    Kopp, Tine Iskov; Lundqvist, J.; Petersen, R. K.

    2015-01-01

    and estrogen biosynthesis ultimately leading to breast cancer. If other organic solvents inhibit PPAR-γ activity, they should also lead to increased oestrogen biosynthesis and thus be potential breast carcinogens. Ten commonly used hydrophilic organic solvents were first tested in a cell-based screening assay...... followed by a well-established steroidogenesis assay for production of sex hormones in exposed H295 R cells may provide a screening tool for potential breast carcinogens. This initial screening thus identified ethylene glycol and possibly ethyl acetate as potential breast carcinogens....

  14. Radiobiology in clinical radiation therapy: Long term risks - Carcinogenic, hereditary, and teratogenetic effects

    International Nuclear Information System (INIS)

    Brenner, David J.

    1997-01-01

    The long-term risks induced by radiation are of much concern to patients and clinicians alike. As an example, perceived radiation risks are frequently cited in a woman's decision to choose a radical mastectomy over lumpectomy + radiation. In consequence, the actual radiation risks are often considerably overstated, or unreasonably downplayed. In this lecture we will discuss just what is known about the long term risks following radiotherapy, both from the human experience and from the laboratory. We will discuss risks both to the patient and to radiotherapy personnel. A good deal is known about the carcinogenic effects of high and low doses of radiation, in large part thanks to the careful study of the survivors of the atomic bombing in Japan, as well as studies of individuals exposed to medical x rays. It is possible to make an estimate, which is probably good to within a factor of, perhaps, three to five, of the cancer risks faced by a patient of a particular age and sex who is going to undergo a particular radiotherapeutic regimen. It is also possible to make an estimate of the risks faced by radiotherapy and nursing staff exposed to low doses. Brachytherapy related risk estimates are likely to be somewhat more uncertain, due to the poorly known sparing effects of the low dose rates used; for the radiotherapy personnel in brachytherapy, because of the doses which can be received, the risks can be quite significant. A recent complication in external-beam radiotherapy is the advent of high-energy linacs, which can produce a significant fast neutron dose which, dose for dose, may be ten to fifty times more carcinogenic than gamma rays. Data relating to the risks of hereditary effects of radiation come almost entirely from laboratory experiments in animals. Studies involving several million mice form the basis of most of our current understanding of hereditary effects. The results of these studies indicate that radiation is a relatively inefficient mutagen. The

  15. Radiobiology in clinical radiation therapy - Part IV: Long term risks - Carcinogenic, hereditary, and teratogenetic effects

    International Nuclear Information System (INIS)

    Brenner, David J.

    1996-01-01

    The long-term risks induced by radiation are of much concern to patients and clinicians alike. As an example, perceived radiation risks are frequently cited in a woman's decision to choose a radical mastectomy over lumpectomy + radiation. In consequence, the actual radiation risks are often considerably overstated, or unreasonably downplayed. In this lecture we will discuss just what is known about the long term risks following radiotherapy, both from the human experience and from the laboratory. We will discuss risks both to the patient and to radiotherapy personnel. A good deal is known about the carcinogenic effects of high and low doses of radiation, in large part thanks to the careful study of the survivors of the atomic bombing in Japan, as well as studies of individuals exposed to medical x rays. It is possible to make an estimate, which is probably good to within a factor of, perhaps, three to five, of the cancer risks faced by a patient of a particular age and sex who is going to undergo a particular radiotherapeutic regimen. It is also possible to make an estimate of the risks faced by radiotherapy and nursing staff exposed to low doses. Brachytherapy related risk estimates are likely to be somewhat more uncertain, due to the poorly known sparing effects of the low dose rates used; for the radiotherapy personnel in brachytherapy, because of the doses which can be received, the risks can be quite significant. A recent complication in external-beam radiotherapy is the advent of high-energy linacs, which can produce a significant fast neutron dose which, dose for dose, may be ten to fifty times more carcinogenic than gamma rays. Data relating to the risks of hereditary effects of radiation come almost entirely from laboratory experiments in animals. Studies involving several million mice form the basis of most of our current understanding of hereditary effects. The results of these studies indicate that radiation is a relatively inefficient mutagen. The

  16. Enhanced carcinogenicity by coexposure to arsenic and iron and a novel remediation system for the elements in well drinking water.

    Science.gov (United States)

    Kumasaka, Mayuko Y; Yamanoshita, Osamu; Shimizu, Shingo; Ohnuma, Shoko; Furuta, Akio; Yajima, Ichiro; Nizam, Saika; Khalequzzaman, Md; Shekhar, Hossain U; Nakajima, Tamie; Kato, Masashi

    2013-03-01

    Various carcinomas including skin cancer are explosively increasing in arsenicosis patients who drink arsenic-polluted well water, especially in Bangladesh. Although well drinking water in the cancer-prone areas contains various elements, very little is known about the effects of elements except arsenic on carcinogenicity. In order to clarify the carcinogenic effects of coexposure to arsenic and iron, anchorage-independent growth and invasion in human untransformed HaCaT and transformed A431 keratinocytes were examined. Since the mean ratio of arsenic and iron in well water was 1:10 in cancer-prone areas of Bangladesh, effects of 1 μM arsenic and 10 μM iron were investigated. Iron synergistically promoted arsenic-mediated anchorage-independent growth in untransformed and transformed keratinocytes. Iron additionally increased invasion in both types of keratinocytes. Activities of c-SRC and ERK that regulate anchorage-independent growth and invasion were synergistically enhanced in both types of keratinocytes. Our results suggest that iron promotes arsenic-mediated transformation of untransformed keratinocytes and progression of transformed keratinocytes. We then developed a low-cost and high-performance adsorbent composed of a hydrotalcite-like compound for arsenic and iron. The adsorbent rapidly reduced concentrations of both elements from well drinking water in cancer-prone areas of Bangladesh to levels less than those in WHO health-based guidelines for drinking water. Thus, we not only demonstrated for the first time increased carcinogenicity by coexposure to arsenic and iron but also proposed a novel remediation system for well drinking water.

  17. Review of the Evidence from Epidemiology, Toxicology, and Lung Bioavailability on the Carcinogenicity of Inhaled Iron Oxide Particulates.

    Science.gov (United States)

    Pease, Camilla; Rücker, Thomas; Birk, Thomas

    2016-03-21

    iron oxide is not a human carcinogen, and therefore, based upon the complete weight of evidence, we conclude that "bulk" iron oxides are not human carcinogens.

  18. Assessing carcinogenic risks associated with ingesting arsenic in farmed smeltfish (Ayu, Plecoglossus altirelis) in aseniasis-endemic area of Taiwan

    International Nuclear Information System (INIS)

    Lee, J.-J.; Jang, C.-S.; Liang, C.-P.; Liu, C.-W.

    2008-01-01

    This study spatially analyzed potential carcinogenic risks associated with ingesting arsenic (As) contents in aquacultural smeltfish (Plecoglossus altirelis) from the Lanyang Plain of northeastern Taiwan. Sequential indicator simulation (SIS) was adopted to reproduce As exposure distributions in groundwater based on their three-dimensional variability. A target cancer risk (TR) associated with ingesting As in aquacultural smeltfish was employed to evaluate the potential risk to human health. The probabilistic risk assessment determined by Monte Carlo simulation and SIS is used to propagate properly the uncertainty of parameters. Safe and hazardous aquacultural regions were mapped to elucidate the safety of groundwater use. The TRs determined from the risks at the 95th percentiles exceed one millionth, indicating that ingesting smeltfish that are farmed in the highly As-affected regions represents a potential cancer threat to human health. The 95th percentile of TRs is considered in formulating a strategy for the aquacultural use of groundwater in the preliminary stage

  19. Morpho-chemical characterization and surface properties of carcinogenic zeolite fibers

    International Nuclear Information System (INIS)

    Mattioli, Michele; Giordani, Matteo; Dogan, Meral; Cangiotti, Michela; Avella, Giuseppe; Giorgi, Rodorico; Dogan, A. Umran; Ottaviani, Maria Francesca

    2016-01-01

    Highlights: • Differently carcinogenic zeolite fibers were investigated combining physico-chemical methods. • For the first time, zeolite fibers were studied by means of the EPR technique using different spin probes. • The structural properties and the adsorption capability are function of different types and distributions of adsorption sites. • The interacting ability of erionite is higher than that of other fibrous zeolites. • The surface interacting properties may be related with the carcinogenicity of the zeolite fibers. - Abstract: Erionite belonging to the zeolite family is a human health-hazard, since it was demonstrated to be carcinogenic. Conversely, offretite family zeolites were suspected carcinogenic. Mineralogical, morphological, chemical, and surface characterizations were performed on two erionites (GF1, MD8) and one offretite (BV12) fibrous samples and, for comparison, one scolecite (SC1) sample. The specific surface area analysis indicated a larger availability of surface sites for the adsorption onto GF1, while SC1 shows the lowest one and the presence of large pores in the poorly fibrous zeolite aggregates. Selected spin probes revealed a high adsorption capacity of GF1 compared to the other zeolites, but the polar/charged interacting sites were well distributed, intercalated by less polar sites (Si–O–Si). MD8 surface is less homogeneous and the polar/charged sites are more interacting and closer to each other compared to GF1. The interacting ability of BV12 surface is much lower than that found for GF1 and MD8 and the probes are trapped in small pores into the fibrous aggregates. In comparison with the other zeolites, the non-carcinogenic SC1 shows a poor interacting ability and a lower surface polarity. These results helped to clarify the chemical properties and the surface interacting ability of these zeolite fibers which may be related to their carcinogenicity.

  20. Synergistic and Antagonistic Mutation Responses of Human MCL-5 Cells to Mixtures of Benzo[a]pyrene and 2-Amino-1-Methyl-6-Phenylimidazo[4,5-b]pyridine: Dose-Related Variation in the Joint Effects of Common Dietary Carcinogens.

    Science.gov (United States)

    David, Rhiannon; Ebbels, Timothy; Gooderham, Nigel

    2016-01-01

    Chemical carcinogens such as benzo[a]pyrene (BaP) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) may contribute to the etiology of human diet-associated cancer. Individually, these compounds are genotoxic, but the consequences of exposure to mixtures of these chemicals have not been systematically examined. We determined the mutagenic response to mixtures of BaP and PhIP at concentrations relevant to human exposure (micromolar to subnanomolar). Human MCL-5 cells (metabolically competent) were exposed to BaP or PhIP individually or in mixtures. Mutagenicity was assessed at the thymidine kinase (TK) locus, CYP1A activity was determined by ethoxyresorufin-O-deethylase (EROD) activity and qRT-PCR, and cell cycle was measured by flow cytometry. Mixtures of BaP and PhIP produced dose responses different from those of the individual chemicals; we observed remarkably increased mutant frequency (MF) at lower concentrations of the mixtures (not mutagenic individually), and decreased MF at higher concentrations of the mixtures, than the calculated predicted additive MF of the individual chemicals. EROD activity and CYP1A1 mRNA levels were correlated with TK MF, supporting involvement of the CYP1A family in mutation. Moreover, a cell cycle G2/M phase block was observed at high-dose combinations, consistent with DNA damage sensing and repair. Mixtures of these genotoxic chemicals produced mutation responses that differed from those expected for the additive effects of the individual chemicals. The increase in MF for certain combinations of chemicals at low concentrations that were not genotoxic for the individual chemicals, as well as the nonmonotonic dose response, may be important for understanding the mutagenic potential of food and the etiology of diet-associated cancers. David R, Ebbels T, Gooderham N. 2016. Synergistic and antagonistic mutation responses of human MCL-5 cells to mixtures of benzo[a]pyrene and 2-amino-1-methyl-6-phenylimidazo[4,5-b

  1. Mequindox Induced Genotoxicity and Carcinogenicity in Mice

    Directory of Open Access Journals (Sweden)

    Qianying Liu

    2018-04-01

    Full Text Available Mequindox (MEQ, acting as an inhibitor of deoxyribonucleic acid (DNA synthesis, is a synthetic heterocyclic N-oxides. To investigate the potential carcinogenicity of MEQ, four groups of Kun-Ming (KM mice (50 mice/sex/group were fed with diets containing MEQ (0, 25, 55, and 110 mg/kg for one and a half years. The result showed adverse effects on body weights, feed consumption, hematology, serum chemistry, organ weights, relative organ weights, and incidence of tumors during most of the study period. Treatment-related changes in hematology, serum chemistry, relative weights and histopathological examinations revealed that the hematological system, liver, kidneys, and adrenal glands, as well as the developmental and reproductive system, were the main targets after MEQ administration. Additionally, MEQ significantly increased the frequency of micronucleated normochromatic erythrocytes in bone marrow cells of mice. Furthermore, MEQ increased the incidence of tumors, including mammary fibroadenoma, breast cancer, corticosuprarenaloma, haemangiomas, hepatocarcinoma, and pulmonary adenoma. Interestingly, the higher incidence of tumors was noted in M25 mg/kg group, the lowest dietary concentration tested, which was equivalent to approximately 2.25 and 1.72 mg/kg b.w./day in females and males, respectively. It was assumed that the lower toxicity might be a reason for its higher tumor incidence in M25 mg/kg group. This finding suggests a potential relationships among the dose, general toxicity and carcinogenicity in vivo, and further study is required to reveal this relationship. In conclusion, the present study demonstrates that MEQ is a genotoxic carcinogen in KM mice.

  2. Repair of DNA treated with γ-irradiation and chemical carcinogens. Final report, June 1, 1981-May 31, 1984

    International Nuclear Information System (INIS)

    Goldthwait, D.A.

    1984-01-01

    Work done in the past three years has been on DNA repair, on genetic transposition and on the effect of carcinogens on alu sequence transcription. DNA repair work was completed on β-propiolactone DNA adducts, on procaryotic and eucaryotic enzymes capable of removal of 3-methyladenine from DNA, and on in vitro repair of neucleosomal core particle DNA and chromatin DNA. Attempts were made to isolate a human transposable element through the isolation of double stranded RNA and probing of a human library. Experiments were also done to determine whether carcinogens altered the expression of alu sequences in human DNA

  3. Critical effective methods to detect genotoxic carcinogens and neoplasm-promoting agents.

    Science.gov (United States)

    Weisburger, J H; Williams, G M

    1991-01-01

    Neoplasia in fish can result from contamination of waters with carcinogens and promoters. Cancer in fish, therefore, is a possible indicator of cancer risk to man and serves as a guide to the need for preventive approaches involving improved means of waste disposal and environmental hygiene. Moreover, cancer in fish indicates that this important food source may be contaminated. Detection of genotoxic carcinogens to which fish are exposed can be achieved quickly and efficiently by carefully selected batteries of complementary in vitro and in vivo bioassays. One such battery consists of the Ames test, a reverse mutation assay in prokaryotic Salmonella typhimurium, and the Williams test, involving DNA repair in freshly explanted metabolically highly competent liver cells from diverse species, including humans. Determination of DNA-carcinogen adducts by varied techniques, including 32P-postlabeling, as well as DNA breakage, mammalian cell mutagenicity, chromosome aberrations, sister chromatid exchange, or cell transformation represent additional approaches, each with its own advantages and disadvantages. More research is needed on systems to apprehend neoplasm promoters, but tests to determine interruption of intercellular communications through gap junctions appear promising. Other approaches rely on measurement of enzymes such as ornithine decarboxylase and protein kinase C. Approaches to the definition of risk to fish or humans require characterization of the genotoxic or nongenotoxic properties of a chemical, relative potency data obtained in select, limited rodent bioassays, and knowledge of prevailing environmental concentrations of specific carcinogens.

  4. Indoor air-assessment: Indoor concentrations of environmental carcinogens

    International Nuclear Information System (INIS)

    Gold, K.W.; Naugle, D.F.; Berry, M.A.

    1991-01-01

    In the report, indoor concentration data are presented for the following general categories of air pollutants: radon-222, environmental tobacco smoke (ETS), asbestos, gas phase organic compounds, formaldehyde, polycyclic aromatic hydrocarbons (PAH), pesticides, and inorganic compounds. These pollutants are either known or suspect carcinogens (i.e., radon-222, asbestos) or more complex mixtures or classes of compounds which contain known or suspect carcinogens. Concentration data for individual carcinogenic compounds in complex mixtures are usually far from complete. The data presented for complex mixtures often include compounds which are not carcinogenic or for which data are insufficient to evaluate carcinogenicity. Their inclusion is justified, however, by the possibility that further work may show them to be carcinogens, cocarcinogens, initiators or promotors, or that they may be employed as markers (e.g., nicotine, acrolein) for the estimation of exposure to complex mixtures

  5. The metabolic activation and nucleic acid adducts of naturally-occurring carcinogens: recent results with ethyl carbamate and the spice flavors safrole and estragole

    Energy Technology Data Exchange (ETDEWEB)

    Miller, J A; Miller, E C

    1983-07-01

    A small (approximately 30) but varied group of organic and inorganic compounds appear to be carcinogenic in both humans and experimental animals. A much larger number and wider variety of chemical carcinogens, primarily synthetic organic compounds, are known for experimental animals. These agents include a small (approximately 30) and varied group of metabolites of green plants and fungi. Many more of these carcinogens must exist in the living world. As with the synthetic carcinogens, the majority of these naturally occurring carcinogens are procarcinogens that require metabolic conversion into reactive electrophilic and mutagenic ultimate carcinogens. These strong electrophiles combine covalently and non-enzymatically with nucleophilic sites in DNAs, RNAs, proteins, and small molecules in target tissues. One or more of the DNA adducts appear to initiate carcinogenesis in an irreversible manner. The subsequent promotion step leading to gross tumours may be completed by further administration of carcinogen or by treatment with non-carcinogenic promoters. Roles for the RNA and protein adducts in the carcinogenic process have not been excluded. Recent data on the metabolic activation and reactivity in vivo of the naturally occurring carcinogens ethyl carbamate and certain of the alkenylbenzene spice flavours are illustrative of these principles. These agents can initiate the carcinogenic process in male mouse liver with small doses given prior to weaning. Subsequent growth of the liver and male hormonal factors appear to function as promoters leading to gross hepatic tumors after one year. Reactive electrophilic metabolites of ethyl carbamate and of safrole and estragole and their nucleic acid adducts formed during initiation in mouse liver have been characterized.

  6. Chocolate Bars Based on Human Nutritional Requirements

    OpenAIRE

    Robson , Anthony ,

    2013-01-01

    International audience; Key Points * The nutritional value of chocolate bars should be based on the nutritional value of the low energy dense late Paleolithic human diet to help reduce mental ill health, obesity, and other postprandial insults. * Current chocolate bars have a high energy density (>2 kcal/g). * Cocoa can be sweetened by the addition of calorie-free Purefruit™ (Tate & Lyle) monk fruit ( Siraitia grosvenorii ) extract. PUREFRUIT™ is approximately 200 times sweeter than sugar and...

  7. Nutrition in adult and childhood cancer: role of carcinogens and anti-carcinogens.

    Science.gov (United States)

    Mosby, Terezie T; Cosgrove, Maeve; Sarkardei, Samiramis; Platt, Karl L; Kaina, Bernd

    2012-10-01

    There is no doubt that diet is one of the main modifiable risk factors for many degenerative diseases, including cancer. More than 30% of adult cancers can be prevented or delayed by diet, being physically active and having a healthy body weight. Plant-based foods, including fruit, vegetables, and whole grains, a favorable omega-6/omega-3 polyunsaturated fatty acids ratio, and fish consumption have a protective effect against cancer. On the contrary, a low intake of fruit and vegetables, high intake of red and processed meat, high intake of sodium, alcohol consumption, a diet rich in refined carbohydrates, and a high intake of total fat may increase risk of cancer. Furthermore, calorie restriction and having a body/mass index on the lower end of the normal range can significantly decrease or delay the onset of cancers. Most studies were performed on adults and thus the role of diet in childhood cancer is less well-understood. In the past, diet was not considered to play any role in its etiology in children. However, nowadays there is a growing body of evidence that prolonged and frequent breastfeeding, the maternal diet during pregnancy and vitamin intake during pregnancy, may impart benefit for reduced cancer risk in children. Usually, decades of healthy dietary habits are needed to see significant difference in cancer risk. Therefore, diet choices and diet preparation starting early in life deserve more attention. Here we review data focusing on which dietary factors, including food-borne carcinogens, affect the onset of cancers in adults and stress out the potential role of diet in childhood cancer prevention.

  8. A physiologically based pharmacokinetic model for ethylene oxide in mouse, rat, and human.

    Science.gov (United States)

    Fennell, T R; Brown, C D

    2001-06-15

    Ethylene oxide (EO) is widely used as a gaseous sterilant and industrial intermediate and is a direct-acting mutagen and carcinogen. The objective of these studies was to develop physiologically based pharmacokinetic (PB-PK) models for EO to describe the exposure-tissue dose relationship in rodents and humans. We previously reported results describing in vitro and in vivo kinetics of EO metabolism in male and female F344 rats and B6C3F1 mice. These studies were extended by determining the kinetics of EO metabolism in human liver cytosol and microsomes. The results indicate enzymatically catalyzed GSH conjugation via cytosolic glutathione S-transferase (cGST) and hydrolysis via microsomal epoxide hydrolase (mEH) occur in both rodents and humans. The in vitro kinetic constants were scaled to account for cytosolic (cGST) and microsomal (mEH) protein content and incorporated into PB-PK descriptions for mouse, rat, and human. Flow-limited models adequately predicted blood and tissue EO levels, disposition, and elimination kinetics determined experimentally in rats and mice, with the exception of testis concentrations, which were overestimated. Incorporation of a diffusion-limited description for testis improved the ability of the model to describe testis concentrations. The model accounted for nonlinear increases in blood and tissue concentrations that occur in mice on exposure to EO concentrations greater than 200 ppm. Species differences are predicted in the metabolism and exposure-dose relationship, with a nonlinear relationship observed in the mouse as a result of GSH depletion. These models represent an essential step in developing a mechanistically based EO exposure-dose-response description for estimating human risk from exposure to EO. Copyright 2001 Academic Press.

  9. Gait Correlation Analysis Based Human Identification

    Directory of Open Access Journals (Sweden)

    Jinyan Chen

    2014-01-01

    Full Text Available Human gait identification aims to identify people by a sequence of walking images. Comparing with fingerprint or iris based identification, the most important advantage of gait identification is that it can be done at a distance. In this paper, silhouette correlation analysis based human identification approach is proposed. By background subtracting algorithm, the moving silhouette figure can be extracted from the walking images sequence. Every pixel in the silhouette has three dimensions: horizontal axis (x, vertical axis (y, and temporal axis (t. By moving every pixel in the silhouette image along these three dimensions, we can get a new silhouette. The correlation result between the original silhouette and the new one can be used as the raw feature of human gait. Discrete Fourier transform is used to extract features from this correlation result. Then, these features are normalized to minimize the affection of noise. Primary component analysis method is used to reduce the features’ dimensions. Experiment based on CASIA database shows that this method has an encouraging recognition performance.

  10. Carcinogenicity/tumour promotion by NDL PCB

    Energy Technology Data Exchange (ETDEWEB)

    Schrenk, D. [Kaiserslautern Univ. (Germany). Food Chemistry and Environmental Toxicology

    2004-09-15

    Polychlorinated biphenyls (PCBs) belong to the group of persistent environmental pollutants exhibiting neurotoxic, teratogenic and tumour-promoting effects in experimental animal models. PCB congeners can be divided into 'dioxinlike' and 'non-dioxinlike' congeners on the basis of their ability to act as aryl hydrocarbon receptor (AhR) agonists. Like the most toxic dioxin congener 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) 'dioxinlike' PCBs bind to the AhR and show characteristic effects on the expression of AhR-regulated genes including the induction of cytochrome P450 (CYP) 1A1. On the other hand, 'non-dioxinlike' PCB congeners have a lower or no binding affinity to the AhR, but exhibit a 'phenobarbital-type' induction of CYP 2B1/2 activity. A carcinogenic potential of PCBs has been demonstrated with technical mixtures such as Aroclors or Clophens. In these studies the liver and the thyroid gland were found to be the principal target organs of PCB-mediated carcinogenesis in rodents. No studies have been published, however, on the carcinogenicity of individual congeners. In two-stage initiation-promotion protocols in rats, both technical mixtures and individual 'dioxinlike' and 'non-dioxinlike' congeners were reported to act as liver tumour promoters.

  11. Indian women with higher serum concentrations of folate and vitamin B12 are significantly less likely to be infected with carcinogenic or high-risk (HR types of human papillomaviruses (HPVs

    Directory of Open Access Journals (Sweden)

    Chandrika J Piyathilake

    2010-01-01

    , type of fuel used for cooking and smoking status.Results: Women with higher concentrations of serum folate (>6 ng/mL and vitamin B12 (>356 pg/mL were at lower risk of being positive for HR-HPVs compared to those with serum folate ≤6 ng/mL and serum vitamin B12 ≤ 356 pg/mL (odds ratio = 0.26; 95% confidence interval: 0.08–0.89; P = 0.03.Conclusions: These results demonstrated that improving folate and vitamin B12 status in Indian women may have a beneficial impact on the prevention of CC. Micronutrient based interventions for control of HR-HPV infections may represent feasible alternatives to vaccine based approaches to HPV disease prevention, which are currently unaffordable for use in resource limited areas in rural India.Keywords: folate, vitamin B12, human papillomavirus, cervical cancer

  12. Observer-Based Human Knee Stiffness Estimation.

    Science.gov (United States)

    Misgeld, Berno J E; Luken, Markus; Riener, Robert; Leonhardt, Steffen

    2017-05-01

    We consider the problem of stiffness estimation for the human knee joint during motion in the sagittal plane. The new stiffness estimator uses a nonlinear reduced-order biomechanical model and a body sensor network (BSN). The developed model is based on a two-dimensional knee kinematics approach to calculate the angle-dependent lever arms and the torques of the muscle-tendon-complex. To minimize errors in the knee stiffness estimation procedure that result from model uncertainties, a nonlinear observer is developed. The observer uses the electromyogram (EMG) of involved muscles as input signals and the segmental orientation as the output signal to correct the observer-internal states. Because of dominating model nonlinearities and nonsmoothness of the corresponding nonlinear functions, an unscented Kalman filter is designed to compute and update the observer feedback (Kalman) gain matrix. The observer-based stiffness estimation algorithm is subsequently evaluated in simulations and in a test bench, specifically designed to provide robotic movement support for the human knee joint. In silico and experimental validation underline the good performance of the knee stiffness estimation even in the cases of a knee stiffening due to antagonistic coactivation. We have shown the principle function of an observer-based approach to knee stiffness estimation that employs EMG signals and segmental orientation provided by our own IPANEMA BSN. The presented approach makes realtime, model-based estimation of knee stiffness with minimal instrumentation possible.

  13. Proposed changes in the classification of carcinogenic chemicals in the work area.

    Science.gov (United States)

    Neumann, H G; Thielmann, H W; Filser, J G; Gelbke, H P; Greim, H; Kappus, H; Norpoth, K H; Reuter, U; Vamvakas, S; Wardenbach, P; Wichmann, H E

    1997-12-01

    Carcinogenic chemicals in the work area are currently classified into three categories in Section III of the German List of MAK and BAT Values. This classification is based on qualitative criteria and reflects essentially the weight of evidence available for judging the carcinogenic potential of the chemicals. It is proposed that these Categories--IIIA1, IIIA2, and IIIB--be retained as Categories 1, 2, and 3, to conform with EU regulations. On the basis of our advancing knowledge of reaction mechanisms and the potency of carcinogens, it is now proposed that these three categories be supplemented with two additional categories. The essential feature of substances classified in the new categories is that exposure to these chemicals does not convey a significant risk of cancer to man, provided that an appropriate exposure limit (MAK value) is observed. It is proposed that chemicals known to act typically by nongenotoxic mechanisms and for which information is available that allows evaluation of the effects of low-dose exposures be classified in Category 4. Genotoxic chemicals for which low carcinogenic potency can be expected on the basis of dose-response relationships and toxicokinetics and for which risk at low doses can be assessed will be classified in Category 5. The basis for a better differentiation of carcinogens is discussed, the new categories are defined, and possible criteria for classification are described. Examples for Category 4 (1,4-dioxane) and Category 5 (styrene) are presented. The proposed changes in classifying carcinogenic chemicals in the work area are presented for further discussion.

  14. Neuron-Based Heredity and Human Evolution

    Directory of Open Access Journals (Sweden)

    Don Marshall Gash

    2015-06-01

    Full Text Available Abstract:Abstract: It is widely recognized that human evolution has been driven by two systems of heredity: one DNA-based and the other based on the transmission of behaviorally acquired information via nervous system functions. The genetic system is ancient, going back to the appearance of life on Earth. It is responsible for the evolutionary processes described by Darwin. By comparison, the nervous system is relatively newly minted and in its highest form, responsible for ideation and mind-to-mind transmission of information. Here the informational capabilities and functions of the two systems are compared. While employing quite different mechanisms for encoding, storing and transmission of information, both systems perform these generic hereditary functions. Three additional features of neuron-based heredity in humans are identified: the ability to transfer hereditary information to other members of their population, not just progeny; a selection process for the information being transferred; and a profoundly shorter time span for creation and dissemination of survival-enhancing information in a population. The mechanisms underlying neuron-based heredity involve hippocampal neurogenesis and memory and learning processes modifying and creating new neural assemblages changing brain structure and functions. A fundamental process in rewiring brain circuitry is through increased neural activity (use strengthening and increasing the number of synaptic connections. Decreased activity in circuitry (disuse leads to loss of synapses. Use and disuse modifying an organ to bring about new modes of living, habits and functions are processes are in line with Neolamarckian concepts of evolution (Packard, 1901. Evidence is presented of bipartite evolutionary processes – Darwinian and Neolamarckian – driving human descent from a common ancestor shared with the great apes.

  15. Metal inhibition of human alkylpurine-DNA-N-glycosylase activityin base excision repair

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Ping; Guliaev, Anton B.; Hang, Bo

    2006-02-28

    Cadmium (Cd{sup 2+}), nickel (Ni{sup 2+}) and cobalt (Co{sup 2+}) are human and/or animal carcinogens. Zinc (Zn{sup 2+}) is not categorized as a carcinogen, and rather an essential element to humans. Metals were recently shown to inhibit DNA repair proteins that use metals for their function and/or structure. Here we report that the divalent ions Cd{sup 2+}, Ni{sup 2+}, and Zn{sup 2+} can inhibit the activity of a recombinant human N-methylpurine-DNA glycosylase (MPG) toward a deoxyoligonucleotide with ethenoadenine (var epsilonA). MPG removes a variety of toxic/mutagenic alkylated bases and does not require metal for its catalytic activity or structural integrity. At concentrations starting from 50 to 1000 {micro}M, both Cd{sup 2+} and Zn{sup 2+} showed metal-dependent inhibition of the MPG catalytic activity. Ni{sup 2+} also inhibited MPG, but to a lesser extent. Such an effect can be reversed with EDTA addition. In contrast, Co{sup 2+} and Mg{sup 2+} did not inhibit the MPG activity in the same dose range. Experiments using HeLa cell-free extracts demonstrated similar patterns of inactivation of the var epsilonA excision activity by the same metals. Binding of MPG to the substrate was not significantly affected by Cd{sup 2+}, Zn{sup 2+}, and Ni{sup 2+} at concentrations that show strong inhibition of the catalytic function, suggesting that the reduced catalytic activity is not due to altered MPG binding affinity to the substrate. Molecular dynamics (MD) simulations with Zn{sup 2+} showed that the MPG active site has a potential binding site for Zn{sup 2+}, formed by several catalytically important and conserved residues. Metal binding to such a site is expected to interfere with the catalytic mechanism of this protein. These data suggest that inhibition of MPG activity may contribute to metal genotoxicity and depressed repair of alkylation damage by metals in vivo.

  16. Morpho-chemical characterization and surface properties of carcinogenic zeolite fibers.

    Science.gov (United States)

    Mattioli, Michele; Giordani, Matteo; Dogan, Meral; Cangiotti, Michela; Avella, Giuseppe; Giorgi, Rodorico; Dogan, A Umran; Ottaviani, Maria Francesca

    2016-04-05

    Erionite belonging to the zeolite family is a human health-hazard, since it was demonstrated to be carcinogenic. Conversely, offretite family zeolites were suspected carcinogenic. Mineralogical, morphological, chemical, and surface characterizations were performed on two erionites (GF1, MD8) and one offretite (BV12) fibrous samples and, for comparison, one scolecite (SC1) sample. The specific surface area analysis indicated a larger availability of surface sites for the adsorption onto GF1, while SC1 shows the lowest one and the presence of large pores in the poorly fibrous zeolite aggregates. Selected spin probes revealed a high adsorption capacity of GF1 compared to the other zeolites, but the polar/charged interacting sites were well distributed, intercalated by less polar sites (Si-O-Si). MD8 surface is less homogeneous and the polar/charged sites are more interacting and closer to each other compared to GF1. The interacting ability of BV12 surface is much lower than that found for GF1 and MD8 and the probes are trapped in small pores into the fibrous aggregates. In comparison with the other zeolites, the non-carcinogenic SC1 shows a poor interacting ability and a lower surface polarity. These results helped to clarify the chemical properties and the surface interacting ability of these zeolite fibers which may be related to their carcinogenicity. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Combining QSAR Modeling and Text-Mining Techniques to Link Chemical Structures and Carcinogenic Modes of Action.

    Science.gov (United States)

    Papamokos, George; Silins, Ilona

    2016-01-01

    There is an increasing need for new reliable non-animal based methods to predict and test toxicity of chemicals. Quantitative structure-activity relationship (QSAR), a computer-based method linking chemical structures with biological activities, is used in predictive toxicology. In this study, we tested the approach to combine QSAR data with literature profiles of carcinogenic modes of action automatically generated by a text-mining tool. The aim was to generate data patterns to identify associations between chemical structures and biological mechanisms related to carcinogenesis. Using these two methods, individually and combined, we evaluated 96 rat carcinogens of the hematopoietic system, liver, lung, and skin. We found that skin and lung rat carcinogens were mainly mutagenic, while the group of carcinogens affecting the hematopoietic system and the liver also included a large proportion of non-mutagens. The automatic literature analysis showed that mutagenicity was a frequently reported endpoint in the literature of these carcinogens, however, less common endpoints such as immunosuppression and hormonal receptor-mediated effects were also found in connection with some of the carcinogens, results of potential importance for certain target organs. The combined approach, using QSAR and text-mining techniques, could be useful for identifying more detailed information on biological mechanisms and the relation with chemical structures. The method can be particularly useful in increasing the understanding of structure and activity relationships for non-mutagens.

  18. Combining QSAR Modeling and Text-Mining Techniques to Link Chemical Structures and Carcinogenic Modes of Action

    Science.gov (United States)

    Papamokos, George; Silins, Ilona

    2016-01-01

    There is an increasing need for new reliable non-animal based methods to predict and test toxicity of chemicals. Quantitative structure-activity relationship (QSAR), a computer-based method linking chemical structures with biological activities, is used in predictive toxicology. In this study, we tested the approach to combine QSAR data with literature profiles of carcinogenic modes of action automatically generated by a text-mining tool. The aim was to generate data patterns to identify associations between chemical structures and biological mechanisms related to carcinogenesis. Using these two methods, individually and combined, we evaluated 96 rat carcinogens of the hematopoietic system, liver, lung, and skin. We found that skin and lung rat carcinogens were mainly mutagenic, while the group of carcinogens affecting the hematopoietic system and the liver also included a large proportion of non-mutagens. The automatic literature analysis showed that mutagenicity was a frequently reported endpoint in the literature of these carcinogens, however, less common endpoints such as immunosuppression and hormonal receptor-mediated effects were also found in connection with some of the carcinogens, results of potential importance for certain target organs. The combined approach, using QSAR and text-mining techniques, could be useful for identifying more detailed information on biological mechanisms and the relation with chemical structures. The method can be particularly useful in increasing the understanding of structure and activity relationships for non-mutagens. PMID:27625608

  19. Synthetic risks, risk potency, and carcinogen regulation.

    Science.gov (United States)

    Viscusi, W K; Hakes, J K

    1998-01-01

    This article analyzes a comprehensive sample of over 350 chemicals tested for carcinogenicity to assess the determinants of the probability of regulation. Controlling for differences in the risk potency and noncancer risks, synthetic chemicals have a significantly higher probability of regulation overall: this is due to the greater likelihood of U.S. Food and Drug Administration (FDA) regulation. Measures of risk potency increase the probability of regulation by the U.S. Environmental Protection Agency (EPA), have a somewhat weaker positive effect on regulation by the U.S. Occupational Safety and Health Administration (OSHA), and decrease the likelihood of regulation by the FDA. The overall regulatory pattern is one in which the FDA targets synthetic chemicals and chemicals that pose relatively minor cancer risk. The EPA particularly performed more sensibly than many critics have suggested.

  20. Genotoxicity of Swimming Pool Water and Carcinogenicity of Drinking Water

    Science.gov (United States)

    Among the 11 disinfection by-products (DBPs) in drinking water that are regulated by the U.S. EPA, (a) 2 DBPs (chloroaceticacid and chlorite) are not carcinogenic-in either of2 species; (b) chlorite is not carcinogenic in 3 rodent assays and has never been tested for genotoxicity...

  1. Genotoxicity of Swimming Pool Water and Carcinogenicity of Drinking Water**

    Science.gov (United States)

    Among the 11 disinfection by-products (DBPs) in drinking water that are regulated by the U.S. EPA, (a) 2 DBPs (chloroaceticacid and chlorite) are not carcinogenic-in either of2 species; (b) chlorite is not carcinogenic in 3 rodent assays and has never been tested for genotoxicity...

  2. QSAR ligand dataset for modelling mutagenicity, genotoxicity, and rodent carcinogenicity

    Directory of Open Access Journals (Sweden)

    Davy Guan

    2018-04-01

    Full Text Available Five datasets were constructed from ligand and bioassay result data from the literature. These datasets include bioassay results from the Ames mutagenicity assay, Greenscreen GADD-45a-GFP assay, Syrian Hamster Embryo (SHE assay, and 2 year rat carcinogenicity assay results. These datasets provide information about chemical mutagenicity, genotoxicity and carcinogenicity.

  3. Workshop on problem areas associated with developing carcinogen guidelines

    Energy Technology Data Exchange (ETDEWEB)

    1984-06-01

    A workshop was conducted to discuss problem areas associated with developing carcinogen guidelines. Session topics included (1) definition of a carcinogen for regulatory purposes; (2) potency; (3) risk assessment; (4) uncertainties; (5) de minimis quantity; and (6) legal and regulatory issues. Separate abstracts have been prepared for individual papers. (ACR)

  4. Example-based human motion denoising.

    Science.gov (United States)

    Lou, Hui; Chai, Jinxiang

    2010-01-01

    With the proliferation of motion capture data, interest in removing noise and outliers from motion capture data has increased. In this paper, we introduce an efficient human motion denoising technique for the simultaneous removal of noise and outliers from input human motion data. The key idea of our approach is to learn a series of filter bases from precaptured motion data and use them along with robust statistics techniques to filter noisy motion data. Mathematically, we formulate the motion denoising process in a nonlinear optimization framework. The objective function measures the distance between the noisy input and the filtered motion in addition to how well the filtered motion preserves spatial-temporal patterns embedded in captured human motion data. Optimizing the objective function produces an optimal filtered motion that keeps spatial-temporal patterns in captured motion data. We also extend the algorithm to fill in the missing values in input motion data. We demonstrate the effectiveness of our system by experimenting with both real and simulated motion data. We also show the superior performance of our algorithm by comparing it with three baseline algorithms and to those in state-of-art motion capture data processing software such as Vicon Blade.

  5. Exemplar-based human action pose correction.

    Science.gov (United States)

    Shen, Wei; Deng, Ke; Bai, Xiang; Leyvand, Tommer; Guo, Baining; Tu, Zhuowen

    2014-07-01

    The launch of Xbox Kinect has built a very successful computer vision product and made a big impact on the gaming industry. This sheds lights onto a wide variety of potential applications related to action recognition. The accurate estimation of human poses from the depth image is universally a critical step. However, existing pose estimation systems exhibit failures when facing severe occlusion. In this paper, we propose an exemplar-based method to learn to correct the initially estimated poses. We learn an inhomogeneous systematic bias by leveraging the exemplar information within a specific human action domain. Furthermore, as an extension, we learn a conditional model by incorporation of pose tags to further increase the accuracy of pose correction. In the experiments, significant improvements on both joint-based skeleton correction and tag prediction are observed over the contemporary approaches, including what is delivered by the current Kinect system. Our experiments for the facial landmark correction also illustrate that our algorithm can improve the accuracy of other detection/estimation systems.

  6. Comparative experimental study of cancer induced by ionizing radiations or by chemical carcinogens

    International Nuclear Information System (INIS)

    Lafuma, J.

    1983-01-01

    Animal experiments have contributed to specify a number of parameters used in setting human safety limits for ionizing radiation. In the same way, comparisons have been made between cancers induced in man and in animals in well-defined conditions. In order to use the same experimental data for chemical carcinogens, the mechanisms of carcinogenesis should be the same, i.e. additivity of responses instead of synergy of effects, which requires the development of a new experimental method [fr

  7. Potential for occupational and environmental exposure to ten carcinogens in Toronto

    Energy Technology Data Exchange (ETDEWEB)

    Muller, P. [ToxProbe Inc., Toronto, ON (Canada)

    2002-03-01

    A study was conducted in which several contaminants were assessed for their toxicological properties, potencies and occupational and environmental exposures in the city of Toronto. The contaminants included 1,3-butadiene, asbestos, benzene, cadmium, chromium, dioxins, formaldehyde, polycyclic aromatic hydrocarbons (PAHs), tetrachloroethylene, and trichloroethylene. The International Agency for Research on Cancer, the United States Environmental Protection Agency, and Health Canada have classified 9 of the 10 substances as human carcinogens. Tetrachloroethylene was classified as a probable human carcinogen. It was noted that there is no level of exposure for these chemicals that is without some risk. The information on the levels of selected contaminants in the workplace were obtained from existing literature. The sectors with the highest number of potentially exposed workers to these contaminants include the textiles industry, footwear manufacturing, wood products manufacturing, rubber products manufacturing, non-metallic mineral products manufacturing, fabricated metal products manufacturing, construction, land transport, and household services. The report discussed sources of emissions, routes and pathways of exposures and environmental levels, including outdoor air levels water concentrations, soil concentrations, and food concentrations. The report does not estimate the actual risk to Toronto residents due to environmental exposure to these carcinogens because data are insufficient to conduct such an assessment. However, some previous studies have indicated that exposure from ambient and indoor air has the greatest impact on human health. It is recommended that the city of Toronto remain up to date on the regulatory status of these chemicals. refs., tabs., figs., appendices.

  8. DNA-adducts in fish exposed to alkylating carcinogens

    International Nuclear Information System (INIS)

    Giam, C.S.; Holliday, T.L.; Williams, J.L.; Bahnson, A.; Weller, R.; Hinton, D.E.

    1988-01-01

    There are limited studies on DNA-adduct formation following exposure of fish or fish cells to carcinogens. It will be essential to determine if procarcinogens and carcinogens form the same DNA-adducts in different liver cells and how these compare to those reported in mammalian livers. They are also interested in the influence of different alkylating agents on the type and quantity of DNA-adduct formation and repair in fish. While eggs or small fish are ideal for routine screening, large fish such as trout (Salmo gairdneri) is needed initially for the development of analytical procedures for the isolation, quantitation and identification of various adducts. Trout (Salmo gairdneri) weighing approximately 250 grams were acclimatized at 13 degree C before being given i.p. injection of diethylnitrosoamine (DEN). The exposure period varied, though most animals were sacrificed after 24 hours. Their livers were excised and DNA was isolated mainly according the procedure of Croy et al. The neutral thermal hydrolysate and the acid hydrolysate were analyzed by HPLC-Fluorescent detector for 7-ethylguanine and O 6 -ethylguanine, respectively. O 6 -ethylguanine was detected, 7-ethylguanine was not detected. Attempts are being made to improve the detection of the latter compound. Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) was used to establish nanogram quantities of the ethylated bases. Laser desorption FT-IC-MS is particularly useful for characterizing thermally-labile and involatile nucleosides or nucleotides. Excretion of DEN was rapid and high. Exposure of trout (and other fish) to various ethylating agents will be discussed

  9. Unlocking the transcriptomes of two carcinogenic parasites, Clonorchis sinensis and Opisthorchis viverrini.

    Directory of Open Access Journals (Sweden)

    Neil D Young

    Full Text Available The two parasitic trematodes, Clonorchis sinensis and Opisthorchis viverrini, have a major impact on the health of tens of millions of humans throughout Asia. The greatest impact is through the malignant cancer ( = cholangiocarcinoma that these parasites induce in chronically infected people. Therefore, both C. sinensis and O. viverrini have been classified by the World Health Organization (WHO as Group 1 carcinogens. Despite their impact, little is known about these parasites and their interplay with the host at the molecular level. Recent advances in genomics and bioinformatics provide unique opportunities to gain improved insights into the biology of parasites as well as their relationships with their hosts at the molecular level. The present study elucidates the transcriptomes of C. sinensis and O. viverrini using a platform based on next-generation (high throughput sequencing and advanced in silico analyses. From 500,000 sequences, >50,000 sequences were assembled for each species and categorized as biologically relevant based on homology searches, gene ontology and/or pathway mapping. The results of the present study could assist in defining molecules that are essential for the development, reproduction and survival of liver flukes and/or that are linked to the development of cholangiocarcinoma. This study also lays a foundation for future genomic and proteomic research of C. sinensis and O. viverrini and the cancers that they are known to induce, as well as novel intervention strategies.

  10. COMPARATIVE GENOTOXIC RESPONSES TO ARSENITE IN GUINEA PIG, MOUSE, RAT AND HUMAN LYMPHOCYTES

    Science.gov (United States)

    Comparative genotoxic responses to arsenite in guinea pig, mouse, rat and human lymphocytes.Inorganic arsenic is a known human carcinogen causing skin, lung, and bladder cancer following chronic exposures. Yet, long-term laboratory animal carcinogenicity studies have ...

  11. Human physiologically based pharmacokinetic model for propofol

    Directory of Open Access Journals (Sweden)

    Schnider Thomas W

    2005-04-01

    Full Text Available Abstract Background Propofol is widely used for both short-term anesthesia and long-term sedation. It has unusual pharmacokinetics because of its high lipid solubility. The standard approach to describing the pharmacokinetics is by a multi-compartmental model. This paper presents the first detailed human physiologically based pharmacokinetic (PBPK model for propofol. Methods PKQuest, a freely distributed software routine http://www.pkquest.com, was used for all the calculations. The "standard human" PBPK parameters developed in previous applications is used. It is assumed that the blood and tissue binding is determined by simple partition into the tissue lipid, which is characterized by two previously determined set of parameters: 1 the value of the propofol oil/water partition coefficient; 2 the lipid fraction in the blood and tissues. The model was fit to the individual experimental data of Schnider et. al., Anesthesiology, 1998; 88:1170 in which an initial bolus dose was followed 60 minutes later by a one hour constant infusion. Results The PBPK model provides a good description of the experimental data over a large range of input dosage, subject age and fat fraction. Only one adjustable parameter (the liver clearance is required to describe the constant infusion phase for each individual subject. In order to fit the bolus injection phase, for 10 or the 24 subjects it was necessary to assume that a fraction of the bolus dose was sequestered and then slowly released from the lungs (characterized by two additional parameters. The average weighted residual error (WRE of the PBPK model fit to the both the bolus and infusion phases was 15%; similar to the WRE for just the constant infusion phase obtained by Schnider et. al. using a 6-parameter NONMEM compartmental model. Conclusion A PBPK model using standard human parameters and a simple description of tissue binding provides a good description of human propofol kinetics. The major advantage of a

  12. Base pair mismatches and carcinogen-modified bases in DNA: an NMR study of G x T and G x O4meT pairing in dodecanucleotide duplexes

    International Nuclear Information System (INIS)

    Kalnik, M.W.; Kouchakdjian, M.; Li, B.F.L.; Swann, P.F.; Patel, D.J.

    1988-01-01

    High-resolution two-dimensional NMR studies have been completed on the self-complementary d(C-G-C-G-A-G-C-T-T-G-C-G) duplex (designated G x T 12-mer) and the self-complementary d(C-G-C-G-A-G-C-T-O 4 meT-G-C-G) duplex (designated G x O 4 meT 12-mer) containing G x T and G x O 4 meT pairs at identical positions four base pairs in from either end of the duplex. The exchangeable and nonexchangeable proton resonances have been assigned from an analysis of two-dimensional nuclear Overhauser enhancement (NOESY) spectra for the G x T 12-mer and G x O 4 meT 12-mer duplexes in H 2 O and D 2 O solution. The guanosine and thymidine imino protons in the G x T mismatch resonate at 10.57 and 11.98 ppm, respectively, and exhibit a strong NOE between themselves and to imino protons of flanking base pairs in the G x T 12-mer duplex. The large upfield chemical shift of this proton relative to that of the imino proton resonance of G in the G x T mismatch or in G x C base pairs indicates that hydrogen bonding to O 4 meT is either very weak or absent. This guanosine imino proton has an NOE to the OCH 3 group of O 4 meT across the pair and NOEs to the imino protons of flanking base pairs. Taken together with data from the NMR of nonexchangeable protons, this shows that both G and O 4 meT have anti-glycosidic torsion angles and are stacked into the duplex. Comparison of the intensity of the NOEs between the guanosine imino proton and the OCH 3 of O 4 meT as well as other protons in its vicinity demonstrates that the OCH 3 group of O 4 meT adopts the syn orientation with respect to N3 of the methylated thymidine. The authors propose an alternate base pairing mode stabilized by one short hydrogen bond between the 2-amino group of guanosine and the 2-carbonyl group of O 4 met

  13. Environmental carcinogens and prophylaxis of malignant tumors

    Energy Technology Data Exchange (ETDEWEB)

    Shabad, L M

    1977-01-01

    A short history of a relatively new branch of cancer research, hygienic oncology, is reviewed. Occupational skin tumors (papillomas and even squamous-cell carcinoma) are described not only among chimney-sweepers, but also among the workers of petroleum refineries. Of 512 workers who had prolonged exposure to various petroleum products, 53.2% developed skin carcinoma. Occupational malignant tumors of the respiratory tract are observed among the workers of nickel industries. Workers who experienced prolonged exposure to asbestos had an increased incidence of lung and stomach cancer. To prevent occuptional cancer of the urinary bladder, such carcinogens as 2-napthylamine, 3,3-dichlorobenzidine, 3,3-dioxybenzidine, and para-amino-azobenzene were banned. Environmental pollution with the products of incomplete fuel combustion, especially with polycyclic aromatic carbohydrates constitutes a hazard to the urban population. The level of benzopyrene (BP) in soil samples taken in different localities averaged 5 microg/kg. Legislatively approved permissible concentrations of BP in the air are 0.1 microg/100 cubic meters, and in the water 0.005 microg/liter. 23 references.

  14. [HUMAN RESOURCES MANAGEMENT BASED ON COMPETENCIES].

    Science.gov (United States)

    Larumbe Andueza, Ma Carmen; De Mendoza Cánton, Juana Hermoso

    2016-05-01

    We are living in a time with a lot of changes in which health organizations have more challenges to face. One of them is to recognize, strengthen, develop and retain the talent they have. Competency-based human resources management is emerging as a tool that contributes to achieve that aim. Competencies from the generic or characteristic perspective: personality traits, values and motivations, which are deeply rooted in the person. Through elaborating a competencies map for the organization, and identifying the job competencies profile, above all in key jobs, the employees know what it is going to expect from them. After, detect and cover the learning needs, it is possible to achieve better adjust between worker-job. The nursing unit manager is a key job because it is a link between management team and nursing team. The way that it is performed, it will have impact on the quality of care and its team motivation. So, the most adequate person who covers this job would have a part of knowledge, skills, attitudes and compatible interests with her job. Competency-based management helps identify both the potential and learning needs to performing this job.

  15. CAPTCHA Based on Human Cognitive Factor

    OpenAIRE

    Chowdhury, Mohammad Jabed Morshed; Chakraborty, Narayan Ranjan

    2013-01-01

    A CAPTCHA (Completely Automated Public Turing test to tell Computers and Humans Apart) is an automatic security mechanism used to determine whether the user is a human or a malicious computer program. It is a program that generates and grades tests that are human solvable, but intends to be beyond the capabilities of current computer programs. CAPTCHA should be designed to be very easy for humans but very hard for machines. Unfortunately, the existing CAPTCHA systems while trying to maximize ...

  16. Carcinogenicity of individual and a mixture of dioxin-like compounds in female Harlan Sprague Dawley rats

    Energy Technology Data Exchange (ETDEWEB)

    Walker, N.; Nyska, A. [National Institute of Environmental Health Sciences, Research Triangle Park, NC (United States); Crockett, P. [Constella Group, Research Triangle Park, NC (US)] (and others)

    2004-09-15

    The human health risk posed by exposure to persistent organochlorine pollutants (POPs), including polychlorinated-dioxins (PCDDs), -furans (PCDFs) and - biphenyls (PCBs), present in the food and the environment is one of widespread concern throughout the industrialized world. The dioxin Toxic Equivalency Factor (TEF) approach is currently the most feasible interim approach for assessing and managing the risk posed by exposure to mixtures of these compounds and has been formally adopted by regulatory bodies in many countries, the International Programme on Chemical Safety and the World Health Organization. The TEF methodology is a relative potency scheme that estimates the total exposure and biological effects of a mixture of chemicals based on a common mechanism of action involving an initial binding of the compound to the Aryl hydrocarbon receptor (AhR). An implicit assumption of the TEF methodology is that the combined risk of effects of the different congeners is dose additive. Therefore, the total dioxin toxic equivalents (TEQs) of a mixture of PCDDs, PCDFs, and PCBs may be estimated by the summation of the mass of each compound in the mixture after adjustment for its potency relative to that of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). While dose additivity is supported for certain mixtures for some biological endpoints in some experimental models, this has never been evaluated for cancer risk. Here we present a summary of four chronic rodent bioassay conducted by the National Toxicology Program (US Department of Health and Human Services) that evaluated the carcinogenicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 3.3',4,4',5- pentachlorobiphenyl (PCB126) and 2,3,4,7,8 pentachlorodibenzofuran (PeCDF) and a mixture of these three dioxin-like compounds in female Harlan Sprague Dawley rats. Data from these studies will be used to test the hypothesis of dose-additivity of carcinogenicity by a defined mixture of dioxin-like compounds.

  17. Assessment of predictivity of volatile organic compounds carcinogenicity and mutagenicity by freeware in silico models.

    Science.gov (United States)

    Guerra, Lília Ribeiro; de Souza, Alessandra Mendonça Teles; Côrtes, Juliana Alves; Lione, Viviane de Oliveira Freitas; Castro, Helena Carla; Alves, Gutemberg Gomes

    2017-12-01

    The application of in silico methods is increasing on toxicological risk prediction for human and environmental health. This work aimed to evaluate the performance of three in silico freeware models (OSIRIS v.2.0, LAZAR, and Toxtree) on the prediction of carcinogenicity and mutagenicity of thirty-eight volatile organic compounds (VOC) related to chemical risk assessment for occupational exposure. Theoretical data were compared with assessments available in international databases. Confusion matrices and ROC curves were used to evaluate the sensitivity, specificity, and accuracy of each model. All three models (OSIRIS, LAZAR and Toxtree) were able to identify VOC with a potential carcinogenicity or mutagenicity risk for humans, however presenting differences concerning the specificity, sensitivity, and accuracy. The best predictive performances were found for OSIRIS and LAZAR for carcinogenicity and OSIRIS for mutagenicity, as these softwares presented a combination of negative predictive power and lower risk of false positives (high specificity) for those endpoints. The heterogeneity of results found with different softwares reinforce the importance of using a combination of in silico models to occupational toxicological risk assessment. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. CarcinoPred-EL: Novel models for predicting the carcinogenicity of chemicals using molecular fingerprints and ensemble learning methods.

    Science.gov (United States)

    Zhang, Li; Ai, Haixin; Chen, Wen; Yin, Zimo; Hu, Huan; Zhu, Junfeng; Zhao, Jian; Zhao, Qi; Liu, Hongsheng

    2017-05-18

    Carcinogenicity refers to a highly toxic end point of certain chemicals, and has become an important issue in the drug development process. In this study, three novel ensemble classification models, namely Ensemble SVM, Ensemble RF, and Ensemble XGBoost, were developed to predict carcinogenicity of chemicals using seven types of molecular fingerprints and three machine learning methods based on a dataset containing 1003 diverse compounds with rat carcinogenicity. Among these three models, Ensemble XGBoost is found to be the best, giving an average accuracy of 70.1 ± 2.9%, sensitivity of 67.0 ± 5.0%, and specificity of 73.1 ± 4.4% in five-fold cross-validation and an accuracy of 70.0%, sensitivity of 65.2%, and specificity of 76.5% in external validation. In comparison with some recent methods, the ensemble models outperform some machine learning-based approaches and yield equal accuracy and higher specificity but lower sensitivity than rule-based expert systems. It is also found that the ensemble models could be further improved if more data were available. As an application, the ensemble models are employed to discover potential carcinogens in the DrugBank database. The results indicate that the proposed models are helpful in predicting the carcinogenicity of chemicals. A web server called CarcinoPred-EL has been built for these models ( http://ccsipb.lnu.edu.cn/toxicity/CarcinoPred-EL/ ).

  19. Transplacental exposure to environmental carcinogens: Association with childhood cancer risks and the role of modulating factors.

    Science.gov (United States)

    Fucic, A; Guszak, V; Mantovani, A

    2017-09-01

    Biological responses to carcinogens from environmental exposure during adulthood are modulated over years or decades. Conversely, during transplacental exposure, the effects on the human foetus change within weeks, intertwining with developmental mechanisms: even short periods of transplacental exposure may be imprinted in the organism for a lifetime. The pathways leading to childhood and juvenile cancers, such as leukaemias, neuroblastoma/brain tumours, hepatoblastoma, and Willm's tumour involve prenatally-induced genomic, epigenomic and/or non-genomic effects caused by xenobiotics. Pregnant women most often live in complex environmental settings that cause transplacental exposure of the foetus to xenobiotic mixtures. Mother-child biomonitoring should integrate the analysis of chemicals/radiation present in the living and workplace environment with relevant risk modulators related to life style. The interdisciplinary approach for transplacental cancer risk assessment in high-pressure areas should be based on an integrated model for mother-child exposure estimation via profiling the exposure level by water quality analysis, usage of emission grids, and land use maps. Copyright © 2017. Published by Elsevier Inc.

  20. Game Design Principles based on Human Error

    Directory of Open Access Journals (Sweden)

    Guilherme Zaffari

    2016-03-01

    Full Text Available This paper displays the result of the authors’ research regarding to the incorporation of Human Error, through design principles, to video game design. In a general way, designers must consider Human Error factors throughout video game interface development; however, when related to its core design, adaptations are in need, since challenge is an important factor for fun and under the perspective of Human Error, challenge can be considered as a flaw in the system. The research utilized Human Error classifications, data triangulation via predictive human error analysis, and the expanded flow theory to allow the design of a set of principles in order to match the design of playful challenges with the principles of Human Error. From the results, it was possible to conclude that the application of Human Error in game design has a positive effect on player experience, allowing it to interact only with errors associated with the intended aesthetics of the game.

  1. Factors affecting the prevalence of strongly and weakly carcinogenic and lower-risk human papillomaviruses in anal specimens in a cohort of men who have sex with men (MSM.

    Directory of Open Access Journals (Sweden)

    Dorothy J Wiley

    Full Text Available MSM are at higher risk for invasive anal cancer. Twelve human papillomaviruses (HPVs cause cervical cancer in women (Group 1 high-risk HPVs (hrHPVs and 13 HPVs are probable/possible causes (Group 2 hrHPVs of cervical malignancy. HPVs rarely associated with malignancy are classified as lower-risk HPVs (lrHPVs.Dacron-swab anal-cytology specimens were collected from and data complete for 97% (1262/1296 of Multicenter AIDS Cohort Study (MACS men tested for HPVs using the Linear Array assay. Multivariate Poisson regression analyses estimated adjusted prevalence ratios for Group 1/2 hrHPVs and lrHPVs, controlling for the effects of age, race, ethnicity, sexual partnerships, smoking; HIV-infection characteristics, treatment, and immune status among HIV-infected men.HIV-infected men showed 35-90% higher prevalence of Group 1/2 hrHPVs and lrHPVs than HIV-uninfected men, and higher prevalence of multi-Type, and multiple risk-group infections. CD4+ T-cell count was inversely associated with HPV Group 2 prevalence (p<0.0001. The number of receptive anal intercourse (RAI partners reported in the 24 months preceding HPV testing predicted higher prevalence of Group 1/2 hrHPVs. Men reporting ≥30 lifetime male sex partners before their first MACS visit and men reporting ≥1 RAI partners during the 24 months before HPV testing showed 17-24% and 13-17% higher prevalence of lrHPVs (p-values ≤0.05. Men reporting smoking between MACS visit 1 and 24 months before HPV testing showed 1.2-fold higher prevalence of Group 2 hrHPVs (p = 0.03. Both complete adherence to CART (p = 0.02 and HIV load <50 copies/mL (p = 0.04 were protective for Group 1 hrHPVs among HIV-infected men.HIV-infected men more often show multi-type and multi-group HPV infections HIV-uninfected men. Long-term mutual monogamy and smoking cessation, generally, and CART-adherence that promotes (HIV viremia control and prevents immunosuppression, specifically among HIV-infected MSM, are

  2. Carcinogenicity tests of certain environmental and industrial chemicals

    International Nuclear Information System (INIS)

    Weisburger, E.K.; Ulland, B.M.; Nam, J.; Gart, J.J.; Weisburger, J.H.

    1981-01-01

    Fourteen chemicals of varied uses were tested for carcinogenicity by oral administration in male and female Charles River CD rats. Under the conditions of the tests, propane sultone, propylene imine, and ethylenethiourea, in addition to the positive control N-2-fluorenylacetamide, were carcinogenic. Avadex, bis(2-chloroethyl) ether, the potassium salt of bis(2-hydroxyethyl) dithiocarbamic acid, ethylene carbonate, and semicarbazide hydrochloride were not carcinogenic under the test conditions. Dithiooxamide, glycerol alpha-monochlorohydrin, and thiosemicarbazide gave somewhat ambiguous results, though administered at high enough dose levels to be toxic. An inadequate number of animals survived treatments with sodium azide, sodium bisulfide, and vinylene carbonate, or the animals may not have received sufficiently high doses of the test chemicals to provide maximum test sensitivity. However, there were no indications that these three chemicals were carcinogenic under the test conditions

  3. Advances in Carcinogenic Metal Toxicity and Potential Molecular Markers

    Directory of Open Access Journals (Sweden)

    Preeyaporn Koedrith

    2011-12-01

    Full Text Available Metal compounds such as arsenic, cadmium, chromium, cobalt, lead, mercury, and nickel are classified as carcinogens affecting human health through occupational and environmental exposure. However, the underlying mechanisms involved in tumor formation are not well clarified. Interference of metal homeostasis may result in oxidative stress which represents an imbalance between production of free radicals and the system’s ability to readily detoxify reactive intermediates. This event consequently causes DNA damage, lipid peroxidation, protein modification, and possibly symptomatic effects for various diseases including cancer. This review discusses predominant modes of action and numerous molecular markers. Attention is paid to metal-induced generation of free radicals, the phenomenon of oxidative stress, damage to DNA, lipid, and proteins, responsive signal transduction pathways with major roles in cell growth and development, and roles of antioxidant enzymatic and DNA repair systems. Interaction of non-enzymatic antioxidants (carotenoids, flavonoids, glutathione, selenium, vitamin C, vitamin E, and others with cellular oxidative stress markers (catalase, glutathione peroxidase, and superoxide dismutase as well as certain regulatory factors, including AP-1, NF-κB, Ref-1, and p53 is also reviewed. Dysregulation of protective pathways, including cellular antioxidant network against free radicals as well as DNA repair deficiency is related to oncogenic stimulation. These observations provide evidence that emerging oxidative stress-responsive regulatory factors and DNA repair proteins are putative predictive factors for tumor initiation and progression.

  4. Relative potency estimation for synthetic petroleum skin carcinogens.

    OpenAIRE

    Holland, J M; Wolf, D A; Clark, B R

    1981-01-01

    A procedure for quantitative analysis of skin carcinogenesis data, for the purpose of establishing carcinogenic potency, has been applied to observations obtained from C3H mice exposed continuously to synthetic and natural petroleums. The importance of total polynuclear aromatic (PNA) content to the skin carcinogenic activity of the crude materials was also examined. Of three synthetic petroleums evaluated, all were shown capable of inducing skin neoplasms within a two-year exposure period. U...

  5. Carcinogenic and mutagenic properties of chemicals in drinking water

    Energy Technology Data Exchange (ETDEWEB)

    Bull, R J

    1985-12-01

    Isolated cases of careless handling of industrial and domestic waste has lead to a wide variety of dangerous chemicals being inadvertently introduced into drinking water. However, chemicals with established carcinogenic and mutagenic properties that occur with a high frequency and in multiple locations are limited in number. To date, the chief offenders have been chemicals of relatively low carcinogenic potency. Some of the more common chemicals are formed as by-products of disinfection. The latter process is generally regarded as essential to the production of a ''microbiologically safe'' drinking water. Consequently, any reductions in what may be a relatively small carcinogenic risk must be balanced against a potential for a higher frequency of waterborne infectious disease. The results of recent toxicological investigations will be reviewed to place the potential carcinogenic and mutagenic hazards frequently associated with drinking water into perspective. First, evidence for the carcinogenicity of certain volatile organic compounds such as trichloroethylene, tetrachloroethylene and carbon tetrachloride is considered. Second, the carcinogenic activity that can be ascribed to various by-products of chlorination is reviewed in some detail. Finally, recent evidence that other chemicals derived from the treatment and distribution of drinking water is highlighted as an area requiring move systematic attention. 72 references.

  6. Carcinogen inducibility in vivo and down-regulation of DMBT1 during breast carcinogenesis

    DEFF Research Database (Denmark)

    Mollenhauer, Jan; Helmke, Burkhard; Medina, Daniel

    2004-01-01

    unambiguous inactivating DMBT1 mutations in breast cancer. Expression analyses in the human and mouse mammary glands pointed to the necessity of DMBT1 induction. While age-dependent and hormonal effects could be ruled out, 9 of 10 mice showed induction of Dmbt1 expression after administration...... of the carcinogen 7,12-dimethybenz(alpha)anthracene prior to the onset of tumorigenesis or other histopathological changes. DMBT1 displayed significant up-regulation in human tumor-flanking tissues compared to in normal breast tissues (P displayed a switch from lumenal...

  7. Probe for the mutagenic activity of the carcinogen 4-aminobiphenyl: synthesis and characterization of an M13mp10 genome containing the major carcinogen-DNA adduct at a unique site

    International Nuclear Information System (INIS)

    Lasko, D.D.; Basu, A.K.; Kadlubar, F.F.; Evans, F.E.; Lay, J.O. Jr.; Essigmann, J.M.

    1987-01-01

    The duplex genome of Escherichia coli virus M13mp10 was modified at a unique site to contain N-(deoxyguanosin-8-yl)-4-aminobiphenyl (dG/sup 8-ABP/), the major carcinogen-DNA adduct of the human bladder carcinogen 4-aminobiphenyl. A tetradeoxynucleotide containing a single dG/sup 8-ABP/ residue was synthesized by reacting 5'-d(TpGpCpA)-3' with N-acetoxy-N-(trifluoroacetyl)-4-aminobiphenyl, followed by high-performance liquid chromatography purification of the principal reaction product 5'-d(TpG/sup 8-ABP/pCpA)-3' (yield 15-30%). Characterization by fast atom bombardment mass spectrometry confirmed the structure as an intact 4-aminobiphenyl-modified tetranucleotide, while 1 H nuclear magnetic resonance spectroscopy established the site of substitution and the existence of ring stacking between the carcinogen residue and DNA bases. Experiments in which the tetranucleotides were 5' end labeled with [ 32 P]phosphate revealed the following: 1)the adducted oligomer, when incubated in a 1000-fold molar excess in the presence of T4 DNA ligase and ATP, was found to be incorporated into the gapped DNA molecules with an efficiency of approximately 30%, as compared to the unadducted d(pTpGpCpA), which was incorporated with 60% ligation efficiency; 2)radioactivity from the 5' end of each tetranucleotide was physically mapped to a restriction fragment that contained the PstI site and represented 0.2% of the genome; 3) the presence of the lesion within the PstI recognition site inhibited the ability of PstI to cleave the genome at this site; 4)in genomes in which ligation occurred, T4 DNA ligase was capable of covalently joining both modified and unmodified tetranucleotides to the gapped structures on both the 5' and the 3' ends with at least 90% efficiency. On the basis of these and other data, the dG/sup 8-ABP/-modified genome was judged to be a useful probe for investigation of site-specific mutagenesis in E. coli

  8. Coal-tar-based pavement sealcoat and PAHs: implications for the environment, human health, and stormwater management.

    Science.gov (United States)

    Mahler, Barbara J; Metre, Peter C Van; Crane, Judy L; Watts, Alison W; Scoggins, Mateo; Williams, E Spencer

    2012-03-20

    Coal-tar-based sealcoat products, widely used in the central and eastern U.S. on parking lots, driveways, and even playgrounds, are typically 20-35% coal-tar pitch, a known human carcinogen that contains about 200 polycyclic aromatic hydrocarbon (PAH) compounds. Research continues to identify environmental compartments-including stormwater runoff, lake sediment, soil, house dust, and most recently, air-contaminated by PAHs from coal-tar-based sealcoat and to demonstrate potential risks to biological communities and human health. In many cases, the levels of contamination associated with sealed pavement are striking relative to levels near unsealed pavement: PAH concentrations in air over pavement with freshly applied coal-tar-based sealcoat, for example, were hundreds to thousands of times higher than those in air over unsealed pavement. Even a small amount of sealcoated pavement can be the dominant source of PAHs to sediment in stormwater-retention ponds; proper disposal of such PAH-contaminated sediment can be extremely costly. Several local governments, the District of Columbia, and the State of Washington have banned use of these products, and several national and regional hardware and home-improvement retailers have voluntarily ceased selling them.

  9. Coal-tar-based pavement sealcoat and PAHs: implications for the environment, human health, and stormwater management

    Science.gov (United States)

    Mahler, Barbara J.; Van Metre, Peter C.; Crane, Judy L.; Watts, Alison W.; Scoggins, Mateo; Williams, E. Spencer

    2012-01-01

    Coal-tar-based sealcoat products, widely used in the central and eastern U.S. on parking lots, driveways, and even playgrounds, are typically 20-35% coal-tar pitch, a known human carcinogen that contains about 200 polycyclic aromatic hydrocarbon (PAH) compounds. Research continues to identify environmental compartments—including stormwater runoff, lake sediment, soil, house dust, and most recently, air—contaminated by PAHs from coal-tar-based sealcoat and to demonstrate potential risks to biological communities and human health. In many cases, the levels of contamination associated with sealed pavement are striking relative to levels near unsealed pavement: PAH concentrations in air over pavement with freshly applied coal-tar-based sealcoat, for example, were hundreds to thousands of times higher than those in air over unsealed pavement. Even a small amount of sealcoated pavement can be the dominant source of PAHs to sediment in stormwater-retention ponds; proper disposal of such PAH-contaminated sediment can be extremely costly. Several local governments, the District of Columbia, and the State of Washington have banned use of these products, and several national and regional hardware and home-improvement retailers have voluntarily ceased selling them.

  10. Toxicity and carcinogenicity of acidogenic or alkalogenic diets in rats; effects of feeding NH4Cl, KHCO3 or KCl

    NARCIS (Netherlands)

    Lina, B.A.R.; Kuijpers, M.H.M.

    2004-01-01

    The effects of diet-induced acid-base disturbances were examined in 4-week, 13-week and 18-month toxicity studies, and in a 30-month carcinogenicity study. Rats were fed a natural ingredient diet (controls), supplemented with 2% or 4% KHCO3 (base-forming diets), or with 1% or 2.1% NH4Cl

  11. Emotion based human-robot interaction

    Directory of Open Access Journals (Sweden)

    Berns Karsten

    2018-01-01

    Full Text Available Human-machine interaction is a major challenge in the development of complex humanoid robots. In addition to verbal communication the use of non-verbal cues such as hand, arm and body gestures or mimics can improve the understanding of the intention of the robot. On the other hand, by perceiving such mechanisms of a human in a typical interaction scenario the humanoid robot can adapt its interaction skills in a better way. In this work, the perception system of two social robots, ROMAN and ROBIN of the RRLAB of the TU Kaiserslautern, is presented in the range of human-robot interaction.

  12. Pesticides and public health: an analysis of the regulatory approach to assessing the carcinogenicity of glyphosate in the European Union.

    Science.gov (United States)

    Clausing, Peter; Robinson, Claire; Burtscher-Schaden, Helmut

    2018-03-13

    The present paper scrutinises the European authorities' assessment of the carcinogenic hazard posed by glyphosate based on Regulation (EC) 1272/2008. We use the authorities' own criteria as a benchmark to analyse their weight of evidence (WoE) approach. Therefore, our analysis goes beyond the comparison of the assessments made by the European Food Safety Authority and the International Agency for Research on Cancer published by others. We show that not classifying glyphosate as a carcinogen by the European authorities, including the European Chemicals Agency, appears to be not consistent with, and in some instances, a direct violation of the applicable guidance and guideline documents. In particular, we criticise an arbitrary attenuation by the authorities of the power of statistical analyses; their disregard of existing dose-response relationships; their unjustified claim that the doses used in the mouse carcinogenicity studies were too high and their contention that the carcinogenic effects were not reproducible by focusing on quantitative and neglecting qualitative reproducibility. Further aspects incorrectly used were historical control data, multisite responses and progression of lesions to malignancy. Contrary to the authorities' evaluations, proper application of statistical methods and WoE criteria inevitably leads to the conclusion that glyphosate is 'probably carcinogenic' (corresponding to category 1B in the European Union). © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  13. A mode-of-action approach for the identification of genotoxic carcinogens.

    Directory of Open Access Journals (Sweden)

    Lya G Hernández

    Full Text Available Distinguishing between clastogens and aneugens is vital in cancer risk assessment because the default assumption is that clastogens and aneugens have linear and non-linear dose-response curves, respectively. Any observed non-linearity must be supported by mode of action (MOA analyses where biological mechanisms are linked with dose-response evaluations. For aneugens, the MOA has been well characterised as disruptors of mitotic machinery where chromosome loss via micronuclei (MN formation is an accepted endpoint used in risk assessment. In this study we performed the cytokinesis-block micronucleus assay and immunofluorescence mitotic machinery visualisation in human lymphoblastoid (AHH-1 and Chinese Hamster fibroblast (V79 cell lines after treatment with the aneugen 17-β-oestradiol (E₂. Results were compared to previously published data on bisphenol-A (BPA and Rotenone data. Two concentration-response approaches (the threshold-[Td] and benchmark-dose [BMD] approaches were applied to derive a point of departure (POD for in vitro MN induction. BMDs were also derived from the most sensitive carcinogenic endpoint. Ranking comparisons of the PODs from the in vitro MN and the carcinogenicity studies demonstrated a link between these two endpoints for BPA, E₂ and Rotenone. This analysis was extended to include 5 additional aneugens, 5 clastogens and 3 mutagens and further concentration and dose-response correlations were observed between PODs from the in vitro MN and carcinogenicity. This approach is promising and may be further extended to other genotoxic carcinogens, where MOA and quantitative information from the in vitro MN studies could be used in a quantitative manner to further inform cancer risk assessment.

  14. Smartphone-based human activity recognition

    OpenAIRE

    Reyes Ortiz, Jorge Luis

    2014-01-01

    Cotutela Universitat Politècnica de Catalunya i Università degli Studi di Genova Human Activity Recognition (HAR) is a multidisciplinary research field that aims to gather data regarding people's behavior and their interaction with the environment in order to deliver valuable context-aware information. It has nowadays contributed to develop human-centered areas of study such as Ambient Intelligence and Ambient Assisted Living, which concentrate on the improvement of people's Quality of Lif...

  15. Prediction of thyroid C-cell carcinogenicity after chronic administration of GLP1-R agonists in rodents

    Energy Technology Data Exchange (ETDEWEB)

    Brink, Willem van den; Emerenciana, Annette [Systems Pharmacology, Division of Pharmacology, Leiden Academic Centre for Drug Research, Leiden University, Leiden (Netherlands); Medicines Evaluation Board, Utrecht (Netherlands); Bellanti, Francesco [Systems Pharmacology, Division of Pharmacology, Leiden Academic Centre for Drug Research, Leiden University, Leiden (Netherlands); Della Pasqua, Oscar [Systems Pharmacology, Division of Pharmacology, Leiden Academic Centre for Drug Research, Leiden University, Leiden (Netherlands); Clinical Pharmacology Modelling & Simulation, GlaxoSmithKline, Stockley Park, Uxbridge (United Kingdom); Clinical Pharmacology & Therapeutics, UCL, School of Life and Medical Sciences, London (United Kingdom); Laan, Jan Willem van der, E-mail: jw.vd.laan@cbg-meb.nl [Division of Toxicology, Leiden Academic Centre for Drug Research, Leiden University, Leiden (Netherlands); Medicines Evaluation Board, Utrecht (Netherlands)

    2017-04-01

    Increased incidence of C-cell carcinogenicity has been observed for glucagon-like-protein-1 receptor (GLP-1r) agonists in rodents. It is suggested that the duration of exposure is an indicator of carcinogenic potential in rodents of the different products on the market. Furthermore, the role of GLP-1-related mechanisms in the induction of C-cell carcinogenicity has gained increased attention by regulatory agencies. This study proposes an integrative pharmacokinetic/pharmacodynamic (PKPD) framework to identify explanatory factors and characterize differences in carcinogenic potential of the GLP-1r agonist products. PK models for four products (exenatide QW (once weekly), exenatide BID (twice daily), liraglutide and lixisenatide) were developed using nonlinear mixed effects modelling. Predicted exposure was subsequently linked to GLP-1r stimulation using in vitro GLP-1r potency data. A logistic regression model was then applied to exenatide QW and liraglutide data to assess the relationship between GLP-1r stimulation and thyroid C-cell hyperplasia incidence as pre-neoplastic predictor of a carcinogenic response. The model showed a significant association between predicted GLP-1r stimulation and C-cell hyperplasia after 2 years of treatment. The predictive performance of the model was evaluated using lixisenatide, for which hyperplasia data were accurately described during the validation step. The use of a model-based approach provided insight into the relationship between C-cell hyperplasia and GLP-1r stimulation for all four products, which is not possible with traditional data analysis methods. It can be concluded that both pharmacokinetics (exposure) and pharmacodynamics (potency for GLP-1r) factors determine C-cell hyperplasia incidence in rodents. Our work highlights the pharmacological basis for GLP-1r agonist-induced C-cell carcinogenicity. The concept is promising for application to other drug classes. - Highlights: • An integrative PKPD model is applied to

  16. Prediction of thyroid C-cell carcinogenicity after chronic administration of GLP1-R agonists in rodents

    International Nuclear Information System (INIS)

    Brink, Willem van den; Emerenciana, Annette; Bellanti, Francesco; Della Pasqua, Oscar; Laan, Jan Willem van der

    2017-01-01

    Increased incidence of C-cell carcinogenicity has been observed for glucagon-like-protein-1 receptor (GLP-1r) agonists in rodents. It is suggested that the duration of exposure is an indicator of carcinogenic potential in rodents of the different products on the market. Furthermore, the role of GLP-1-related mechanisms in the induction of C-cell carcinogenicity has gained increased attention by regulatory agencies. This study proposes an integrative pharmacokinetic/pharmacodynamic (PKPD) framework to identify explanatory factors and characterize differences in carcinogenic potential of the GLP-1r agonist products. PK models for four products (exenatide QW (once weekly), exenatide BID (twice daily), liraglutide and lixisenatide) were developed using nonlinear mixed effects modelling. Predicted exposure was subsequently linked to GLP-1r stimulation using in vitro GLP-1r potency data. A logistic regression model was then applied to exenatide QW and liraglutide data to assess the relationship between GLP-1r stimulation and thyroid C-cell hyperplasia incidence as pre-neoplastic predictor of a carcinogenic response. The model showed a significant association between predicted GLP-1r stimulation and C-cell hyperplasia after 2 years of treatment. The predictive performance of the model was evaluated using lixisenatide, for which hyperplasia data were accurately described during the validation step. The use of a model-based approach provided insight into the relationship between C-cell hyperplasia and GLP-1r stimulation for all four products, which is not possible with traditional data analysis methods. It can be concluded that both pharmacokinetics (exposure) and pharmacodynamics (potency for GLP-1r) factors determine C-cell hyperplasia incidence in rodents. Our work highlights the pharmacological basis for GLP-1r agonist-induced C-cell carcinogenicity. The concept is promising for application to other drug classes. - Highlights: • An integrative PKPD model is applied to

  17. Tissue-based map of the human proteome

    DEFF Research Database (Denmark)

    Uhlén, Mathias; Fagerberg, Linn; Hallström, Björn M.

    2015-01-01

    Resolving the molecular details of proteome variation in the different tissues and organs of the human body will greatly increase our knowledge of human biology and disease. Here, we present a map of the human tissue proteome based on an integrated omics approach that involves quantitative transc...

  18. Metabolic activation and carcinogenicity of polycyclic hydrocarbons: A new quantum mechanical theory

    International Nuclear Information System (INIS)

    Mohammad, S.N.

    1986-01-01

    This investigation aims to describe a quantum mechanical theory of cancer, which, on the basis of certain electronic indices calculated for the parent compound, would give prediction of its P-450 mediated metabolic activation and would provide better representation of its relative carcinogenic potency when activated to its PUM. The author's theory is based on the assumption that electronic charge distribution of activated species resembles at least qualitatively the charge distribution of the parent compound, and a careful analysis of electronic characteristics of the parent compound would suffice to give reasonable estimation of the carcinogenic activities of the metabolic products. The details of the theoretical method is given and the results for some alternant and non-alternant PAHs are presented

  19. Adaboost-based algorithm for human action recognition

    KAUST Repository

    Zerrouki, Nabil

    2017-11-28

    This paper presents a computer vision-based methodology for human action recognition. First, the shape based pose features are constructed based on area ratios to identify the human silhouette in images. The proposed features are invariance to translation and scaling. Once the human body features are extracted from videos, different human actions are learned individually on the training frames of each class. Then, we apply the Adaboost algorithm for the classification process. We assessed the proposed approach using the UR Fall Detection dataset. In this study six classes of activities are considered namely: walking, standing, bending, lying, squatting, and sitting. Results demonstrate the efficiency of the proposed methodology.

  20. Adaboost-based algorithm for human action recognition

    KAUST Repository

    Zerrouki, Nabil; Harrou, Fouzi; Sun, Ying; Houacine, Amrane

    2017-01-01

    This paper presents a computer vision-based methodology for human action recognition. First, the shape based pose features are constructed based on area ratios to identify the human silhouette in images. The proposed features are invariance to translation and scaling. Once the human body features are extracted from videos, different human actions are learned individually on the training frames of each class. Then, we apply the Adaboost algorithm for the classification process. We assessed the proposed approach using the UR Fall Detection dataset. In this study six classes of activities are considered namely: walking, standing, bending, lying, squatting, and sitting. Results demonstrate the efficiency of the proposed methodology.

  1. Heterogeneous Community-based mobility model for human opportunistic network

    DEFF Research Database (Denmark)

    Hu, Liang; Dittmann, Lars

    2009-01-01

    a heterogeneous community-based random way-point (HC-RWP) mobility model that captures the four important properties of real human mobility. These properties are based on both intuitive observations of daily human mobility and analysis of empirical mobility traces. By discrete event simulation, we show HC...

  2. Exploring the Molecular Mechanisms of Nickel-Induced Genotoxicity and Carcinogenicity: A Literature Review

    Science.gov (United States)

    Cameron, Keyuna S.; Buchner, Virginia; Tchounwou, Paul B.

    2011-01-01

    Nickel, a naturally occurring element that exists in various mineral forms, is mainly found in soil and sediment, and its mobilization is influenced by the physicochemical properties of the soil. Industrial sources of nickel include metallurgical processes such as electroplating, alloy production, stainless steel, and nickel-cadmium batteries. Nickel industries, oil- and coal-burning power plants, and trash incinerators have been implicated in its release into the environment. In humans, nickel toxicity is influenced by the route of exposure, dose, and solubility of the nickel compound. Lung inhalation is the major route of exposure for nickel-induced toxicity. Nickel may also be ingested or absorbed through the skin. The primary target organs are the kidneys and lungs. Other organs such as the liver, spleen, heart and testes may also be affected to a lesser extent. Although the most common health effect is an allergic reaction, research has also demonstrated that nickel is carcinogenic to humans. The focus of the present review is on recent research concerning the molecular mechanisms of nickel-induced genotoxicity and carcinogenicity. We first present a background on the occurrence of nickel in the environment, human exposure, and human health effects. PMID:21905451

  3. Feasibility of preventing the effects of carcinogens on man

    Energy Technology Data Exchange (ETDEWEB)

    Shabad, L M; Wittig, K; Khesina, I A

    1973-01-01

    Measures are considered for reducing atmospheric levels of polycyclic aromatic hydrocarbons produced by domestic heating, industry, and motor vehicles. Older home heating systems should be replaced with ones which can burn more efficiently. It is recommended that emissions from industrial sources, such as by-product coke plants, petroleum refineries, and plants producing carbon black, resins, and gas, should be reduced by the use of filters or by more complete combustion. The amount of polycyclic aromatic hydrocarbons in motor vehicle exhaust can be reduced by using oil additives, changing the ratio of gasoline to oil, and using neutralizers, but more appropriate long-term solutions would be to use vehicles powered by gas or electricity. Since the largest amounts of benzyprene (BP) are produced by idling motors, traffic flow should be improved by separating foot and automobile traffic. The amount of BP in airplane emissions has been reduced by more than 30% by adding magnesium to the fuel and by about 60% by using dearomatized fuels. To prevent lung cancer it is necessary to reduce the levels of not only carcinogens and cocarcinogens, but also of toxic substances, e.g., sulfur dioxide, oxides of nitrogen, and acrolein, which reduce ciliary activity in the bronchial epithelium. Since it is impractical to eliminate polycyclic aromatic hydrocarbons from the human environment at present, maximum permissible concentrations of BP have been established in the Soviet Union. They are 0.01 microg/100 m/sup 3/ BP for the atmosphere and 15 microg/100 m/sup 3/ in work places.

  4. Indoor air - assessment: Methods of analysis for environmental carcinogens

    International Nuclear Information System (INIS)

    Peterson, M.R.; Naugle, D.F.; Berry, M.A.

    1990-06-01

    The monograph describes, in a general way, published sampling procedures and analytical approaches for known and suspected carcinogens. The primary focus is upon carcinogens found in indoor air, although the methods described are applicable to other media or environments. In cases where there are no published methods for a particular pollutant in indoor air, methods developed for the workplace and for ambient air are included since they should be adaptable to indoor air. Known and suspected carcinogens have been grouped into six categories for the purposes of this and related work. The categories are radon, asbestos, organic compounds, inorganic species, particles, and non-ionizing radiation. Some methods of assessing exposure that are not specific to any particular pollutant category are covered in a separate section. The report is the fifth in a series of EPA/Environmental Criteria and Assessment Office Monographs

  5. Genome-wide characterization of microsatelittes and marker development in the carcinogenic liver fluke Clonorchis sinensis

    Science.gov (United States)

    Nguyen, Thao T.B.; Arimatsu, Yuji; Hong, Sung-Jong; Brindley, Paul J.; Blair, David; Laha, Thewarach; Sripa, Banchob

    2015-01-01

    Clonorchis sinensis is an important carcinogenic human liver fluke endemic in East and Southeast Asia. There are several conventional molecular markers have been used for identification and genetic diversity, however, no information about microsatellites of this liver fluke published so far. We here report microsatellite characterization and marker development for genetic diversity study in C. sinensis using genome-wide bioinformatics approach. Based on our search criteria, a total of 256,990 microsatellites (≥ 12 base pairs) were identified from genome database of C. sinensis with hexa-nucleotide motif being the most abundant (51%) followed by penta-nucleotide (18.3%) and tri-nucleotide (12.7%). The tetra-nucleotide, di-nucleotide and mononucleotide motifs accounted for 9.75 %, 7.63% and 0.14%, respectively. The total length of all microsatellites accounts for 0. 72 % of 547 Mb of the whole genome size and the frequency of microsatellites were found to be one microsatellite in every 2.13 kb of DNA. For the di-, tri, and tetra-nucleotide, the repeat numbers redundant are six (28%), four (45%) and three (76%), respectively. The ATC repeat is the most abundant microsatellites followed by AT, AAT and AC, respectively. Within 40 microsatellite loci developed, 24 microsatellite markers showed potential to differentiate between C. sinensis and O. viverrini. Seven out of 24 loci showed heterozygous with observed heterozygosity ranged from 0.467 to 1. Four-primer sets could amplify both C. sinensis and O. viverrini DNA with different sizes. This study provides basic information of C. sinensis microsatellites and the genome-wide markers developed may be a useful tool for genetic study of C. sinensis. PMID:25782682

  6. Genome-wide characterization of microsatellites and marker development in the carcinogenic liver fluke Clonorchis sinensis.

    Science.gov (United States)

    Nguyen, Thao T B; Arimatsu, Yuji; Hong, Sung-Jong; Brindley, Paul J; Blair, David; Laha, Thewarach; Sripa, Banchob

    2015-06-01

    Clonorchis sinensis is an important carcinogenic human liver fluke endemic in East and Southeast Asia. There are several conventional molecular markers that have been used for identification and genetic diversity; however, no information about microsatellites of this liver fluke is published so far. We here report microsatellite characterization and marker development for a genetic diversity study in C. sinensis, using a genome-wide bioinformatics approach. Based on our search criteria, a total of 256,990 microsatellites (≥12 base pairs) were identified from a genome database of C. sinensis, with hexanucleotide motif being the most abundant (51%) followed by pentanucleotide (18.3%) and trinucleotide (12.7%). The tetranucleotide, dinucleotide, and mononucleotide motifs accounted for 9.75, 7.63, and 0.14%, respectively. The total length of all microsatellites accounts for 0. 72% of 547 Mb of the whole genome size, and the frequency of microsatellites was found to be one microsatellite in every 2.13 kb of DNA. For the di-, tri-, and tetranucleotide, the repeat numbers redundant are six (28%), four (45%), and three (76%), respectively. The ATC repeat is the most abundant microsatellites followed by AT, AAT, and AC, respectively. Within 40 microsatellite loci developed, 24 microsatellite markers showed potential to differentiate between C. sinensis and Opisthorchis viverrini. Seven out of 24 loci showed to be heterozygous with observed heterozygosity that ranged from 0.467 to 1. Four primer sets could amplify both C. sinensis and O. viverrini DNA with different sizes. This study provides basic information of C. sinensis microsatellites, and the genome-wide markers developed may be a useful tool for the genetic study of C. sinensis.

  7. Carcinogenic effect of petroleum and its by-products

    Energy Technology Data Exchange (ETDEWEB)

    Gimadeev, M M

    1962-01-01

    A review of literature on the carcinogenic effect of petroleum and its by-products are briefly discussed. Many of the products can induce hyperkeratosis, folliculitis, verruca, pulmonary adenoma, skin cancer, etc. Their action is mainly local but they can also be multicentric. Although a number of groups have made chemical analyses of various petroleums and peroleum products, results were generally negative with respect to 3,4-benzypyrene, although 40 to 68 microg/g was found in 1 crude petroleum. At present it appears that much of the carcinogenic action of these materials resides in polycyclic hydrocarbons about which little is known.

  8. Cannabis and tobacco smoke are not equally carcinogenic

    Directory of Open Access Journals (Sweden)

    Melamede Robert

    2005-10-01

    Full Text Available Abstract More people are using the cannabis plant as modern basic and clinical science reaffirms and extends its medicinal uses. Concomitantly, concern and opposition to smoked medicine has occurred, in part due to the known carcinogenic consequences of smoking tobacco. Are these reactions justified? While chemically very similar, there are fundamental differences in the pharmacological properties between cannabis and tobacco smoke. Cannabis smoke contains cannabinoids whereas tobacco smoke contains nicotine. Available scientific data, that examines the carcinogenic properties of inhaling smoke and its biological consequences, suggests reasons why tobacco smoke, but not cannabis smoke, may result in lung cancer.

  9. Modification of carcinogenic and antitumor radiation effects (biomedical aspects)

    International Nuclear Information System (INIS)

    Vilenchik, M.M.

    1985-01-01

    In the book the data on modification of carcinogenic radiation effects by physiologicaly active compounds (caffeine, hormones, promoters and others) as well as on potentiation of antitumor radiation effects by means of hyperthermia are systematized. It is shown that as a basis of synergetic (superadditive) carcinogenic or antitumor radiation effects combined with other factor can be the inhibiting effects of the latter on the reparation process of radiation-induced DNA injuries. The results of experimental investigations and the data on quantitative analysis can be used as a theoretical basis for improvement of the ways and means of the prophylaxis of tumor diseases as well as for increasing the efficiency of radiotherapy

  10. Glyphosate toxicity and carcinogenicity: a review of the scientific basis of the European Union assessment and its differences with IARC.

    Science.gov (United States)

    Tarazona, Jose V; Court-Marques, Daniele; Tiramani, Manuela; Reich, Hermine; Pfeil, Rudolf; Istace, Frederique; Crivellente, Federica

    2017-08-01

    Glyphosate is the most widely used herbicide worldwide. It is a broad spectrum herbicide and its agricultural uses increased considerably after the development of glyphosate-resistant genetically modified (GM) varieties. Since glyphosate was introduced in 1974, all regulatory assessments have established that glyphosate has low hazard potential to mammals, however, the International Agency for Research on Cancer (IARC) concluded in March 2015 that it is probably carcinogenic. The IARC conclusion was not confirmed by the EU assessment or the recent joint WHO/FAO evaluation, both using additional evidence. Glyphosate is not the first topic of disagreement between IARC and regulatory evaluations, but has received greater attention. This review presents the scientific basis of the glyphosate health assessment conducted within the European Union (EU) renewal process, and explains the differences in the carcinogenicity assessment with IARC. Use of different data sets, particularly on long-term toxicity/carcinogenicity in rodents, could partially explain the divergent views; but methodological differences in the evaluation of the available evidence have been identified. The EU assessment did not identify a carcinogenicity hazard, revised the toxicological profile proposing new toxicological reference values, and conducted a risk assessment for some representatives uses. Two complementary exposure assessments, human-biomonitoring and food-residues-monitoring, suggests that actual exposure levels are below these reference values and do not represent a public concern.

  11. Dehydropyrrolizidine alkaloid toxicity, cytotoxicity, and carcinogenicity

    Science.gov (United States)

    Dehyro-pyrrolizidine alkaloid (PA)-containing plants compose about 5% of the world’s flowering plants and they commonly poison livestock, wildlife and humans. Previous work has produced considerable understanding of PA toxicity, species susceptibility, conditions and routes of exposure, toxin metab...

  12. The carcinogenic risks of low-LET and high-LET ionizing radiations

    International Nuclear Information System (INIS)

    Fabrikant, J.I.

    1991-08-01

    This report presents a discussion on risk from ionizing radiations to human populations. Important new information on human beings has come mainly from further follow-up of existing epidemiological studies, notably the Japanese atomic bomb survivors and the ankylosing spondylitis patients; from new epidemiological surveys, such as the patients treated for cancer of the uterine cervix; and from combined surveys, including workers exposed in underground mines. Since the numerous and complex differences among the different study populations introduce factors that influence the risk estimates derived in ways that are not completely understood, it is not clear how to combine the different risk estimates obtained. These factors involve complex biological and physical variables distributed over time. Because such carcinogenic effects occur too infrequently to be demonstrated at low doses, the risks of low-dose radiation can be estimated only by interpolation from observations at high doses on the basis of theoretical concepts, mathematical models and available empirical evidence, primarily the epidemiological surveys of large populations exposed to ionizing radiation. In spite of a considerable amount of research, only recently has there has been efforts to apply the extensive laboratory data in animals to define the dose-incidence relationship in the low dose region. There simply are insufficient data in the epidemiological studies of large human populations to estimate risk coefficients directly from exposure to low doses. The risk estimates for the carcinogenic effects of radiation have been, in the past, somewhat low and reassessment of the numerical values is now necessary

  13. Impact of environmental exposures on the mutagenicity/carcinogenicity of heterocyclic amines

    Energy Technology Data Exchange (ETDEWEB)

    Felton, James S; Knize, Mark G; Bennett, L Michelle; Malfatti, Michael A; Colvin, Michael E; Kulp, Kristen S

    2004-05-20

    Carcinogenic heterocyclic amines are produced from overcooked foods and are highly mutagenic in most short-term test systems. One of the most abundant of these amines, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), induces breast, colon and prostate tumors in rats. Human dietary epidemiology studies suggest a strong correlation between either meat consumption or well-done muscle meat consumption and cancers of the colon, breast, stomach, lung and esophagus. For over 20 years our laboratory has helped define the human exposure to these dietary carcinogens. In this report we describe how various environmental exposures may modulate the risk from exposure to heterocyclic amines, especially PhIP. To assess the impact of foods on PhIP metabolism in humans, we developed an LC/MS/MS method to analyze the four major PhIP urinary metabolites following the consumption of a single portion of grilled chicken. Adding broccoli to the volunteers' diet altered the kinetics of PhIP metabolism. At the cellular level we have found that PhIP itself stimulates a significant estrogenic response in MCF-7 cells, but even more interestingly, co-incubation of the cells with herbal teas appear to enhance the response. Numerous environmental chemicals found in food or the atmosphere can impact the exposure, metabolism, and cell proliferation response of heterocyclic amines.

  14. Impact of environmental exposures on the mutagenicity/carcinogenicity of heterocyclic amines

    International Nuclear Information System (INIS)

    Felton, James S.; Knize, Mark G.; Bennett, L. Michelle; Malfatti, Michael A.; Colvin, Michael E.; Kulp, Kristen S.

    2004-01-01

    Carcinogenic heterocyclic amines are produced from overcooked foods and are highly mutagenic in most short-term test systems. One of the most abundant of these amines, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), induces breast, colon and prostate tumors in rats. Human dietary epidemiology studies suggest a strong correlation between either meat consumption or well-done muscle meat consumption and cancers of the colon, breast, stomach, lung and esophagus. For over 20 years our laboratory has helped define the human exposure to these dietary carcinogens. In this report we describe how various environmental exposures may modulate the risk from exposure to heterocyclic amines, especially PhIP. To assess the impact of foods on PhIP metabolism in humans, we developed an LC/MS/MS method to analyze the four major PhIP urinary metabolites following the consumption of a single portion of grilled chicken. Adding broccoli to the volunteers' diet altered the kinetics of PhIP metabolism. At the cellular level we have found that PhIP itself stimulates a significant estrogenic response in MCF-7 cells, but even more interestingly, co-incubation of the cells with herbal teas appear to enhance the response. Numerous environmental chemicals found in food or the atmosphere can impact the exposure, metabolism, and cell proliferation response of heterocyclic amines

  15. DNA repair studies in mouse germ cells exposed to two carcinogens and two non-carcinogens

    International Nuclear Information System (INIS)

    Sega, G.A.; Owens, J.G.

    1987-01-01

    An in vivo test was used to measure induced unscheduled DNA synthesis (UDS) in the germ cells of male mice exposed to the carcinogens benzo(a)pyrene [B(a)P] and 2-acetylaminofluorene (2AAF), and to the noncarcinogens pyrene (PYR) and 4-acetylaminofluorene (4AAF). Early spermatids, a DNA-repair competent stage, were used to test the effects of all chemicals. After chemical treatment and testicular injection of [ 3 H]dThd, sperm were recovered 16 days later from the caudal epididymides (these sperm were in early spermatid stages at the time of treatment) and assayed for the unscheduled incorporation of [ 3 H]dThd using liquid scintillation counting (LSC). Exposures of 2AAF ranged from 125 to 1600 mg/kg, 4AAF from 125 to 2000 mg/kg, PYR from 100 to 600 mg/kg, B(a)P from 100 to 400 mg/kg. Chemicals were administered both by intraperitoneal (i.p.) injection and by gavage. Methyl methanesulfonate (MMS) was used as a positive control

  16. The limits of two-year bioassay exposure regimens for identifying chemical carcinogens.

    Science.gov (United States)

    Huff, James; Jacobson, Michael F; Davis, Devra Lee

    2008-11-01

    Chemical carcinogenesis bioassays in animals have long been recognized and accepted as valid predictors of potential cancer hazards to humans. Most rodent bioassays begin several weeks after birth and expose animals to chemicals or other substances, including workplace and environmental pollutants, for 2 years. New findings indicate the need to extend the timing and duration of exposures used in the rodent bioassay. In this Commentary, we propose that the sensitivity of chemical carcinogenesis bio-assays would be enhanced by exposing rodents beginning in utero and continuing for 30 months (130 weeks) or until their natural deaths at up to about 3 years. Studies of three chemicals of different structures and uses-aspartame, cadmium, and toluene-suggest that exposing experimental animals in utero and continuing exposure for 30 months or until their natural deaths increase the sensitivity of bioassays, avoid false-negative results, and strengthen the value and validity of results for regulatory agencies. Government agencies, drug companies, and the chemical industry should conduct and compare the results of 2-year bioassays of known carcinogens or chemicals for which there is equivocal evidence of carcinogenicity with longer-term studies, with and without in utero exposure. If studies longer than 2 years and/or with in utero exposure are found to better identify potential human carcinogens, then regulatory agencies should promptly revise their testing guidelines, which were established in the 1960s and early 1970s. Changing the timing and dosing of the animal bioassay would enhance protection of workers and consumers who are exposed to potentially dangerous workplace or home contaminants, pollutants, drugs, food additives, and other chemicals throughout their lives.

  17. Acquisition of Human Operation Characteristics for Kite-based Tethered Flying Robot using Human Operation Data

    OpenAIRE

    Todoroki, Chiaki; Takahashi, Yasutake; Nakamura, Takayuki

    2015-01-01

    This paper shows human skill acquisition systems to control the kite-based tethered flying robot. The kite-based tethered flying robot has been proposed as a flying observation system with long-term activity capability[1]. It is a relatively new system and aimed to complement other information gathering systems using a balloon or an air vehicle. This paper shows some approaches of human operation characteristics acquisition based on fuzzy learning controller, knearest neighbor algorithm, and ...

  18. Human cooperation based on punishment reputation.

    Science.gov (United States)

    dos Santos, Miguel; Rankin, Daniel J; Wedekind, Claus

    2013-08-01

    The threat of punishment usually promotes cooperation. However, punishing itself is costly, rare in nonhuman animals, and humans who punish often finish with low payoffs in economic experiments. The evolution of punishment has therefore been unclear. Recent theoretical developments suggest that punishment has evolved in the context of reputation games. We tested this idea in a simple helping game with observers and with punishment and punishment reputation (experimentally controlling for other possible reputational effects). We show that punishers fully compensate their costs as they receive help more often. The more likely defection is punished within a group, the higher the level of within-group cooperation. These beneficial effects perish if the punishment reputation is removed. We conclude that reputation is key to the evolution of punishment. © 2013 The Author(s). Evolution © 2013 The Society for the Study of Evolution.

  19. Case study: an evaluation of the human relevance of the synthetic pyrethroid metofluthrin-induced liver tumors in rats based on mode of action.

    Science.gov (United States)

    Yamada, Tomoya; Uwagawa, Satoshi; Okuno, Yasuyoshi; Cohen, Samuel M; Kaneko, Hideo

    2009-03-01

    In recent years, mode of action (MOA) frameworks have been developed through the International Life Sciences Institute Risk Science Institute and the International Programme on Chemical Safety, including an evaluation of the human relevance of the animal MOA data. In the present paper, the MOA for rat liver tumors induced by Metofluthrin is first analyzed through this framework based on data from studies on Metofluthrin and information on related chemicals from the literature. The human relevance of the rat liver carcinogenic response is then discussed based upon the human relevance framework. Two-year treatment with high dose of Metofluthrin produced hepatocellular tumors in both sexes of the Wistar rats. Metofluthrin induced CYP2B (increased smooth endoplasmic reticulum), resulted in increased liver weights which were associated with centrilobular hepatocyte hypertrophy, and induction of increased hepatocellular DNA replications. The above parameters related to the key events in Metofluthrin-induced liver tumors were observed at or below tumorigenic dose levels. Furthermore, CYP2B induction by Metofluthrin was shown to involve activation of the constitutive androstane receptor in rat hepatocytes. Based on the evidence, including a comparison with the results with another chemical, phenobarbital, acting by a similar MOA, it is reasonable to conclude that Metofluthrin will not have any hepatocarcinogenic activity in humans.

  20. 1,2,3-Trichloropropane: a multisite carcinogen in rats and mice.

    Science.gov (United States)

    Irwin, R D; Haseman, J K; Eustis, S L

    1995-05-01

    1,2,3-Trichloropropane was evaluated in 2-year toxicology and carcinogenesis studies by the National Toxicology Program. The selection of this chemical for study was based on the potential for human exposure, its positive in vitro genotoxicity, and the carcinogenicity of structurally related chemicals. During the 2-year study 1,2,3-trichloropropane was administered in corn oil by gavage 5 days per week; groups of 60 F344/N rats received 0, 3, 10, or 30 mg/kg, while groups of 60 B6C3F1 mice received 0,6,20, or 60 mg/kg. Because of reduced survival associated with the development of chemical-related neoplasms, rats that received 30 mg/kg were terminated at 65 weeks (females) or 76 weeks (males). Similarly, mice that received 60 mg/kg were terminated at 73 weeks (females) or 79 weeks (males), while groups of mice that received 20 mg/kg were terminated at 88 weeks. 1,2,3-Trichloropropane induced benign and/or malignant neoplasms at multiple sites in both rats and mice; this included increased incidences of benign and malignant neoplasms of the squamous epithelium of the oral mucosa and forestomach of male and female rats, benign neoplasms of the kidney and pancreas and benign or malignant neoplasms of the preputial gland in male rats, malignant neoplasms of the mammary gland, and benign or malignant neoplasms of the clitoral gland in female rats. In mice, 1,2,3-trichloropropane induced a low incidence of malignant neoplasms of the oral mucosa in females, high incidences of benign and malignant neoplasms of the forestomach in males and females, benign neoplasms of the liver and harderian gland of males and females, and uterine neoplasms in females.

  1. Land management of bracken needs to account for bracken carcinogens--a case study from Britain.

    Science.gov (United States)

    Rasmussen, Lars Holm; Donnelly, Eric; Strobel, Bjarne W; Holm, Peter E; Hansen, Hans Christian Bruun

    2015-03-15

    Bracken ferns are some of the most widespread ferns in the World causing immense problems for land managers, foresters and rangers. Bracken is suspected of causing cancer in Humans due to its content of the carcinogen ptaquiloside. Ingestion of bracken, or food and drinking water contaminated with ptaquiloside may be the cause. The aim of this study was to monitor the content of ptaquiloside in 20 bracken stands from Britain to obtain a better understanding of the ptaquiloside dynamics and to evaluate the environmental implications of using different cutting regimes in bracken management. The ptaquiloside content in fronds ranged between 50 and 5790 μg/g corresponding to a ptaquiloside load in the standing biomass of up to 590 mg/m(2) in mature fronds. Ptaquiloside was also found in the underground rhizome system (11-657 μg/g) and in decaying litter (0.1-5.8 μg/g). The amount of ptaquiloside present in bracken stands at any given time is difficult to predict and did not show any correlations with edaphic growth factors. The content of ptaquiloside turned out to be higher in fronds emerging after cutting compared to uncut fronds. Environmental risk assessment and bracken management must therefore be based on actual and site specific determinations of the ptaquiloside content. Care must be taken to avoid leaching from cut ferns to aquifers and other recipients and appropriate precautionary measures must be taken to protect staff from exposure to bracken dust. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. The Relationship between Robot's Nonverbal Behaviour and Human's Likability Based on Human's Personality.

    Science.gov (United States)

    Thepsoonthorn, Chidchanok; Ogawa, Ken-Ichiro; Miyake, Yoshihiro

    2018-05-30

    At current state, although robotics technology has been immensely developed, the uncertainty to completely engage in human-robot interaction is still growing among people. Many current studies then started to concern about human factors that might influence human's likability like human's personality, and found that compatibility between human's and robot's personality (expressions of personality characteristics) can enhance human's likability. However, it is still unclear whether specific means and strategy of robot's nonverbal behaviours enhances likability from human with different personality traits and whether there is a relationship between robot's nonverbal behaviours and human's likability based on human's personality. In this study, we investigated and focused on the interaction via gaze and head nodding behaviours (mutual gaze convergence and head nodding synchrony) between introvert/extravert participants and robot in two communication strategies (Backchanneling and Turn-taking). Our findings reveal that the introvert participants are positively affected by backchanneling in robot's head nodding behaviour, which results in substantial head nodding synchrony whereas the extravert participants are positively influenced by turn-taking in gaze behaviour, which leads to significant mutual gaze convergence. This study demonstrates that there is a relationship between robot's nonverbal behaviour and human's likability based on human's personality.

  3. Trichloroethylene: Mechanistic, epidemiologic and other supporting evidence of carcinogenic hazard

    NARCIS (Netherlands)

    Rusyn, Ivan; Chiu, Weihsueh A.; Lash, Lawrence H.; Kromhout, Hans; Hansen, Johnni; Guyton, Kathryn Z.

    2014-01-01

    The chlorinated solvent trichloroethylene (TCE) is a ubiquitous environmental pollutant. The carcinogenic hazard of TCE was the subject of a 2012 evaluation by a Working Group of the International Agency for Research on Cancer (IARC). Information on exposures, relevant data from epidemiologic

  4. Classification of carcinogenic and mutagenic properties using machine learning method

    DEFF Research Database (Denmark)

    Moorthy, N. S.Hari Narayana; Kumar, Surendra; Poongavanam, Vasanthanathan

    2017-01-01

    An accurate calculation of carcinogenicity of chemicals became a serious challenge for the health assessment authority around the globe because of not only increased cost for experiments but also various ethical issues exist using animal models. In this study, we provide machine learning...

  5. In vitro transformation: interactions of chemical carcinogens and radiation

    International Nuclear Information System (INIS)

    DiPaolo, J.A.

    1976-01-01

    The development of reproducible quantitative in vitro procedures resulting in neoplastic transformation of mammalian cells has made possible the separation of events related to the process leading to transformation from secondary events that interfere with the early recognition of transformation. The use of chemical carcinogens on Syrian hamster cell strains results in a dose-response relation consistent with a Poisson distribution, indicating that the transformation phenomenon is inductive. In some circumstances, the joint action or interaction of chemical carcinogens with other agents results in an increased incidence of transformation. The pretreatment of Syrian hamster cells with ionizing radiation (250 R) or alkylating chemicals enhances the frequency of transformation on a cell or colony basis ordinarily obtained with known chemical carcinogens. Pretreatment with non-ionizing irradiation (uv, 254 nm) did not have a similar effect. The two types of irradiation and the alkylating agents reduced the cloning efficiency of the cells. X ray alone produced no transformation; the alkylating chemicals produced transformations infrequently, whereas uv produced a significant number of transformations. The number of transformations associated with uv is increased by pretreatment of the cells by x-irradiation. The enhancement of transformation by x-ray or x-ray-type agents appears to be independent of the type of second carcinogen used

  6. Chemical procedures to detect carcinogenic compound in domestic wastewater

    International Nuclear Information System (INIS)

    Abd Manan T S; Malakahmad A

    2013-01-01

    This review presents chemical methods to detect carcinogenic compound in wastewater. Atomic absorption spectroscopy (AAS), high performance liquid chromatography (HPLC) and gas chromatography mass spectroscopy (GCMS) and their alternative attached equipments were discussed. The application of each method is elaborated using related studies in the field.

  7. CARCINOGENIC EFFECTS OF LOW DOSES OF IONIZING RADIATION

    Science.gov (United States)

    Carcinogenic Effects of Low Doses of Ionizing RadiationR Julian Preston, Environmental Carcinogenesis Division, NHEERL, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711The form of the dose-response curve for radiation-induced cancers, particu...

  8. Vision-based human motion analysis: An overview

    NARCIS (Netherlands)

    Poppe, Ronald Walter

    2007-01-01

    Markerless vision-based human motion analysis has the potential to provide an inexpensive, non-obtrusive solution for the estimation of body poses. The significant research effort in this domain has been motivated by the fact that many application areas, including surveillance, Human-Computer

  9. School-based human papillomavirus vaccination: An opportunity to ...

    African Journals Online (AJOL)

    School-based human papillomavirus vaccination: An opportunity to increase knowledge about cervical cancer and improve uptake of ... Poor knowledge about cervical cancer plays a role in limiting screening uptake. HPV ... Article Metrics.

  10. Exoskeleton Power and Torque Requirements Based on Human Biomechanics

    National Research Council Canada - National Science Library

    Crowell, Harrison

    2002-01-01

    .... In providing design guidance, the authors had two goals. The first goal was to provide estimates of the angles, torques, and powers for the ankles, knees, and hips of an exoskeleton based on data collected from humans...

  11. Human rights literacy: Moving towards rights-based education and ...

    African Journals Online (AJOL)

    Hennie

    Edu-HRight Research Unit, Faculty of Education Sciences, North-West University Potchefstroom Campus, ... Finally, recommendations are made regarding human rights and rights-based .... serve as guidelines for our actions and attitudes.

  12. Work at night and breast cancer--report on evidence-based options for preventive actions

    DEFF Research Database (Denmark)

    Bonde, Jens Peter; Hansen, Johnni; Kolstad, Henrik Albert

    2012-01-01

    In 2007, the International Agency for Research on Cancer classified shift work involving circadian disruption as probably carcinogenic to humans (group 2A), primarily based on experimental and epidemiologic evidence for breast cancer. In order to examine options for evidence-based preventive acti...

  13. Toxic and carcinogenic agents in dry and moist snuff.

    Science.gov (United States)

    Hoffmann, D; Adams, J D; Lisk, D; Fisenne, I; Brunnemann, K D

    1987-12-01

    The oral use of snuff is causatively associated with cancer of the oral cavity. Since most epidemiologic studies to date relate to the long-term use of dry snuff, which has dominated the U.S. smokeless tobacco market in the past, the concentrations of several toxic and carcinogenic agents in the three most popular dry snuff brands have been compared with those in the five most popular moist snuff brands sold in the United States. All eight samples were analyzed for nitrate, alkaloids, polyphenols, volatile carbonyl compounds, lead, cadmium, selenium, and the carcinogenic compounds benzo[a]pyrene (CAS: 50-32-8), polonium-210 (CAS: 13981-52-7), volatile N-nitrosamines (VNAs), N-nitrosodiethanolamine (CAS: 1116-54-7), and the tobacco-specific N-nitrosamines (TSNAs). Most of the snuff brands were rich in nitrate (greater than or equal to 1.5%), total polyphenols (greater than 2%), and in nicotine (greater than or equal to 1.5%), which is the habituating factor in tobacco use. Concentrations of the VNAs were significantly above the permissible limits set for some food products; the concentrations of the TSNAs in both snuff types exceeded the levels of nitrosamines in other consumer products by at least two to three orders of magnitude. The extremely high levels of the TSNAs in snuff have remained unchanged during the last decade and present the major carcinogenic risk factor for the oral use of snuff. Polonium-210 contributes further to the carcinogenic risk associated with snuff. The chemical-analytical data presented in this study do not indicate marked differences in the carcinogenic potential of moist snuff compared to dry snuff.

  14. Diagnostic tests based on human basophils

    DEFF Research Database (Denmark)

    Kleine-Tebbe, Jörg; Erdmann, Stephan; Knol, Edward F

    2006-01-01

    -maximal responses, termed 'intrinsic sensitivity'. These variables give rise to shifts in the dose-response curves which, in a diagnostic setting where only a single antigen concentration is employed, may produce false-negative data. Thus, in order to meaningfully utilize the current basophil activation tests....... Diagnostic studies using CD63 or CD203c in hymenoptera, food and drug allergy are critically discussed. Basophil-based tests are indicated for allergy testing in selected cases but should only be performed by experienced laboratories....

  15. Evaluation of carcinogenic hazard of diesel engine exhaust needs to consider revolutionary changes in diesel technology.

    Science.gov (United States)

    McClellan, Roger O; Hesterberg, Thomas W; Wall, John C

    2012-07-01

    Diesel engines, a special type of internal combustion engine, use heat of compression, rather than electric spark, to ignite hydrocarbon fuels injected into the combustion chamber. Diesel engines have high thermal efficiency and thus, high fuel efficiency. They are widely used in commerce prompting continuous improvement in diesel engines and fuels. Concern for health effects from exposure to diesel exhaust arose in the mid-1900s and stimulated development of emissions regulations and research to improve the technology and characterize potential health hazards. This included epidemiological, controlled human exposure, laboratory animal and mechanistic studies to evaluate potential hazards of whole diesel exhaust. The International Agency for Research on Cancer (1989) classified whole diesel exhaust as - "probably carcinogenic to humans". This classification stimulated even more stringent regulations for particulate matter that required further technological developments. These included improved engine control, improved fuel injection system, enhanced exhaust cooling, use of ultra low sulfur fuel, wall-flow high-efficiency exhaust particulate filters, exhaust catalysts, and crankcase ventilation filtration. The composition of New Technology Diesel Exhaust (NTDE) is qualitatively different and the concentrations of particulate constituents are more than 90% lower than for Traditional Diesel Exhaust (TDE). We recommend that future reviews of carcinogenic hazards of diesel exhaust evaluate NTDE separately from TDE. Copyright © 2012 Elsevier Inc. All rights reserved.

  16. Methylation of ribonucleic acid by the carcinogens dimethyl sulphate, N-methyl-N-nitrosourea and N-methyl-N′-nitro-N-nitrosoguanidine. Comparisons of chemical analyses at the nucleoside and base levels

    Science.gov (United States)

    Lawley, P. D.; Shah, S. A.

    1972-01-01

    1. The following methods for hydrolysis of methyl-14C-labelled RNA, and for chromatographic isolation and determination of the products, were investigated: enzymic digestion to nucleosides at pH6 or 8; alkaline hydrolysis and conversion into nucleosides; hydrolysis by acid to pyrimidine nucleotides and purine bases, or completely to bases; chromatography on Dowex 50 (NH4+ form) at pH6 or 8.9, or on Dowex 50 (H+ form), or on Sephadex G-10. 2. The suitability of the various methods for determination of methylation products was assessed. The principal product, 7-methylguanosine, was unstable under the conditions used for determinations of nucleosides. 3- and 7-Methyladenine and 3- and 7-methylguanine are best determined as bases; 1-methyladenine and 3-methylcytosine can be isolated as either nucleosides or bases; O6-methylguanine is unstable under the acid hydrolysis conditions used and can be determined as the nucleoside; 3-methyluracil was detected, but may be derived from methylation of the ionized form of uracil. 3. Differences between the patterns of methylation of RNA and homopolyribonucleotides by the N-methyl-N-nitroso compounds and dimethyl sulphate were found: the nitroso compounds were able to methylate O-6 of guanine, were relatively more reactive at N-7 of adenine and probably at N-3 of guanine, but less reactive at N-1 of adenine, N-3 of cytosine and probably at N-3 of uridine. They probably reacted more with the ribose–phosphate chain, but no products from this were identified. 4. The possible influences of these differences on biological action of the methylating agents is discussed. Nitroso compounds may differ principally in their ability to induce miscoding in the Watson–Crick sense by reaction at O-6 of guanine. Both types of agent may induce miscoding to a lesser extent through methylation at N-3 of guanine; both can methylate N atoms, presumably preventing Watson–Crick hydrogen-bonding. N-Methyl-N-nitrosourea can degrade RNA, possibly

  17. Deployable structures for a human lunar base

    Science.gov (United States)

    Gruber, Petra; Häuplik, Sandra; Imhof, Barbara; Özdemir, Kürsad; Waclavicek, Rene; Perino, Maria Antoinetta

    2007-06-01

    The study Lunar exploration architecture—deployable structures for a lunar base was performed within the Alcatel Alenia Space “Lunar Exploration Architecture” study for the European Space Agency. The purpose of the study was to investigate bionic concepts applicable to deployable structures and to interpret the findings for possible implementation concepts. The study aimed at finding innovative solutions for deployment possibilities. Translating folding/unfolding principles from nature, candidate geometries were developed and researched using models, drawings and visualisations. The use of materials, joints between structural elements and construction details were investigated for these conceptual approaches. Reference scenarios were used to identify the technical and environmental conditions, which served as design drivers. Mechanical issues and the investigation of deployment processes narrowed the selection down to six chosen concepts. Their applicability was evaluated at a conceptual stage in relation to the timescale of the mission.

  18. Evaluation of the interindividual human variation in bioactivation of methyleugenol using physiologically based kinetic modeling and Monte Carlo simulations

    Energy Technology Data Exchange (ETDEWEB)

    Al-Subeihi, Ala' A.A., E-mail: subeihi@yahoo.com [Division of Toxicology, Wageningen University, Tuinlaan 5, 6703 HE Wageningen (Netherlands); BEN-HAYYAN-Aqaba International Laboratories, Aqaba Special Economic Zone Authority (ASEZA), P. O. Box 2565, Aqaba 77110 (Jordan); Alhusainy, Wasma; Kiwamoto, Reiko; Spenkelink, Bert [Division of Toxicology, Wageningen University, Tuinlaan 5, 6703 HE Wageningen (Netherlands); Bladeren, Peter J. van [Division of Toxicology, Wageningen University, Tuinlaan 5, 6703 HE Wageningen (Netherlands); Nestec S.A., Avenue Nestlé 55, 1800 Vevey (Switzerland); Rietjens, Ivonne M.C.M.; Punt, Ans [Division of Toxicology, Wageningen University, Tuinlaan 5, 6703 HE Wageningen (Netherlands)

    2015-03-01

    The present study aims at predicting the level of formation of the ultimate carcinogenic metabolite of methyleugenol, 1′-sulfooxymethyleugenol, in the human population by taking variability in key bioactivation and detoxification reactions into account using Monte Carlo simulations. Depending on the metabolic route, variation was simulated based on kinetic constants obtained from incubations with a range of individual human liver fractions or by combining kinetic constants obtained for specific isoenzymes with literature reported human variation in the activity of these enzymes. The results of the study indicate that formation of 1′-sulfooxymethyleugenol is predominantly affected by variation in i) P450 1A2-catalyzed bioactivation of methyleugenol to 1′-hydroxymethyleugenol, ii) P450 2B6-catalyzed epoxidation of methyleugenol, iii) the apparent kinetic constants for oxidation of 1′-hydroxymethyleugenol, and iv) the apparent kinetic constants for sulfation of 1′-hydroxymethyleugenol. Based on the Monte Carlo simulations a so-called chemical-specific adjustment factor (CSAF) for intraspecies variation could be derived by dividing different percentiles by the 50th percentile of the predicted population distribution for 1′-sulfooxymethyleugenol formation. The obtained CSAF value at the 90th percentile was 3.2, indicating that the default uncertainty factor of 3.16 for human variability in kinetics may adequately cover the variation within 90% of the population. Covering 99% of the population requires a larger uncertainty factor of 6.4. In conclusion, the results showed that adequate predictions on interindividual human variation can be made with Monte Carlo-based PBK modeling. For methyleugenol this variation was observed to be in line with the default variation generally assumed in risk assessment. - Highlights: • Interindividual human differences in methyleugenol bioactivation were simulated. • This was done using in vitro incubations, PBK modeling

  19. Evaluation of the interindividual human variation in bioactivation of methyleugenol using physiologically based kinetic modeling and Monte Carlo simulations

    International Nuclear Information System (INIS)

    Al-Subeihi, Ala' A.A.; Alhusainy, Wasma; Kiwamoto, Reiko; Spenkelink, Bert; Bladeren, Peter J. van; Rietjens, Ivonne M.C.M.; Punt, Ans

    2015-01-01

    The present study aims at predicting the level of formation of the ultimate carcinogenic metabolite of methyleugenol, 1′-sulfooxymethyleugenol, in the human population by taking variability in key bioactivation and detoxification reactions into account using Monte Carlo simulations. Depending on the metabolic route, variation was simulated based on kinetic constants obtained from incubations with a range of individual human liver fractions or by combining kinetic constants obtained for specific isoenzymes with literature reported human variation in the activity of these enzymes. The results of the study indicate that formation of 1′-sulfooxymethyleugenol is predominantly affected by variation in i) P450 1A2-catalyzed bioactivation of methyleugenol to 1′-hydroxymethyleugenol, ii) P450 2B6-catalyzed epoxidation of methyleugenol, iii) the apparent kinetic constants for oxidation of 1′-hydroxymethyleugenol, and iv) the apparent kinetic constants for sulfation of 1′-hydroxymethyleugenol. Based on the Monte Carlo simulations a so-called chemical-specific adjustment factor (CSAF) for intraspecies variation could be derived by dividing different percentiles by the 50th percentile of the predicted population distribution for 1′-sulfooxymethyleugenol formation. The obtained CSAF value at the 90th percentile was 3.2, indicating that the default uncertainty factor of 3.16 for human variability in kinetics may adequately cover the variation within 90% of the population. Covering 99% of the population requires a larger uncertainty factor of 6.4. In conclusion, the results showed that adequate predictions on interindividual human variation can be made with Monte Carlo-based PBK modeling. For methyleugenol this variation was observed to be in line with the default variation generally assumed in risk assessment. - Highlights: • Interindividual human differences in methyleugenol bioactivation were simulated. • This was done using in vitro incubations, PBK modeling

  20. EVALUATING HUMAN CAPITAL IN A KNOWLEDGE – BASED APPROACH

    Directory of Open Access Journals (Sweden)

    Emanoil MUSCALU

    2014-04-01

    Full Text Available The widespread enthusiasm for a knowledge-based approach to understanding the nature of a business and the possible basis for sustained competitive advantage have renewed interest in human capital evaluation or measurement. While many attempts have been made to develop methods for measuring intellectual capital, none have been widely adopted in the business world. In the knowledge-based organizations, and generally, in the information society, human capital is recognized as the fundamental factor of overall progress, and experts agree that long-term investment in human capital has strong drive-propagation effects at the individual, organizational, national and global level. In this paper, we consider that a knowledge-based approach can offer new possibilities and answers to illustrate the importance of evaluation the human capital and knowledge assets by consistently generating added value in the business world.

  1. Evaluation of the Humanity Research Paradigms based on Analysis of Human – Environment Interaction

    Directory of Open Access Journals (Sweden)

    Reza Sameh

    2015-09-01

    Full Text Available As claimed by many behavioral scientists, designing should be based on the knowledge of interaction between human and environment. Environmental quality is also created in the context in which humans interact with their environment. To achieve such quality, designers should develop appropriate models for explaining this relationship, and this requires an understanding of human nature and the environment. Criticisms on the Modern Movement have shown that architects have often used incomplete and simplistic models in this regard, while most of design ideas are based on the definitions of human and environment and the interaction between them. However, the most important question that is raised is that how understanding of human nature and the environment and their interaction, which depends on foundations of different views, can affect the pursuit of quality in designing? Therefore, the present paper, in addition to introduction and comparison of common paradigms in humanities as the and methodological foundation of human sciences, aims to deal with the relationship of human and the environment from the perspective of objectivist, relativist, and critical paradigms in order to identify the characteristics and differences in their views on the analysis of the quality of this interaction. This is the most important step that paves the way for understanding the qualitative foundations of the environment and human life quality and also the quality of interaction between them.

  2. Detection and impact on cancer causation of persons exhibiting abnormal susceptibility to carcinogenic agents

    International Nuclear Information System (INIS)

    Gentner, N.E.; Morrison, D.P.

    1988-01-01

    The so-called 'late biological effects', like cancer and genetic consequences and cytotoxic effects (cell killing, at higher doses), were once thought to be an inevitable consequence of a given level of exposure, whether to background radiation, to chemicals in our biosphere, or form spontaneous damage, the 'wear and tear' of living. The measurement of exposure, which results in living organisms in the formation of a related amount of DNA damage, became a surrogate for the end-effects that constitute risk. This may not be entirely appropriate. The concept of 'equal exposure -- equal risk' assumes a homogeneous response of individuals. However, there are subgroups within the human population of persons whose cultured cells exhibit abnormal sensitivity to specific carcinogenic agents and who may be at increased risk of cancer induced by these of similar agents. Modern molecular biology has shown that the majority of the damage in DNA is repaired by enzymatic DNA repair processes that restitute or ameliorate the lesions and restore normal DNA structure and function. In this view, it is not the initial damage that is of consequence but rather the residual damage left after the repair processes have acted. Since the vast majority of the initial DNA damage undergoes repair normally, variation in the efficiency of these processes in different persons may affect the actual risk of exposure. The human side of the cancer causation formula, that is, considerable importance. To understand how human DNA repair processes function, our laboratories at Chalk River have studied 'mutant' human cell strains in tissue culture. Generally, these DNA repair-defective cell strains are derived from individual donors with heritable disorders that are associated with carcinogen-hypersensitivity and cancer-proneness. Such studies, together with related epidemiological research, have highlighted the importance of this new 'human' factor in carcinogenesis

  3. Video-based lectures: An emerging paradigm for teaching human ...

    African Journals Online (AJOL)

    Video-based teaching material is a rich and powerful medium being used in computer assisted learning. This paper aimed to assess the learning outcomes and student nurses' acceptance and satisfaction with the video-based lectures versus the traditional method of teaching human anatomy and physiology courses.

  4. Estudo de variáveis demográficas, ocupacionais e co-carcinogenéticas no carcinoma espinocelular da base de língua nas mulheres

    Directory of Open Access Journals (Sweden)

    Amorim Filho Francisco S.

    2003-01-01

    Full Text Available Avaliar a relação entre carcinógenos e o carcinoma espinocelular no sexo feminino. FORMA DE ESTUDO: Retrospectivo não randomizado. OBJETIVO: Determinar a relação entre carcinógenos (álcool e fumo e o carcinoma espinocelular no sexo feminino na base da língua. MATERIAL E MÉTODOS: Estudo retrospectivo de 31 pacientes do sexo feminino realizado no Departamento de Cirurgia de Cabeça e Pescoço e Otorrinolaringologia do Hospital Heliópolis, Hosphel, São Paulo (1977 a 2000. Foram analisados variáveis como etnia, idade, profissão, tabagismo, etilismo, queixa principal, o intervalo de tempo entre o início da queixa e a procura do médico e o estadiamento clínico. Quanto ao tratamento estatístico, foram utilizados os Testes de Kappa e o de Mc Nemar. RESULTADOS: Houve predomínio da raça branca (58,1% sobre a negra (35,5% e a amarela (6,4%, bem como da 6feminine décadade vida; sendo profissionais do lar (83,9% trabalhadoras na agricultura 6,4%. Indústria (3,2%, comércio e liberais (3,2%. Houve mais consumo isolado do tabagismo (48,4%, ambos (45,2% e nenhum (6,4%. Quanto à sintomatologia, odinofagia (48,4%, nódulo no pescoço (19,3%, disfagia (12,9%; otalgia (9,7%, ferida na língua (6,4% e rouquidão (3,2%. Quanto ao estadiamento, T3-4 (74,1%, T1-2 (25,8%, N0 (29,0%, N1(29,0%, N2-3 (42,0%. CONCLUSÕES: O carcinoma espinocelular em mulheres predominou na 6feminine década, na raça branca, tendo como principais sintomas odinofagia e linfonodo cervical metastático. Houve predomínio do tabagismo sobre o etilismo, em paciente T3-4, sendo que a maioria já portador de metástase linfonodal à 1feminine consulta.

  5. Detection of environmental carcinogens-DNA

    International Nuclear Information System (INIS)

    Pfohl-Leszkowicz, A.; Guillemaut, G.; Rether, B.; Masfaraud, J.F.; Haguenoer, J.M.

    1995-01-01

    It has been estimated that majority of human cancer is due to environmental factors including pollutants in air, soil, water and food, work places exposure and personal habits such as smoking. After penetration in organism, xenobiotics could be directly excreted or are bio transformed by oxidation or reduction in more hydrophilic compounds which could be conjugate and then eliminated in urine. But in some case, the biotransformation leads to electrophilic compounds which interact with macromolecules such as DNA, forming addition products named adduct. The 32 P post-labelling method, inspired by recent developments in the methodology for sequencing nucleic acids, is an extremely sensitive method for assessing and quantifying DNA adducts and is applicable to structurally diverse classes of chemicals. In the first study, we have analysed hepatic DNA from fish living in the River Rhone downstream and upstream from a polychlorinated biphenyl incineration plant. Our results suggest that fish are exposed to genotoxic chemicals. In another study, leave DNA from healthy and declining hop were analysed. The total adduct level is 3 time higher in declining hop. A comparison between DNA adducts from several vegetal cells cultured in presence of heptachlor and DNA adduct in declining hop, confirmed the implication of heptachlor. In these examples, our data indicate the usefulness of the 32 P-post labelling method to assess the contamination of the environment by genotoxic pollutants. Epidemiological data suggested that increasing exposure to airborne PAH contributes to increase risk cancer in this population. Exposure-dependent adducts were detected in while blood cells in coke oven workers. The adduct levels is function of the level of pollutant. In the last example we have analysed lung tissue from patient with cancer. We observed many adducts in peritumoral tissue, while few adducts could be detected in tumoral tissues. (author)

  6. A Review on Video-Based Human Activity Recognition

    Directory of Open Access Journals (Sweden)

    Shian-Ru Ke

    2013-06-01

    Full Text Available This review article surveys extensively the current progresses made toward video-based human activity recognition. Three aspects for human activity recognition are addressed including core technology, human activity recognition systems, and applications from low-level to high-level representation. In the core technology, three critical processing stages are thoroughly discussed mainly: human object segmentation, feature extraction and representation, activity detection and classification algorithms. In the human activity recognition systems, three main types are mentioned, including single person activity recognition, multiple people interaction and crowd behavior, and abnormal activity recognition. Finally the domains of applications are discussed in detail, specifically, on surveillance environments, entertainment environments and healthcare systems. Our survey, which aims to provide a comprehensive state-of-the-art review of the field, also addresses several challenges associated with these systems and applications. Moreover, in this survey, various applications are discussed in great detail, specifically, a survey on the applications in healthcare monitoring systems.

  7. Automatic Video-based Analysis of Human Motion

    DEFF Research Database (Denmark)

    Fihl, Preben

    The human motion contains valuable information in many situations and people frequently perform an unconscious analysis of the motion of other people to understand their actions, intentions, and state of mind. An automatic analysis of human motion will facilitate many applications and thus has...... received great interest from both industry and research communities. The focus of this thesis is on video-based analysis of human motion and the thesis presents work within three overall topics, namely foreground segmentation, action recognition, and human pose estimation. Foreground segmentation is often...... the first important step in the analysis of human motion. By separating foreground from background the subsequent analysis can be focused and efficient. This thesis presents a robust background subtraction method that can be initialized with foreground objects in the scene and is capable of handling...

  8. Retraction: Evaluation of Carcinogenic Effects of Electromagnetic Fields (Emf

    Directory of Open Access Journals (Sweden)

    Bakir Mehic

    2010-08-01

    Full Text Available This retracts the article "EVALUATION OF CARCINOGENIC EFFECTS OF ELECTROMAGNETIC FIELDS (EMF" on page 245. The Editor-in-chief of the Bosnian Journal ofBasic Medical Sciences has decided to retract the article from Bayazit V et al. [1] entitled as: “Evaluation of carcinogenic effects of electromagnetic fields (EMF” published in Bosn J Basic Med Sci. 2010 Aug;10(3:245-50.After the editorial office was alerted of possible plagiarism in the article, it conducted thorough investigation and concluded that the article apparently represents plagiarized material from two World Health Organization reports, one European Commission report and other sources. Since this is considered scientific plagiarism and scientific misconduct, Editor-in-chief has decided to withdraw the article. The authors have agreed with the editorial office decision.

  9. Quantitative structure carcinogenicity relationship for detecting structural alerts in nitroso-compounds

    International Nuclear Information System (INIS)

    Helguera, Aliuska Morales; Cordeiro, M. Natalia D.S.; Perez, Miguel Angel Cabrera; Combes, Robert D.; Gonzalez, Maykel Perez

    2008-01-01

    In this work, Quantitative Structure-Activity Relationship (QSAR) modelling was used as a tool for predicting the carcinogenic potency of a set of 39 nitroso-compounds, which have been bioassayed in male rats by using the oral route of administration. The optimum QSAR model provided evidence of good fit and performance of predicitivity from training set. It was able to account for about 84% of the variance in the experimental activity and exhibited high values of the determination coefficients of cross validations, leave one out and bootstrapping (q 2 LOO = 78.53 and q 2 Boot = 74.97). Such a model was based on spectral moments weighted with Gasteiger-Marsilli atomic charges, polarizability and hydrophobicity, as well as with Abraham indexes, specifically the summation solute hydrogen bond basicity and the combined dipolarity/polarizability. This is the first study to have explored the possibility of combining Abraham solute descriptors with spectral moments. A reasonable interpretation of these molecular descriptors from a toxicological point of view was achieved by means of taking into account bond contributions. The set of relationships so derived revealed the importance of the length of the alkyl chains for determining carcinogenic potential of the chemicals analysed, and were able to explain the difference between mono-substituted and di-substituted nitrosoureas as well as to discriminate between isomeric structures with hydroxyl-alkyl and alkyl substituents in different positions. Moreover, they allowed the recognition of structural alerts in classical structures of two potent nitrosamines, consistent with their biotransformation. These results indicate that this new approach has the potential for improving carcinogenicity predictions based on the identification of structural alerts

  10. Carcinogenicity of glyphosate: why is New Zealand's EPA lost in the weeds?

    Science.gov (United States)

    Douwes, Jeroen; 't Mannetje, Andrea; McLean, Dave; Pearce, Neil; Woodward, Alistair; Potter, John D

    2018-03-23

    In 2015, the International Agency for Research on Cancer (IARC) concluded that glyphosate is "probably carcinogenic to humans". The New Zealand Environmental Protection Authority (NZEPA) rejected this and commissioned a new report, concluding that glyphosate was unlikely to be genotoxic or carcinogenic to humans. The NZEPA has argued that the difference arose because IARC is a "hazard-identification authority", whereas NZEPA is a "regulatory body that needs to cast the net more widely". We conclude that the NZEPA process for evaluating the carcinogenicity of glyphosate was flawed and the post hoc justification invalid: there is no mention of risk assessment or "net-benefit approach" in the NZEPA report; and there is no discussion of current New Zealand glyphosate exposures. Further, the NZEPA report quotes heavily from the European Food Safety Authority (EFSA) report, which is itself markedly flawed, and like the NZEPA report, relies heavily on industry-funded and industry-manipulated reviews. Given the scientific flaws in both reports we urge that: the NZEPA report be withdrawn; the NZEPA respond to the concerns raised and for a reassessment to be conducted; and clearer process and better understanding of science be used to inform any future review of hazardous substances in New Zealand.

  11. Population variability in biological adaptive responses to DNA damage and the shapes of carcinogen dose-response curves

    International Nuclear Information System (INIS)

    Conolly, Rory B.; Gaylor, David W.; Lutz, Werner K.

    2005-01-01

    Carcinogen dose-response curves for both ionizing radiation and chemicals are typically assumed to be linear at environmentally relevant doses. This assumption is used to ensure protection of the public health in the absence of relevant dose-response data. A theoretical justification for the assumption has been provided by the argument that low dose linearity is expected when an exogenous agent adds to an ongoing endogenous process. Here, we use computational modeling to evaluate (1) how two biological adaptive processes, induction of DNA repair and cell cycle checkpoint control, may affect the shapes of dose-response curves for DNA-damaging carcinogens and (2) how the resulting dose-response behaviors may vary within a population. Each model incorporating an adaptive process was capable of generating not only monotonic dose-responses but also nonmonotonic (J-shaped) and threshold responses. Monte Carlo analysis suggested that all these dose-response behaviors could coexist within a population, as the spectrum of qualitative differences arose from quantitative changes in parameter values. While this analysis is largely theoretical, it suggests that (a) accurate prediction of the qualitative form of the dose-response requires a quantitative understanding of the mechanism (b) significant uncertainty is associated with human health risk prediction in the absence of such quantitative understanding and (c) a stronger experimental and regulatory focus on biological mechanisms and interindividual variability would allow flexibility in regulatory treatment of environmental carcinogens without compromising human health

  12. Risk assessment of nickel carcinogenicity and occupational lung cancer.

    OpenAIRE

    Shen, H M; Zhang, Q F

    1994-01-01

    Recent progress in risk assessment of nickel carcinogenicity and its correlation with occupational lung cancer in nickel-exposed workers is reviewed. Epidemiological investigations provide reliable data indicating the close relation between nickel exposure and high lung cancer risk, especially in nickel refineries. The nickel species-specific effects and the dose-response relationship between nickel exposure and lung cancer are among the main questions that are explored extensively. It is als...

  13. Biomarkers for exposure to ambient air pollution - Comparison of carcinogen-DNA adduct levels with other exposure markers and markers for oxidative stress

    DEFF Research Database (Denmark)

    Autrup, Herman; Daneshvar, Bahram; Dragsted, Lars Ove

    1999-01-01

    Human exposure to genotoxic compounds present in ambient air has been studied using selected biomarkers in nonsmoking Danish bus drivers and postal workers. A large interindividual variation in biomarker levels was observed. Significantly higher levels of bulky carcinogen-DNA adducts (75.42 adducts...... correlations were observed between bulky carcinogen-DNA adduct and PAM-albumin levels (p = 0.005), and between DNA adduct and gamma-glutamyl semialdehyde (GGS) in hemoglobin (p = 0.11). Highly significant correlations were found between PAM-albumin adducts and AAS in plasma (r = 0.001) and GGS in hemoglobin (p...... in the combined group. A significant negative correlation was only observed between bulky carcinogen-DNA adducts and PAM-albumin adducts (p = 0.02) and between DNA adduct and urinary mutagenic activity (p = 0.02) in the GSTM1 null group, bur not in the workers who were homozygotes or heterozygotes for GSTM1. Our...

  14. A novel polar-based human face recognition computational model

    Directory of Open Access Journals (Sweden)

    Y. Zana

    2009-07-01

    Full Text Available Motivated by a recently proposed biologically inspired face recognition approach, we investigated the relation between human behavior and a computational model based on Fourier-Bessel (FB spatial patterns. We measured human recognition performance of FB filtered face images using an 8-alternative forced-choice method. Test stimuli were generated by converting the images from the spatial to the FB domain, filtering the resulting coefficients with a band-pass filter, and finally taking the inverse FB transformation of the filtered coefficients. The performance of the computational models was tested using a simulation of the psychophysical experiment. In the FB model, face images were first filtered by simulated V1- type neurons and later analyzed globally for their content of FB components. In general, there was a higher human contrast sensitivity to radially than to angularly filtered images, but both functions peaked at the 11.3-16 frequency interval. The FB-based model presented similar behavior with regard to peak position and relative sensitivity, but had a wider frequency band width and a narrower response range. The response pattern of two alternative models, based on local FB analysis and on raw luminance, strongly diverged from the human behavior patterns. These results suggest that human performance can be constrained by the type of information conveyed by polar patterns, and consequently that humans might use FB-like spatial patterns in face processing.

  15. Ardipithecus ramidus and the evolution of the human cranial base.

    Science.gov (United States)

    Kimbel, William H; Suwa, Gen; Asfaw, Berhane; Rak, Yoel; White, Tim D

    2014-01-21

    The early Pliocene African hominoid Ardipithecus ramidus was diagnosed as a having a unique phylogenetic relationship with the Australopithecus + Homo clade based on nonhoning canine teeth, a foreshortened cranial base, and postcranial characters related to facultative bipedality. However, pedal and pelvic traits indicating substantial arboreality have raised arguments that this taxon may instead be an example of parallel evolution of human-like traits among apes around the time of the chimpanzee-human split. Here we investigated the basicranial morphology of Ar. ramidus for additional clues to its phylogenetic position with reference to African apes, humans, and Australopithecus. Besides a relatively anterior foramen magnum, humans differ from apes in the lateral shift of the carotid foramina, mediolateral abbreviation of the lateral tympanic, and a shortened, trapezoidal basioccipital element. These traits reflect a relative broadening of the central basicranium, a derived condition associated with changes in tympanic shape and the extent of its contact with the petrous. Ar. ramidus shares with Australopithecus each of these human-like modifications. We used the preserved morphology of ARA-VP 1/500 to estimate the missing basicranial length, drawing on consistent proportional relationships in apes and humans. Ar. ramidus is confirmed to have a relatively short basicranium, as in Australopithecus and Homo. Reorganization of the central cranial base is among the earliest morphological markers of the Ardipithecus + Australopithecus + Homo clade.

  16. Meat intake, cooking methods, dietary carcinogens, and colorectal cancer risk: findings from the Colorectal Cancer Family Registry

    International Nuclear Information System (INIS)

    Joshi, Amit D; Kim, Andre; Lewinger, Juan Pablo; Ulrich, Cornelia M; Potter, John D; Cotterchio, Michelle; Le Marchand, Loic; Stern, Mariana C

    2015-01-01

    Diets high in red meat and processed meats are established colorectal cancer (CRC) risk factors. However, it is still not well understood what explains this association. We conducted comprehensive analyses of CRC risk and red meat and poultry intakes, taking into account cooking methods, level of doneness, estimated intakes of heterocyclic amines (HCAs) that accumulate during meat cooking, tumor location, and tumor mismatch repair proficiency (MMR) status. We analyzed food frequency and portion size data including a meat cooking module for 3364 CRC cases, 1806 unaffected siblings, 136 unaffected spouses, and 1620 unaffected population-based controls, recruited into the CRC Family Registry. Odds ratios (OR) and 95% confidence intervals (CI) for nutrient density variables were estimated using generalized estimating equations. We found no evidence of an association between total nonprocessed red meat or total processed meat and CRC risk. Our main finding was a positive association with CRC for pan-fried beefsteak (P trend < 0.001), which was stronger among MMR deficient cases (heterogeneity P = 0.059). Other worth noting associations, of borderline statistical significance after multiple testing correction, were a positive association between diets high in oven-broiled short ribs or spareribs and CRC risk (P trend = 0.002), which was also stronger among MMR-deficient cases, and an inverse association with grilled hamburgers (P trend = 0.002). Our results support the role of specific meat types and cooking practices as possible sources of human carcinogens relevant for CRC risk

  17. Lunasin-aspirin combination against NIH/3T3 cells transformation induced by chemical carcinogens.

    Science.gov (United States)

    Hsieh, Chia-Chien; Hernández-Ledesma, Blanca; de Lumen, Ben O

    2011-06-01

    Carcinogenesis is a multistage process involving a number of molecular pathways sensitive to intervention. Chemoprevention is defined as the use of natural and/or synthetic substances to block, reverse, or retard the process of carcinogenesis. To achieve greater inhibitory effects on cancer cells, combination of two or more chemopreventive agents is commonly considered as a better preventive and/or therapeutic strategy. Lunasin is a promising cancer preventive peptide identified in soybean and other seeds. Its efficacy has been demonstrated by both in vitro and in vivo models. This peptide has been found to inhibit human breast cancer MDA-MB-231 cells proliferation, suppressing cell cycle progress and inducing cell apoptosis. Moreover, lunasin potentiates the effects on these cells of different synthetic and natural compounds, such as aspirin and anacardic acid. This study explored the role of lunasin, alone and in combination with aspirin and anacardic acid on cell proliferation and foci formation of transformed NIH/3T3 cells induced by chemical carcinogens 7,12-dimethylbenz[a]anthracene or 3-methylcholanthrene. The results revealed that lunasin, acting as a single agent, inhibits cell proliferation and foci formation. When combined with aspirin, these effects were significantly increased, indicating that this combination might be a promising strategy to prevent/treat cancer induced by chemical carcinogens.

  18. DNA damage by ethylbenzenehydroperoxide formed from carcinogenic ethylbenzene by sunlight irradiation

    International Nuclear Information System (INIS)

    Toda, Chitose; Uchida, Takafumi; Midorikawa, Kaoru; Murata, Mariko; Hiraku, Yusuke; Okamoto, Yoshinori; Ueda, Koji; Kojima, Nakao; Kawanishi, Shosuke

    2003-01-01

    Ethylbenzene, widely used in human life, is a non-mutagenic carcinogen. Sunlight-irradiated ethylbenzene caused DNA damage in the presence of Cu 2+ , but unirradiated ethylbenzene did not. A Cu + -specific chelator bathocuproine inhibited DNA damage and catalase showed a little inhibitory effect. The scopoletin assay revealed that peroxides and H 2 O 2 were formed in ethylbenzene exposed to sunlight. These results suggest that Cu + and alkoxyl radical mainly participate in DNA damage, and H 2 O 2 partially does. When catalase was added, DNA damage at thymine and cytosine was inhibited. Ethylbenzenehydroperoxide, identified by GC/MS analysis, induced the formation of 8-oxo-7,8-dihydro-2 ' -deoxyguanosine and caused DNA damage at consecutive guanines, as observed with cumenehydroperoxide. Equimolar concentrations of H 2 O 2 and acetophenone were produced by the sunlight-irradiation of 1-phenylethanol, a further degraded product of ethylbenzene. These results indicate a novel pathway that oxidative DNA damage induced by the peroxide and H 2 O 2 derived from sunlight-irradiated ethylbenzene may lead to expression of the carcinogenicity

  19. Carcinogenic nitrosamines in traditional beer as the cause of oesophageal squamous cell carcinoma in black South Africans.

    Science.gov (United States)

    Pillay, Viness; Isaacson, Charles; Mothobi, Pride; Hale, Martin; Tomar, Lomas Kumar; Tyagi, Charu; Altini, Mario; Choonara, Yahya Essop; Kumar, Pradeep

    2015-09-21

    Before the 1930s, squamous cell carcinoma (SCC) of the oesophagus was almost unknown among black South Africans. From the 1930s the annual frequency rose. A dietary cause was sought, the staple diet of black people having changed from sorghum to maize (corn), with traditional beer being brewed from maize. Carcinogenic N-nitrosamines in traditional beer were suggested as a cause of SCC of the oesophagus, with Fusarium moniliforme, a corn saprophyte, thought to play a role. To confirm the presence of N-nitrosamines in traditional beer and demonstrate a mechanism for the oncogenesis of oesophageal carcinoma. Analysis by high-performance liquid chromatography was conducted for the identification of nitrosamines in traditional beer samples, and molecular docking studies were employed to predict the affinity between N-nitrosamines and the S100A2 protein. Carcinogenic N-nitrosamines were identified in all six samples of traditional beer examined (N=18 analyses), and docking studies confirmed a high affinity of the nitrosamine N-nitrosopyrrolidone with the S100A2 protein. This may result in the altered expression of the S100A2 protein, leading to tumour progression and prognosis. It is suggested that carcinogenic N-nitrosamines in traditional beer are a major factor in the causation of SCC of the oesophagus in black South Africans. N-nitrosamines have been shown to produce cancer experimentally, but there has not been conclusive epidemiological evidence that N-nitrosamines are carcinogenic to humans. This study is the first to demonstrate the potential link between N-nitrosamines and a human tumour.

  20. Developing Hydrogeological Site Characterization Strategies based on Human Health Risk

    Science.gov (United States)

    de Barros, F.; Rubin, Y.; Maxwell, R. M.

    2013-12-01

    In order to provide better sustainable groundwater quality management and minimize the impact of contamination in humans, improved understanding and quantification of the interaction between hydrogeological models, geological site information and human health are needed. Considering the joint influence of these components in the overall human health risk assessment and the corresponding sources of uncertainty aid decision makers to better allocate resources in data acquisition campaigns. This is important to (1) achieve remediation goals in a cost-effective manner, (2) protect human health and (3) keep water supplies clean in order to keep with quality standards. Such task is challenging since a full characterization of the subsurface is unfeasible due to financial and technological constraints. In addition, human exposure and physiological response to contamination are subject to uncertainty and variability. Normally, sampling strategies are developed with the goal of reducing uncertainty, but less often they are developed in the context of their impacts on the overall system uncertainty. Therefore, quantifying the impact from each of these components (hydrogeological, behavioral and physiological) in final human health risk prediction can provide guidance for decision makers to best allocate resources towards minimal prediction uncertainty. In this presentation, a multi-component human health risk-based framework is presented which allows decision makers to set priorities through an information entropy-based visualization tool. Results highlight the role of characteristic length-scales characterizing flow and transport in determining data needs within an integrated hydrogeological-health framework. Conditions where uncertainty reduction in human health risk predictions may benefit from better understanding of the health component, as opposed to a more detailed hydrogeological characterization, are also discussed. Finally, results illustrate how different dose

  1. Carcinogenic Air Toxics Exposure and Their Cancer-Related Health Impacts in the United States.

    Directory of Open Access Journals (Sweden)

    Ying Zhou

    Full Text Available Public health protection from air pollution can be achieved more effectively by shifting from a single-pollutant approach to a multi-pollutant approach. To develop such multi-pollutant approaches, identifying which air pollutants are present most frequently is essential. This study aims to determine the frequently found carcinogenic air toxics or hazardous air pollutants (HAPs combinations across the United States as well as to analyze the health impacts of developing cancer due to exposure to these HAPs. To identify the most commonly found carcinogenic air toxics combinations, we first identified HAPs with cancer risk greater than one in a million in more than 5% of the census tracts across the United States, based on the National-Scale Air Toxics Assessment (NATA by the U.S. EPA for year 2005. We then calculated the frequencies of their two-component (binary, and three-component (ternary combinations. To quantify the cancer-related health impacts, we focused on the 10 most frequently found HAPs with national average cancer risk greater than one in a million. Their cancer-related health impacts were calculated by converting lifetime cancer risk reported in NATA 2005 to years of healthy life lost or Disability-Adjusted Life Years (DALYs. We found that the most frequently found air toxics with cancer risk greater than one in a million are formaldehyde, carbon tetrachloride, acetaldehyde, and benzene. The most frequently occurring binary pairs and ternary mixtures are the various combinations of these four air toxics. Analysis of urban and rural HAPs did not reveal significant differences in the top combinations of these chemicals. The cumulative annual cancer-related health impacts of inhaling the top 10 carcinogenic air toxics included was about 1,600 DALYs in the United States or 0.6 DALYs per 100,000 people. Formaldehyde and benzene together contribute nearly 60 percent of the total cancer-related health impacts. Our study shows that although

  2. Carcinogenic Air Toxics Exposure and Their Cancer-Related Health Impacts in the United States.

    Science.gov (United States)

    Zhou, Ying; Li, Chaoyang; Huijbregts, Mark A J; Mumtaz, M Moiz

    2015-01-01

    Public health protection from air pollution can be achieved more effectively by shifting from a single-pollutant approach to a multi-pollutant approach. To develop such multi-pollutant approaches, identifying which air pollutants are present most frequently is essential. This study aims to determine the frequently found carcinogenic air toxics or hazardous air pollutants (HAPs) combinations across the United States as well as to analyze the health impacts of developing cancer due to exposure to these HAPs. To identify the most commonly found carcinogenic air toxics combinations, we first identified HAPs with cancer risk greater than one in a million in more than 5% of the census tracts across the United States, based on the National-Scale Air Toxics Assessment (NATA) by the U.S. EPA for year 2005. We then calculated the frequencies of their two-component (binary), and three-component (ternary) combinations. To quantify the cancer-related health impacts, we focused on the 10 most frequently found HAPs with national average cancer risk greater than one in a million. Their cancer-related health impacts were calculated by converting lifetime cancer risk reported in NATA 2005 to years of healthy life lost or Disability-Adjusted Life Years (DALYs). We found that the most frequently found air toxics with cancer risk greater than one in a million are formaldehyde, carbon tetrachloride, acetaldehyde, and benzene. The most frequently occurring binary pairs and ternary mixtures are the various combinations of these four air toxics. Analysis of urban and rural HAPs did not reveal significant differences in the top combinations of these chemicals. The cumulative annual cancer-related health impacts of inhaling the top 10 carcinogenic air toxics included was about 1,600 DALYs in the United States or 0.6 DALYs per 100,000 people. Formaldehyde and benzene together contribute nearly 60 percent of the total cancer-related health impacts. Our study shows that although there are many

  3. Effectiveness of a Mass Media Campaign on Oral Carcinogens and Their Effects on the Oral Cavity

    Science.gov (United States)

    Shrestha, Ashish; Rimal, Jyotsna

    2018-03-27

    Objective: To develop a mass media campaign on oral carcinogens and their effects on the oral cavity in order to increase awareness among the general population. Methods: Documentary and public service announcements highlighting the effects of tobacco and its products were designed and developed based on principles of behavior change. A questionnaire, designed to determine the knowledge, attitude and practice of people regarding oral carcinogens, was used to conduct a baseline survey at various sites in eastern Nepal. Local television channels and radio stations broadcasted the documentary and public service announcements. An evaluation survey was then performed to assess the effectiveness of the campaign. Results: Baseline and evaluation surveys covered 1,972 and 2,140 individuals, respectively. A third of the baseline population consumed quid, 22% chewing tobacco, 16% gutka (commercial preparation of arecanut, tobacco, lime and chemicals) and 25% cigarettes. Tobacco consumption differed significantly between 3 ecologic regions with greater use in the Terai region. The knowledge prevalence regarding the oral carcinogens quid (70%), chewing tobacco (82%), gutka (58%) and cigarettes (93%) significantly increased in the evaluation population. Females were more aware about the various tobacco products and their effects on health. More people knew about the harmful effects of tobacco on their health and oral cavity, and had their mouth examined and the frequency of consumption of these products reduced significantly after the campaign. Attitudes towards production, sale and advertisements of tobacco also improved significantly. Conclusions: The mass media campaign was an effective tool for increasing awareness among the population. Creative Commons Attribution License

  4. Evaluation of tests using DNA repair-deficient bacteria for predicting genotoxicity and carcinogenicity

    Energy Technology Data Exchange (ETDEWEB)

    Leifer, Z.; Kada, T.; Mandel, M.; Zeiger, E.; Stafford, R.; Rosenkranz, H.S.

    1981-01-01

    The detection of DNA-damaging agents by repair-deficient bacterial assays is based on the differential inhibition of growth of repair-proficient and repair-deficient bacterial pairs. The various methodologies used are described and recommendations are made for their improved use. In a survey of the literature through April 1979, 91 of 276 papers evaluated contained usable data, resulting in an analysis of 611 compounds that had been assayed in 1 or more of 55 pairs of repair-proficient and repair-deficient strains. The results indicate that a liquid suspension assay is more sensitive than a spot (diffusion) test. There was a 78% correspondence between results obtained with E. coli polA and Bacillus subtilis (H17/M45, 17A/45T) rec assay and between E. coli polA and Proteus mirabilis. In a comparison of test results with carcinogenicity data, 44 of 71 (62%) carcinogenic compounds assayed by the polA system were positive, 10 (14%) were negative, and 17 (24%) gave No Test or doubtful results. The results were analyzed with respect to chemical classes. E. coli polA detected the highest percentage of hydroxylamines and alkyl epoxides. The B. subtilis rec assay detected the highest percentage of nitrosamines and sulfur and nitrogen oxides. It is concluded that some of these test systems are effective tools for the detection of DNA-damaging and potentially carcinogenic compounds, especially if the assay is done in liquid suspension and if more than 1 pair of tester strains is used. Advantages and disadvantages of the assay are discussed and suggestions are made for improvements in the system.

  5. Cost-based industrial enterprise human capital management

    Directory of Open Access Journals (Sweden)

    Glukhov Sergei

    2017-01-01

    Full Text Available The paper focuses on importance of human capital in development of industrial enterprises, issues of their management and methods of achieving balance between interests of owners and employees. Difference between such concepts as human and labor potential as well as human and working capital is clarified. The special attention is paid to the fact that an effective system of motivation and incentivation of labor is to serve as means of rapprochement of human and labor capital. The authors point out the limited scope of the traditional forms of labor motivation and incentivation mechanisms and highlight the complexity of their encouragement for collective work results. The authors suggest using the cost-based approach to workforce management, which is based on assessment of market and intrinsic value of human capital in view of investment and quality characteristics. The proposed approach is attended by methodological support and operational calculations. The study states that the suggested human capital management model can be introduced into practice, as well as substantiates the necessity for boosting the performance of industrial enterprises and their cost by increasing production, stimulating the staff for selfrealization and self-improvement by bringing the owners’ corporate interests closer to the interests of the employees.

  6. Exposure to polycyclic aromatic hydrocarbons in atmospheric PM1.0 of urban environments: Carcinogenic and mutagenic respiratory health risk by age groups.

    Science.gov (United States)

    Agudelo-Castañeda, Dayana M; Teixeira, Elba C; Schneider, Ismael L; Lara, Sheila Rincón; Silva, Luis F O

    2017-05-01

    We investigated the carcinogenic and mutagenic respiratory health risks related to the exposure to atmospheric PAHs in an urban area. Our study focused in the association of these pollutants and their possible effect in human health, principally respiratory and circulatory diseases. Also, we determined a relationship between the inhalation risk of PAHs and meteorological conditions. We validated the hypothesis that in winter PAHs with high molecular weight associated to submicron particles (PM 1 ) may increase exposure risk, especially for respiratory diseases, bronchitis and pneumonia diseases. Moreover, in our study we verified the relationship between diseases and several carcinogenic PAHs (Ind, BbkF, DahA, BaP, and BghiP). These individual PAHs contributed the most to the potential risk of exposure for inhalation of PM 1.0 . Even at lower ambient concentrations of BaP and DahA in comparison with individual concentrations of other PAHs associated to PM 1.0 . Mainly, research suggests to include carcinogenic and mutagenic PAHs in future studies of environmental health risk due to their capacity to associate to PM 10 . Such carcinogenic and mutagenic PAHs are likely to provide the majority of the human exposure, since they originate from dense traffic urban areas were humans congregate. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Human Posture and Movement Prediction based on Musculoskeletal Modeling

    DEFF Research Database (Denmark)

    Farahani, Saeed Davoudabadi

    2014-01-01

    Abstract This thesis explores an optimization-based formulation, so-called inverse-inverse dynamics, for the prediction of human posture and motion dynamics performing various tasks. It is explained how this technique enables us to predict natural kinematic and kinetic patterns for human posture...... and motion using AnyBody Modeling System (AMS). AMS uses inverse dynamics to analyze musculoskeletal systems and is, therefore, limited by its dependency on input kinematics. We propose to alleviate this dependency by assuming that voluntary postures and movement strategies in humans are guided by a desire...... expenditure, joint forces and other physiological properties derived from the detailed musculoskeletal analysis. Several attempts have been made to uncover the principles underlying motion control strategies in the literature. In case of some movements, like human squat jumping, there is almost no doubt...

  8. Identification of walking human model using agent-based modelling

    Science.gov (United States)

    Shahabpoor, Erfan; Pavic, Aleksandar; Racic, Vitomir

    2018-03-01

    The interaction of walking people with large vibrating structures, such as footbridges and floors, in the vertical direction is an important yet challenging phenomenon to describe mathematically. Several different models have been proposed in the literature to simulate interaction of stationary people with vibrating structures. However, the research on moving (walking) human models, explicitly identified for vibration serviceability assessment of civil structures, is still sparse. In this study, the results of a comprehensive set of FRF-based modal tests were used, in which, over a hundred test subjects walked in different group sizes and walking patterns on a test structure. An agent-based model was used to simulate discrete traffic-structure interactions. The occupied structure modal parameters found in tests were used to identify the parameters of the walking individual's single-degree-of-freedom (SDOF) mass-spring-damper model using 'reverse engineering' methodology. The analysis of the results suggested that the normal distribution with the average of μ = 2.85Hz and standard deviation of σ = 0.34Hz can describe human SDOF model natural frequency. Similarly, the normal distribution with μ = 0.295 and σ = 0.047 can describe the human model damping ratio. Compared to the previous studies, the agent-based modelling methodology proposed in this paper offers significant flexibility in simulating multi-pedestrian walking traffics, external forces and simulating different mechanisms of human-structure and human-environment interaction at the same time.

  9. Coal-tar-based pavement sealcoat, polycyclic aromatic Hydrocarbons (PAHs), and environmental health

    Science.gov (United States)

    Mahler, B.J.; Van Metre, P.C.

    2011-01-01

    Studies by the U.S. Geological Survey (USGS) have identified coal-tar-based sealcoat-the black, viscous liquid sprayed or painted on asphalt pavement such as parking lots-as a major source of polycyclic aromatic hydrocarbon (PAH) contamination in urban areas for large parts of the Nation. Several PAHs are suspected human carcinogens and are toxic to aquatic life.

  10. Training together: how another human's presence affects behavior during virtual human-based team training

    Directory of Open Access Journals (Sweden)

    Andrew Robb

    2016-08-01

    developing virtual human-based training programs, designers should consider that the presence of other humans may reduce involvement during training moments perceived to be the responsibility of other trainees, and should consider that a virtual teammate's limitations may cause human teammates to limit their own behaviors in corresponding ways (e.g. searching less.

  11. Carcinogenic effect of sequential artificial sunlight and UV-A irradiation in hairless mice. Consequences for solarium 'therapy'

    International Nuclear Information System (INIS)

    Staberg, B.; Wulf, H.C.; Poulsen, T.; Klemp, P.; Brodthagen, H.

    1983-01-01

    The carcinogenic effect of artificial UV sunlight followed by UV-A irradiation in human solaria doses has been studied with the use of the hairless mouse as an animal model. Artificial sunlight exposure alone induced only a moderate skin tumor incidence (animals with at least one tumor) of 0.15 after one year, and UV-A irradiation alone induced no tumor formation. However, the combination of artificial sunlight exposure and subsequent UV-A irradiation significantly increased the tumor incidence to 0.72. We conclude that, in humans, tanning with UV-A for cosmetic purposes may not be an innocuous procedure

  12. Human skin wetness perception: psychophysical and neurophysiological bases

    Science.gov (United States)

    Filingeri, Davide; Havenith, George

    2015-01-01

    The ability to perceive thermal changes in the surrounding environment is critical for survival. However, sensing temperature is not the only factor among the cutaneous sensations to contribute to thermoregulatory responses in humans. Sensing skin wetness (i.e. hygrosensation) is also critical both for behavioral and autonomic adaptations. Although much has been done to define the biophysical role of skin wetness in contributing to thermal homeostasis, little is known on the neurophysiological mechanisms underpinning the ability to sense skin wetness. Humans are not provided with skin humidity receptors (i.e., hygroreceptors) and psychophysical studies have identified potential sensory cues (i.e. thermal and mechanosensory) which could contribute to sensing wetness. Recently, a neurophysiological model of human wetness sensitivity has been developed. In helping clarifying the peripheral and central neural mechanisms involved in sensing skin wetness, this model has provided evidence for the existence of a specific human hygrosensation strategy, which is underpinned by perceptual learning via sensory experience. Remarkably, this strategy seems to be shared by other hygroreceptor-lacking animals. However, questions remain on whether these sensory mechanisms are underpinned by specific neuromolecular pathways in humans. Although the first study on human wetness perception dates back to more than 100 years, it is surprising that the neurophysiological bases of such an important sensory feature have only recently started to be unveiled. Hence, to provide an overview of the current knowledge on human hygrosensation, along with potential directions for future research, this review will examine the psychophysical and neurophysiological bases of human skin wetness perception. PMID:27227008

  13. Simulation and Non-Simulation Based Human Reliability Analysis Approaches

    Energy Technology Data Exchange (ETDEWEB)

    Boring, Ronald Laurids [Idaho National Lab. (INL), Idaho Falls, ID (United States); Shirley, Rachel Elizabeth [Idaho National Lab. (INL), Idaho Falls, ID (United States); Joe, Jeffrey Clark [Idaho National Lab. (INL), Idaho Falls, ID (United States); Mandelli, Diego [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2014-12-01

    Part of the U.S. Department of Energy’s Light Water Reactor Sustainability (LWRS) Program, the Risk-Informed Safety Margin Characterization (RISMC) Pathway develops approaches to estimating and managing safety margins. RISMC simulations pair deterministic plant physics models with probabilistic risk models. As human interactions are an essential element of plant risk, it is necessary to integrate human actions into the RISMC risk model. In this report, we review simulation-based and non-simulation-based human reliability assessment (HRA) methods. Chapter 2 surveys non-simulation-based HRA methods. Conventional HRA methods target static Probabilistic Risk Assessments for Level 1 events. These methods would require significant modification for use in dynamic simulation of Level 2 and Level 3 events. Chapter 3 is a review of human performance models. A variety of methods and models simulate dynamic human performance; however, most of these human performance models were developed outside the risk domain and have not been used for HRA. The exception is the ADS-IDAC model, which can be thought of as a virtual operator program. This model is resource-intensive but provides a detailed model of every operator action in a given scenario, along with models of numerous factors that can influence operator performance. Finally, Chapter 4 reviews the treatment of timing of operator actions in HRA methods. This chapter is an example of one of the critical gaps between existing HRA methods and the needs of dynamic HRA. This report summarizes the foundational information needed to develop a feasible approach to modeling human interactions in the RISMC simulations.

  14. Do domestic dogs learn words based on humans' referential behaviour?

    Directory of Open Access Journals (Sweden)

    Sebastian Tempelmann

    Full Text Available Some domestic dogs learn to comprehend human words, although the nature and basis of this learning is unknown. In the studies presented here we investigated whether dogs learn words through an understanding of referential actions by humans rather than simple association. In three studies, each modelled on a study conducted with human infants, we confronted four word-experienced dogs with situations involving no spatial-temporal contiguity between the word and the referent; the only available cues were referential actions displaced in time from exposure to their referents. We found that no dogs were able to reliably link an object with a label based on social-pragmatic cues alone in all the tests. However, one dog did show skills in some tests, possibly indicating an ability to learn based on social-pragmatic cues.

  15. Fuzzy Modelling for Human Dynamics Based on Online Social Networks.

    Science.gov (United States)

    Cuenca-Jara, Jesus; Terroso-Saenz, Fernando; Valdes-Vela, Mercedes; Skarmeta, Antonio F

    2017-08-24

    Human mobility mining has attracted a lot of attention in the research community due to its multiple implications in the provisioning of innovative services for large metropolises. In this scope, Online Social Networks (OSN) have arisen as a promising source of location data to come up with new mobility models. However, the human nature of this data makes it rather noisy and inaccurate. In order to deal with such limitations, the present work introduces a framework for human mobility mining based on fuzzy logic. Firstly, a fuzzy clustering algorithm extracts the most active OSN areas at different time periods. Next, such clusters are the building blocks to compose mobility patterns. Furthermore, a location prediction service based on a fuzzy rule classifier has been developed on top of the framework. Finally, both the framework and the predictor has been tested with a Twitter and Flickr dataset in two large cities.

  16. Carcinogenic risk of chromium, copper and arsenic in CCA-treated wood

    International Nuclear Information System (INIS)

    Ohgami, Nobutaka; Yamanoshita, Osamu; Thang, Nguyen Dinh; Yajima, Ichiro; Nakano, Chihiro; Wenting, Wu; Ohnuma, Shoko

    2015-01-01

    We showed that 2.1% of 233 pieces of lumber debris after the Great East Japan Earthquake was chromated copper arsenate (CCA)-treated wood. Since hexavalent chromium (Cr), copper (Cu) and pentavalent arsenic (As) in the debris may be diffused in the air via incineration, we exposed human lung normal (BEAS-2B) and carcinoma (A549) cells to Cr, Cu and As at the molar ratio in a representative CCA-treated wood. Co-exposure to 0.10 μM Cr and 0.06 μM As, which solely had no effect on colony formation, synergistically promoted colony formation in BEAS-2B cells, but not A549 cells, with activation of the PI3K/AKT pathway. Sole exposure and co-exposure to Cu showed limited effects. Since previous reports showed Cr and As concentrations to which human lungs might be exposed, our results suggest the importance to avoid diffusion of Cr and As in the air via incineration of debris including CCA-treated wood after the disaster. - Highlights: • CCA-treated wood was found in debris after the Great East Japan Earthquake in 2011. • Carcinogenic risk of CCA-treated woods was evaluated with human lung cell lines. • Co-exposure to Cr and As synergistically promoted colony formation. • Co-exposure to Cr and As synergistically activated the PI3/AKT pathway. • Effects of sole exposure and co-exposure to Cu on colony formation were limited. - Co-exposure to Cr and As, but not Cu, in CCA-treated wood debris from the Great East Japan Earthquake showed carcinogenicity in vitro.

  17. Probabilistic health risk assessment of carcinogenic emissions from a MSW gasification plant.

    Science.gov (United States)

    Lonati, Giovanni; Zanoni, Francesca

    2012-09-01

    Health risk assessment due to the atmospheric emissions of carcinogenic pollutants (PCDD/Fs and Cd) from a waste gasification plant is performed by means of a probabilistic approach based on probability density functions for the description of the input data of the model parameters involved in the assessment. These functions incorporate both the epistemic and stochastic uncertainty of the input data (namely, the emission rate of the pollutants) and of all the parameters used for individual exposure assessment through the pathways of inhalation, soil ingestion and dermal contact, and diet. The uncertainty is propagated throughout the evaluation by Monte Carlo technique, resulting in the probability distribution of the individual risk. The median risk levels nearby the plant are in the 10(-8)-10(-10) range, ten-fold lower than the deterministic estimate based on precautionary values for the input data; however, the very upper percentiles (>95th) of the risk distribution can exceed the conventional 10(-6) reference value. The estimated risk is almost entirely determined by the Cd exposure through the diet; the pathways arising from PCDD/Fs exposure are without any practical significance, suggesting that the emission control should focus on Cd in order to reduce the carcinogenic risk. Risk variance decomposition shows the prevailing influence on the estimated risk of the Cd concentration at the emission stack: thus, for a more accurate risk assessment the efforts should focus primarily on the definition of its probability density function. Copyright © 2012 Elsevier Ltd. All rights reserved.

  18. Two-dimensional PCA-based human gait identification

    Science.gov (United States)

    Chen, Jinyan; Wu, Rongteng

    2012-11-01

    It is very necessary to recognize person through visual surveillance automatically for public security reason. Human gait based identification focus on recognizing human by his walking video automatically using computer vision and image processing approaches. As a potential biometric measure, human gait identification has attracted more and more researchers. Current human gait identification methods can be divided into two categories: model-based methods and motion-based methods. In this paper a two-Dimensional Principal Component Analysis and temporal-space analysis based human gait identification method is proposed. Using background estimation and image subtraction we can get a binary images sequence from the surveillance video. By comparing the difference of two adjacent images in the gait images sequence, we can get a difference binary images sequence. Every binary difference image indicates the body moving mode during a person walking. We use the following steps to extract the temporal-space features from the difference binary images sequence: Projecting one difference image to Y axis or X axis we can get two vectors. Project every difference image in the difference binary images sequence to Y axis or X axis difference binary images sequence we can get two matrixes. These two matrixes indicate the styles of one walking. Then Two-Dimensional Principal Component Analysis(2DPCA) is used to transform these two matrixes to two vectors while at the same time keep the maximum separability. Finally the similarity of two human gait images is calculated by the Euclidean distance of the two vectors. The performance of our methods is illustrated using the CASIA Gait Database.

  19. Some Biomaterials based on Collagen in Human Health care

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. Some Biomaterials based on Collagen in Human Health care. Ophthalmology. Wound healing. Burn Dressing. Tumor Treatment. Tissue Engineered devices. for cardio-vascular functions; For managing chronic illnesses including diabetic ulcers and foot. Smart shoe.

  20. Human rights literacy: Moving towards rights-based education and ...

    African Journals Online (AJOL)

    Our theoretical framework examines the continual process of moving towards an open and democratic society through the facilitation of human rights literacy, rights-based education and transformative action. We focus specifically on understandings of dignity, equality and freedom, as both rights (legal claims) and values ...

  1. A Virtual Campus Based on Human Factor Engineering

    Science.gov (United States)

    Yang, Yuting; Kang, Houliang

    2014-01-01

    Three Dimensional or 3D virtual reality has become increasingly popular in many areas, especially in building a digital campus. This paper introduces a virtual campus, which is based on a 3D model of The Tourism and Culture College of Yunnan University (TCYU). Production of the virtual campus was aided by Human Factor and Ergonomics (HF&E), an…

  2. Incorporating Campus-Based Cultural Resources into Humanities Courses

    Science.gov (United States)

    Traver, Amy E.; Nedd, Rolecia

    2018-01-01

    In this article, the authors reviewed one effort to deepen students' connections to the humanities through the use of campus-based cultural resources at Queensborough Community College (QCC) of the City University of New York (CUNY), a minority-serving institution in one of the most diverse counties in the United States. Focusing specifically on…

  3. Human action recognition using trajectory-based representation

    Directory of Open Access Journals (Sweden)

    Haiam A. Abdul-Azim

    2015-07-01

    Full Text Available Recognizing human actions in video sequences has been a challenging problem in the last few years due to its real-world applications. A lot of action representation approaches have been proposed to improve the action recognition performance. Despite the popularity of local features-based approaches together with “Bag-of-Words” model for action representation, it fails to capture adequate spatial or temporal relationships. In an attempt to overcome this problem, a trajectory-based local representation approaches have been proposed to capture the temporal information. This paper introduces an improvement of trajectory-based human action recognition approaches to capture discriminative temporal relationships. In our approach, we extract trajectories by tracking the detected spatio-temporal interest points named “cuboid features” with matching its SIFT descriptors over the consecutive frames. We, also, propose a linking and exploring method to obtain efficient trajectories for motion representation in realistic conditions. Then the volumes around the trajectories’ points are described to represent human actions based on the Bag-of-Words (BOW model. Finally, a support vector machine is used to classify human actions. The effectiveness of the proposed approach was evaluated on three popular datasets (KTH, Weizmann and UCF sports. Experimental results showed that the proposed approach yields considerable performance improvement over the state-of-the-art approaches.

  4. A survey on vision-based human action recognition

    NARCIS (Netherlands)

    Poppe, Ronald Walter

    Vision-based human action recognition is the process of labeling image sequences with action labels. Robust solutions to this problem have applications in domains such as visual surveillance, video retrieval and human–computer interaction. The task is challenging due to variations in motion

  5. A review of mammalian carcinogenicity study design and potential effects of alternate test procedures on the safety evaluation of food ingredients.

    Science.gov (United States)

    Hayes, A W; Dayan, A D; Hall, W C; Kodell, R L; Williams, G M; Waddell, W D; Slesinski, R S; Kruger, C L

    2011-06-01

    of test procedures, dose selection, histopathology procedures, application of historical control data, statistical evaluations and whether statistical extrapolations are supported by, or are beyond the limits of, the data generated. Without due consideration, there can be result conflicting data interpretations and uncertainty about the relevance of a study's results to human risk. This paper discusses the critical elements of rodent (rat) carcinogenicity studies, particularly with respect to the study of food ingredients. It also highlights study practices and procedures that can detract from the appropriate evaluation of human relevance of results, indicating the importance of adherence to international consensus protocols, such as those detailed by OECD. Copyright © 2010. Published by Elsevier Inc.

  6. Vision-based Human Action Classification Using Adaptive Boosting Algorithm

    KAUST Repository

    Zerrouki, Nabil; Harrou, Fouzi; Sun, Ying; Houacine, Amrane

    2018-01-01

    Precise recognition of human action is a key enabler for the development of many applications including autonomous robots for medical diagnosis and surveillance of elderly people in home environment. This paper addresses the human action recognition based on variation in body shape. Specifically, we divide the human body into five partitions that correspond to five partial occupancy areas. For each frame, we calculated area ratios and used them as input data for recognition stage. Here, we consider six classes of activities namely: walking, standing, bending, lying, squatting, and sitting. In this paper, we proposed an efficient human action recognition scheme, which takes advantages of superior discrimination capacity of AdaBoost algorithm. We validated the effectiveness of this approach by using experimental data from two publicly available databases fall detection databases from the University of Rzeszow’s and the Universidad de Málaga fall detection datasets. We provided comparisons of the proposed approach with state-of-the-art classifiers based on the neural network, K-nearest neighbor, support vector machine and naïve Bayes and showed that we achieve better results in discriminating human gestures.

  7. Vision-based Human Action Classification Using Adaptive Boosting Algorithm

    KAUST Repository

    Zerrouki, Nabil

    2018-05-07

    Precise recognition of human action is a key enabler for the development of many applications including autonomous robots for medical diagnosis and surveillance of elderly people in home environment. This paper addresses the human action recognition based on variation in body shape. Specifically, we divide the human body into five partitions that correspond to five partial occupancy areas. For each frame, we calculated area ratios and used them as input data for recognition stage. Here, we consider six classes of activities namely: walking, standing, bending, lying, squatting, and sitting. In this paper, we proposed an efficient human action recognition scheme, which takes advantages of superior discrimination capacity of AdaBoost algorithm. We validated the effectiveness of this approach by using experimental data from two publicly available databases fall detection databases from the University of Rzeszow’s and the Universidad de Málaga fall detection datasets. We provided comparisons of the proposed approach with state-of-the-art classifiers based on the neural network, K-nearest neighbor, support vector machine and naïve Bayes and showed that we achieve better results in discriminating human gestures.

  8. Changes in the classification of carcinogenic chemicals in the work area. (Section III of the German List of MAK and BAT values).

    Science.gov (United States)

    Neumann, H G; Thielmann, H W; Filser, J G; Gelbke, H P; Greim, H; Kappus, H; Norpoth, K H; Reuter, U; Vamvakas, S; Wardenbach, P; Wichmann, H E

    1998-01-01

    Carcinogenic chemicals in the work area were previously classified into three categories in section III of the German List of MAK and BAT values (the list of values on maximum workplace concentrations and biological tolerance for occupational exposures). This classification was based on qualitative criteria and reflected essentially the weight of evidence available for judging the carcinogenic potential of the chemicals. In the new classification scheme the former sections IIIA1, IIIA2, and IIIB are retained as categories 1, 2, and 3, to correspond with European Union regulations. On the basis of our advancing knowledge of reaction mechanisms and the potency of carcinogens, these three categories are supplemented with two additional categories. The essential feature of substances classified in the new categories is that exposure to these chemicals does not contribute significantly to the risk of cancer to man, provided that an appropriate exposure limit (MAK value) is observed. Chemicals known to act typically by non-genotoxic mechanisms, and for which information is available that allows evaluation of the effects of low-dose exposures, are classified in category 4. Genotoxic chemicals for which low carcinogenic potency can be expected on the basis of dose/response relationships and toxicokinetics and for which risk at low doses can be assessed are classified in category 5. The basis for a better differentiation of carcinogens is discussed, the new categories are defined, and possible criteria for classification are described. Examples for category 4 (1,4-dioxane) and category 5 (styrene) are presented.

  9. Changes in the classification of carcinogenic chemicals in the work area. Section III of the German List of MAK and BAT Values.

    Science.gov (United States)

    Neumann, H G; Vamvakas, S; Thielmann, H W; Gelbke, H P; Filser, J G; Reuter, U; Greim, H; Kappus, H; Norpoth, K H; Wardenbach, P; Wichmann, H E

    1998-11-01

    Carcinogenic chemicals in the work area are currently classified into three categories in section III of the German List of MAK and BAT Values (list of values on maximum workplace concentrations and biological tolerance for occupational exposures). This classification is based on qualitative criteria and reflects essentially the weight of evidence available for judging the carcinogenic potential of the chemicals. It is proposed that these categories - IIIA1, IIIA2, IIIB - be retained as Categories 1, 2, and 3, to correspond with European Union regulations. On the basis of our advancing knowledge of reaction mechanisms and the potency of carcinogens, these three categories are supplemented with two additional categories. The essential feature of substances classified in the new categories is that exposure to these chemicals does not contribute significantly to risk of cancer to man, provided that an appropriate exposure limit (MAK value) is observed. Chemicals known to act typically by nongenotoxic mechanisms and for which information is available that allows evaluation of the effects of low-dose exposures, are classified in Category 4. Genotoxic chemicals for which low carcinogenic potency can be expected on the basis of dose-response relationships and toxicokinetics, and for which risk at low doses can be assessed are classified in Category 5. The basis for a better differentiation of carcinogens is discussed, the new categories are defined, and possible criteria for classification are described. Examples for Category 4 (1,4-dioxane) and Category 5 (styrene) are presented.

  10. Human health tradeoffs in wellhead drinking water treatment: Comparing exposure reduction to embedded life cycle risks.

    Science.gov (United States)

    Gifford, Mac; Chester, Mikhail; Hristovski, Kiril; Westerhoff, Paul

    2018-01-01

    Treatment of drinking water decreases human health risks by reducing pollutants, but the required materials, chemicals, and energy emit pollutants and increase health risks. We explored human carcinogenic and non-carcinogenic disease tradeoffs of water treatment by comparing pollutant dose-response curves against life cycle burden using USEtox methodology. An illustrative wellhead sorbent groundwater treatment system removing hexavalent chromium or pentavalent arsenic serving 3200 people was studied. Reducing pollutant concentrations in drinking water from 20 μg L -1 to 10 μg L -1 avoided 37 potential cancer cases and 64 potential non-cancer disease cases. Human carcinogenicity embedded in treatment was 0.2-5.3 cases, and non-carcinogenic toxicity was 0.2-14.3 cases, depending on technology and degree of treatment. Embedded toxicity impacts from treating Cr(VI) using strong-base anion exchange were 90% of the toxicity impacts for treatment options requiring pH control. In scenarios where benefits exceeded burdens, tradeoffs still existed. Benefits are experienced by a local population but burdens are born externally where the materials and energy are produced, thus exporting the health risks. Even when burdens clearly exceeded benefits, cost considerations may still drive selecting a detrimental treatment level or technology. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Exposure to dust-bound PAHs and associated carcinogenic risk in primitive and traditional cooking practices in Pakistan.

    Science.gov (United States)

    Kamal, Atif; Malik, Riffat Naseem; Martellini, Tania; Cincinelli, Alessandra

    2015-08-01

    The aim of this study was to determine the abundance and distribution of polycyclic aromatic hydrocarbons (PAHs) in dust samples collected from the selected professional cooking workplaces (WCs) and residential household cooking areas (WRs), where traditional and primitive cooking practices are still prevelent. Another aim of this study was to investigate the carcinogenic risk for Pakistani human exposure to dust-bound PAHs via the routes of inhalation, ingestion, and dermal contact. Generally, the concentration of individual congeners of PAHs in surface dust samples of WC sites was higher than those measured in WR sites (p < 0.05). The benzo(a)pyrene (B(a)P), a very high carcinogenic compound, was present in the dust samples from WC sites in the highest mean concentration (630 ng g(-1) dry weight (d.w.)). The BaP mean concentration in WC workplaces was almost eight times higher than the mean value found in WR exposure sites. Moreover, the average concentration of ∑PAHs, combustion origin PAHs (∑COMB) and sum total of 7-carcinogenic PAHs (∑7-carcinogens) were also significantly higher in WC dusts samples than that in WR workplaces. Principal component analysis (PCA) and diagnostic ratios suggested coal/wood combustion as major PAH emission sources in both exposure sites. The average incremental lifetime cancer risk (ILCR) suggested a moderate to potential high cancer risk for adults and children exposed to dust-bound PAHs in both exposure sites, in particular via both dermal and ingestion contact pathways.

  12. A Research Roadmap for Computation-Based Human Reliability Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Boring, Ronald [Idaho National Lab. (INL), Idaho Falls, ID (United States); Mandelli, Diego [Idaho National Lab. (INL), Idaho Falls, ID (United States); Joe, Jeffrey [Idaho National Lab. (INL), Idaho Falls, ID (United States); Smith, Curtis [Idaho National Lab. (INL), Idaho Falls, ID (United States); Groth, Katrina [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2015-08-01

    The United States (U.S.) Department of Energy (DOE) is sponsoring research through the Light Water Reactor Sustainability (LWRS) program to extend the life of the currently operating fleet of commercial nuclear power plants. The Risk Informed Safety Margin Characterization (RISMC) research pathway within LWRS looks at ways to maintain and improve the safety margins of these plants. The RISMC pathway includes significant developments in the area of thermalhydraulics code modeling and the development of tools to facilitate dynamic probabilistic risk assessment (PRA). PRA is primarily concerned with the risk of hardware systems at the plant; yet, hardware reliability is often secondary in overall risk significance to human errors that can trigger or compound undesirable events at the plant. This report highlights ongoing efforts to develop a computation-based approach to human reliability analysis (HRA). This computation-based approach differs from existing static and dynamic HRA approaches in that it: (i) interfaces with a dynamic computation engine that includes a full scope plant model, and (ii) interfaces with a PRA software toolset. The computation-based HRA approach presented in this report is called the Human Unimodels for Nuclear Technology to Enhance Reliability (HUNTER) and incorporates in a hybrid fashion elements of existing HRA methods to interface with new computational tools developed under the RISMC pathway. The goal of this research effort is to model human performance more accurately than existing approaches, thereby minimizing modeling uncertainty found in current plant risk models.

  13. A Research Roadmap for Computation-Based Human Reliability Analysis

    International Nuclear Information System (INIS)

    Boring, Ronald; Mandelli, Diego; Joe, Jeffrey; Smith, Curtis; Groth, Katrina

    2015-01-01

    The United States (U.S.) Department of Energy (DOE) is sponsoring research through the Light Water Reactor Sustainability (LWRS) program to extend the life of the currently operating fleet of commercial nuclear power plants. The Risk Informed Safety Margin Characterization (RISMC) research pathway within LWRS looks at ways to maintain and improve the safety margins of these plants. The RISMC pathway includes significant developments in the area of thermalhydraulics code modeling and the development of tools to facilitate dynamic probabilistic risk assessment (PRA). PRA is primarily concerned with the risk of hardware systems at the plant; yet, hardware reliability is often secondary in overall risk significance to human errors that can trigger or compound undesirable events at the plant. This report highlights ongoing efforts to develop a computation-based approach to human reliability analysis (HRA). This computation-based approach differs from existing static and dynamic HRA approaches in that it: (i) interfaces with a dynamic computation engine that includes a full scope plant model, and (ii) interfaces with a PRA software toolset. The computation-based HRA approach presented in this report is called the Human Unimodels for Nuclear Technology to Enhance Reliability (HUNTER) and incorporates in a hybrid fashion elements of existing HRA methods to interface with new computational tools developed under the RISMC pathway. The goal of this research effort is to model human performance more accurately than existing approaches, thereby minimizing modeling uncertainty found in current plant risk models.

  14. Human rights-based approach to unintentional injury prevention.

    Science.gov (United States)

    MacKay, J Morag; Ryan, Mark Andrew

    2018-06-01

    Unintentional injury remains an important global public health issue, and efforts to address it are often hampered by a lack of visibility, leadership, funding, infrastructure, capacity and evidence of effective solutions. The growing support for a socioecological model and a systems approach to prevention-along with the acknowledgement that injury prevention can be a byproduct of salutogenic design and activities-has increased opportunities to integrate unintentional injury prevention into other health promotion and disease prevention agendas. It has also helped to integrate it into the broader human development agenda through the Sustainable Development Goals. This growing support provides new opportunities to use a human rights-based approach to address the issue. The human rights-based approach is based on the idea that all members of society have social, economic and cultural rights and that governments are responsible and accountable for upholding those rights. It incorporates a systems approach, addresses inequity and places an emphasis on the most vulnerable corners of humanity. It also leverages legal statutes and provides organisations with the opportunity to build existing international goals and benchmarks into their monitoring efforts. This paper describes the approach and highlights how it can leverage attention and investment to address current challenges for unintentional injury. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  15. Assessment of Industry-Induced Urban Human Health Risks Related to Benzo[a]pyrene based on a Multimedia Fugacity Model: Case Study of Nanjing, China

    Directory of Open Access Journals (Sweden)

    Linyu Xu

    2015-05-01

    Full Text Available Large amounts of organic pollutants emitted from industries have accumulated and caused serious human health risks, especially in urban areas with rapid industrialization. This paper focused on the carcinogen benzo[a]pyrene (BaP from industrial effluent and gaseous emissions, and established a multi-pathway exposure model based on a Level IV multimedia fugacity model to analyze the human health risks in a city that has undergone rapid industrialization. In this study, GIS tools combined with land-use data was introduced to analyze smaller spatial scales so as to enhance the spatial resolution of the results. An uncertainty analysis using a Monte Carlo simulation was also conducted to illustrate the rationale of the probabilistic assessment mode rather than deterministic assessment. Finally, the results of the case study in Nanjing, China indicated the annual average human cancer risk induced by local industrial emissions during 2002–2008 (lowest at 1.99´10–6 in 2008 and highest at 3.34´10–6 in 2004, which was lower than the USEPA prescriptive level (1´10–6–1´10–4 but cannot be neglected in the long term. The study results could not only instruct the BaP health risk management but also help future health risk prediction and control.

  16. Land management of bracken needs to account for bracken carcinogens - a case study from Britain

    DEFF Research Database (Denmark)

    Rasmussen, Lars Holm; Donnelly, Eric; Strobel, Bjarne W.

    2015-01-01

    with ptaquiloside may be the cause. The aim of this study was to monitor the content of ptaquiloside in 20 bracken stands from Britain to obtain a better understanding of the ptaquiloside dynamics and to evaluate the environmental implications of using different cutting regimes in bracken management...... in bracken stands at any given time is difficult to predict and did not show any correlations with edaphic growth factors. The content of ptaquiloside turned out to be higher in fronds emerging after cutting compared to uncut fronds. Environmental risk assessment and bracken management must therefore......Bracken ferns are some of the most widespread ferns in the World causing immense problems for land managers, foresters and rangers. Bracken is suspected of causing cancer in Humans due to its content of the carcinogen ptaquiloside. Ingestion of bracken, or food and drinking water contaminated...

  17. 7-Glutathione-pyrrole and 7-cysteine-pyrrole are potential carcinogenic metabolites of pyrrolizidine alkaloids.

    Science.gov (United States)

    He, Xiaobo; Xia, Qingsu; Fu, Peter P

    2017-04-03

    Many pyrrolizidine alkaloids (PAs) are hepatotoxic, genotoxic, and carcinogenic phytochemicals. Metabolism of PAs in vivo generates four (±)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP)-DNA adducts that have been proposed to be responsible for PA-induced liver tumor formation in rats. In this present study, we determined that the same set of DHP-DNA adducts was formed upon the incubation of 7-glutathione-DHP and 7-cysteine-DHP with cultured human hepatocarcinoma HepG2 cells. These results suggest that 7-glutathione-DHP and 7-cysteine-DHP are reactive metabolites of PAs that can bind to cellular DNA to form DHP-DNA adducts in HepG2 cells, and can potentially initiate liver tumor formation.

  18. Towards discrete wavelet transform-based human activity recognition

    Science.gov (United States)

    Khare, Manish; Jeon, Moongu

    2017-06-01

    Providing accurate recognition of human activities is a challenging problem for visual surveillance applications. In this paper, we present a simple and efficient algorithm for human activity recognition based on a wavelet transform. We adopt discrete wavelet transform (DWT) coefficients as a feature of human objects to obtain advantages of its multiresolution approach. The proposed method is tested on multiple levels of DWT. Experiments are carried out on different standard action datasets including KTH and i3D Post. The proposed method is compared with other state-of-the-art methods in terms of different quantitative performance measures. The proposed method is found to have better recognition accuracy in comparison to the state-of-the-art methods.

  19. Optimizing Human Diet Problem Based on Price and Taste Using

    Directory of Open Access Journals (Sweden)

    Hossein EGHBALI

    2012-07-01

    Full Text Available Low price and good taste of foods are regarded as two major factors for optimal human nutrition. Due to price fluctuations and taste diversity, these two factors cannot be certainly and determinately evaluated. This problem must be viewed from another perspective because of the uncertainty about the amount of nutrients per unit of foods and also diversity of people’s daily needs to receive them.This paper discusses human diet problem in fuzzy environment. The approach deals with multi-objective fuzzy linear programming problem using a fuzzy programming technique for its solution. By prescribing a diet merely based on crisp data, some ofthe realities are neglected. For the same reason, we dealt with human diet problem through fuzzy approach. Results indicated uncertainty about factors of nutrition diet -including taste and price, amount of nutrients and their intake- would affect diet quality, making the proposed diet more realistic.

  20. Results of screening NCI/NTP nongenotoxic carcinogens and genotoxic noncarcinogens with the ke test

    International Nuclear Information System (INIS)

    Mendelsohn, M.L.; Bakale, G.; McCreary, R.D.

    1989-01-01

    The interdependence of the electrophilic and carcinogenic properties of chemicals that was demonstrated two decades ago rekindled interest in the somatic mutation theory of carcinogenesis. Interest in this theory grew with the development of a reverse-mutation bacterial assay in the laboratory of B.N. Ames that permitted the mutagenic properties of the chemicals to be determined quickly and yielded results which indicated that ''carcinogens are mutagens.'' Subsequent validation studies of this bioassay, the Salmonella typhimurium/microsome or ''Ames test,'' by Ames' group and others provided additional support for the correlation between mutagenicity and carcinogenicity which led to the worldwide deployment of the Ames test in thousands of laboratories and to the development of more than 100 other short-term tests that continue to be used to identify potential carcinogens via various end-points of genotoxicity. This document discusses electrophilicity, mutagenicity, and carcinogenicity relationships as well as carcinogen-screening of chemicals. 28 refs., 4 tabs

  1. Basing Science Ethics on Respect for Human Dignity.

    Science.gov (United States)

    Aközer, Mehmet; Aközer, Emel

    2016-12-01

    A "no ethics" principle has long been prevalent in science and has demotivated deliberation on scientific ethics. This paper argues the following: (1) An understanding of a scientific "ethos" based on actual "value preferences" and "value repugnances" prevalent in the scientific community permits and demands critical accounts of the "no ethics" principle in science. (2) The roots of this principle may be traced to a repugnance of human dignity, which was instilled at a historical breaking point in the interrelation between science and ethics. This breaking point involved granting science the exclusive mandate to pass judgment on the life worth living. (3) By contrast, respect for human dignity, in its Kantian definition as "the absolute inner worth of being human," should be adopted as the basis to ground science ethics. (4) The pathway from this foundation to the articulation of an ethical duty specific to scientific practice, i.e., respect for objective truth, is charted by Karl Popper's discussion of the ethical principles that form the basis of science. This also permits an integrated account of the "external" and "internal" ethical problems in science. (5) Principles of the respect for human dignity and the respect for objective truth are also safeguards of epistemic integrity. Plain defiance of human dignity by genetic determinism has compromised integrity of claims to knowledge in behavioral genetics and other behavioral sciences. Disregard of the ethical principles that form the basis of science threatens epistemic integrity.

  2. Human action recognition based on estimated weak poses

    Science.gov (United States)

    Gong, Wenjuan; Gonzàlez, Jordi; Roca, Francesc Xavier

    2012-12-01

    We present a novel method for human action recognition (HAR) based on estimated poses from image sequences. We use 3D human pose data as additional information and propose a compact human pose representation, called a weak pose, in a low-dimensional space while still keeping the most discriminative information for a given pose. With predicted poses from image features, we map the problem from image feature space to pose space, where a Bag of Poses (BOP) model is learned for the final goal of HAR. The BOP model is a modified version of the classical bag of words pipeline by building the vocabulary based on the most representative weak poses for a given action. Compared with the standard k-means clustering, our vocabulary selection criteria is proven to be more efficient and robust against the inherent challenges of action recognition. Moreover, since for action recognition the ordering of the poses is discriminative, the BOP model incorporates temporal information: in essence, groups of consecutive poses are considered together when computing the vocabulary and assignment. We tested our method on two well-known datasets: HumanEva and IXMAS, to demonstrate that weak poses aid to improve action recognition accuracies. The proposed method is scene-independent and is comparable with the state-of-art method.

  3. Mode of carcinogenic action of pesticides inducing thyroid follicular cell tumors in rodents.

    OpenAIRE

    Hurley, P M

    1998-01-01

    Of 240 pesticides screened for carcinogenicity by the U.S. Environmental Protection Agency Office of Pesticide Programs, at least 24 (10%) produce thyroid follicular cell tumors in rodents. Thirteen of the thyroid carcinogens also induce liver tumors, mainly in mice, and 9 chemicals produce tumors at other sites. Some mutagenic data are available on all 24 pesticides producing thyroid tumors. Mutagenicity does not seem to be a major determinant in thyroid carcinogenicity, except for possibly ...

  4. Development and application of non-invasive biomarkers for carcinogen-DNA adduct analysis in occupationally exposed populations.

    Science.gov (United States)

    Talaska, G; Cudnik, J; Jaeger, M; Rothman, N; Hayes, R; Bhatnagar, V J; Kayshup, S J

    1996-07-17

    Biological monitoring of exposures to carcinogenic compounds in the workplace can be a valuable adjunct to environmental sampling and occupational medicine. Carcinogen-DNA adduct analysis has promise as a biomarker of effective dose if target organ samples can be obtained non-invasively. We have developed non-invasive techniques using exfoliated urothelial and bronchial cells collected in urine and sputum, respectively. First morning urine samples were collected from 33 workers exposed to benzidine or benzidine-based dyes and controls matched for age, education, and smoking status. Sufficient DNA for 32P-postlabelling analysis was obtained from every sample. Mean levels of a specific DNA adduct (which co-chromatographed with standard characterized by MS) were elevated significantly in the benzidine-exposed workers relative to controls. In addition, workers exposed to benzidine had higher adduct levels than those exposed to benzidine-based dyes. This study demonstrates the usefulness of these non-invasive techniques for exposure/effect assessment. To be useful in occupational studies, biomarkers must also be sensitive to exposure interventions. We have conducted topical application studies of used gasoline engine oils in mice and found that the levels of carcinogen-DNA adducts in skin and lung can be significantly lowered if skin cleaning is conducted in a timely manner. The combination of useful, non-invasive techniques to monitor exposure and effect and industrial hygiene interventions can be used to detect and prevent exposures to a wide range of carcinogens including those found in used gasoline engine oils and jet exhausts.

  5. Absence of multiplicative interactions between occupational lung carcinogens and tobacco smoking: a systematic review involving asbestos, crystalline silica and diesel engine exhaust emissions

    Directory of Open Access Journals (Sweden)

    Mohamad El Zoghbi

    2017-02-01

    Full Text Available Abstract Background Tobacco smoking is the main cause of lung cancer, but it is not the sole causal factor. Significant proportions of workers are smokers and exposed to occupational lung carcinogens. This study aims to systematically review the statistical interaction between occupational lung carcinogens and tobacco smoking, in particular asbestos, crystalline silica and diesel engine exhaust emissions. Methods Articles were identified using Scopus, PubMed, and Web of Science, and were limited to those published in English or French, without limitation of time. The reference list of selected studies was reviewed to identify other relevant papers. One reviewer selected the articles based on the inclusion and exclusion criteria. Two reviewers checked the eligibility of articles to be included in the systematic review. Data were extracted by one reviewer and revised by two other reviewers. Cohorts and case–control studies were analyzed separately. The risk of bias was evaluated for each study based on the outcome. The results of the interaction between the tobacco smoking and each carcinogen was evaluated and reported separately. Results Fifteen original studies were included for asbestos-smoking interaction, seven for silica-smoking interaction and two for diesel-smoking interaction. The results suggested the absence of multiplicative interaction between the three occupational lung carcinogens and smoking. There is no enough evidence from the literature to conclude for the additive interaction. We believe there is a limited risk of publication bias as several studies reporting negative results were published. Conclusion There are no multiplicative interactions between tobacco smoking and occupational lung carcinogens, in particular asbestos, crystalline silica and diesel engine exhaust emissions. Even though, specific programs should be developed and promoted to reduce concomitantly the exposure to occupational lung carcinogens and tobacco

  6. A Framework for Agent-based Human Interaction Support

    Directory of Open Access Journals (Sweden)

    Axel Bürkle

    2008-10-01

    Full Text Available In this paper we describe an agent-based infrastructure for multimodal perceptual systems which aims at developing and realizing computer services that are delivered to humans in an implicit and unobtrusive way. The framework presented here supports the implementation of human-centric context-aware applications providing non-obtrusive assistance to participants in events such as meetings, lectures, conferences and presentations taking place in indoor "smart spaces". We emphasize on the design and implementation of an agent-based framework that supports "pluggable" service logic in the sense that the service developer can concentrate on coding the service logic independently of the underlying middleware. Furthermore, we give an example of the architecture's ability to support the cooperation of multiple services in a meeting scenario using an intelligent connector service and a semantic web oriented travel service.

  7. Human resource recommendation algorithm based on ensemble learning and Spark

    Science.gov (United States)

    Cong, Zihan; Zhang, Xingming; Wang, Haoxiang; Xu, Hongjie

    2017-08-01

    Aiming at the problem of “information overload” in the human resources industry, this paper proposes a human resource recommendation algorithm based on Ensemble Learning. The algorithm considers the characteristics and behaviours of both job seeker and job features in the real business circumstance. Firstly, the algorithm uses two ensemble learning methods-Bagging and Boosting. The outputs from both learning methods are then merged to form user interest model. Based on user interest model, job recommendation can be extracted for users. The algorithm is implemented as a parallelized recommendation system on Spark. A set of experiments have been done and analysed. The proposed algorithm achieves significant improvement in accuracy, recall rate and coverage, compared with recommendation algorithms such as UserCF and ItemCF.

  8. Evidence supporting product standards for carcinogens in smokeless tobacco products.

    Science.gov (United States)

    Hatsukami, Dorothy K; Stepanov, Irina; Severson, Herb; Jensen, Joni A; Lindgren, Bruce R; Horn, Kimberly; Khariwala, Samir S; Martin, Julia; Carmella, Steven G; Murphy, Sharon E; Hecht, Stephen S

    2015-01-01

    Smokeless tobacco products sold in the United States vary significantly in yields of nicotine and tobacco-specific nitrosamines (TSNA). With the passage of the Family Smoking Prevention and Tobacco Control Act, the Food and Drug Administration now has the authority to establish product standards. However, limited data exist determining the relative roles of pattern of smokeless tobacco use versus constituent levels in the smokeless tobacco product in exposure of users to carcinogens. In this study, smokeless tobacco users of brands varying in nicotine and TSNA content were recruited from three different regions in the U.S. Participants underwent two assessment sessions. During these sessions, demographic and smokeless tobacco use history information along with urine samples to assess biomarkers of exposure and effect were collected. During the time between data collection, smokeless tobacco users recorded the amount and duration of smokeless tobacco use on a daily basis using their diary cards. Results showed that independent of pattern of smokeless tobacco use and nicotine yields, levels of TSNA in smokeless tobacco products played a significant role in carcinogen exposure levels. Product standards for reducing levels of TSNA in smokeless tobacco products are necessary to decrease exposure to these toxicants and potentially to reduce risk for cancer. ©2014 American Association for Cancer Research.

  9. Polyamines modulate carcinogen-induced mutagenesis in vivo.

    Science.gov (United States)

    Wallon, U Margaretha; O'Brien, Thomas G

    2005-01-01

    Elevated polyamine levels as a consequence of targeted overexpression of ornithine decarboxylase (ODC) to murine skin enhance susceptibility to tumorigenesis in this tissue. A possible mechanism for the enhanced susceptibility phenotype is an increased sensitivity of tissues with elevated polyamine levels to the mutagenic action of carcinogens. To test this hypothesis, a transgenic mouse model containing the Big Blue transgene and also expressing a K6/ODC transgene was developed. Incorporation of the K6/ODC transgene into the Big Blue model did not affect the spontaneous lacI mutant frequency in either skin or epidermis of the double-transgenic mice. After skin treatment with single doses of either 7,12-dimethylbenz[a]anthracene or N-methyl-N'-nitro-N-nitrosoguanidine, however, the mutant frequency was significantly increased in the skin of double-transgenic Big Blue;K6/ODC mice compared to Big Blue controls. The increases in mutant frequency were clearly due to ODC transgene activity, since treatment of mice with the ODC inhibitor, alpha-difluoromethylornithine, completely abolished the difference in mutant frequencies between double-transgenic and Big Blue mice. These results demonstrate that intracellular polyamine levels modulate mutation induction following carcinogen exposure. 2004 Wiley-Liss, Inc.

  10. Metabolic activation of the bladder carcinogen 4-nitrobiphenyl (NBP)

    International Nuclear Information System (INIS)

    Swaminathan, S.

    1986-01-01

    The metabolism of NBP, a dog bladder carcinogen, was examined in vitro using rat liver tissues. NBP was metabolized by enzymes localized both in the microsomes and cytosol. The microsomal enzyme activity was inducible by Aroclor 1254 and phenobarbital. High pressure liquid chromatography analysis of the ethyl acetate extract of the reaction mixture, following incubation of [ 3 H]NBP with NADPH and microsomes, revealed four radioactive and UV absorbing peaks with retention times of 5, 8, 14 and 28 min. The peaks at 8, 14 and 28 min corresponded with 4-aminobiphenyl (ABP), NBP and azoxy biphenyl, respectively. The early eluting component with a retention time of 5 min has been tentatively identified as a ring hydroxylated derivative. In contrast to microsomal metabolism, cytosol-mediated metabolism yielded only one major metabolite identified as ABP. Cytosol-mediate reduction was inhibited by the xanthine oxidase inhibitor allopurinol. In vitro incubation of NBP with NADH and commercial preparations of xanthine oxidase also yielded ABP and the formation of the latter was blocked by allopurinol. Xanthine oxidase catalyzed also the binding of [ 3 H]NBP to DNA and proteins; the binding was inhibited by allopurinol. These data support the hypothesis that the nitro reduction step is involved in the activation of the bladder carcinogen NBP, and that the nitroreductases occur in both the microsomes and cytosol. The cytosolic activity is primarily due to xanthine oxidase

  11. Carcinogenicity of a medicinal ozokerite and its constituents

    Energy Technology Data Exchange (ETDEWEB)

    Ruchkovskii, B; Borisiuk, I P; Tiktin, L A

    1970-01-01

    Fluorimetric analysis and skin painting tests on mice demonstrated that ceresin (a medicinal ozokerite) contains carcinogens. In the USSR, ceresin is applied to the skin or rectal and vaginal mucosa for the treatment of a variety of diseases. Ceresin and its components were tested on 460 male non-inbred mice (aged 2 to 2.5 mo) by applying either the melted substance or a 60% benzene solution of it to the skin in 30-mg doses (2 admin./week x 10 mo). Skin papillomas were produced after latent periods of 4.5 to 9 mo by paraffin, petrolatum, heavy mineral oil and 1/2 ceresin samples. Squamous cell carcinomas of the skin were seen in 2 mice painted with mineral oil. Fluorimetric analysis of ceresin demonstrated several polycyclic hydrocarbons, identified as 3,4-benzpyrene (BP) benzo(ghi) perylene, and perylene. An aqueous extract of crude ozokerite contained traces of BP, while a benzene extract contained 70 to 77 microg/kg. It is recommended that petroleum products which are commonly used to improve the consistency of ceresin be analyzed for the presence of carcinogens before use.

  12. Induction of prophage lambda by chlorinated organics: Detection of some single-species/single-site carcinogens

    Energy Technology Data Exchange (ETDEWEB)

    DeMarini, D.M.; Brooks, H.G. (Environmental Protection Agency, Research Triangle Park, NC (United States))

    1992-01-01

    Twenty-eight chlorinated organic compounds were evaluated for their ability to induce DNA damage using the Microscreen prophage-induction assay in Escherichia coli. Comparison of the performance characteristics of the prophage-induction and Salmonella assays to rodent carcinogenicity assays showed that the prophage-induction assay had a somewhat higher specificity than did the Salmonella assay (70% vs. 50%); sensitivity, concordance, and positive and negative predictivity were similar for the two microbial assays. The Microscreen prophage-induction assay failed to detect eight carcinogens, perhaps due to toxicity or other unknown factors; five of these eight carcinogens were detected by the Salmonella assay. However, the prophage-induction assay did detect six carcinogens that were not detected by the Salmonella assay, and five of these were single-species, single-site carcinogens, mostly mouse liver carcinogens. Some of these carcinogens, such as the chloroethanes, produce free radicals, which may be the basis for their carcinogenicity and ability to induce prophage. The prophage-induction (or other SOS) assay may be useful in identifying some genotoxic chlorinated carcinogens that induce DNA damage that do not revert the standard Salmonella tester strains.

  13. Predicting carcinogenicity of diverse chemicals using probabilistic neural network modeling approaches

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Kunwar P., E-mail: kpsingh_52@yahoo.com [Academy of Scientific and Innovative Research, Council of Scientific and Industrial Research, New Delhi (India); Environmental Chemistry Division, CSIR-Indian Institute of Toxicology Research, Post Box 80, Mahatma Gandhi Marg, Lucknow 226 001 (India); Gupta, Shikha; Rai, Premanjali [Academy of Scientific and Innovative Research, Council of Scientific and Industrial Research, New Delhi (India); Environmental Chemistry Division, CSIR-Indian Institute of Toxicology Research, Post Box 80, Mahatma Gandhi Marg, Lucknow 226 001 (India)

    2013-10-15

    Robust global models capable of discriminating positive and non-positive carcinogens; and predicting carcinogenic potency of chemicals in rodents were developed. The dataset of 834 structurally diverse chemicals extracted from Carcinogenic Potency Database (CPDB) was used which contained 466 positive and 368 non-positive carcinogens. Twelve non-quantum mechanical molecular descriptors were derived. Structural diversity of the chemicals and nonlinearity in the data were evaluated using Tanimoto similarity index and Brock–Dechert–Scheinkman statistics. Probabilistic neural network (PNN) and generalized regression neural network (GRNN) models were constructed for classification and function optimization problems using the carcinogenicity end point in rat. Validation of the models was performed using the internal and external procedures employing a wide series of statistical checks. PNN constructed using five descriptors rendered classification accuracy of 92.09% in complete rat data. The PNN model rendered classification accuracies of 91.77%, 80.70% and 92.08% in mouse, hamster and pesticide data, respectively. The GRNN constructed with nine descriptors yielded correlation coefficient of 0.896 between the measured and predicted carcinogenic potency with mean squared error (MSE) of 0.44 in complete rat data. The rat carcinogenicity model (GRNN) applied to the mouse and hamster data yielded correlation coefficient and MSE of 0.758, 0.71 and 0.760, 0.46, respectively. The results suggest for wide applicability of the inter-species models in predicting carcinogenic potency of chemicals. Both the PNN and GRNN (inter-species) models constructed here can be useful tools in predicting the carcinogenicity of new chemicals for regulatory purposes. - Graphical abstract: Figure (a) shows classification accuracies (positive and non-positive carcinogens) in rat, mouse, hamster, and pesticide data yielded by optimal PNN model. Figure (b) shows generalization and predictive

  14. CSI Frequency Domain Fingerprint-Based Passive Indoor Human Detection

    Directory of Open Access Journals (Sweden)

    Chong Han

    2018-04-01

    Full Text Available Passive indoor personnel detection technology is now a hot topic. Existing methods have been greatly influenced by environmental changes, and there are problems with the accuracy and robustness of detection. Passive personnel detection based on Wi-Fi not only solves the above problems, but also has the advantages of being low cost and easy to implement, and can be better applied to elderly care and safety monitoring. In this paper, we propose a passive indoor personnel detection method based on Wi-Fi, which we call FDF-PIHD (Frequency Domain Fingerprint-based Passive Indoor Human Detection. Through this method, fine-grained physical layer Channel State Information (CSI can be extracted to generate feature fingerprints so as to help determine the state in the scene by matching online fingerprints with offline fingerprints. In order to improve accuracy, we combine the detection results of three receiving antennas to obtain the final test result. The experimental results show that the detection rates of our proposed scheme all reach above 90%, no matter whether the scene is human-free, stationary or a moving human presence. In addition, it can not only detect whether there is a target indoors, but also determine the current state of the target.

  15. Glucosamine-Based Supramolecular Nanotubes for Human Mesenchymal Cell Therapy.

    Science.gov (United States)

    Talloj, Satish Kumar; Cheng, Bill; Weng, Jen-Po; Lin, Hsin-Chieh

    2018-04-23

    Herein, we demonstrate an example of glucosamine-based supramolecular hydrogels that can be used for human mesenchymal cell therapy. We designed and synthesized a series of amino acid derivatives based on a strategy of capping d-glucosamine moiety at the C-terminus and fluorinated benzyl group at the N-terminus. From a systematic study on chemical structures, we discovered that the glucosamine-based supramolecular hydrogel [pentafluorobenzyl (PFB)-F-Glu] self-assembled with one-dimensional nanotubular structures at physiological pH. The self-assembly of a newly discovered PFB-F-Glu motif is attributed to the synergistic effect of π-π stacking and extensive intermolecular hydrogen bonding network in aqueous medium. Notably, PFB-F-Glu nanotubes are proven to be nontoxic to human mesenchymal stem cells (hMSCs) and have been shown to enhance hMSC proliferation while maintaining their pluripotency. Retaining of pluripotency capabilities provides potentially unlimited source of undifferentiated cells for the treatment of future cell therapies. Furthermore, hMSCs cultured on PFB-F-Glu are able to secrete paracrine factors that downregulate profibrotic gene expression in lipopolysaccharide-treated human skin fibroblasts, which demonstrates that PFB-F-Glu nanotubes have the potential to be used for wound healing applications. Overall, this article addresses the importance of chemical design to generate supramolecular biomaterials for stem cell therapy.

  16. Adaptive Human aware Navigation based on Motion Pattern Analysis

    DEFF Research Database (Denmark)

    Tranberg, Søren; Svenstrup, Mikael; Andersen, Hans Jørgen

    2009-01-01

    Respecting people’s social spaces is an important prerequisite for acceptable and natural robot navigation in human environments. In this paper, we describe an adaptive system for mobile robot navigation based on estimates of whether a person seeks to interact with the robot or not. The estimates...... are based on run-time motion pattern analysis compared to stored experience in a database. Using a potential field centered around the person, the robot positions itself at the most appropriate place relative to the person and the interaction status. The system is validated through qualitative tests...

  17. Upper limits for air humidity based on human comfort

    DEFF Research Database (Denmark)

    Toftum, Jørn; Fanger, Povl Ole; Jørgensen, Anette S.

    1998-01-01

    respiratory cooling. Human subjects perceived the condition of their skin to be less acceptable with increasing skin humidity. Inhaled air was rated warmer, more stuffy and less acceptable with increasing air humidity and temperature. Based on the subjects' comfort responses, new upper limits for air humidity......The purpose of this study was to verify the hypothesis that insufficient respiratory cooling and a high level of skin humidity are two reasons for thermal discomfort at high air humidities, and to prescribe upper limits for humidity based on discomfort due to elevated skin humidity and insufficient...

  18. A digital interactive human brain atlas based on Chinese visible human datasets for anatomy teaching.

    Science.gov (United States)

    Li, Qiyu; Ran, Xu; Zhang, Shaoxiang; Tan, Liwen; Qiu, Mingguo

    2014-01-01

    As we know, the human brain is one of the most complicated organs in the human body, which is the key and difficult point in neuroanatomy and sectional anatomy teaching. With the rapid development and extensive application of imaging technology in clinical diagnosis, doctors are facing higher and higher requirement on their anatomy knowledge. Thus, to cultivate medical students to meet the needs of medical development today and to improve their ability to read and understand radiographic images have become urgent challenges for the medical teachers. In this context, we developed a digital interactive human brain atlas based on the Chinese visible human datasets for anatomy teaching (available for free download from http://www.chinesevisiblehuman.com/down/DHBA.rar). The atlas simultaneously provides views in all 3 primary planes of section. The main structures of the human brain have been anatomically labeled in all 3 views. It is potentially useful for anatomy browsing, user self-testing, and automatic student assessment. In a word, it is interactive, 3D, user friendly, and free of charge, which can provide a new, intuitive means for anatomy teaching.

  19. Physiologically Based Pharmacokinetic Model for Terbinafine in Rats and Humans

    Science.gov (United States)

    Hosseini-Yeganeh, Mahboubeh; McLachlan, Andrew J.

    2002-01-01

    The aim of this study was to develop a physiologically based pharmacokinetic (PB-PK) model capable of describing and predicting terbinafine concentrations in plasma and tissues in rats and humans. A PB-PK model consisting of 12 tissue and 2 blood compartments was developed using concentration-time data for tissues from rats (n = 33) after intravenous bolus administration of terbinafine (6 mg/kg of body weight). It was assumed that all tissues except skin and testis tissues were well-stirred compartments with perfusion rate limitations. The uptake of terbinafine into skin and testis tissues was described by a PB-PK model which incorporates a membrane permeability rate limitation. The concentration-time data for terbinafine in human plasma and tissues were predicted by use of a scaled-up PB-PK model, which took oral absorption into consideration. The predictions obtained from the global PB-PK model for the concentration-time profile of terbinafine in human plasma and tissues were in close agreement with the observed concentration data for rats. The scaled-up PB-PK model provided an excellent prediction of published terbinafine concentration-time data obtained after the administration of single and multiple oral doses in humans. The estimated volume of distribution at steady state (Vss) obtained from the PB-PK model agreed with the reported value of 11 liters/kg. The apparent volume of distribution of terbinafine in skin and adipose tissues accounted for 41 and 52%, respectively, of the Vss for humans, indicating that uptake into and redistribution from these tissues dominate the pharmacokinetic profile of terbinafine. The PB-PK model developed in this study was capable of accurately predicting the plasma and tissue terbinafine concentrations in both rats and humans and provides insight into the physiological factors that determine terbinafine disposition. PMID:12069977

  20. Determination of carcinogenic threshold limit values using the tumorigenic dose rate 50% (TD50)

    International Nuclear Information System (INIS)

    Bonvalot, Y.; Oudiz, A.; Hubert, P.; Abenhaim, L.

    1989-01-01

    The objective of the present study is to propose a simple procedure for the determination of Occupational Limit Values (OLVs) based on the TD 50 concept (Tumorigenic Dose Rate 50%). The TD 50 concept was introduced by Peto R. and al. to help classify chemical substances according to their carcinogenic potency. The TD 50 is that dose rate (in mg/KXg body weight/day) which, if administered chronically for the standard lifespan of the species will halve the probability of remaining tumorless throughout that period. Using TD 50 values available for 776 substances, the procedure presented here allows one to determine OLVs corresponding to a fixed excess risk. It is based on a mathematical high-to-low doses extrapolation of the TD 50 . OLVs obtained with this procedure are compared with currently available TLVs and other occupational guidelines. (author)

  1. Impact of beta-naphthoflavone on genotoxicity of food-derived carcinogens.

    Science.gov (United States)

    Hodek, Petr; Krizkova, Jitka; Frei, Eva; Singh, Rajinder; Arlt, Volker M; Stiborova, Marie

    2011-01-01

    Benzo[a]pyrene (BaP) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) are carcinogens, which frequently occur in the human diet. Their metabolic activation to reactive species binding to DNA is mediated by cytochromes P450 (CYPs) 1A1 and 1A2. Thus, levels and activities of these CYPs are crucial for initiation of BaP- and PhPI-mediated carcinogenesis. Here, the effect of CYP1A1/2 induction due to their prototype flavonoid inducer, β-naphthoflavone (BNF), on BaP- and PhPI-derived DNA adduct formation in rats was examined. Male rats pretreated with BNF were treated with a single dose of either carcinogen by oral gavage. Nuclease P1 version of 32P-postlabeling assay and online column-switching liquid chromatography-electrospray ionization-tandem mass spectrometry were used to detect and quantify covalent DNA adducts formed by BaP and PhIP in-vivo, respectively. Expression of CYP1A1/2 enzymes was examined by Western blot. Enzymatic activities of CYP1A1/2 were assessed using their marker substrates (ethoxyresorufin and methoxyresorufin). Treatment of rats with a single dose of BNF produced an increase in levels CYP1A1/2 and CYP1A1 proteins in liver and small intestine, respectively. An increase in CYP1A1 protein expression found in both organs correlated well with specific activities of these CYPs. The CYP1A1 expression levels and its specific activity in small intestine decreased along the length of the organ, being highest in its proximal part and lowest in its distal part. The BNF induction of CYP1A1/2 resulted in a significant increase in the formation of BaP- and PhIP-DNA adducts in liver and in the distal part of the small intestine, respectively. Thus, pretreatment of rats with BNF did not prevent the PhIP and BaP activation, but vice versa, enhanced their genotoxicity. The results of this study demonstrate that the administration of only a single dose of CYP-inducing flavonoid prior to the intake of food carcinogens may increase the risk of a tumor

  2. Source apportionment of the carcinogenic potential of polycyclic aromatic hydrocarbons (PAH) associated to airborne PM10 by a PMF model.

    Science.gov (United States)

    Callén, M S; Iturmendi, A; López, J M; Mastral, A M

    2014-02-01

    In order to perform a study of the carcinogenic potential of polycyclic aromatic hydrocarbons (PAH), benzo(a)pyrene equivalent (BaP-eq) concentration was calculated and modelled by a receptor model based on positive matrix factorization (PMF). Nineteen PAH associated to airborne PM10 of Zaragoza, Spain, were quantified during the sampling period 2001-2009 and used as potential variables by the PMF model. Afterwards, multiple linear regression analysis was used to quantify the potential sources of BaP-eq. Five sources were obtained as the optimal solution and vehicular emission was identified as the main carcinogenic source (35 %) followed by heavy-duty vehicles (28 %), light-oil combustion (18 %), natural gas (10 %) and coal combustion (9 %). Two of the most prevailing directions contributing to this carcinogenic character were the NE and N directions associated with a highway, industrial parks and a paper factory. The lifetime lung cancer risk exceeded the unit risk of 8.7 x 10(-5) per ng/m(3) BaP in both winter and autumn seasons and the most contributing source was the vehicular emission factor becoming an important issue in control strategies.

  3. Novel Uses of In Vitro Data to Develop Quantitative Biological Activity Relationship Models for in Vivo Carcinogenicity Prediction.

    Science.gov (United States)

    Pradeep, Prachi; Povinelli, Richard J; Merrill, Stephen J; Bozdag, Serdar; Sem, Daniel S

    2015-04-01

    The availability of large in vitro datasets enables better insight into the mode of action of chemicals and better identification of potential mechanism(s) of toxicity. Several studies have shown that not all in vitro assays can contribute as equal predictors of in vivo carcinogenicity for development of hybrid Quantitative Structure Activity Relationship (QSAR) models. We propose two novel approaches for the use of mechanistically relevant in vitro assay data in the identification of relevant biological descriptors and development of Quantitative Biological Activity Relationship (QBAR) models for carcinogenicity prediction. We demonstrate that in vitro assay data can be used to develop QBAR models for in vivo carcinogenicity prediction via two case studies corroborated with firm scientific rationale. The case studies demonstrate the similarities between QBAR and QSAR modeling in: (i) the selection of relevant descriptors to be used in the machine learning algorithm, and (ii) the development of a computational model that maps chemical or biological descriptors to a toxic endpoint. The results of both the case studies show: (i) improved accuracy and sensitivity which is especially desirable under regulatory requirements, and (ii) overall adherence with the OECD/REACH guidelines. Such mechanism based models can be used along with QSAR models for prediction of mechanistically complex toxic endpoints. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Science, politics, and health in the brave new world of pharmaceutical carcinogenic risk assessment: technical progress or cycle of regulatory capture?

    Science.gov (United States)

    Abraham, John; Ballinger, Rachel

    2012-10-01

    The carcinogenicity (cancer-inducing potential) of pharmaceuticals is an important risk factor for health when considering whether thousands of patients on drug trials or millions/billions of consumers in the marketplace should be exposed to a new drug. Drawing on fieldwork involving over 50 interviews and documentary research spanning 2002-2010 in Europe and the US, and on regulatory capture theory, this article investigates how the techno-regulatory standards for carcinogenicity testing of pharmaceuticals have altered since 1998. It focuses on the replacement of long-term carcinogenicity tests in rodents (especially mice) with shorter-term tests involving genetically-engineered mice (GEM). Based on evidence regarding financial/organizational control, methodological design, and interpretation of the validation and application of these new GEM tests, it is argued that regulatory agencies permitted the drug industry to shape such validation and application in ways that prioritized commercial interests over the need to protect public health. Boundary-work enabling industry scientists to define some standards of public-health policy facilitated such capture. However, as the scientific credibility of GEM tests as tools to protect public health by screening out carcinogens became inescapably problematic, a regulatory resurgence, impelled by reputational concerns, exercised more control over industry's construction and use of the tests, The extensive problems with GEM tests as public-health protective regulatory science raises the spectre that alterations to pharmaceutical carcinogenicity-testing standards since the 1990s may have been boundary-work in which the political project of decreasing the chance that companies' products are defined as carcinogenic has masqueraded as techno-science. Copyright © 2012. Published by Elsevier Ltd.

  5. Impact of Oat-Based Products on Human Gastrointestinal Tract

    Directory of Open Access Journals (Sweden)

    Staka Aiga

    2015-09-01

    Full Text Available Oat is rich in valuable nutrients. In comparison to other cereals, oat contains more total proteins, carbohydrate, fat, non-starch fibre, as well as unique antioxidants (one of them - avenanthramides, vitamins, and minerals. One of the most often studied components of oats is β-glucan - a type of soluble dietary fibre located throughout the starch endosperm, but with highest concentration in the bran. Many studies have shown the beneficial health effects of oat β-glucan as a soluble dietary fibre. Until now, most of the studies on this nutrient have been conducted in the cardiovascular and diabetology field. This article aimed to review the literature on studies that investigated the effects of oat-based products on human gastrointestinal tract - gastrointestinal microflora, irritable bowel syndrome, inflammatory bowel disease as well as prevention/treatment of colorectal cancer. A literature search was conducted using PubMed database. More than 80 potential articles were identified, which were selected afterwards according to aims of our study. Studies done on human were preferred. A long-term dietary intake of oat-based products improves human intestinal microflora, could have benefits in irritable bowel syndrome, and probable effects were seen in patients with ulcerative colitis, but this remains to be proven. There are few studies regarding prevention/treatment of colorectal cancer and they do not show clear benefit nor provide recommendations.

  6. Agent-based simulation for human-induced hazard analysis.

    Science.gov (United States)

    Bulleit, William M; Drewek, Matthew W

    2011-02-01

    Terrorism could be treated as a hazard for design purposes. For instance, the terrorist hazard could be analyzed in a manner similar to the way that seismic hazard is handled. No matter how terrorism is dealt with in the design of systems, the need for predictions of the frequency and magnitude of the hazard will be required. And, if the human-induced hazard is to be designed for in a manner analogous to natural hazards, then the predictions should be probabilistic in nature. The model described in this article is a prototype model that used agent-based modeling (ABM) to analyze terrorist attacks. The basic approach in this article of using ABM to model human-induced hazards has been preliminarily validated in the sense that the attack magnitudes seem to be power-law distributed and attacks occur mostly in regions where high levels of wealth pass through, such as transit routes and markets. The model developed in this study indicates that ABM is a viable approach to modeling socioeconomic-based infrastructure systems for engineering design to deal with human-induced hazards. © 2010 Society for Risk Analysis.

  7. Disruption of spindle checkpoint function in rats following 28 days of repeated administration of renal carcinogens.

    Science.gov (United States)

    Kimura, Masayuki; Mizukami, Sayaka; Watanabe, Yousuke; Hasegawa-Baba, Yasuko; Onda, Nobuhiko; Yoshida, Toshinori; Shibutani, Makoto

    2016-02-01

    We previously reported that 28-day exposure to hepatocarcinogens that facilitate cell proliferation specifically alters the expression of G1/S checkpoint-related genes and proteins, induces aberrant early expression of ubiquitin D (UBD) at the G2 phase, and increases apoptosis in the rat liver, indicating G1/S and spindle checkpoint dysfunction. The present study aimed to determine the time of onset of carcinogen-specific cell-cycle disruption after repeated administration of renal carcinogens for up to 28 days. Rats were orally administered the renal carcinogens nitrofurantoin (NFT), 1-amino-2,4-dibromoantraquinone (ADAQ), and 1,2,3-trichloropropane (TCP) or the non-carcinogenic renal toxicants 1-chloro-2-propanol, triamterene, and carboxin for 3, 7 or 28 days. Both immunohistochemical single-molecule analysis and real-time RT-PCR analysis revealed that carcinogen-specific expression changes were not observed after 28 days of administration. However, the renal carcinogens ADAQ and TCP specifically reduced the number of cells expressing phosphorylated-histone H3 at Ser10 in both UBD(+) cells and proliferating cells, suggestive of insufficient UBD expression at the M phase and early transition of proliferating cells from the M phase, without increasing apoptosis, after 28 days of administration. In contrast, NFT, which has marginal carcinogenic potential, did not induce such cellular responses. These results suggest that it may take 28 days to induce spindle checkpoint dysfunction by renal carcinogens; however, induction of apoptosis may not be essential. Thus, induction of spindle checkpoint dysfunction may be dependent on carcinogenic potential of carcinogen examined, and marginal carcinogens may not exert sufficient responses even after 28 days of administration.

  8. The effects of environmental chemical carcinogens on the microRNA machinery.

    Science.gov (United States)

    Izzotti, A; Pulliero, A

    2014-07-01

    The first evidence that microRNA expression is early altered by exposure to environmental chemical carcinogens in still healthy organisms was obtained for cigarette smoke. To date, the cumulative experimental data indicate that similar effects are caused by a variety of environmental carcinogens, including polycyclic aromatic hydrocarbons, nitropyrenes, endocrine disruptors, airborne mixtures, carcinogens in food and water, and carcinogenic drugs. Accordingly, the alteration of miRNA expression is a general mechanism that plays an important pathogenic role in linking exposure to environmental toxic agents with their pathological consequences, mainly including cancer development. This review summarizes the existing experimental evidence concerning the effects of chemical carcinogens on the microRNA machinery. For each carcinogen, the specific microRNA alteration signature, as detected in experimental studies, is reported. These data are useful for applying microRNA alterations as early biomarkers of biological effects in healthy organisms exposed to environmental carcinogens. However, microRNA alteration results in carcinogenesis only if accompanied by other molecular damages. As an example, microRNAs altered by chemical carcinogens often inhibits the expression of mutated oncogenes. The long-term exposure to chemical carcinogens causes irreversible suppression of microRNA expression thus allowing the transduction into proteins of mutated oncogenes. This review also analyzes the existing knowledge regarding the mechanisms by which environmental carcinogens alter microRNA expression. The underlying molecular mechanism involves p53-microRNA interconnection, microRNA adduct formation, and alterations of Dicer function. On the whole, reported findings provide evidence that microRNA analysis is a molecular toxicology tool that can elucidate the pathogenic mechanisms activated by environmental carcinogens. Copyright © 2014 Elsevier GmbH. All rights reserved.

  9. Carcinogenic 3-nitrobenzanthrone but not 2-nitrobenzanthrone is metabolised to an unusual mercapturic acid in rats.

    Science.gov (United States)

    Linhart, Igor; Mráz, Jaroslav; Hanzlíková, Iveta; Silhánková, Alexandra; Frantík, Emil; Himl, Michal

    2012-02-05

    3-Nitrobenzanthrone (3-NBA) is an extremely potent mutagen and suspect human carcinogen found in diesel exhaust. Its isomer 2-nitrobenzanthrone (2-NBA) has also been found in ambient air. These isomers differ in mutagenicity in Salmonella by 2-3 orders of magnitude. To identify their urinary metabolites and also to assess the assumed differences in their excretion, rats were dosed orally with 2mg/kg b.w. of either 2-NBA or 3-NBA. Their urine was collected for two consecutive days after dosage. Both LC-ESI-MS and GC-MS confirmed formation of the corresponding aminobenzanthrones (ABA). Excretion of these metabolites within the first day after dosing with 2- and 3-ABA amounted to 0.32±0.06 and 0.83±0.40% of the doses, respectively, while the excretion within the second day was by one order of magnitude lower. A novel mercapturic acid metabolite of 3-NBA was identified in urine by LC-ESI-MS as N-acetyl-S-(3-aminobenzanthron-2-yl)cysteine (3-ABA-MA) by comparison with the authentic standard. Its excretion amounted to 0.49±0.15 and 0.02±0.01% of dose within the first and second day after dosing, respectively. In contrast, no mercapturic acid was detected in the urine of rats dosed with 2-NBA. Observed difference in the mercapturic acid formation between 2- and 3-NBA is a new distinctive feature reflecting differences in the critical step of their metabolism, i.e., benzanthronylnitrenium ion formation that is intrinsically associated with biological activities of these two isomers. Moreover, 3-ABA-MA is a promising candidate biomarker of exposure to the carcinogenic 3-NBA. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  10. Matrix of occupational exposures to carcinogenic agents and pesticides in Costa Rica

    International Nuclear Information System (INIS)

    Chaves, Jorge; Partanen, Timo; Wesseling, Catharina; Chaverri, Fabio; Monge, Patricia; Ruepert, Clemens; Guardado, Jorge; Aragon, Aurora; Kauppinen, Timo

    2004-01-01

    The European data system CAREX converts national numbers of workers in 55 sectors and estimated proportions of workers exposed to carcinogenic agents into numbers of workers exposed to each agent. CAREX is applied and modified in Costa Rica (TICAREX) for the first time outside Europe. 27 carcinogenic agents and 7 groups of pesticides were included. Numbers of exposed were estimated separately for men and women. The most frequent agents in the 1.3 million labor force of Costa Rica were solar radiation (333,000 workers); diesel engine emissions (278,000); paraquat and diquat (175,000); environmental tobacco smoke (71,000); chromium (VI) compounds (55,000); benzene (52,000); mancozeb, maneb and zineb (49,000); chlorothalonil (38,000); wood dust (32,000); silica dust (27,000); benomyl (19,000); lead and its inorganic compounds (19,000); tetrachloroethylene (18,000); and polycyclic aromatic hydrocarbons (17,000). Owing to the different occupational distribution between the genders, formaldehyde, radon and methylene chloride were more frequent than pesticides, chromium (VI), wood dust, and silica dust in women. Agriculture, construction, personal and domestic services, land and water transport and allied services, pottery and similar industries, manufacture of wood products, mining, forestry, fishing, manufacture of electric products, and bars and restaurants were sectors with frequent exposures. Substantial reduction of occupational and environmental exposures to these agents would improve considerably public and occupational health. Reduction of occupational exposures is usually also followed by improvement of environmental quality. Monitoring of exposures and health of workers and the general public is essential in the control of environmental contamination and human exposures. This report presents details of the exposures matrix, which is the basis of TICAREX. (author) [es

  11. Molecular biomarkers of oxidative stress associated with bromate carcinogenicity

    International Nuclear Information System (INIS)

    Delker, Don; Hatch, Gary; Allen, James; Crissman, Bobby; George, Michael; Geter, David; Kilburn, Steve; Moore, Tanya; Nelson, Gail; Roop, Barbara; Slade, Ralph; Swank, Adam; Ward, William; DeAngelo, Anthony

    2006-01-01

    Potassium bromate (KBrO 3 ) is a chemical oxidizing agent found in drinking water as a disinfection byproduct of surface water ozonation. Chronic exposures to KBrO 3 cause renal cell tumors in rats, hamsters and mice and thyroid and testicular mesothelial tumors in rats. Experimental evidence indicates that bromate mediates toxicological effects via the induction of oxidative stress. To investigate the contribution of oxidative stress in KBrO 3 -induced cancer, male F344 rats were administered KBrO 3 in their drinking water at multiple concentrations for 2-100 weeks. Gene expression analyses were performed on kidney, thyroid and mesothelial cell RNA. Families of mRNA transcripts differentially expressed with respect to bromate treatment included multiple cancer, cell death, ion transport and oxidative stress genes. Multiple glutathione metabolism genes were up-regulated in kidney following carcinogenic (400 mg/L) but not non-carcinogenic (20 mg/L) bromate exposures. 8-Oxodeoxyguanosine glycosylase (Ogg1) mRNA was up-regulated in response to bromate treatment in kidney but not thyroid. A dramatic decrease in global gene expression changes was observed following 1 mg/L compared to 20 mg/L bromate exposures. In a separate study oxygen-18 ( 18 O) labeled KBrO 3 was administered to male rats by oral gavage and tissues were analyzed for 18 O deposition. Tissue enrichment of 18 O was observed at 5 and 24 h post-KBr 18 O 3 exposure with the highest enrichment occurring in the liver followed by the kidney, thyroid and testes. The kidney dose response observed was biphasic showing similar statistical increases in 18 O deposition between 0.25 and 50 mg/L (equivalent dose) KBr 18 O 3 followed by a much greater increase above 50 mg/L. These results suggest that carcinogenic doses of potassium bromate require attainment of a threshold at which oxidation of tissues occurs and that gene expression profiles may be predictive of these physiological changes in renal homeostasis

  12. Advancing the 3Rs in regulatory toxicology - Carcinogenicity testing: Scope for harmonisation and advancing the 3Rs in regulated sectors of the European Union.

    Science.gov (United States)

    Annys, Erwin; Billington, Richard; Clayton, Rick; Bremm, Klaus-Dieter; Graziano, Michael; McKelvie, Jo; Ragan, Ian; Schwarz, Michael; van der Laan, Jan Willem; Wood, Charles; Öberg, Mattias; Wester, Piet; Woodward, Kevin N

    2014-07-01

    Different government agencies operating in the European Union regulate different types of chemical products but all require testing for carcinogenicity to support applications for product marketing and commercialisation. A conference was held in Brussels in 2013 where representatives of the pharmaceutical, animal health, chemical and plant protection industries, together with representatives of regulatory agencies, universities and other stakeholders, met under the auspices of The European Partnership for Alternative Approaches to Animal Testing (EPAA) to discuss the varying requirements for carcinogenicity testing, and how these studies might be refined to improve hazard evaluation and risk assessment while implementing principles of the 3Rs (replacement, refinement and reduction in animal studies). While there are some similarities, the regulatory approaches in pharmaceutical, animal health, chemical and plant protection sectors have varying degrees of flexibility in requirements for carcinogenicity testing, to an extent reflecting concerns over the magnitude and duration of human exposure, either directly as in therapeutic exposure to pharmaceuticals, or indirectly through the ingestion of residues of veterinary drugs or plant protection chemicals. The article discusses these differences and other considerations for modified carcinogenicity testing paradigms on the basis of scientific and 3Rs approaches. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Modulation of DNA polymerase beta-dependent base excision repair in cultured human cells after low dose exposure to arsenite

    International Nuclear Information System (INIS)

    Sykora, Peter; Snow, Elizabeth T.

    2008-01-01

    Base excision repair (BER) is crucial for development and for the repair of endogenous DNA damage. However, unlike nucleotide excision repair, the regulation of BER is not well understood. Arsenic, a well-established human carcinogen, is known to produce oxidative DNA damage, which is repaired primarily by BER, whilst high doses of arsenic can also inhibit DNA repair. However, the mechanism of repair inhibition by arsenic and the steps inhibited are not well defined. To address this question we have investigated the regulation of DNA polymerase β (Pol β) and AP endonuclease (APE1), in response to low, physiologically relevant doses of arsenic. GM847 lung fibroblasts and HaCaT keratinocytes were exposed to sodium arsenite, As(III), and mRNA, protein levels and BER activity were assessed. Both Pol β and APE1 mRNA exhibited significant dose-dependant down regulation at doses of As(III) above 1 μM. However, at lower doses Pol β mRNA and protein levels, and consequently, BER activity were significantly increased. In contrast, APE1 protein levels were only marginally increased by low doses of As(III) and there was no correlation between APE1 and overall BER activity. Enzyme supplementation of nuclear extracts confirmed that Pol β was rate limiting. These changes in BER correlated with overall protection against sunlight UV-induced toxicity at low doses of As(III) and produced synergistic toxicity at high doses. The results provide evidence that changes in BER due to low doses of arsenic could contribute to a non-linear, threshold dose response for arsenic carcinogenesis

  14. Skeleton-based human action recognition using multiple sequence alignment

    Science.gov (United States)

    Ding, Wenwen; Liu, Kai; Cheng, Fei; Zhang, Jin; Li, YunSong

    2015-05-01

    Human action recognition and analysis is an active research topic in computer vision for many years. This paper presents a method to represent human actions based on trajectories consisting of 3D joint positions. This method first decompose action into a sequence of meaningful atomic actions (actionlets), and then label actionlets with English alphabets according to the Davies-Bouldin index value. Therefore, an action can be represented using a sequence of actionlet symbols, which will preserve the temporal order of occurrence of each of the actionlets. Finally, we employ sequence comparison to classify multiple actions through using string matching algorithms (Needleman-Wunsch). The effectiveness of the proposed method is evaluated on datasets captured by commodity depth cameras. Experiments of the proposed method on three challenging 3D action datasets show promising results.

  15. Managing Human Resource based Intellectual Capital in a Global setting

    DEFF Research Database (Denmark)

    Gretzinger, Susanne; Lemke, Sarah; Matiaske, Wenzel

    2014-01-01

    From a strategic management perspective human capital and the embedded knowledge can be viewed as intellectual capital and became inevitably important for companies in general as well as for multinationals. While national companies just have to (re-)combine resources within a homogeneous...... if culturally differentiated incentive systems are necessary for optimised retention management? In the empirical part of this study it was made us of data from 32 countries. The research results reveal a moderating impact of cultural dimensions and therefore a cultural dependency for the effectiveness...... of incentives on retention management and therewith implicates that retention management is significant for the process of developing and fostering a MNCs intellectual capital. To improve their human-resource based intellectual capital MNCs have to adapt their initiatives to the cultural background...

  16. HINT-KB: The human interactome knowledge base

    KAUST Repository

    Theofilatos, Konstantinos A.

    2012-01-01

    Proteins and their interactions are considered to play a significant role in many cellular processes. The identification of Protein-Protein interactions (PPIs) in human is an open research area. Many Databases, which contain information about experimentally and computationally detected human PPIs as well as their corresponding annotation data, have been developed. However, these databases contain many false positive interactions, are partial and only a few of them incorporate data from various sources. To overcome these limitations, we have developed HINT-KB (http://150.140.142.24:84/Default.aspx) which is a knowledge base that integrates data from various sources, provides a user-friendly interface for their retrieval, estimates a set of features of interest and computes a confidence score for every candidate protein interaction using a modern computational hybrid methodology. © 2012 IFIP International Federation for Information Processing.

  17. Metrology of human-based and other qualitative measurements

    Science.gov (United States)

    Pendrill, Leslie; Petersson, Niclas

    2016-09-01

    The metrology of human-based and other qualitative measurements is in its infancy—concepts such as traceability and uncertainty are as yet poorly developed. This paper reviews how a measurement system analysis approach, particularly invoking as performance metric the ability of a probe (such as a human being) acting as a measurement instrument to make a successful decision, can enable a more general metrological treatment of qualitative observations. Measures based on human observations are typically qualitative, not only in sectors, such as health care, services and safety, where the human factor is obvious, but also in customer perception of traditional products of all kinds. A principal challenge is that the usual tools of statistics normally employed for expressing measurement accuracy and uncertainty will probably not work reliably if relations between distances on different portions of scales are not fully known, as is typical of ordinal or other qualitative measurements. A key enabling insight is to connect the treatment of decision risks associated with measurement uncertainty to generalized linear modelling (GLM). Handling qualitative observations in this way unites information theory, the perceptive identification and choice paradigms of psychophysics. The Rasch invariant measure psychometric GLM approach in particular enables a proper treatment of ordinal data; a clear separation of probe and item attribute estimates; simple expressions for instrument sensitivity; etc. Examples include two aspects of the care of breast cancer patients, from diagnosis to rehabilitation. The Rasch approach leads in turn to opportunities of establishing metrological references for quality assurance of qualitative measurements. In psychometrics, one could imagine a certified reference for knowledge challenge, for example, a particular concept in understanding physics or for product quality of a certain health care service. Multivariate methods, such as Principal Component

  18. Metrology of human-based and other qualitative measurements

    International Nuclear Information System (INIS)

    Pendrill, Leslie; Petersson, Niclas

    2016-01-01

    The metrology of human-based and other qualitative measurements is in its infancy—concepts such as traceability and uncertainty are as yet poorly developed. This paper reviews how a measurement system analysis approach, particularly invoking as performance metric the ability of a probe (such as a human being) acting as a measurement instrument to make a successful decision, can enable a more general metrological treatment of qualitative observations. Measures based on human observations are typically qualitative, not only in sectors, such as health care, services and safety, where the human factor is obvious, but also in customer perception of traditional products of all kinds. A principal challenge is that the usual tools of statistics normally employed for expressing measurement accuracy and uncertainty will probably not work reliably if relations between distances on different portions of scales are not fully known, as is typical of ordinal or other qualitative measurements. A key enabling insight is to connect the treatment of decision risks associated with measurement uncertainty to generalized linear modelling (GLM). Handling qualitative observations in this way unites information theory, the perceptive identification and choice paradigms of psychophysics. The Rasch invariant measure psychometric GLM approach in particular enables a proper treatment of ordinal data; a clear separation of probe and item attribute estimates; simple expressions for instrument sensitivity; etc. Examples include two aspects of the care of breast cancer patients, from diagnosis to rehabilitation. The Rasch approach leads in turn to opportunities of establishing metrological references for quality assurance of qualitative measurements. In psychometrics, one could imagine a certified reference for knowledge challenge, for example, a particular concept in understanding physics or for product quality of a certain health care service. Multivariate methods, such as Principal Component

  19. Science-Based Simulation Model of Human Performance for Human Reliability Analysis

    International Nuclear Information System (INIS)

    Kelly, Dana L.; Boring, Ronald L.; Mosleh, Ali; Smidts, Carol

    2011-01-01

    Human reliability analysis (HRA), a component of an integrated probabilistic risk assessment (PRA), is the means by which the human contribution to risk is assessed, both qualitatively and quantitatively. However, among the literally dozens of HRA methods that have been developed, most cannot fully model and quantify the types of errors that occurred at Three Mile Island. Furthermore, all of the methods lack a solid empirical basis, relying heavily on expert judgment or empirical results derived in non-reactor domains. Finally, all of the methods are essentially static, and are thus unable to capture the dynamics of an accident in progress. The objective of this work is to begin exploring a dynamic simulation approach to HRA, one whose models have a basis in psychological theories of human performance, and whose quantitative estimates have an empirical basis. This paper highlights a plan to formalize collaboration among the Idaho National Laboratory (INL), the University of Maryland, and The Ohio State University (OSU) to continue development of a simulation model initially formulated at the University of Maryland. Initial work will focus on enhancing the underlying human performance models with the most recent psychological research, and on planning follow-on studies to establish an empirical basis for the model, based on simulator experiments to be carried out at the INL and at the OSU.

  20. Retraction: Evaluation of carcinogenic effects of electromagnetic fields (EMF).

    Science.gov (United States)

    Mehic, Bakir

    2010-11-01

    The Editor-in-chief of the Bosnian Journal of Basic Medical Sciences has decided to retract the article from Bayazit V et al. [1] entitled as: "Evaluation of carcinogenic effects of electromagnetic fields (EMF)" published in Bosn J Basic Med Sci. 2010 Aug;10(3):245-50. After the editorial office was alerted of possible plagiarism in the article, it conducted thorough investigation and concluded that the article apparently represents plagiarized material from two World Health Organization reports, one European Commission report and other sources. Since this is considered scientific plagiarism and scientific misconduct, Editor-in-chief has decided to withdraw the article. The authors have agreed with the editorial office decision.

  1. Chemistry of mutagens and carcinogens in broiled food.

    Science.gov (United States)

    Nishimura, S

    1986-01-01

    From a chemical point of view, the following subjects are important areas in studies on mutagens and carcinogens in broiled foods. In addition to heterocyclic amines which need microsomal activation, the structural elucidation of more labile direct-acting mutagens is necessary. It is known that there are still various unknown minor mutagens in broiled foods. Although the structural characterization of such compounds is more difficult, it is important since they might be hazardous in spite of their low mutagenicity. A more feasible and easier method for quantitative analysis of mutagens, in addition to HPLC and GC/MS methods presently employed, must be developed. The mechanism of formation of mutagens by broiling of food should be studied. An effective chemical method to prevent formation of mutagens or to destroy them, once formed, should be developed. PMID:3757944

  2. The assessment of the carcinogenic effects of low dose radiation

    International Nuclear Information System (INIS)

    Tubiana, M.; Lafuma, J.; Masse, R.; Latarjet, R.

    1991-01-01

    It is concluded that the exclusion of patients for the purposes of risk estimation, the choice of a particular relative risk projection model and of a dose reduction factor equal to 2 are all decisions which result in an overestimation of the actual risk. These choices can be understood when the aim is radiation protection and when it is safer to overestimate the risk; however, they are open to criticism if the aim is a realistic assessment of the risk. For low doses, below 50 mSv/year, and when all causes of uncertainty are added, the actual risk might be markedly lower than the risk estimated with the ICRP (1991) carcinogenic risk coefficient and the DRF estimated by ICRP. Future studies should aim at providing direct and more precise assessments of risk coefficients in the low dose region. (Author)

  3. [Comparative carcinogenic properties of basalt fiber and chrysotile-asbestos].

    Science.gov (United States)

    Nikitina, O V; Kogan, F M; Vanchugova, N N; Frash, V N

    1989-01-01

    In order to eliminate asbestos adverse effect on workers' health it was necessary to use mineral rayon, primarily basalt fibre, instead of asbestos. During a chronic experiment on animals the oncogenicity of 2 kinds of basalt fibre was studied compared to chrysotile asbestos. The dust dose of 25 mg was twice administered by intraperitonial route. All types of dust induced the onset of intraperitonial mesotheliomas but neoplasm rates were significantly lower in the groups exposed to basalt fibre. There was no credible data on the differences between the groups exposed to various types of basalt fibre. Since the latter produced some oncogenic effect, it was necessary to develop a complex of antidust measures, fully corresponding to the measures adopted for carcinogenic dusts.

  4. Appearance-based human gesture recognition using multimodal features for human computer interaction

    Science.gov (United States)

    Luo, Dan; Gao, Hua; Ekenel, Hazim Kemal; Ohya, Jun

    2011-03-01

    The use of gesture as a natural interface plays an utmost important role for achieving intelligent Human Computer Interaction (HCI). Human gestures include different components of visual actions such as motion of hands, facial expression, and torso, to convey meaning. So far, in the field of gesture recognition, most previous works have focused on the manual component of gestures. In this paper, we present an appearance-based multimodal gesture recognition framework, which combines the different groups of features such as facial expression features and hand motion features which are extracted from image frames captured by a single web camera. We refer 12 classes of human gestures with facial expression including neutral, negative and positive meanings from American Sign Languages (ASL). We combine the features in two levels by employing two fusion strategies. At the feature level, an early feature combination can be performed by concatenating and weighting different feature groups, and LDA is used to choose the most discriminative elements by projecting the feature on a discriminative expression space. The second strategy is applied on decision level. Weighted decisions from single modalities are fused in a later stage. A condensation-based algorithm is adopted for classification. We collected a data set with three to seven recording sessions and conducted experiments with the combination techniques. Experimental results showed that facial analysis improve hand gesture recognition, decision level fusion performs better than feature level fusion.

  5. Multiple resistance to carcinogens and xenobiotics: P-glycoproteins as universal detoxifiers.

    Science.gov (United States)

    Efferth, Thomas; Volm, Manfred

    2017-07-01

    The detoxification of toxic substances is of general relevance in all biological systems. The plethora of exogenous xenobiotic compounds and endogenous toxic metabolic products explains the evolutionary pressure of all organisms to develop molecular mechanisms to detoxify and excrete harmful substances from the body. P-glycoprotein and other members of the ATP-binding cassette (ABC) transporter family extrude innumerous chemical compounds out of cells. Their specific expression in diverse biological contexts cause different phenotypes: (1) multidrug resistance (MDR) and thus failure of cancer chemotherapy, (2) avoidance of accumulation of carcinogens and prevention of carcinogenesis in healthy tissues, (3) absorption, distribution, metabolization and excretion (ADME) of pharmacological drugs in human patients, (4) protection from environmental toxins in aquatic organisms (multi-xenobiotic resistance, MXR). Hence ABC-transporters may have opposing effects for organismic health reaching from harmful in MDR of tumors to beneficial for maintenance of health in MXR. While their inhibition by specific inhibitors may improve treatment success in oncology and avoid carcinogenesis, blocking of ABC-transporter-driven efflux by environmental pollutants leads to ecotoxicological consequences in marine biotopes. Poisoned seafood may enter the food-chain and cause intoxications in human beings. As exemplified with ABC-transporters, joining forces in interdisciplinary research may, therefore, be a wise strategy to fight problems in human medicine and environmental sciences.

  6. Use of short-term test systems for the prediction of the hazard represented by potential chemical carcinogens

    International Nuclear Information System (INIS)

    Glass, L.R.; Jones, T.D.; Easterly, C.E.; Walsh, P.J.

    1990-10-01

    It has been hypothesized that results from short-term bioassays will ultimately provide information that will be useful for human health hazard assessment. Historically, the validity of the short-term tests has been assessed using the framework of the epidemiologic/medical screens. In this context, the results of the carcinogen (long-term) bioassay is generally used as the standard. However, this approach is widely recognized as being biased and, because it employs qualitative data, cannot be used to assist in isolating those compounds which may represent a more significant toxicologic hazard than others. In contrast, the goal of this research is to address the problem of evaluating the utility of the short-term tests for hazard assessment using an alternative method of investigation. Chemicals were selected mostly from the list of carcinogens published by the International Agency for Research on Carcinogens (IARC); a few other chemicals commonly recognized as hazardous were included. Tumorigenicity and mutagenicity data on 52 chemicals were obtained from the Registry of Toxic Effects of Chemical Substances (RTECS) and were analyzed using a relative potency approach. The data were evaluated in a format which allowed for a comparison of the ranking of the mutagenic relative potencies of the compounds (as estimated using short-term data) vs. the ranking of the tumorigenic relative potencies (as estimated from the chronic bioassays). Although this was a preliminary investigation, it offers evidence that the short-term tests systems may be of utility in ranking the hazards represented by chemicals which may contribute to increased carcinogenesis in humans as a result of occupational or environmental exposures. 177 refs., 8 tabs

  7. Use of short-term test systems for the prediction of the hazard represented by potential chemical carcinogens

    Energy Technology Data Exchange (ETDEWEB)

    Glass, L.R.; Jones, T.D.; Easterly, C.E.; Walsh, P.J.

    1990-10-01

    It has been hypothesized that results from short-term bioassays will ultimately provide information that will be useful for human health hazard assessment. Historically, the validity of the short-term tests has been assessed using the framework of the epidemiologic/medical screens. In this context, the results of the carcinogen (long-term) bioassay is generally used as the standard. However, this approach is widely recognized as being biased and, because it employs qualitative data, cannot be used to assist in isolating those compounds which may represent a more significant toxicologic hazard than others. In contrast, the goal of this research is to address the problem of evaluating the utility of the short-term tests for hazard assessment using an alternative method of investigation. Chemicals were selected mostly from the list of carcinogens published by the International Agency for Research on Carcinogens (IARC); a few other chemicals commonly recognized as hazardous were included. Tumorigenicity and mutagenicity data on 52 chemicals were obtained from the Registry of Toxic Effects of Chemical Substances (RTECS) and were analyzed using a relative potency approach. The data were evaluated in a format which allowed for a comparison of the ranking of the mutagenic relative potencies of the compounds (as estimated using short-term data) vs. the ranking of the tumorigenic relative potencies (as estimated from the chronic bioassays). Although this was a preliminary investigation, it offers evidence that the short-term tests systems may be of utility in ranking the hazards represented by chemicals which may contribute to increased carcinogenesis in humans as a result of occupational or environmental exposures. 177 refs., 8 tabs.

  8. OVERVIEW OF DRINKING WATER MUTAGENICITY AND CARCINOGENICITY AND RISK FOR BLADDER CANCER

    Science.gov (United States)

    Among the 11 disinfection by-products (DBPs) in drinking water that are regulated by the U.S. EPA, (a) 2 DBPs (chloroacetic acid and chlorite) are not carcinogenic-in either of 2 species; (b) chlorite is not carcinogenic in 3 rodent assays and has never been tested for genotoxici...

  9. Impact of occupational carcinogens on lung cancer risk in a general population

    NARCIS (Netherlands)

    De Matteis, S.; Consonni, D.; Lubin, J.H.; Tucker, M.; Peters, S.; Vermeulen, R.; Kromhout, H.; Bertazzi, P.A.; Caporaso, N.E.; Pesatori, A.C.; Wacholder, S.; Landi, M.T.

    2012-01-01

    BACKGROUND: Exposure to occupational carcinogens is an important preventable cause of lung cancer. Most of the previous studies were in highly exposed industrial cohorts. Our aim was to quantify lung cancer burden attributable to occupational carcinogens in a general population. METHODS: We applied

  10. 78 FR 16681 - International Conference on Harmonisation; Proposed Change to Rodent Carcinogenicity Testing of...

    Science.gov (United States)

    2013-03-18

    ...-evidence (WOE) factors proposed for inclusion in CADs. II. Past Experience With Carcinogenicity Assessment... Medicines Agency; and the Japanese Ministry of Health, Labour and Welfare. We would request that CADs be... WOE factors proposed for inclusion in carcinogenicity assessment documents. Submit either electronic...

  11. Voltammetric Determination of Carcinogenic Nitrobiphenyls at a Hanging Mercury Drop Electrode

    Directory of Open Access Journals (Sweden)

    Jiří Zima

    2003-02-01

    Full Text Available Differential pulse voltammetry (DPV and adsorptive stripping voltammetry (AdSV at a hanging mercury drop electrode (HMDE was used for the determination of trace amounts of carcinogenic nitrobiphenyls, namely 2-nitrobiphenyl (2-NBP, 3-nitrobiphenyl (3-NBP and 4-nitrobiphenyl (4-NBP within the concentration range from 2.10-8 to 1.10-5 mol⋅L-1 for DPV and from 2.10-9 to 1.10-7 mol⋅L-1 for AdSV using a Britton-Robinson buffer – methanol (1:1 mixture with resulting pH 12 as a base electrolyte. The practical applicability of newly developed methods was verified using model samples of drinking and river water and liquid-liquid extraction for a preliminary separation and preconcentration.

  12. Music recommendation according to human motion based on kernel CCA-based relationship

    Science.gov (United States)

    Ohkushi, Hiroyuki; Ogawa, Takahiro; Haseyama, Miki

    2011-12-01

    In this article, a method for recommendation of music pieces according to human motions based on their kernel canonical correlation analysis (CCA)-based relationship is proposed. In order to perform the recommendation between different types of multimedia data, i.e., recommendation of music pieces from human motions, the proposed method tries to estimate their relationship. Specifically, the correlation based on kernel CCA is calculated as the relationship in our method. Since human motions and music pieces have various time lengths, it is necessary to calculate the correlation between time series having different lengths. Therefore, new kernel functions for human motions and music pieces, which can provide similarities between data that have different time lengths, are introduced into the calculation of the kernel CCA-based correlation. This approach effectively provides a solution to the conventional problem of not being able to calculate the correlation from multimedia data that have various time lengths. Therefore, the proposed method can perform accurate recommendation of best matched music pieces according to a target human motion from the obtained correlation. Experimental results are shown to verify the performance of the proposed method.

  13. A statistical frame based TDMA protocol for human body communication.

    Science.gov (United States)

    Nie, Zedong; Li, Zhao; Huang, Renwei; Liu, Yuhang; Li, Jingzhen; Wang, Lei

    2015-07-09

    Human body communication (HBC) using the human body as the transmission medium, which has been regarded as one of the most promising short-range communications in wireless body area networks (WBAN). Compared to the traditional wireless networks, two challenges are existed in HBC based WBAN. (1) Its sensor nodes should be energy saving since it is inconvenient to replace or recharge the battery on these sensor nodes; (2) the coordinator should be able to react dynamically and rapidly to the burst traffic triggered by sensing events. Those burst traffic conditions include vital physical signal (electrocardiogram, electroencephalogram etc.) monitoring, human motion detection (fall detection, activity monitoring, gesture recognition, motion sensing etc.) and so on. To cope with aforementioned challenges, a statistical frame based TDMA (S-TDMA) protocol with multi-constrained (energy, delay, transmission efficiency and emergency management) service is proposed in this paper. The scenarios where burst traffic is often triggered rapidly with low power consumption and low delay is handled in our proposed S-TDMA. A beacon frame with the contained synchronous and poll information is designed to reduce the possibility of collisions of request frames. A statistical frame which broadcasts the unified scheduling information is adopted to avoid packet collisions, idle listening and overhearing. Dynamic time slot allocation mechanism is presented to manage the burst traffic and reduce the active period in each beacon period. An emergency mechanism is proposed for vital signals to be transmitted. The theory analysis is proceed and the result is evaluated in the hardware platform. To verify its feasibility, S-TDMA was fully implemented on our independently-developed HBC platform where four sensor nodes and a coordinator are fastened on a human body. Experiment results show that S-TDMA costs 89.397 mJ every 20 s when the payload size is 122 bytes, 9.51% lower than Lightweight MAC

  14. Evaluation of a chemical risk assessment method of South Korea for chemicals classified as carcinogenic, mutagenic or reprotoxic (CMR).

    Science.gov (United States)

    Kim, Min-Uk; Byeon, Sang-Hoon

    2017-12-12

    Chemicals were used in various fields by the development of industry and science and technology. The Chemical Hazard Risk Management (CHARM) was developed to assess the risk of chemicals in South Korea. In this study, we were to evaluate the CHARM model developed for the effective management of workplace chemicals. We used 59 carcinogenic, mutagenic or reprotoxic (CMR) materials, which are both the work environment measurement result and the usage information among the manufacturer data. The CHARM model determines the risk to human health using the exposure level (based on working environment measurements or a combination of the quantity used and chemical physical properties (e.g., fugacity and volatility)), hazard (using occupational exposure limit (OEL) or Risk phrases (R-phrases)/Hazard statements (H-statements) from the Material Safety Data Sheet (MSDS)). The risk level was lower when using the results of the work environment measurement than when applying the chemical quantity and physical properties in the exposure level evaluation method. It was evaluated as grade 4 for the CMR material in the hazard class determination. The risk assessment method by R-phrases was evaluated more conservatively than the risk assessment method by OEL. And the risk assessment method by H-statements was evaluated more conservatively than the risk assessment method by R-phrases. The CHARM model was gradually conservatively assessed as it proceeded in the next step without quantitative information for individual workplaces. The CHARM is expected to help identify the risk if the hazards and exposure levels of chemicals were identified in individual workplaces. For CMR substances, although CHARM is highly evaluated for hazards, the risk is assessed to be low if exposure levels are assessed low. When evaluating the risk of highly hazardous chemicals such as CMR substances, we believe the model should be adapted to be more conservative and classify these as higher risk. This work is

  15. Pneumatic Artificial Muscles Based on Biomechanical Characteristics of Human Muscles

    Directory of Open Access Journals (Sweden)

    N. Saga

    2006-01-01

    Full Text Available This article reports the pneumatic artificial muscles based on biomechanical characteristics of human muscles. A wearable device and a rehabilitation robot that assist a human muscle should have characteristics similar to those of human muscle. In addition, since the wearable device and the rehabilitation robot should be light, an actuator with a high power to weight ratio is needed. At present, the McKibben type is widely used as an artificial muscle, but in fact its physical model is highly nonlinear. Therefore, an artificial muscle actuator has been developed in which high-strength carbon fibres have been built into the silicone tube. However, its contraction rate is smaller than the actual biological muscles. On the other hand, if an artificial muscle that contracts axially is installed in a robot as compactly as the robot hand, big installing space is required. Therefore, an artificial muscle with a high contraction rate and a tendon-driven system as a compact actuator were developed, respectively. In this study, we report on the basic structure and basic characteristics of two types of actuators.

  16. Moesin Is a Biomarker for the Assessment of Genotoxic Carcinogens in Mouse Lymphoma

    Science.gov (United States)

    Lee, Yoen Jung; Choi, In-Kwon; Sheen, Yhun Yhong; Park, Sue Nie; Kwon, Ho Jeong

    2012-01-01

    1,2-Dibromoethane and glycidol are well known genotoxic carcinogens, which have been widely used in industry. To identify a specific biomarker for these carcinogens in cells, the cellular proteome of L5178Y mouse lymphoma cells treated with these compounds was analyzed by 2-dimensional gel electrophoresis (2-DE) and MALDI-TOF mass spectrometry (MS). Of 50 protein spots showing a greater than 1.5-fold increase or decrease in intensity compared to control cells on a 2-D gel, we focused on the candidate biomarker moesin. Western analysis using monoclonal rabbit anti-moesin confirmed the identity of the protein and its increased level of expression upon exposure to the carcinogenic compounds. Moesin expression also increased in cells treated with six additional genotoxic carcinogens, verifying that moesin could serve as a biomarker to monitor phenotypic change upon exposure to genotoxic carcinogens in L5178Y mouse lymphoma cells. PMID:22358511

  17. The in vivo rodent test systems for assessment of carcinogenic potential

    DEFF Research Database (Denmark)

    van der Laan, Jan-Willem; Spindler, Per

    2002-01-01

    A Drug Information Association (DIA) workshop was held in May 2001 to discuss the outcome of the International Life Sciences Institute-Health and Environmental Sciences Institute (ILSI-HESI) project on alternative models for carcinogenicity assessment such as the P53(+/-) and XPA(+/-) knockout...... mouse models, the RasH2 and Tg.AC transgenic mouse models, and the neonatal mouse model. The "ICH Guideline S1B on Testing for Carcinogenicity of Pharmaceuticals" advocates that carcinogenicity testing of pharmaceuticals, when needed, might be carried out choosing one 2-year rodent carcinogenicity study...... (rat) plus one other study that supplements the 2-year study and providing additional information that is not readily available from the 2-year study: either (1) a short- or medium-term in vivo rodent test system or (2) a 2-year carcinogenicity study in a second rodent species (mouse). Another topic...

  18. Assessment of bullet effectiveness based on a human vulnerability model.

    Science.gov (United States)

    Liu, Susu; Xu, C; Wen, Y; Li, G; Zhou, J

    2017-12-25

    Penetrating wounds from explosively propelled fragments and bullets are the most common causes of combat injury. There is a requirement to assess the potential effectiveness of bullets penetrating human tissues in order to optimise preventive measures and wound trauma management. An advanced voxel model based on the Chinese Visible Human data was built. A digital human vulnerability model was established in combination with wound reconstruction and vulnerability assessment rules, in which wound penetration profiles were obtained by recreating the penetration of projectiles into ballistic gelatin. An effectiveness evaluation method of bullet penetration using the Abbreviated Injury Scale (AIS) was developed and solved using the Monte Carlo sampling method. The effectiveness of rifle bullets was demonstrated to increase with increasing velocity in the range of 300-700 m/s. When imparting the same energy, the effectiveness of the 5.56 mm bullet was higher than the 7.62 mm bullet in this model. The superimposition of simulant penetration profiles produced from ballistic gelatin simulant has been used to predict wound tracts in damaged tissues. The authors recognise that determining clinical effectiveness based on the AIS scores alone without verification of outcome by review of clinical hospital records means that this technique should be seen more as a manner of comparing the effectiveness of bullets than an injury prediction model. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  19. Condition-based Human Reliability Assessment for digitalized control room

    International Nuclear Information System (INIS)

    Kang, H. G.; Jang, S. C.; Eom, H. S.; Ha, J. J.

    2005-04-01

    In safety-critical systems, the generation failure of an actuation signal is caused by the concurrent failures of the automated systems and an operator action. These two sources of safety signals are complicatedly correlated. The failures of sensors or automated systems will cause a lack of necessary information for a human operator and result in error-forcing contexts such as the loss of corresponding alarms and indications. In the conventional analysis, the Human Error Probabilities (HEP) are estimated based on the assumption of 'normal condition of indications and alarms'. In order to construct a more realistic signal-generation failure model, we have to consider more complicated conditions in a more realistic manner. In this study, we performed two kinds of investigation for addressing this issue. We performed the analytic calculations for estimating the effect of sensors failures on the system unavailability and plant risk. For the single-parameter safety signals, the analysis result reveals that the quantification of the HEP should be performed by focusing on the 'no alarm from the automatic system and corresponding indications unavailable' situation. This study also proposes a Condition-Based Human Reliability Assessment (CBHRA) method in order to address these complicated conditions in a practical way. We apply the CBHRA method to the manual actuation of the safety features such as a reactor trip and auxiliary feedwater actuation in Korean Standard Nuclear Power Plants. In the case of conventional single HEP method, it is very hard to consider the multiple HE conditions. The merit of CBHRA is clearly shown in the application to the AFAS generation where no dominating HE condition exits. In this case, even if the HE conditions are carefully investigated, the single HEP method cannot accommodate the multiple conditions in a fault tree. On the other hand, the application result of the reactor trip in SLOCA shows that if there is a dominating condition, the use

  20. Age estimation based on aspartic acid racemization in human sclera.

    Science.gov (United States)

    Klumb, Karolin; Matzenauer, Christian; Reckert, Alexandra; Lehmann, Klaus; Ritz-Timme, Stefanie

    2016-01-01

    Age estimation based on racemization of aspartic acid residues (AAR) in permanent proteins has been established in forensic medicine for years. While dentine is the tissue of choice for this molecular method of age estimation, teeth are not always available which leads to the need to identify other suitable tissues. We examined the suitability of total tissue samples of human sclera for the estimation of age at death. Sixty-five samples of scleral tissue were analyzed. The samples were hydrolyzed and after derivatization, the extent of aspartic acid racemization was determined by gas chromatography. The degree of AAR increased with age. In samples from younger individuals, the correlation of age and D-aspartic acid content was closer than in samples from older individuals. The age-dependent racemization in total tissue samples proves that permanent or at least long-living proteins are present in scleral tissue. The correlation of AAR in human sclera and age at death is close enough to serve as basis for age estimation. However, the precision of age estimation by this method is lower than that of age estimation based on the analysis of dentine which is due to molecular inhomogeneities of total tissue samples of sclera. Nevertheless, the approach may serve as a valuable alternative or addition in exceptional cases.

  1. Nonlinearity and thresholds in dose-response relationships for carcinogenicity due to sampling variation, logarithmic dose scaling, or small differences in individual susceptibility

    International Nuclear Information System (INIS)

    Lutz, W.K.; Gaylor, D.W.; Conolly, R.B.; Lutz, R.W.

    2005-01-01

    Nonlinear and threshold-like shapes of dose-response curves are often observed in tests for carcinogenicity. Here, we present three examples where an apparent threshold is spurious and can be misleading for low dose extrapolation and human cancer risk assessment. Case 1: For experiments that are not replicated, such as rodent bioassays for carcinogenicity, random variation can lead to misinterpretation of the result. This situation was simulated by 20 random binomial samplings of 50 animals per group, assuming a true linear dose response from 5% to 25% tumor incidence at arbitrary dose levels 0, 0.5, 1, 2, and 4. Linearity was suggested only by 8 of the 20 simulations. Four simulations did not reveal the carcinogenicity at all. Three exhibited thresholds, two showed a nonmonotonic behavior with a decrease at low dose, followed by a significant increase at high dose ('hormesis'). Case 2: Logarithmic representation of the dose axis transforms a straight line into a sublinear (up-bent) curve, which can be misinterpreted to indicate a threshold. This is most pronounced if the dose scale includes a wide low dose range. Linear regression of net tumor incidences and intersection with the dose axis results in an apparent threshold, even with an underlying true linear dose-incidence relationship. Case 3: Nonlinear shapes of dose-cancer incidence curves are rarely seen with epidemiological data in humans. The discrepancy to data in rodents may in part be explained by a wider span of individual susceptibilities for tumor induction in humans due to more diverse genetic background and modulation by co-carcinogenic lifestyle factors. Linear extrapolation of a human cancer risk could therefore be appropriate even if animal bioassays show nonlinearity

  2. Knowledge-base for the new human reliability analysis method, A Technique for Human Error Analysis (ATHEANA)

    International Nuclear Information System (INIS)

    Cooper, S.E.; Wreathall, J.; Thompson, C.M., Drouin, M.; Bley, D.C.

    1996-01-01

    This paper describes the knowledge base for the application of the new human reliability analysis (HRA) method, a ''A Technique for Human Error Analysis'' (ATHEANA). Since application of ATHEANA requires the identification of previously unmodeled human failure events, especially errors of commission, and associated error-forcing contexts (i.e., combinations of plant conditions and performance shaping factors), this knowledge base is an essential aid for the HRA analyst

  3. Prevention of cancer and the dose-effect relationship: the carcinogenic effects of ionizing radiations

    International Nuclear Information System (INIS)

    Tubiana, M.

    2009-01-01

    Cancer prevention has to be based on robust biological and epidemiological data, therefore its reappraisal becomes mandatory in view of recent progress in the understanding of carcinogenesis. The first phase of the carcinogenic process, that of initiation, is generally associated with mutation; however the role of extrinsic mutagens is less critical than was thought two decades ago. During intracellular oxygen metabolism, reactive oxygen species (R.O.S.) are made which are potent mutagens. Defense mechanisms against these intrinsic mutagens include scavenger and enzymatic systems which destroy them (catalase, superoxide dismutase). When the radiation dose is low, DNA repair is very effective as well as the elimination of cells with unrepaired or bad repaired DNA. Therefore a small increase in the number of R.O.S., such as that caused by a small dose of radiation has most probably no significant effect on the risk of DNA damage. These conclusions are consistent with the concept of a practical threshold. The second phase, that of promotion, appears to be the key one. During the promotion phase, initiated cells must acquire new properties (immortalization, release of angiogenic factors, resistance to hypoxia, etc.) in order to become pre-cancerous. This evolution is due to the accumulation in the genome of 6 to 10 new alteration defects. In the clone of initiated cells, the occurrence in one cell of a mutation or an epigenetic event gives birth to a sub clone. There is a Darwinian type competition between the sub clones and those with the more rapid growth because dominant (the acceleration of the growth rate can be due to shorter cell cycles or to an alleviation of cell proliferation exerted by the neighboring cells or the microenvironment). In the dominant sub clones new genomic events provoke the appearance of new sub clones growing more rapidly and having greater autonomy. The process is very slow because the specific genetic events that favour this evolution

  4. The effect of radiation in combination with carcinogens on the growth of normal urothelium in explant culture

    International Nuclear Information System (INIS)

    Mothersill, C.; O'Brien, A.

    1990-01-01

    Radiation is known to be carcinogenic to humans but attempts to demonstrate the process using human tissue culture models have met with little success. In the present study explants were established from urothelium and exposed to radiation and a range of chemical carcinogens, suspected promotor or metabolic agents. The resulting outgrowth was monitored for growth rate, proliferating epithelial fraction and development and differentiation of endothelial cells in culture. The results indicate that enhanced growth of epithelial cells can be seen when cultures are irradiated in the presence of various nitrosamines, benzo(a)pyrene or aniline. Radiation alone reduced the overall growth area measured but several proliferative foci developed on the resulting outgrowth. Their ultrastructural appearance reveals that they carry severe mitochondrial damage and exposure of treated cultures to metabolic inhibitors confirms that their respiration is defective. Endothelial cells proliferated over the surface of the epithelial monolayer and both the number and the degree of differentiation of the endothelial cells increased with increasing dose up to 10 Gy. While the cultures are not immortalised by the treatment, it appears that the epithelial cells have an extended lifespan (division capacity) and that a subpopulation has undergone a number of premalignant changes. Changes in endothelial cell proliferation also occur. (orig.)

  5. DNA repair in mammalian cells exposed to combinations of carcinogenic agents

    International Nuclear Information System (INIS)

    Setlow, R.B.; Ahmed, F.E.

    1979-01-01

    Cells defective in one or more aspects of repair are killed and often mutagenized more readily than normal cells by DNA damaging agents, and humans whose cells are deficient in repair are at an increased carcinogenic risk compared to normal individuals. The excision repair of uv induced pyrimidine dimers is a well studied system, but the details of the steps in this repair system are far from being understood in human cells. We know that there are a number of chemicals that mimic uv in that normal human cells repair DNA damage from both these agents and from uv by a long patch excision repair system, and that xeroderma pigmentosum cells defective in repair of uv are also defective in the repair of damage from these chemicals. The chemicals we have investigated are AAAF, 4-NQO, DMBA-epoxide, and ICR-170. We describe experiments, using several techniques, in which DNA excision repair is measured after treatment of various human cell strains with combinations of uv and these agents. If two agents have a common rate limiting step then, at doses high enough to saturate the repair system, one would expect the observed repair after a treatment with a combination of agents to be equal to that from one agent alone. Such is not the case for normal human or excision-deficient XP cells. In the former repair is additive and in the latter repair is usually appreciably less than that observed with either agent alone. Models that attempt to explain these surprising results involve complexes of enzymes and cofactors

  6. A Human-Needs-Based Dynamics to Simulate Technology Policy and Its Effects on Both Business Success and Human Happiness

    Directory of Open Access Journals (Sweden)

    Jong-Yeon Lim

    2016-11-01

    Full Text Available This paper focuses on how human needs are reflected in the market and how several technological and political policies affect the market share of government-supported industries, as well as the satisfaction of human desires and consequent happiness. In this paper, we seek to understand the dynamics of consumer decision-making processes in relation to technology products in the market. In this study, we present a new marketing model based on human needs, wants, and demands, and focus on both holistic and social perspectives. We have shown that human-based policy dynamics and sustainable human happiness can be realized by stimulating national policies for consumer happiness in the human-needs-based sector, e.g., the healthcare industry.

  7. 78 FR 44117 - Notice of a Public Comment Period on the Draft IRIS Carcinogenicity Assessment for Ethylene Oxide

    Science.gov (United States)

    2013-07-23

    ... Public Comment Period on the Draft IRIS Carcinogenicity Assessment for Ethylene Oxide AGENCY... Carcinogenicity of Ethylene Oxide'' (EPA/635/R-13/128a) and on the draft peer review charge questions. The draft... on the draft Evaluation of the Inhalation Carcinogenicity of Ethylene Oxide and on the draft peer...

  8. Enhanced replication of UV-damaged Simian virus 40 DNA in carcinogen-treated mammalian cells

    International Nuclear Information System (INIS)

    Maga, J.A.

    1983-01-01

    The replication of UV-damaged Simian virus 40 (SV40) in carcinogen-treated monkey cells has been studied to elucidate the mechanism of carcinogen-enhanced reactivation. Carcinogen enhanced reactivation is the observed increase in UV-irradiated virus survival in host cells treated with low doses of carcinogen compared to UV-irradiated virus survival in untreated hosts. Carcinogen treatment of monkey kidney cells with either N-acetoxy-2-acetylaminofluorene (AAAF) or UV radiation leads to an enhanced capacity to replicate UV-damaged virus during the first round of infection. To further define the mechanism leading to enhanced replication, a detailed biochemical analysis of replication intermediates in carcinogen-treated cells was performed. Several conclusions can be drawn. First enhanced replication can be observed in the first four rounds of replication after UV irradiation of viral templates. The second major finding is that the relaxed circular intermediate model proposed for the replication of UV-damaged templates in untreated cells appears valid for replication of UV-damaged templates in carcinogen-treated cells. Possible mechanisms and the supporting evidence are discussed and future experiments outlined

  9. Carcinogenicity of petroleum lubricating oil distillates: effects of solvent refining, hydroprocessing, and blending.

    Science.gov (United States)

    Halder, C A; Warne, T M; Little, R Q; Garvin, P J

    1984-01-01

    Certain refining processes were investigated to determine their influence on the dermal carcinogenic activity of petroleum-derived lubricating oil distillates. Specifically, the effects of solvent refining, hydroprocessing, a combination of both processes, and the blending of oils processed using each technique were evaluated in standard mouse skin-painting bioassays. The refining process used as well as the level or severity of treatment greatly influenced the carcinogenic outcome of processed lubricating oils. Solvent refining at severities normally used appeared to eliminate carcinogenicity. In contrast, hydroprocessing alone at mild levels of treatment was successful only in reducing the carcinogenic potency; severe hydroprocessing conditions were necessary to eliminate carcinogenic activity without the use of additional refining processes. Carcinogenic activity could also be eliminated by following moderate solvent refining with mild hydroprocessing. Blending of hydroprocessed oils with solvent-refined oils resulted in a substantial reduction or even elimination of carcinogenic activity. However, the degree of protection obtained varied with the particular distillates used and appeared largely dependent on the inherent biological activity of the hydroprocessed oil.

  10. Is function-based control room design human-centered?

    International Nuclear Information System (INIS)

    Norros, L.; Savioja, P.

    2006-01-01

    Function-based approaches to system interface design appears an appealing possibility in helping designers and operators to cope with the vast amount of information needed to control complex processes. In this paper we provide evidence of operator performance analyses showing that outcome-centered performance measures may not be sufficiently informative for design. We need analyses indicating habitual patterns of using information, operator practices. We argue that practices that portray functional orienting to the task support mastery of the process. They also create potential to make use of function-based information presentation. We see that functional design is not an absolute value. Instead, such design should support communication of the functional significance of the process information to the operators in variable situations. Hence, it should facilitate development of practices that focus to interpreting this message. Successful function-based design facilitates putting operations into their contexts a