2-Amino-1-methyl-6-(5-hydroxy-)phenylimidazo[4,5-b]pyridine (5-OH-PhIP), a biomarker for the genotoxic dose of the heterocyclic amine, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)

DEFF Research Database (Denmark)

Frandsen, H; Frederiksen, H; Alexander, J

2002-01-01

2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a mutagenic and carcinogenic heterocyclic amine formed during ordinary cooking. PhIP is metabolically activated by CYP P450 mediated N-hydroxylation followed by phase II esterification. The ultimate mutagenic metabolite reacts with DNA...

Lactoperoxidase, an Antimicrobial Milk Protein, as a Potential Activator of Carcinogenic Heterocyclic Amines in Breast Cancer.

Science.gov (United States)

Sheikh, Ishfaq Ahmad; Jiffri, Essam Hussain; Kamal, Mohammad Amjad; Ashraf, Ghulam Md; Beg, Mohd Amin

2017-11-01

Lactoperoxidase (LPO) is an antimicrobial protein secreted from mammary, salivary and other mucosal glands. It is an important member of heme peroxidase enzymes and the primary peroxidase enzyme present in breast tissues. In addition to the antimicrobial properties, LPO has been shown to be associated with breast cancer etiology. Heterocyclic amines, an important class of environmental and dietary carcinogens, have been increasingly associated with breast cancer etiology. Heterocyclic amines undergo activation in breast tissue as a result of oxidation by LPO. The current study includes three important heterocyclic amines, 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-1-methy-6-phenylimidazo[4,5-b]-pyridine (PhIP), that have carcinogenic activity. The structural binding characterization of IQ, MeIQx and PhIP with LPO was done using in silico approaches. Their binding pattern and interactions with LPO amino acid residues were analyzed. The three compounds bound in the distal heme cavity of LPO without replacing the important water molecule required for oxidation of substrate compounds. PhIP displayed lesser binding affinity for LPO in comparison to IQ and MeIQx. The binding mode of heterocyclic amines in distal heme cavity of LPO resembled to that of substrate binding pattern. The three heterocyclic amines are suggested to act as LPO substrate. The undisturbed water molecule present in distal heme cavity of the LPO is expected to facilitate the oxidation and activation of the three heterocyclic amines. These activated compounds may potentially bind with DNA in breast tissues forming DNA adducts and may subsequently lead to breast cancer initiation. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Mutagenicity of food-derived carcinogens and the effect of antioxidant vitamins.

Science.gov (United States)

Montgomery, Beverly A; Murphy, Jessica; Chen, James J; Desai, Varsha G; McGarrity, Lynda; Morris, Suzanne M; Casciano, Daniel A; Aidoo, Anane

2002-01-01

The food-derived heterocyclic amines (HCAs) 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) are mutagenic in the Ames test and produce tumors in laboratory animals, including monkeys. These HCAs have also been shown to induce gene mutations in vivo. To assess the antimutagenic effects of dietary antioxidant vitamins, beta-carotene, ascorbic acid (vitamin C), and alpha-tocopherol (vitamin E), on food-borne mutagenes/carcinogens, we evaluated the mutagenic activity of the compounds alone or combined with antioxidant vitamins. We utilized the rat lymphocyte mutation assay at the hypoxanthine guanine phosphoribosyl transferase (Hprt) locus. Female Fischer 344 rats treated with different doses (0, 2.5, 5.0, 25.0, and 50.0 mg/kg) of the carcinogens were sacrificed 5 wk after mutagen treatment. Although IQ and MeIQ slightly increased mutation frequency (MF) at some doses, a significant (P carcinogen metabolism would be affected by ingestion of vitamins. The activities of endogenous detoxification enzymes, glutathione S-transferase and glutathione peroxidase (GPx), were thus examined. Intake of beta-carotene and vitamin C without the carcinogen resulted in an increase (P food or taken as supplements could, in part, counteract such mutagenic activities.

Dietary phenolics as anti-mutagens and inhibitors of tobacco-related DNA adduction in the urothelium of smokers.

Science.gov (United States)

Malaveille, C; Hautefeuille, A; Pignatelli, B; Talaska, G; Vineis, P; Bartsch, H

1996-10-01

Human urine is known to contain substances that strongly inhibit bacterial mutagenicity of aromatic and heterocyclic amines in vitro. The biological relevance of these anti-mutagens was examined by comparing levels of tobacco-related DNA adducts in exfoliated urothelial cells from smokers with the anti-mutagenic activity in corresponding 24-h urine samples. An inverse relationship was found between the inhibition of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-mutagenicity by urine extracts in vitro and two DNA adduct measurements: the level of the putatively identified N-(deoxyguanosine-8-yl)-4-aminobiphenyl adduct and the total level of all tobacco-smoke-related carcinogen adducts including those probably derived from PhIP. Urinary anti-mutagenicity in vitro appears thus to be a good indicator of the anti-genotoxicity exerted by substances excreted in urine, that protect the bladder mucosal cells (and possibly other cells) against DNA damage. These substances appear to be dietary phenolics and/or their metabolites because (i) the anti-mutagenic activity of urine extracts (n = 18) was linearly related to their content in phenolics; (ii) the concentration ranges of these substances in urine extracts were similar to those of various plant phenols (quercetin, isorhamnetin and naringenin) for which an inhibitory effect on the liver S9-mediated mutagenicity of PhIP was obtained; (iii) treatment of urines with beta-glucuronidase and arylsulfatase enhanced both anti-mutagenicity and the levels of phenolics in urinary extracts; (iv) urinary extracts inhibited noncompetitively the liver S9-mediated mutagenicity of PhIP as did quercetin, used as a model phenolics. Several structural features of the flavonoids were identified as necessary for the inhibition of PhIP and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxiline mutagenicity. Fractionation by reverse-phase HPLC and subsequent analysis of two urinary extracts, showed the presence of several anti

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

An in vitro and in silico study on the flavonoid-mediated modulation of the transport of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) through Caco-2 monolayers

International Nuclear Information System (INIS)

Schutte, Maaike E.; Freidig, Andreas P.; Sandt, Johannes J.M. van de; Alink, Gerrit M.; Rietjens, Ivonne M.C.M.; Groten, John P.

2006-01-01

The present study describes the effect of different flavonoids on the absorption of the pro-carcinogen PhIP through Caco-2 monolayers and the development of an in silico model describing this process taking into account passive diffusion and active transport of PhIP. Various flavonoids stimulated the apical to basolateral PhIP transport. Using the in silico model for flavone, kaempferol and chrysoeriol, the apparent Ki value for inhibition of the active transport to the apical side was estimated to be below 53 μM and for morin, robinetin and taxifolin between 164 and 268 μM. For myricetin, luteolin, naringenin and quercetin, the apparent Ki values were determined more accurately and amounted to 37.3, 12.2, 11.7 and 5.6 μM respectively. Additional experiments revealed that the apical to basolateral PhIP transport was also increased in the presence of a typical BCRP or MRP inhibitor with apparent Ki values in the same range as those of the flavonoids. This observation together with the fact that flavonoids are known to be inhibitors of MRPs and BCRP, corroborates that inhibition of these apical membrane transporters is involved in the flavonoid-mediated increased apical to basolateral PhIP transport. Based on the apparent Ki values obtained, it is concluded that the flavonols, at the levels present in the regular Western diet, are capable of stimulating the transport of PhIP through Caco-2 monolayers from the apical to the basolateral compartment. This points to flavonoid-mediated stimulation of the bioavailability of PhIP and, thus, a possible adverse effect of these supposed beneficial food ingredients

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)

Effects of glucose on the formation of PhIP in a model system.

Science.gov (United States)

Skog, K; Jägerstad, M

1991-12-01

The effect of glucose on the formation of the food mutagen PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine) was studied in a model system. When a mixture of creatine (0.9 mmol), phenylalanine (0.9 mmol) and glucose (0.45 mmol) was heated in diethylene glycol and water (3 ml, 5:1) for 10 min at 180 or 225 degrees C several mutagens were produced. Identification by HPLC, UV absorption spectroscopy and mass spectrometry revealed the presence of PhIP as well as 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline and minor amounts of 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline. Heating the system without glucose produced PhIP as a single mutagen, but in considerably lower amount. An inhibiting effect of glucose in high concentrations was demonstrated. When glucose was added in more than or equimolar amounts of the other two reactants, the formation of mutagens was markedly reduced. Tyrosine heated under the same conditions, with creatine and glucose, showed mutagenic activity. However, no PhIP nor any other known food mutagen was identified from the tyrosine mixture.

Influence of beer marinades on the reduction of carcinogenic heterocyclic aromatic amines in charcoal-grilled pork meat.

Science.gov (United States)

Viegas, Olga; Moreira, Patrícia S; Ferreira, Isabel M P L V O

2015-01-01

The effect of beer marinades on the formation of heterocyclic aromatic amines (HAs) was examined in charcoal-grilled pork. Pilsner, non-alcoholic pilsner and black beers (coded respectively as PB, P0B and BB) were assayed and unmarinated samples cooked under similar conditions provided reference HAs levels. Two thermic (PhIP and 4,8-DiMeIQx) and three pyrolytic HAs (Trp-P-1, AαC, MeAαC) were quantified in unmarinated meat samples. Marinating meat in beer resulted in a significant decrease of PhIP, Trp-P-1 and AαC (p beers reduced total HA formation in charcoal-grilled pork, black beer being the most efficient with a level of 90% inhibition. A strong positive correlation was observed between the inhibitory effect of beer on total HA formation and their antioxidant activity. Beer marinades mitigate the impact of consumption of well-done grilled pork meat reducing the formation of cooking carcinogens.

Dietary tocopherols inhibit PhIP-induced prostate carcinogenesis in CYP1A-humanized mice.

Science.gov (United States)

Chen, Jayson X; Li, Guangxun; Wang, Hong; Liu, Anna; Lee, Mao-Jung; Reuhl, Kenneth; Suh, Nanjoo; Bosland, Maarten C; Yang, Chung S

2016-02-01

Tocopherols, the major forms of vitamin E, exist as alpha-tocopherol (α-T), β-T, γ-T and δ-T. The cancer preventive activity of vitamin E is suggested by epidemiological studies, but recent large-scale cancer prevention trials with high dose of α-T yielded disappointing results. Our hypothesis that other forms of tocopherols have higher cancer preventive activities than α-T was tested, herein, in a novel prostate carcinogenesis model induced by 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (PhIP), a dietary carcinogen, in the CYP1A-humanized (hCYP1A) mice. Treatment of hCYP1A mice with PhIP (200 mg/kg b.w., i.g.) induced high percentages of mouse prostatic intraepithelial neoplasia (mPIN), mainly in the dorsolateral glands. Supplementation with a γ-T-rich mixture of tocopherols (γ-TmT, 0.3% in diet) significantly inhibited the development of mPIN lesions and reduced PhIP-induced elevation of 8-oxo-deoxyguanosine, COX-2, nitrotyrosine, Ki-67 and p-AKT, and the loss of PTEN and Nrf2. Further studies with purified δ-T, γ-T or α-T (0.2% in diet) showed that δ-T was more effective than γ-T or α-T in preventing mPIN formations and p-AKT elevation. These results indicate that γ-TmT and δ-T could be effective preventive agents of prostate cancer. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

A highly versatile automatized setup for quantitative measurements of PHIP enhancements

Science.gov (United States)

Kiryutin, Alexey S.; Sauer, Grit; Hadjiali, Sara; Yurkovskaya, Alexandra V.; Breitzke, Hergen; Buntkowsky, Gerd

2017-12-01

The design and application of a versatile and inexpensive experimental extension to NMR spectrometers is described that allows to carry out highly reproducible PHIP experiments directly in the NMR sample tube, i.e. under PASADENA condition, followed by the detection of the NMR spectra of hyperpolarized products with high spectral resolution. Employing this high resolution it is feasible to study kinetic processes in the solution with high accuracy. As a practical example the dissolution of hydrogen gas in the liquid and the PHIP kinetics during the hydrogenation reaction of Fmoc-O-propargyl-L-tyrosine in acetone-d6 are monitored. The timing of the setup is fully controlled by the pulse-programmer of the NMR spectrometer. By flushing with an inert gas it is possible to efficiently quench the hydrogenation reaction in a controlled fashion and to detect the relaxation of hyperpolarization without a background reaction. The proposed design makes it possible to carry out PHIP experiments in an automatic mode and reliably determine the enhancement of polarized signals.

Screening of molecular cell targets for carcinogenic heterocyclic aromatic amines by using CALUX® reporter gene assays.

Science.gov (United States)

Steinberg, Pablo; Behnisch, Peter A; Besselink, Harrie; Brouwer, Abraham A

2017-06-01

Heterocyclic aromatic amines (HCAs) are compounds formed when meat or fish are cooked at high temperatures for a long time or over an open fire. To determine which pathways of toxicity are activated by HCAs, nine out of the ten HCAs known to be carcinogenic in rodents (2-amino-9H-pyrido[2,3-b]indole (AαC), 2-aminodipyrido[1,2-a:3',2-d]imidazole (Glu-P-2), 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3-methyl-9H-pyrido[2,3-b]indole (MeAαC), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1), and 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2)) were tested in the estrogen receptor α (ERα), androgen receptor (AR), glucocorticoid receptor (GR), peroxisome proliferator-activated receptor γ2 (PPARγ2), polycyclic aromatic hydrocarbons (PAH), Nrf2, and p53 CALUX® reporter gene assays. Trp-P-1 was the only HCA that led to a positive response in the ERα, PPARγ2, and Nrf2 CALUX® assays. In the PAH CALUX® assay, Trp-P-2, MeAαC, and AαC induced luciferase activity to a greater extent than MeIQ and PhIP. In the p53 CALUX® assay without a coupled metabolic activation, only Trp-P-1 and Trp-P-2 enhanced luciferase expression; when a metabolic activation step was coupled to the p53 CALUX® assay, Trp-P-1, Glu-P-2, MeIQ, MeIQx, and PhIP induced a positive response. No HCA was positive in the AR and GR CALUX® assays. Taken together, the results obtained show that the battery of CALUX® assays performed in the present study can successfully be used to screen for molecular cell targets of carcinogenic compounds such as HCAs.

A poised fragment library enables rapid synthetic expansion yielding the first reported inhibitors of PHIP(2), an atypical bromodomain

OpenAIRE

Cox, OB; Krojer, T; Collins, P; Monteiro, O; Talon, R; Bradley, A; Fedorov, O; Amin, J; Marsden, B; Spencer, J; von Delft, F; Brennan, P

2016-01-01

Research into the chemical biology of bromodomains has been driven by the development of acetyl-lysine mimetics. The ligands are typically anchored by binding to a highly conserved asparagine residue. Atypical bromodomains, for which the asparagine is mutated, have thus far proven elusive targets, including PHIP(2) whose parent protein, PHIP, has been linked to disease progression in diabetes and cancers. The PHIP(2) binding site contains a threonine in place of asparagine, and solution scree...

PHIPS-HALO: the airborne particle habit imaging and polar scattering probe - Part 2: Characterization and first results

Science.gov (United States)

Schnaiter, Martin; Järvinen, Emma; Abdelmonem, Ahmed; Leisner, Thomas

2018-01-01

The novel aircraft optical cloud probe PHIPS-HALO has been developed to establish clarity regarding the fundamental link between the microphysical properties of single atmospheric ice particles and their appropriated angular light scattering function. After final improvements were implemented in the polar nephelometer part and the acquisition software of PHIPS-HALO, the instrument was comprehensively characterized in the laboratory and was deployed in two aircraft missions targeting cirrus and Arctic mixed-phase clouds. This work demonstrates the proper function of the instrument under aircraft conditions and highlights the uniqueness, quality, and limitations of the data that can be expected from PHIPS-HALO in cloud-related aircraft missions.

Genotoxic and carcinogenic risks associated with the dietary consumption of repeatedly heated coconut oil.

Science.gov (United States)

Srivastava, Smita; Singh, Madhulika; George, Jasmine; Bhui, Kulpreet; Murari Saxena, Anand; Shukla, Yogeshwer

2010-11-01

Repeated heating of vegetable oils at high temperatures during cooking is a very common cooking practice. Repeated heating of edible oils can generate a number of compounds, including polycyclic aromatic hydrocarbons (PAH), some of which have been reported to have carcinogenic potential. Consumption of these repeatedly heated oils can pose a serious health hazard. The objectives of the present study were to evaluate the genotoxic and carcinogenic risks associated with the consumption of repeatedly heated coconut oil (RCO), which is one of the commonly consumed cooking and frying medium. The PAH were analysed using HPLC in fresh CO, single-heated CO (SCO) and RCO. Results revealed the presence of certain PAH, known to possess carcinogenic potential, in RCO when compared with SCO. Oral intake of RCO in Wistar rats resulted in a significant induction of aberrant cells (P<0·05) and micronuclei (P<0·05) in a dose-dependent manner. Oxidative stress analysis showed a significant (P<0·05) decrease in the levels of antioxidant enzymes such as superoxide dismutase and catalase with a concurrent increase in reactive oxygen species and lipid peroxidation in the liver. In addition, RCO given alone and along with diethylnitrosamine for 12 weeks induced altered hepatic foci as noticed by alteration in positive (γ-glutamyl transpeptidase and glutathione-S-transferase) and negative (adenosine triphosphatase, alkaline phosphatase and glucose-6-phosphatase) hepatospecific biomarkers. A significant decrease in the relative and absolute hepatic weight of RCO-supplemented rats was recorded (P<0·05). In conclusion, dietary consumption of RCO can cause a genotoxic and preneoplastic change in the liver.

Presence of heterocyclic amine carcinogens in home-cooked and fast-food camel meat burgers commonly consumed in Saudi Arabia.

Science.gov (United States)

Rizwan Khan, Mohammad; Naushad, Mu; Abdullah Alothman, Zeid

2017-05-10

Heterocyclic amines (HCAs) are formed by cooking protein-rich foods, for instance, meat and fish, and are listed as possible human carcinogens. In the present study, the presence of five potential HCAs (IQ, MeIQ, MeIQx, 4,8-DiMeIQx, and PhIP) in cooked camel meat burgers was analyzed for the first time. The analysis was performed in home-cooked and fast-food burger samples containing food additives. The applied cooking technique for the home-cooked samples was pan frying for a controlled cooking time and temperature. In the control cooked meat samples (samples that contained no food additives), the concentrations of MeIQx, 4,8-DiMeIQx, and PhIP ranged from 2.47 ng/g to 4.89 ng/g, whereas IQ and MeIQ were found to be below the limit of quantification. The concentrations contents of MeIQx, 4,8-DiMeIQx, and PhIP in the home-cooked and fast-food samples ranged from 1.52 ng/g to 2.13 ng/g and 1.85 ng/g to 3.46 ng/g, respectively. IQ and MeIQ were not detected in either type of sample. In comparison to the control samples, the home-cooked and fast-food samples produced lower levels of HCAs. Such observations could result from the existence of antioxidants in incorporated food additives, which induce pro-oxidative effects with the successive formation and/or scavenging of free radicals.

Immunosuppressive effect of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) through the inhibition of T-lymphocyte proliferation and IL-2 production

International Nuclear Information System (INIS)

Yun, Cheol-Heui; Son, Chang Gue; Jung, Uhee; Han, Seung Hyun

2006-01-01

2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is the predominant heterocyclic amine formed in cooked meat and fish and causes cancers in the colon, the mammary glands, and the lymphoid organs. In the present study, we investigated the immunological impact of PhIP using thymocytes isolated from Balb/c mice and a murine thymocyte-derived cell line, EL4. Treatment of the thymocytes with PhIP moderately inhibited T-cell mitogen-induced cell proliferation and interleukin (IL)-2 secretion. Reverse transcription-polymerase chain reaction (RT-PCR) analysis demonstrated that PhIP attenuated IL-2 mRNA expression in the thymocytes and EL4 cells stimulated with phytohemagglutinin (PHA) plus phorbol 12-myristate 13-acetate (PMA). In vitro transient transfection assay using a reporter gene construct containing IL-2 promoter showed that the decrease in the steady-state IL-2 mRNA level by PhIP is partially due to the attenuation of IL-2 mRNA synthesis at the transcriptional level. Furthermore, an electrophoretic mobility shift assay showed that PhIP inhibited DNA binding activity of nuclear factor for immunoglobulin κ chain in B cells (NF-κB), activator protein-1 (AP-1) and nuclear factor of activated T cells (NF-AT), which are known to be responsible for IL-2 transcriptional activation. Concomitantly, PhIP inhibited the PMA/PHA-induced generation of reactive oxygen species (ROS) involved in activation of the transcription factors. These results suggest that PhIP has potential immunosuppressive effects by inhibiting T-cell proliferation and IL-2 expression through down regulation of ROS generation and thereby inhibiting NF-κB, AP-1 and NF-AT activation

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.

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.

Amino Acids Inhibitory Effects and Mechanism on 2-Amino-1-Methyl-6-Phenylimidazo [4,5-b]Pyridine (PhIP) Formation in the Maillard Reaction Model Systems.

Science.gov (United States)

Linghu, Ziyi; Karim, Faris; Smith, J Scott

2017-12-01

This study was to investigate the inhibitory effects of amino acids (AAs) on the formation of 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP) and to evaluate the inhibition mechanism of PhIP in Maillard model systems. Different AAs were individually added into model systems heat-treated at 180 °C/1 h. The PhIP, phenylacetaldehyde (PheAce), and pyrazines derivatives were determined using HPLC and GC-MS. AAs significantly reduced (P Pro > Leu > Met > Val > Ile > Thr > Phe > Asp, at the highest molar ratio. The PheAce content was gradually reduced with increasing AAs levels, suggesting that AAs may inhibit PhIP formation through scavenging the available PheAce. A correlation between PhIP inhibition and PheAce-scavenging activity of AAs was observed when PheAce and AAs were heated. The variety and quantity of pyrazines formed are highly depending on the type of AAs. © 2017 Institute of Food Technologists®.

Biomonitoring of urinary metabolites of 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP) following human consumption of cooked chicken

DEFF Research Database (Denmark)

Frandsen, Henrik Lauritz

2008-01-01

Human risk assessment of exposure to 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) through the diet may be improved by conducting biomonitoring studies comparing metabolism in humans and rodents. Eleven volunteers ingested a meal of cooked chicken containing 4-OH-PhIP and PhIP in amounts...... for detoxification and the last a biomarker for activation. The eleven volunteers eliminated large amounts of 4'-OH-PhiP in the urine. The majority of which Could be accounted for by the presence of 4'-OH-PhIP in the fried chicken, showing that PhIP only to a small extent (11%) was metabolised to 4'-OH...

Lymphoma induction by heterocyclic amines in Eu-pim-1 transgenic mice

DEFF Research Database (Denmark)

Sørensen, Ilona Kryspin; Kristiansen, E.; Mortensen, Alicja

1997-01-01

The usefulness of transgenic E mu-pim-1 mice bearing in their genome the pim-1 oncogene supplemented with an upstream immunoglobulin enhancer and a downstream murine leukaemia virus long terminal repeat, as sensitive test organisms was studied in two short-term carcinogenicity studies. The mice...... to bacteria and cultured mammalian cells. PhIP is a potent mouse lymphomagen, while IQ is a liver, lung and forestomach carcinogen in mice. We found that transgenic E mu-pim-1 mice are highly susceptible to PhIP induced lymphomagenesis but do not respond to IQ treatment. PhIP feeding of E mu-pim-1 mice...... not only increased the total number of T-cell lymphomas but also decreased the latency time compared to either transgenic or wild-type controls. The effect was most pronounced in the treated female E mu-pim-1 mice, which showed a higher incidence of PhIP induced T-cell lymphomas than transgenic males...

Long interspersed element-1 is differentially regulated by food-borne carcinogens via the aryl hydrocarbon receptor.

Science.gov (United States)

Okudaira, N; Okamura, T; Tamura, M; Iijma, K; Goto, M; Matsunaga, A; Ochiai, M; Nakagama, H; Kano, S; Fujii-Kuriyama, Y; Ishizaka, Y

2013-10-10

A single human cell contains more than 5.0 × 10(5) copies of long interspersed element-1 (L1), 80-100 of which are competent for retrotransposition (L1-RTP). Recent observations have revealed the presence of de novo L1 insertions in various tumors, but little is known about its mechanism. Here, we found that 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 2-amino-3,8-dimethyl-imidazo[4,5-f]quinoxaline (MeIQx), food-borne carcinogens that are present in broiled meats, induced L1-RTP. This induction was dependent on a cellular cascade comprising the aryl hydrocarbon receptor (AhR), a mitogen-activated protein kinase, and CCAAT/enhancer-binding protein β. Notably, these compounds exhibited differential induction of L1-RTP. MeIQx-induced L1-RTP was dependent on AhR nuclear translocator 1 (ARNT1), a counterpart of AhR required for gene expression in response to environmental pollutants. By contrast, PhIP-induced L1-RTP did not require ARNT1 but was dependent on estrogen receptor α (ERα) and AhR repressor. In vivo studies using transgenic mice harboring the human L1 gene indicated that PhIP-induced L1-RTP was reproducibly detected in the mammary gland, which is a target organ of PhIP-induced carcinoma. Moreover, picomolar levels of each compound induced L1-RTP, which is comparable to the PhIP concentration detected in human breast milk. Data suggest that somatic cells possess machineries that induce L1-RTP in response to the carcinogenic compounds. Together with data showing that micromolar levels of heterocyclic amines (HCAs) were non-genotoxic, our observations indicate that L1-RTP by environmental compounds is a novel type of genomic instability, further suggesting that analysis of L1-RTP by HCAs is a novel approach to clarification of modes of carcinogenesis.

N-acetyltransferase-dependent activation of 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine: formation of 2-amino-1-methyl-6-(5-hydroxy)phenylimidazo [4,5-b]pyridine, a possible biomarker for the reactive dose of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine

DEFF Research Database (Denmark)

Frandsen, Henrik Lauritz; Alexander, J.

2000-01-01

2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a mutagenic and carcinogenic heterocyclic amine formed during ordinary cooking. PhIP is metabolically activated to the ultimate mutagenic metabolite by CYP P450-mediated N-hydroxylation followed by phase II esterification, Incubation of N...

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.

U.S. dietary exposures to heterocyclic amines.

Science.gov (United States)

Bogen, K T; Keating, G A

2001-01-01

Heterocyclic amines (HAs) formed in fried, broiled or grilled meats are potent mutagens that increase rates of colon, mammary, prostate and other cancers in bioassay rodents. Studies of how human dietary HA exposures may affect cancer risks have so far relied on fairly crudely defined HA-exposure categories. Recently, an integrated, quantitative approach to HA-exposure assessment (HAEA) was developed to estimate compound-specific intakes for particular individuals based on corresponding HA-concentration estimates that reflect their meat-type, intake-rate, cooking-method and meat-doneness preferences. This method was applied in the present study to U.S. national Continuing Survey of Food Intakes by Individuals (CSFII) data on meats consumed and cooking methods used by >25,000 people, after adjusting for underreported energy intake and conditional on meat-doneness preferences estimated from additional survey data. The U.S. population average lifetime time-weighted average of total HAs consumed was estimated to be approximately 9 ng/kg/day, with 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) estimated to comprise about two thirds of this intake. Pan-fried meats were the largest source of HA in the diet and chicken the largest source of HAs among different meat types. Estimated total HA intakes by male vs. female children were generally similar, with those by (0- to 15-year-old) children approximately 25% greater than those by (16+-year-old) adults. Race-, age- and sex-specific mean HA intakes were estimated to be greatest for African American males, who were estimated to consume approximately 2- and approximately 3-fold more PhIP than white males at ages <16 and 30+ years, respectively, after considering a relatively greater preference for more well-done items among African Americans based on national survey data. This difference in PhIP intakes may at least partly explain why prostate cancer (PC) kills approximately 2-fold more African American than white men

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

Inhibition of 2-Amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP) Formation by Alkoxy Radical Scavenging of Flavonoids and Their Quantitative Structure-Activity Relationship in a Model System.

Science.gov (United States)

Yu, Chundi; Shao, Zeping; Liu, Bing; Zhang, Yan; Wang, Shuo

2016-08-01

The inhibitory effect of 10 flavonoids on the formation of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in a creatinine-phenylalanine model system was investigated through electronic spin resonance and a quantitative structure-activity relationship. Alkoxy radicals were observed during the heating process, providing evidence for a radical pathway in the formation of PhIP. The alkoxy radical scavenging capability of the flavonoids was proportional to their inhibition of PhIP formation (IC50 ). We deduced that flavonoid inhibition of PhIP generation occurs via scavenging of alkoxy radicals during the heating process. Multiple linear regression and partial least squares models were used to elucidate the relationship between PhIP inhibition activity and structure characteristics of the flavonoids. The lipo-hydro partition coefficient and molecular fractional polar surface area of the flavonoids were found to be predictive of the inhibition effect. © 2016 Institute of Food Technologists®

The Particle Habit Imaging and Polar Scattering probe PHIPS: First Stereo-Imaging and Polar Scattering Function Measurements of Ice Particles

Science.gov (United States)

Abdelmonem, A.; Schnaiter, M.; Schön, R.; Leisner, T.

2009-04-01

Cirrus clouds impact climate by their influence on the water vapour distribution in the upper troposphere. Moreover, they directly affect the radiative balance of the Earth's atmosphere by the scattering of incoming solar radiation and the absorption of outgoing thermal emission. The link between the microphysical properties of ice cloud particles and the radiative forcing of the clouds is not as yet well understood and the influence of the shapes of ice crystals on the radiative budget of cirrus clouds is currently under debate. PHIPS is a new experimental device for the stereo-imaging of individual cloud particles and the simultaneous measurement of the polar scattering function of the same particle. PHIPS uses an automated particle event triggering system that ensures that only those particles are captured which are located in the field of view - depth of field volume of the microscope unit. Efforts were made to improve the resolution power of the microscope unit down to about 3 µm and to facilitate a 3D morphology impression of the ice crystals. This is realised by a stereo-imaging set up composed of two identical microscopes which image the same particle under an angular viewing distance of 30°. The scattering part of PHIPS enables the measurement of the polar light scattering function of cloud particles with an angular resolution of 1° for forward scattering directions (from 1° to 10°) and 8° for side and backscattering directions (from 18° to 170°). For each particle the light scattering pulse per channel is stored either as integrated intensity or as time resolved intensity function which opens a new category of data analysis concerning details of the particle movement. PHIPS is the first step to PHIPS-HALO which is one of the in situ ice particle and water vapour instruments that are currently under development for the new German research aircraft HALO. The instrument was tested in the ice cloud characterisation campaign HALO-02 which was conducted

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)

Direct reduction of N-acetoxy-PhIP by tea polyphenols: a possible mechanism for chemoprevention against PhIP-DNA adduct formation

International Nuclear Information System (INIS)

Lin Dongxin; Thompson, Patricia A.; Teitel, Candee; Chen Junshi; Kadlubar, Fred F.

2003-01-01

The chemopreventive effect of tea against 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-DNA adduct formation and its mechanism were studied. Rats were exposed to freshly prepared aqueous extracts of green tea (3% (w/v)) as the sole source of drinking water for 10 days prior to administration with a single dose of PhIP (10 mg/kg body weight) by oral gavage. PhIP-DNA adducts in the liver, colon, heart, and lung were measured using the 32 P-postlabelling technique. Rats pre-treated with tea and given PhIP 20 h before sacrifice had significantly reduced levels of PhIP-DNA adducts as compared with controls given PhIP alone. The possible mechanism of protective effect of tea on PhIP-DNA adduct formation was then examined in vitro. It was found that an aqueous extract of green and black tea, mixtures of green and black tea polyphenols, as well as purified polyphenols could strongly inhibit the DNA binding of N-acetoxy-PhIP, a putative ultimate carcinogen of PhIP formed in vivo via metabolic activation. Among these, epigallocatechin gallate was exceptionally potent. HPLC analyses of these incubation mixtures containing N-acetoxy-PhIP and the tea polyphenols each revealed the production of the parent amine, PhIP, indicating the involvement of a redox mechanism. In view of the presence of relatively high levels of tea polyphenols in rat and human plasma after ingestion of tea, this study suggests that direct reduction of the ultimate carcinogen N-acetoxy-PhIP by tea polyphenols is likely to be involved in the mechanism of chemoprotection of tea against this carcinogen

Development and psychometric properties of the Patient-Head Injury Participation Scale (P-HIPS) and the Patient-Head Injury Neurobehavioral Assessment Scale (P-HINAS): patient and family determined outcomes scales.

Science.gov (United States)

Deb, Shoumitro; Bryant, Eleanor; Morris, Paul G; Prior, Lindsay; Lewis, Glyn; Haque, Sayeed

2007-06-01

To develop a measure to assess post-acute outcome following from traumatic brain injury (TBI) with particular emphasis on the emotional and the behavioral outcome. The second objective was to assess the test-retest reliability, internal consistency, and factor structure of the newly developed patient version of the Head Injury Participation Scale (P-HIPS) and Patient-Head Injury Neurobehavioral Scale (P-HINAS). Thirty-two TBI individuals and 27 carers took part in in-depth qualitative interviews exploring the consequences of the TBI. Interview transcripts were analyzed and key themes and concepts were used to construct the 49-item P-HIPS. A postal survey was then conducted on a cohort of 113 TBI patients to 'field test' the P-HIPS and the P-HINAS. All individual 49 items of the P-HIPS and their total score showed good test-retest reliability (0.93) and internal consistency (0.95). The P-HIPS showed a very good correlations with the Mayo Portland Adaptability Inventory-3 (MPAI-3) (0.87) and a moderate negative correlation with the Glasgow Outcome Scale-Extended (GOSE) (-0.51). Factor analysis extracted the following domains: 'Emotion/Behavior,' 'Independence/Community Living,' 'Cognition' and 'Physical'. The 'Emotion/Behavior' factor constituted the P-HINAS, which showed good internal consistency (0.93), test-retest reliability (0.91) and concurrent validity with MPAI subscale (0.82). Both the P-HIPS and the P-HINAS show strong psychometric properties. The qualitative methodology employed in the construction stage of the questionnaires provided good evidence of face and content validity.

Dietary exposure to heterocyclic amines in high-temperature cooked meat and fish in Malaysia.

Science.gov (United States)

Jahurul, M H A; Jinap, S; Ang, S J; Abdul-Hamid, A; Hajeb, P; Lioe, H N; Zaidul, I S M

2010-08-01

The intake of heterocyclic amines is influenced by the amount and type of meat and fish ingested, frequency of consumption, cooking methods, cooking temperature, and duration of cooking. In this study, the dietary intake of heterocyclic amines in Malaysia and their main sources were investigated. Forty-two samples of meat and fish were analysed by high-performance liquid chromatography with photodiode array detector to determine the concentration of the six predominant heterocyclic amines, namely: 2-amino-3-methylimidazo[4,5-f] quinoline (IQ), 2-amino-3,4-dimethylimidazo[4,5-f] quinoline(MeIQ), 2-amino-3,8-dimethylimidazo[4,5-f] quinoxaline (MeIQx), 2-amino-3,4,8-trimethylimidazo[4,5-f] quinoxaline (4,8-DiMeIQx), 2-amino-3,7,8-trimethylimidazo[4,5-f] quinoxaline (7,8-DiMeIQx), and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Dietary intake data were obtained using a food-frequency questionnaire when interviewing 600 Malaysian respondents. The level of total heterocyclic amines in food samples studies ranged from not detected to 38.7 ng g(-1). The average daily intake level of heterocyclic amine was 553.7 ng per capita day(-1). The intake of PhIP was the highest, followed by MeIQx and MeIQ. The results reveal that fried and grilled chicken were the major dietary source of heterocyclic amines in Malaysia. However, the heterocyclic amine intake by the Malaysian population was lower than those reported from other regions.

Influence of food condiments on the formation of carcinogenic heterocyclic amines in cooked chicken and determination by LC-MS/MS.

Science.gov (United States)

Khan, Mohammad Rizwan

2015-01-01

Heterocyclic amines (HCAs) are known to be suspected human carcinogens produced by high-temperature cooking of protein-rich foods such as meat and fish. In the present study, the influence of numerous food condiments on the formation of HCAs in cooked chicken was investigated. Chicken samples were subjected to pan-frying under controlled temperature. The levels of HCAs DMIP, MeIQx, 4,8-DiMeIQx, PhIP, harman and norharman were found to be between 0.93 and 27.52 ng g(-1), whereas IQ, MeIQ, AαC, MeAαC, Trp-P-1 and Trp-P-2 were found either below the limit of quantification or not detected in the control sample. Nevertheless, for samples cooked using food condiments, the amounts of HCAs (DMIP, MeIQx, 4,8-DiMeIQx and PhIP) were between 0.14 and 19.57 ng g(-1); harman and norharman were detected at higher concentrations up to 17.77 ng g(-1) while IQ and MeIQ were at levels below the limit of quantification; and AαC, MeAαC, Trp-P-1 and Trp-P-2 were not detected in any of the samples. The outcomes revealed that the formation of HCAs (except harman and norharman) diminished after the addition of food condiments. Edible oil contributed to the highest levels of HCA formation, followed by garlic, paprika, pepper and tomato.

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

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.

The role of biotransformation in dietary (anti)carcinogenesis

NARCIS (Netherlands)

Iersel, M.L.P.S. van; Verhagen, H.; Bladeren, P.J. van

1999-01-01

The fact that dietary compounds influence the susceptibility of human beings to cancer, is widely accepted. One of the possible mechanisms that is responsible for these (anti)carcinogenic effects is that dietary constituents may modulate biotransformation enzymes, thereby affecting the

Role Of Thymus Vulgaris And/Or Origanum Majorana L. Extract In Ameliorating The Toxicity Induced By 2-Amino-1-Methyl-6-Phenyl imidazo (4,5-b)Pyridine (PHIP) In Adult Male Albino Rats

International Nuclear Information System (INIS)

Salem, F.E.H.

2012-01-01

The present study was conducted to investigate the protective and therapeutic effect of the watery extract of Thymus vulgaris (thyme) and Origanum majorana L. (marjoram) or their mixture on the toxicity induced by 2-amino-1-methyl-6-phenyl imidazo(4,5-b)pyridine (PhIP) which is one of the most abundant toxic heterocyclic amines (HCA) in cooked meat. Oral administration of PhIP (75 ml/kg) twice a week for four weeks resulted in a significant increase in liver function (AST, ALT and ALP) with a percentage change recording 33.79% , 70.96% and 127.64%, respectively, accompanied with decrease in total protein content. Significant increase (P<0.05) was observed in both creatinine (45.33%) and blood urea (109.17%), whereas serum T3 and T4 recorded significant decrease with a percentage change of -57.32% and -42.44%, respectively. A marked significant reduction (P<0.05) in monoamine contents (DA and NE) in total brain was observed after the ingestion of PhIP recording -13.23% and -13.47%, respectively, as percentage change from control. The daily oral administration of thyme, marjoram and their mixture (W/W) in dose of 500 mg/kg alone, before or after PhIP administration caused a decrease in ALT, AST and ALP levels and increase in total protein in serum and also cause decrease in serum creatinine and urea. Non-significant changes in T3 and T4 levels were observed in rats received the herbal extract. On the other hand, the herbal extract improved T3 and T4 levels before and after PhIP treatment bringing the hormonal levels near to that of control. Moreover, rats that received pre and post treatment with thyme, marjoram and their mixture (W/W) after being treated with PhIP showed high significant reduction in the elevated levels of DA and NE produced by PhIP treatment. From the current investigation, it could be concluded that the watery extract polyphenol flavonoids of thyme and marjoram has the protective and therapeutic effect on the toxicity produced by heterocyclic

Dietary Intake of Meat Cooking-Related Mutagens (HCAs) and Risk of Colorectal Adenoma and Cancer: A Systematic Review and Meta-Analysis.

Science.gov (United States)

Chiavarini, Manuela; Bertarelli, Gaia; Minelli, Liliana; Fabiani, Roberto

2017-05-18

Much evidence suggests that the positive association between meat intake and colorectal adenoma (CRA) and cancer (CRC) risk is mediated by mutagenic compounds generated during cooking at high temperature. A number of epidemiological studies have estimated the effect of meat-related mutagens intake on CRC/CRA risk with contradictory and sometimes inconsistent results. A literature search was carried out (PubMed, Web of Science and Scopus) to identify articles reporting the relationship between the intake of meat-related mutagens (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-3,8-dimethylimidazo[4,5-f] quinoxaline (MeIQx), 2-amino-3,4,8-trimethylimidazo[4,5-f] quinoxaline: DiMeIQx, benzo(a) pyrene (B(a)P) and "meat derived mutagenic activity" (MDM)) and CRC/CRA risk. A random-effect model was used to calculate the risk association. Thirty-nine studies were included in the systematic review and meta-analysis. Polled CRA risk (15229 cases) was significantly increased by intake of PhIP (OR = 1.20; 95% CI: 1.13,1.28; p CRA risk in association with PhIP, MDM, and MeIQx. CRC risk (21,344 cases) was increased by uptake of MeIQx (OR = 1.14; 95% CI: 1.04,1.25; p = 0.004), DiMeIQx (OR = 1.12; 95% CI: 1.02,1.22; p = 0.014) and MDM (OR = 1.12; 95% CI: 1.06,1.19; p meat at high temperature may be responsible of its carcinogenicity.

Nutritional knowledge and dietary diversity of cancer patients at the ...

African Journals Online (AJOL)

This increase is possibly attributed to change in behavior and adoption of ... factors such as increase in environmental carcinogens and unhealthy lifestyles. ... during dietary counseling of patients to enable them improve their dietary practice.

The ability of two cooked food mutagens to induce aberrant crypt foci in mice

DEFF Research Database (Denmark)

Kristiansen, E.; Meyer, Otto A.; Thorup, I.

1997-01-01

induced a higher percentage of medium or large sized aberrant crypt foci than PhIP or IQ, The interpretation of the aberrant crypt foci as precursor lesions for colon cancer in the PhIP and IQ mice is difficult because PhIP and IQ have not been reported to be colonic carcinogens, If cooked food mutagens......The aberrant crypt foci assay has been used extensively to study different compounds for chemopreventive action, but almost all investigations have used initiators not normally found in the diet, In the present study two food-borne initiators, 2-amino-3-methyl-imidazo [4,5-f]quinoline (IQ) and 2......-amino-1-methyl-6-phenyl-imidazo[4,5-b]pyridine (PhIP) were used, To simulate the human exposure further, we chose a feeding regimen with continuous low IQ- and PhIP-doses, Throughout the study female mice were given diets with or without 0.03% IQ or 0.03% PhIP, Two additional groups were given...

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

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.

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.

Studies to enhance the hyperpolarization level in PHIP-SAH-produced C13-pyruvate

Science.gov (United States)

Cavallari, Eleonora; Carrera, Carla; Aime, Silvio; Reineri, Francesca

2018-04-01

The use of [1-13C]pyruvate, hyperpolarized by dissolution-Dynamic Nuclear Polarization (d-DNP), in in vivo metabolic studies has developed quickly, thanks to the imaging probe's diagnostic relevance. Nevertheless, the cost of a d-DNP polarizer is quite high and the speed of hyperpolarization process is relatively slow, meaning that its use is limited to few research laboratories. ParaHydrogen Induced Polarization Side Arm Hydrogenation (PHIP-SAH) (Reineri et al., 2015) is a cost effective and easy-to-handle method that produces 13C-MR hyperpolarization in [1-13C]pyruvate and other metabolites. This work aims to identify the main determinants of the hyperpolarization levels observed in C13-pyruvate using this method. By dissecting the various steps of the PHIP-SAH procedure, it has been possible to assess the role of several experimental parameters whose optimization must be pursued if this method is to be made suitable for future translational steps. The search for possible solutions has led to improvements in the polarization of sodium [1-13C]pyruvate from 2% to 5%. Moreover, these results suggest that observed polarization levels could be increased considerably by an automatized procedure which would reduce the time required for the work-up passages that are currently carried out manually. The results reported herein mean that the attainment of polarization levels suitable for the metabolic imaging applications of these hyperpolarized substrates show significant promise.

Meat and components of meat and the risk of bladder cancer in the NIH-AARP Diet and Health Study.

Science.gov (United States)

Ferrucci, Leah M; Sinha, Rashmi; Ward, Mary H; Graubard, Barry I; Hollenbeck, Albert R; Kilfoy, Briseis A; Schatzkin, Arthur; Michaud, Dominique S; Cross, Amanda J

2010-09-15

Meat could be involved in bladder carcinogenesis via multiple potentially carcinogenic meat-related compounds related to cooking and processing, including nitrate, nitrite, heterocyclic amines (HCAs), and polycyclic aromatic hydrocarbons (PAHs). The authors comprehensively investigated the association between meat and meat components and bladder cancer. During 7 years of follow-up, 854 transitional cell bladder-cancer cases were identified among 300,933 men and women who had completed a validated food-frequency questionnaire in the large prospective NIH-AARP Diet and Health Study. The authors estimated intake of nitrate and nitrite from processed meat and HCAs and PAHs from cooked meat by using quantitative databases of measured values. Total dietary nitrate and nitrite were calculated based on literature values. The hazard ratios (HR) and 95% confidence intervals (CI) for red meat (HR for fifth quintile compared with first quintile, 1.22; 95% CI, 0.96-1.54; P(trend) = .07) and the HCA 2-amino-1 methyl-6-phenylimidazo(4,5-b)pyridine (PhIP) (HR, 1.19; 95% CI, 0.95-1.48; P(trend) = .06) conferred a borderline statistically significant increased risk of bladder cancer. Positive associations were observed in the top quintile for total dietary nitrite (HR, 1.28; 95% CI, 1.02-1.61; P(trend) = .06) and nitrate plus nitrite intake from processed meat (HR, 1.29; 95% CI, 1.00-1.67; P(trend) = .11). These findings provided modest support for an increased risk of bladder cancer with total dietary nitrite and nitrate plus nitrite from processed meat. Results also suggested a positive association between red meat and PhIP and bladder carcinogenesis. © 2010 American Cancer Society.

Interaction Between Dietary Factors and Inflammation in Prostate Carcinogenesis

National Research Council Canada - National Science Library

De Marzo, Angelo M

2007-01-01

We are investigating whether inflammation can enhance prostate carcinogenesis in a rat model of dietary charred meat carcinogen induced cancers, and, whether antioxidant and other chemopreventative...

Interactions between Dietary Factors and Inflammation in Prostate Carcinogenesis

National Research Council Canada - National Science Library

DeMarzo, Angelo M

2006-01-01

We are investigating whether inflammation can enhance prostate carcinogenesis in a rat model of dietary charred meat carcinogen induced cancers, and, whether antioxidant and other chemopreventative...

Effects of flavonoid mixtures on the transport of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) through Caco-2 monolayers: An in vitro and kinetic modeling approach to predict the combined effects on transporter inhibition

NARCIS (Netherlands)

Schutte, M.E.; Boersma, M.G.; Verhallen, D.A.M.; Groten, J.P.; Rietjens, I.M.C.M.

2008-01-01

This study describes and kinetically models the effect of flavonoid mixtures on PhIP transport through Caco-2 monolayers. Previously it was shown that quercetin, luteolin, naringenin and myricetin increase the apical to basolateral PhIP transport in Caco-2 monolayers. In this study, apigenin was

Quercetin increases the bioavailability of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in rats

NARCIS (Netherlands)

Schutte, M.E.; Alink, G.M.; Freidig, A.P.; Spenkelink, B.; Vaessen, J.C.H.; Sandt, J.J.M. van de; Groten, J.P.; Rietjens, I.M.C.M.

2008-01-01

This study investigates whether the previous observation that quercetin increases the transport of PhIP through Caco-2 monolayers in vitro could be confirmed in an in vivo rat model. Co-administration of 1.45 μmol PhIP/kg bw and 30 μmol quercetin/kg bw significantly increased the blood AUC(0-8 h) of

Carcinogenic and antitumor effects of aminotriazole on acatalasemic and normal catalase mice

International Nuclear Information System (INIS)

Feinstein, R.N.; Fry, R.J.M.; Staffeidt, E.F.

1978-01-01

Dietary 3-amino-1H-1,2,4-triazole (AT), although carcinogenic when administered alone, was an antitumor agent when combined with certain other carcinogenic stimuli. The carcinogenic effect was prominent in the livers of C3H mice; thyroid tumors were less common because they required a longer period of development, and the life-span of the animal was shortened by the AT diet. The antitumor effects of AT included: delay in appearance of mammary tumors, striking reduction in γ-radiation-induced lymphomas, and sharp reduction in neutron radiation-induced harderian gland and ovarian tumors. On an AT diet, the inbred C3H acatalasemic mouse substrain developed more liver tumors, starting earlier, than did the C3H normal catalase substrain. We suggest that our findings pointed to a possible relevance of catalase and H 2 O 2 in carcinogenesis. The most probable mechanism for the increased incidence of liver tumors in AT-treated acatalasemic mice was the diminished rate of degradation of endogenous H 2 O 2

Carcinogenic and neurotoxic risks of acrylamide consumed through caffeinated beverages among the lebanese population.

Science.gov (United States)

El-Zakhem Naous, Ghada; Merhi, Areej; Abboud, Martine I; Mroueh, Mohamad; Taleb, Robin I

2018-06-06

The present study aims to quantify acrylamide in caffeinated beverages including American coffee, Lebanese coffee, espresso, instant coffee and hot chocolate, and to determine their carcinogenic and neurotoxic risks. A survey was carried for this purpose whereby 78% of the Lebanese population was found to consume at least one type of caffeinated beverages. Gas Chromatography Mass Spectrometry analysis revealed that the average acrylamide level in caffeinated beverages is 29,176 μg/kg sample. The daily consumption of acrylamide from Lebanese coffee (10.9 μg/kg-bw/day), hot chocolate (1.2 μg/kg-bw/day) and Espresso (7.4 μg/kg-bw/day) was found to be higher than the risk intake for carcinogenicity and neurotoxicity as set by World Health Organization (WHO; 0.3-2 μg/kg-bw/day) at both the mean (average consumers) and high (high consumers) dietary exposures. On the other hand, American coffee (0.37 μg/kg-bw/day) was shown to pose no carcinogenic or neurotoxic risks among the Lebanese community for consumers with a mean dietary exposure. The study shows alarming results that call for regulating the caffeinated product industry by setting legislations and standard protocols for product preparation in order to limit the acrylamide content and protect consumers. In order to avoid carcinogenic and neurotoxic risks, we propose that WHO/FAO set acrylamide levels in caffeinated beverages to 7000 μg acrylamide/kg sample, a value which is 4-folds lower than the average acrylamide levels of 29,176 μg/kg sample found in caffeinated beverages sold in the Lebanese market. Alternatively, consumers of caffeinated products, especially Lebanese coffee and espresso, would have to lower their daily consumption to 0.3-0.4 cups/day. Copyright © 2018 Elsevier Ltd. All rights reserved.

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.

Dietary nitrates, nitrites, and cardiovascular disease.

Science.gov (United States)

Hord, Norman G

2011-12-01

Dietary nitrate (NO(3)), nitrite (NO(2)), and arginine can serve as sources for production of NO(x) (a diverse group of metabolites including nitric oxide, nitrosothiols, and nitroalkenes) via ultraviolet light exposure to skin, mammalian nitrate/nitrite reductases in tissues, and nitric oxide synthase enzymes, respectively. NO(x) are responsible for the hypotensive, antiplatelet, and cytoprotective effects of dietary nitrates and nitrites. Current regulatory limits on nitrate intakes, based on concerns regarding potential risk of carcinogenicity and methemoglobinemia, are exceeded by normal daily intakes of single foods, such as soya milk and spinach, as well as by some recommended dietary patterns such as the Dietary Approaches to Stop Hypertension diet. This review includes a call for regulatory bodies to consider all available data on the beneficial physiologic roles of nitrate and nitrite in order to derive rational bases for dietary recommendations.

Renal deterioration caused by carcinogens as a consequence of free radical mediated tissue damage: a review of the protective action of melatonin

Energy Technology Data Exchange (ETDEWEB)

Gultekin, Fatih; Hicyilmaz, Hicran [Suleyman Demirel University, School of Medicine, Department of Biochemistry, Isparta (Turkey)

2007-10-15

This brief review summarizes some of the publications that document the preventive role of melatonin in kidney damage caused by carcinogens such as 2-nitropropane, arsenic, carbon tetrachloride, nitrilotriacetic acid and potassium bromate. Numerous chemicals generate excessive free radicals that eventually induce renal worsening. Melatonin partially or totally prevents free radical mediated tissue damages induced by many carcinogens. Protective actions of melatonin against the harmful effects of carcinogens are believed to stem from its direct free radical scavenging and indirect antioxidant activities. Dietary or pharmacologically given melatonin may attenuate the oxidative stress, thereby mitigating the subsequent renal damage. (orig.)

In vitro synthesis and purification of PhIP-deoxyguanosine and PhIP-DNA oligomer covalent complexes

Energy Technology Data Exchange (ETDEWEB)

Freeman, J.

1994-12-01

2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a heterocyclic amine compound formed when meats are cooked at high temperatures. PhIP damages DNA by forming covalent complexes with DNA carcinogen. In an effort to understand how the binding of PhIP to DNA may cause cancer, it is important to characterize the structures of PhIP-damaged DNA molecules. Our HPLC data support fluorescence and {sup 32}P Post-labeling studies which indicate the formation of several species of 2{prime}deoxyguanosine-(dG) or oligodeoxynucleotide-PhIP adducts. The reaction of PhIP with dG resulted in a reddish precipitate that was likely the major adduct, N-(deoxyguanosin-8-yl)-PhIP (dG-C8-PhIP) adduct, with a more polar adduct fraction remaining in the supernatant. Reversed-phase HPLC analysis of the adducts in the supernatant revealed the existence of species of much shorter retention times than the dG-C8-PhIP adduct, confirming that these species are more polar than dG-C8-PhIP. At least four adducts were formed in the reaction of PhIP with DNA oligomer. HPLC analysis of the PhIP-DNA oligomer supernatant after butanol extractions revealed four unresolved peaks which spectra had maximum wavelengths between 340 and 360 nm. Though adduct peaks were not completely resolved, there was {approximately}3 minutes interval between the DNA oligomer peak and the adduct peaks. Furthermore, fluorescence emission data of the DNA oligomer-PhIP adduct solution show heterogeneous binding. The more polar PhIP adducts were fraction-collected and their structures will be solved by nuclear magnetic resonance or x-ray crystallography.

Rice bran phytochemicals and dietary colon chemoprevention teamwork

Science.gov (United States)

A growing body of evidence supports that dietary rice bran exhibits gastrointestinal cancer control and prevention activity using carcinogen induced animal models and human colon cancer cell lines. Our laboratory has recently reported metabolomic differences in rice from globally and genetically dis...

Heterocyclic amine content in beef cooked by different methods to varying degrees of doneness and gravy made from meat drippings.

Science.gov (United States)

Sinha, R; Rothman, N; Salmon, C P; Knize, M G; Brown, E D; Swanson, C A; Rhodes, D; Rossi, S; Felton, J S; Levander, O A

1998-04-01

Meats cooked at high temperatures sometimes contain heterocyclic amines (HCAs) that are known mutagens and animal carcinogens, but their carcinogenic potential in humans has not been established. To investigate the association between HCAs and cancer, sources of exposure to these compounds need to be determined. Beef is the most frequently consumed meat in the United States and for this study we determined HCA values in beef samples cooked in ways to represent US cooking practices, the results of which can be used in epidemiological studies to estimate HCA exposure from dietary questionnaires. We measured five HCAs [2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)] in different types of cooked beef using solid-phase extraction and HPLC. Steak and hamburger patties were pan-fried, oven-broiled, and grilled/barbecued to four levels of doneness (rare, medium, well done or very well done), while beef roasts were oven cooked to three levels of doneness (rare, medium or well done). The measured values of the specific HCAs varied with the cut of beef, cooking method, and doneness level. In general, MeIQx content increased with doneness under each cooking condition for steak and hamburger patties, up to 8.2 ng/g. PhIP was the predominant HCA produced in steak (1.9 to 30 ng/g), but was formed only in very well done fried or grilled hamburger. DiMeIQx was found in trace levels in pan-fried steaks only, while IQ and MeIQ were not detectable in any of the samples. Roast beef did not contain any of the HCAs, but the gravy made from the drippings from well done roasts had 2 ng/g of PhIP and 7 ng/g of MeIQx. Epidemiological studies need to consider the type of meat, cooking method and degree of doneness/surface browning in survey questions to adequately assess

Dietary mutagen exposure and risk of pancreatic cancer.

Science.gov (United States)

Li, Donghui; Day, Rena Sue; Bondy, Melissa L; Sinha, Rashmi; Nguyen, Nga T; Evans, Douglas B; Abbruzzese, James L; Hassan, Manal M

2007-04-01

To investigate the association between dietary exposure to food mutagens and risk of pancreatic cancer, we conducted a hospital-based case-control study at the University of Texas M. D. Anderson Cancer Center during June 2002 to May 2006. A total of 626 cases and 530 noncancer controls were frequency matched for race, sex and age (+/-5 years). Dietary exposure information was collected via personal interview using a meat preparation questionnaire. A significantly greater portion of the cases than controls showed a preference to well-done pork, bacon, grilled chicken, and pan-fried chicken, but not to hamburger and steak. Cases had a higher daily intake of food mutagens and mutagenicity activity (revertants per gram of daily meat intake) than controls did. The daily intakes of 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) and benzo(a)pyrene (BaP), as well as the mutagenic activity, were significant predictors for pancreatic cancer (P = 0.008, 0.031, and 0.029, respectively) with adjustment of other confounders. A significant trend of elevated cancer risk with increasing DiMeIQx intake was observed in quintile analysis (P(trend) = 0.024). A higher intake of dietary mutagens (those in the two top quintiles) was associated with a 2-fold increased risk of pancreatic cancer among those without a family history of cancer but not among those with a family history of cancer. A possible synergistic effect of dietary mutagen exposure and smoking was observed among individuals with the highest level of exposure (top 10%) to PhIP and BaP, P(interaction) = 0.09 and 0.099, respectively. These data support the hypothesis that dietary mutagen exposure alone and in interaction with other factors contribute to the development of pancreatic cancer.

Dietary nitrates, nitrites, and N-nitroso compounds and cancer risk: a review of the epidemiologic evidence.

Science.gov (United States)

Eichholzer, M; Gutzwiller, F

1998-04-01

Experimental animal studies have shown N-nitroso compounds (NOC) to be potent carcinogens. Epidemiologic evidence of the carcinogenic potential of dietary NOC and precursor nitrates and nitrites in humans remains inconclusive with regard to the risk of stomach, brain, esophageal, and nasopharyngeal cancers. Inadequate available data could obscure a small to moderate effect of NOC.

Dietary Nitrates, Nitrites, and N-Nitroso Compounds and Cancer Risk: a Review of the Epidemiologic Evidence

OpenAIRE

Eichholzer, Monika; Gutzwiller, Felix

2017-01-01

Experimental animal studies have shown N-nitroso compounds (NOC) to be potent carcinogens. Epidemiologic evidence of the carcinogenic potential of dietary NOC and precursor nitrates and nitrites in humans remains inconclusive with regard to the risk of stomach, brain, esophageal, and nasopharyngeal cancers. Inadequate available data could obscure a small to moderate effect of NOC

MACROMOLECULAR ADDUCT FORMATION AND METABOLISM OF HETEROCYCLIC AMINES IN HUMANS AND RODENTS AT LOW DOSES. (R825280)

Science.gov (United States)

Abstract2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) are heterocyclic amines formed during the cooking of meat and fish. Both are genotoxic in a number of test systems and are carcinogen...

Mechanisms linking dietary fiber, gut microbiota and colon cancer prevention.

Science.gov (United States)

Zeng, Huawei; Lazarova, Darina L; Bordonaro, Michael

2014-02-15

Many epidemiological and experimental studies have suggested that dietary fiber plays an important role in colon cancer prevention. These findings may relate to the ability of fiber to reduce the contact time of carcinogens within the intestinal lumen and to promote healthy gut microbiota, which modifies the host's metabolism in various ways. Elucidation of the mechanisms by which dietary fiber-dependent changes in gut microbiota enhance bile acid deconjugation, produce short chain fatty acids, and modulate inflammatory bioactive substances can lead to a better understanding of the beneficial role of dietary fiber. This article reviews the current knowledge concerning the mechanisms via which dietary fiber protects against colon cancer.

First correlated measurements of the shape and scattering properties of cloud particles using the new Particle Habit Imaging and Polar Scattering (PHIPS) probe

Science.gov (United States)

Abdelmonem, A.; Schnaiter, M.; Amsler, P.; Hesse, E.; Meyer, J.; Leisner, T.

2011-05-01

Studying the radiative impact of cirrus clouds requires the knowledge of the link between their microphysics and the single scattering properties of the cloud particles. Usually, this link is created by modeling the optical scattering properties from in situ measurements of ice crystal size distributions. The measured size distribution and the assumed particle shape might be erroneous in case of non-spherical ice particles. We present here a novel optical sensor (the Particle Habit Imaging and Polar Scattering probe, PHIPS) designed to measure the 3-D morphology and the corresponding optical and microphysical parameters of individual cloud particles, simultaneously. Clouds containing particles ranging in size from a few micrometers to about 800 μm diameter can be systematically characterized with an optical resolution power of 2 μm and polar scattering resolution of 1° for forward scattering directions (from 1° to 10°) and 8° for side and backscattering directions (from 18° to 170°). The maximum acquisition rates for scattering phase functions and images are 262 KHz and 10 Hz, respectively. Some preliminary results collected in two ice cloud campaigns which were conducted in the AIDA cloud simulation chamber are presented. PHIPS showed reliability in operation and produced comparable size distributions and images to those given by other certified cloud particles instruments. A 3-D model of a hexagonal ice plate is constructed and the corresponding scattering phase function is compared to that modeled using the Ray Tracing with Diffraction on Facets (RTDF) program. PHIPS is candidate to be a novel air borne optical sensor for studying the radiative impact of cirrus clouds and correlating the particle habit-scattering properties which will serve as a reference for other single, or multi-independent, measurements instruments.

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.

First correlated measurements of the shape and light scattering properties of cloud particles using the new Particle Habit Imaging and Polar Scattering (PHIPS probe

Directory of Open Access Journals (Sweden)

A. Abdelmonem

2011-10-01

Full Text Available Studying the radiative impact of cirrus clouds requires knowledge of the relationship between their microphysics and the single scattering properties of cloud particles. Usually, this relationship is obtained by modeling the optical scattering properties from in situ measurements of ice crystal size distributions. The measured size distribution and the assumed particle shape might be erroneous in case of non-spherical ice particles. We present here a novel optical sensor (the Particle Habit Imaging and Polar Scattering probe, PHIPS designed to measure simultaneously the 3-D morphology and the corresponding optical and microphysical parameters of individual cloud particles. Clouds containing particles ranging from a few micrometers to about 800 μm diameter in size can be characterized systematically with an optical resolution power of 2 μm and polar scattering resolution of 1° for forward scattering directions (from 1° to 10° and 8° for side and backscattering directions (from 18° to 170°. The maximum acquisition rates for scattering phase functions and images are 262 KHz and 10 Hz, respectively. Some preliminary results collected in two ice cloud campaigns conducted in the AIDA cloud simulation chamber are presented. PHIPS showed reliability in operation and produced size distributions and images comparable to those given by other certified cloud particles instruments. A 3-D model of a hexagonal ice plate is constructed and the corresponding scattering phase function is compared to that modeled using the Ray Tracing with Diffraction on Facets (RTDF program. PHIPS is a highly promising novel airborne optical sensor for studying the radiative impact of cirrus clouds and correlating the particle habit-scattering properties which will serve as a reference for other single, or multi-independent, measurement instruments.

First correlated measurements of the shape and light scattering properties of cloud particles using the new Particle Habit Imaging and Polar Scattering (PHIPS) probe

Science.gov (United States)

Abdelmonem, A.; Schnaiter, M.; Amsler, P.; Hesse, E.; Meyer, J.; Leisner, T.

2011-10-01

Studying the radiative impact of cirrus clouds requires knowledge of the relationship between their microphysics and the single scattering properties of cloud particles. Usually, this relationship is obtained by modeling the optical scattering properties from in situ measurements of ice crystal size distributions. The measured size distribution and the assumed particle shape might be erroneous in case of non-spherical ice particles. We present here a novel optical sensor (the Particle Habit Imaging and Polar Scattering probe, PHIPS) designed to measure simultaneously the 3-D morphology and the corresponding optical and microphysical parameters of individual cloud particles. Clouds containing particles ranging from a few micrometers to about 800 μm diameter in size can be characterized systematically with an optical resolution power of 2 μm and polar scattering resolution of 1° for forward scattering directions (from 1° to 10°) and 8° for side and backscattering directions (from 18° to 170°). The maximum acquisition rates for scattering phase functions and images are 262 KHz and 10 Hz, respectively. Some preliminary results collected in two ice cloud campaigns conducted in the AIDA cloud simulation chamber are presented. PHIPS showed reliability in operation and produced size distributions and images comparable to those given by other certified cloud particles instruments. A 3-D model of a hexagonal ice plate is constructed and the corresponding scattering phase function is compared to that modeled using the Ray Tracing with Diffraction on Facets (RTDF) program. PHIPS is a highly promising novel airborne optical sensor for studying the radiative impact of cirrus clouds and correlating the particle habit-scattering properties which will serve as a reference for other single, or multi-independent, measurement instruments.

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

Dietary exposure to heterocyclic amines in a Chinese population.

Science.gov (United States)

Wong, Kin-Yoke; Su, Jin; Knize, Mark G; Koh, Woon-Puay; Seow, Adeline

2005-01-01

Heterocyclic aromatic amines (HAAs) formed in meat during high-temperature cooking have been associated with risk of colorectal and breast cancer. Incidence of these cancers is increasing in Singapore, a country with 77% ethnic Chinese. The purpose of this study was to estimate HAA levels in the Chinese diet and individual levels of exposure to these compounds because little is known. Twenty-five samples (each pooled from three sources) of meat and fish, cooked as commonly consumed, were analyzed by high-performance liquid chromatography for concentrations (ng/g) of 2-amino-3-methylimidazo[4,5-f]quinoline, 2-amino-3, 4-dimethylimidazo[4,5-f]quinoline (MeIQ), 2-amino-3,8- dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3, 4,8-trimethylimidazo[4,5-f]quinoxaline (4,8-DiMeIQx), 2- amino-3,7,8-trimethylimidazo[4,5-f]quinoxaline, 2-amino -1,6-dimethylfuro[3,2-e]imidazo[4,5-b]pyridine, and 2- amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Dietary meat consumption data (g/day), including meat type and cooking method, were gathered from food-frequency questionnaires completed by 497 randomly sampled Chinese men and women aged 20-59 yr. PhIP, MeIQx, and 4,8-DiMeIQx were the most abundant HAAs detected. Total HAA concentrations ranged from roasted pork had the highest levels. The estimated mean daily exposure to HAA was 49.95 ng/day (P10 14.0 ng/day, P90 95.8 ng/day); this was 50% higher among younger (20-39 yr) compared with older individuals. Seven specific meat-cooking method combinations contributed 90.1% of this intake, namely, pan-fried fish, pork, and chicken, deep-fried chicken as well as fish, roasted/barbecued pork, and grilled minced beef.

Colon preneoplasia after carcinogen exposure is enhanced and colonic serotonergic system is suppressed by food deprivation.

Science.gov (United States)

Kannen, Vinicius; Fernandes, Cleverson R; Stopper, Helga; Zanette, Dalila L; Ferreira, Frederico R; Frajacomo, Fernando T; Carvalho, Milene C; Brandão, Marcus L; Elias Junior, Jorge; Jordão Junior, Alceu Afonso; Uyemura, Sérgio Akira; Waaga-Gasser, Ana Maria; Garcia, Sérgio B

2013-10-04

Calorie restriction regimens usually promote health and extend life-span in mammals. This is partially related to their preventive effects against malignancies. However, certain types of nutritional restriction failed to induce beneficial effects. The American Institute of Nutrition defines calorie restriction as diets which have only 40% fewer calories, but provide normal amounts of necessary food components such as protein, vitamins and minerals; whereas, food restriction means 40% less of all dietary ingredients plus 40% less calories. Our study aimed to test the hypothesis that the latter type of food deprivation (40% less food than consumed by standard fed rats) might increase cancer risk instead of reducing it, as is generally assumed for all dietary restrictive regimens. Since the endogenous modulation of the colon serotonergic system has been observed to play a role during the early steps of carcinogenesis we also investigated whether the serotoninergic system could be involved in the food intake modulation of cancer risk. For this, rats were exposed to a carcinogen and subjected to food deprivation for 56 days. Triglyceride levels and visceral adipose tissue were reduced while hepatic and colonic lipid peroxidation was increased. This dietary restriction also decreased serotonin levels in colon, and gene expression of its intestinal transporter and receptors. Finally, the numbers of preneoplastic lesions in the colon tissue of carcinogen-exposed rats were increased. Our data suggest that food deprivation enhances formation of early tumorigenic lesions by suppressing serotonergic activity in colon tissue. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

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)

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.

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

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.

The synthesis of [3H]-indole-3-carbinol, a natural anti-carcinogen from cruciferous vegetables

International Nuclear Information System (INIS)

Dashwood, R.H.; Uyetake, Lyle; Fong, A.T.; Hendricks, J.D.; Bailey, G.S.

1989-01-01

Indole-3-carbinol is a natural anti-carcinogen found as a glucosinolate in cruciferous vegetables such as cabbage, cauliflower and broccoli. A complete understanding of the mechanisms of anti-carcinogenesis by this dietary inhibitor requires improved insight into the disposition and metabolic fate of indole-3-carbinol in vivo. Such metabolic studies have been hampered by the lack of a commercial source of radiolabelled compound. This provided the main impetus for the work reported here, the synthesis of 5-[ 3 H]-indole-3-carbinol from 5-bromoindole. (author)

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

Dietary controlled carcinogenicity study of chloral hydrate in male B6C3F1 mice

International Nuclear Information System (INIS)

Leakey, Julian E.A.; Seng, John E.; Latendresse, John R.; Hussain, Nursreen; Allen, Laura J.; Allaben, William T.

2003-01-01

Chloral hydrate, which is used as a sedative in pediatric medicine and is a by-product of water chlorination, is hepatocarcinogenic in B6C3F 1 mice, a strain that can exhibit high rates of background liver tumor incidence, which are associated with increased body weight. In this study, dietary control was used to manipulate body growth in male B6C3F 1 mice in a 2-year bioassay of chloral hydrate. Male B6C3F 1 mice were treated with water or 25, 50, or 100 mg/kg chloral hydrate by gavage. The study compared ad libitum-fed mice with dietary controlled mice. The latter received variably restricted feed allocations to maintain their body weights on a predetermined 'idealized' weight curve predictive of a terminal background liver tumor incidence of 15-20%. These mice exhibited less individual body weight variation than did their ad libitum-fed counterparts. This was associated with a decreased variation in liver to body weight ratios, which allowed the demonstration of a statistically significant dose response to chloral hydrate in the dietary controlled, but not the ad libitum-fed, test groups. Chloral hydrate increased terminally adjusted liver tumor incidence in both dietary controlled (23.4, 23.9, 29.7, and 38.6% for the four dose groups, respectively) and ad libitum-fed mice (33.4, 52.6, 50.6, and 46.2%), but a statistically significant dose response was observed only in the dietary controlled mice. This dose response positively correlated with markers of peroxisomal proliferation in the dietary controlled mice only. The study suggests that dietary control not only improves terminal survival and decreases interassay variation, but also can increase assay sensitivity by decreasing intra-assay variation

Responses of genes involved in cell cycle control to diverse DNA damaging chemicals in human lung adenocarcinoma A549 cells

Directory of Open Access Journals (Sweden)

Gooderham Nigel J

2005-08-01

Full Text Available Abstract Background Many anticancer agents and carcinogens are DNA damaging chemicals and exposure to such chemicals results in the deregulation of cell cycle progression. The molecular mechanisms of DNA damage-induced cell cycle alteration are not well understood. We have studied the effects of etoposide (an anticancer agent, cryptolepine (CLP, a cytotoxic alkaloid, benzo [a]pyrene (BaP, a carcinogenic polycyclic aromatic hydrocarbon and 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP, a cooked-meat derived carcinogen on the expression of cell cycle regulatory genes to understand the molecular mechanisms of the cell cycle disturbance. Results A549 cells were treated with DMSO or chemicals for up to 72 h and periodically sampled for cell cycle analysis, mRNA and protein expression. DMSO treated cells showed a dominant G1 peak in cell cycle at all times examined. Etoposide and CLP both induced G2/M phase arrest yet the former altered the expression of genes functioning at multiple phases, whilst the latter was more effective in inhibiting the expression of genes in G2-M transition. Both etoposide and CLP induced an accumulation of p53 protein and upregulation of p53 transcriptional target genes. Neither BaP nor PhIP had substantial phase-specific cell cycle effect, however, they induced distinctive changes in gene expression. BaP upregulated the expression of CYP1B1 at 6–24 h and downregulated many cell cycle regulatory genes at 48–72 h. By contrast, PhIP increased the expression of many cell cycle regulatory genes. Changes in the expression of key mRNAs were confirmed at protein level. Conclusion Our experiments show that DNA damaging agents with different mechanisms of action induced distinctive changes in the expression pattern of a panel of cell cycle regulatory genes. We suggest that examining the genomic response to chemical exposure provides an exceptional opportunity to understand the molecular mechanism involved in cellular

Interactions between Dietary Factors and Inflammation in Prostate Carcinogenesis

National Research Council Canada - National Science Library

DeMarzo, Angelo M

2006-01-01

.... We completed part of aim 1 by treating PhIP treated Fisher rats with broccoli tea extract and celecoxib and discovered that both broccoli tea extract and the non-steroidal anti-inflammatory agent...

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.

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

[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.

The synthesis of ( sup 3 H)-indole-3-carbinol, a natural anti-carcinogen from cruciferous vegetables

Energy Technology Data Exchange (ETDEWEB)

Dashwood, R H; Uyetake, Lyle; Fong, A T; Hendricks, J D; Bailey, G S [Oregon State Univ., Corvallis, OR (USA). Dept. of Food Science and Technology

1989-08-01

Indole-3-carbinol is a natural anti-carcinogen found as a glucosinolate in cruciferous vegetables such as cabbage, cauliflower and broccoli. A complete understanding of the mechanisms of anti-carcinogenesis by this dietary inhibitor requires improved insight into the disposition and metabolic fate of indole-3-carbinol in vivo. Such metabolic studies have been hampered by the lack of a commercial source of radiolabelled compound. This provided the main impetus for the work reported here, the synthesis of 5-({sup 3}H)-indole-3-carbinol from 5-bromoindole. (author).

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...

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

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

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.

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.

On Enzyme-Based Anticancer Molecular Dietary Manipulations

Directory of Open Access Journals (Sweden)

Andrea Sapone

2012-01-01

Full Text Available Evidence from both epidemiological and experimental observations has fuelled the belief that the high consumption of fruits and vegetables rich in nutrients and phytochemicals may help prevent cancer and heart disease in humans. This concept has been drastically simplified from the dietary approaches to the use of single bioactive components both as a single supplement or in functional foods to manipulate xenobiotic metabolism. These procedures, which aim to induce mutagen/carcinogen detoxification or inhibit their bioactivation, fail to take into account the multiple and paradoxical biological outcomes of enzyme modulators that make their effects unpredictable. Here, we show that the idea that the physiological roles of specific catalysts may be easily manipulated by regular long-term administration of isolated nutrients and other chemicals derived from food plants is not viable. In contrast, we claim that the consumption of healthy diets is most likely to reduce mutagenesis and cancer risk, and that both research endeavours and dietary recommendations should be redirected away from single molecules to dietary patterns as a main strategy for public health policy.

δ- and γ-tocopherols inhibit phIP/DSS-induced colon carcinogenesis by protection against early cellular and DNA damages.

Science.gov (United States)

Chen, Jayson X; Liu, Anna; Lee, Mao-Jung; Wang, Hong; Yu, Siyuan; Chi, Eric; Reuhl, Kenneth; Suh, Nanjoo; Yang, Chung S

2017-01-01

Tocopherols, the major forms of vitamin E, are a family of fat-soluble compounds that exist in alpha (α-T), beta (β-T), gamma (γ-T), and delta (δ-T) variants. A cancer preventive effect of vitamin E is suggested by epidemiological studies. However, past animal studies and human intervention trials with α-T, the most active vitamin E form, have yielded disappointing results. A possible explanation is that the cancer preventive activity of α-T is weak compared to other tocopherol forms. In the present study, we investigated the effects of δ-T, γ-T, and α-T (0.2% in diet) in a novel colon cancer model induced by the meat-derived dietary carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and promoted by dextran sodium sulfate (DSS)-induced colitis in CYP1A-humanized (hCYP1A) mice. PhIP/DSS treatments induced multiple polypoid tumors, mainly tubular adenocarcinomas, in the middle to distal colon of the hCYP1A mice after 10 wk. Dietary supplementation with δ-T and γ-T significantly reduced colon tumor formation and suppressed markers of oxidative and nitrosative stress (i.e., 8-oxo-dG and nitrotyrosine) as well as pro-inflammatory mediators (i.e., NF-κB p65 and p-STAT3) in tumors and adjacent tissues. By administering δ-T at different time periods, we obtained results suggesting that the inhibitory effect of δ-T against colon carcinogenesis is mainly due to protection against early cellular and DNA damages caused by PhIP. α-T was found to be ineffective in inhibiting colon tumors and less effective in attenuating the molecular changes. Altogether, we demonstrated strong cancer preventive effects of δ-T and γ-T in a physiologically relevant model of human colon cancer. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Dietary nitrate and nitrite: Benefits, risks, and evolving perceptions.

Science.gov (United States)

Bedale, Wendy; Sindelar, Jeffrey J; Milkowski, Andrew L

2016-10-01

Consumers have an illogical relationship with nitrite (and its precursor, nitrate) in food. Despite a long history of use, nitrite was nearly banned from use in foods in the 1970s due to health concerns related to the potential for carcinogenic nitrosamine formation. Changes in meat processing methods reduced those potential risks, and nitrite continued to be used in foods. Since then, two opposing movements continue to shape how consumers view dietary nitrate and nitrite. The discovery of the profound physiological importance of nitric oxide led to the realization that dietary nitrate contributes significantly to the nitrogen reservoir for nitric oxide formation. Numerous clinical studies have also demonstrated beneficial effects from dietary nitrate consumption, especially in vascular and metabolic health. However, the latest wave of consumer sentiment against food additives, the clean-label movement, has renewed consumer fear and avoidance of preservatives, including nitrite. Education is necessary but may not be sufficient to resolve this disconnect in consumer perception. Copyright © 2016 Elsevier Ltd. All rights reserved.

Dietary compounds that induce cancer preventive phase 2 enzymes activate apoptosis at comparable doses in HT29 colon carcinoma cells.

Science.gov (United States)

Kirlin, W G; Cai, J; DeLong, M J; Patten, E J; Jones, D P

1999-10-01

Dietary agents that induce glutathione S-transferases and related detoxification systems (Phase 2 enzyme inducers) are thought to prevent cancer by enhancing elimination of chemical carcinogens. The present study shows that compounds of this group (benzyl isothiocyanate, allyl sulfide, dimethyl fumarate, butylated hydroxyanisole) activated apoptosis in human colon carcinoma (HT29) cells in culture over the same concentration ranges that elicited increases in enzyme activity (5-25, 25-100, 10-100, 15-60 micromol/L, respectively). Pretreatment of cells with sodium butyrate, an agent that induces HT29 cell differentiation, resulted in parallel increases in Phase 2 enzyme activities and induction of apoptosis in response to the inducers. Cell death characteristics included apoptotic morphological changes, appearance of cells at sub-G1 phase on flow cytometry, caspase activation, DNA fragmentation and TUNEL-positive staining. The results suggest that dietary Phase 2 inducers may protect against cancer by a mechanism distinct from and in addition to that associated with enhanced elimination of carcinogens. If this occurs in vivo, diets high in such compounds could eliminate precancerous cells by apoptosis at time points well after initial exposure to chemical mutagens and carcinogens.

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.

Methemoglobin Formation and Characterization of Hemoglobin Adducts of Carcinogenic Aromatic Amines and Heterocyclic Aromatic Amines.

Science.gov (United States)

Pathak, Khyatiben V; Chiu, Ting-Lan; Amin, Elizabeth Ambrose; Turesky, Robert J

2016-03-21

Arylamines (AAs) and heterocyclic aromatic amines (HAAs) are structurally related carcinogens formed during the combustion of tobacco or cooking of meat. They undergo cytochrome P450 mediated N-hydroxylation to form metabolites which bind to DNA and lead to mutations. The N-hydroxylated metabolites of many AAs also can undergo a co-oxidation reaction with oxy-hemolgobin (HbO2) to form methemoglobin (met-Hb) and the arylnitroso intermediates, which react with the β-Cys(93) chain of Hb to form Hb-arylsulfinamide adducts. The biochemistry of arylamine metabolism has been exploited to biomonitor certain AAs through their Hb arylsulfinamide adducts in humans. We examined the reactivity of HbO2 with the N-hydroxylated metabolites of 4-aminobiphenyl (ABP, HONH-ABP), aniline (ANL, HONH-ANL), and the HAAs 2-amino-9H-pyrido[2,3-b]indole (AαC, HONH-AαC), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP, HONH-PhIP), and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx, HONH-MeIQx). HONH-ABP, HO-ANL, and HONH-AαC induced methemoglobinemia and formed Hb sulfinamide adducts. However, HONH-MeIQx and HONH-PhIP did not react with the oxy-heme complex, and met-Hb formation and chemical modification of the β-Cys(93) residue were negligible. Molecular modeling studies showed that the distances between the H-ON-AA or H-ON-HAA substrates and the oxy-heme complex of HbO2 were too far away to induce methemoglobinemia. Different conformational changes in flexible helical and loop regions around the heme pocket induced by the H-ON-AA or H-ON-HAAs may explain the different proclivities of these chemicals to induce methemoglobinemia. Hb-Cys(93β) sulfinamide and sulfonamide adducts of ABP, ANL, and AαC were identified, by Orbitrap MS, following the proteolysis of Hb with trypsin, Glu-C, or Lys-C. Hb sulfinamide and sulfonamide adducts of ABP were identified in the blood of mice exposed to ABP, by Orbitrap MS. This is the first report of the identification of intact Hb

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 ...

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.

Dietary sucrose and starch affect dysplastic characteristics in carcinogen-induced aberrant crypt foci in rat colon.

Science.gov (United States)

Caderni, G; Lancioni, L; Luceri, C; Giannini, A; Lodovici, M; Biggeri, A; Dolara, P

1997-03-19

To study whether dietary carbohydrates affect dysplasia in aberrant crypt foci (ACF), rats treated with 1,2-dimethilhydrazine (DMH) were fed for three months with diets containing 46% sucrose or corn starch. The number of ACF/colon in the two dietary groups was similar (P = 0.58), but ACF were smaller in the starch than in sucrose group (P colon carcinogenesis while sucrose in the diet is detrimental, promoting the dysplasia of preneoplastic lesions like ACF.

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

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

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.

Chronic toxicity/carcinogenicity studies of FD & C Yellow No. 5 (tartrazine) in rats.

Science.gov (United States)

Borzelleca, J F; Hallagan, J B

1988-03-01

FD & C Yellow No. 5 was fed to Charles River CD rats as a dietary admixture in two long-term toxicity/carcinogenicity studies. The studies were conducted with an in utero phase in which the compound was administered to the F0 generation rats (60/sex/group) at levels of 0.0, 0.0, 0.1, 1.0 or 2.0% ('original study') and 0.0 or 5.0% ('high-dose study'). The concurrent control groups received the basal diet. After random selection of the F1 animals, the long-term phase was initiated using the same dietary levels with 70 rats of each sex/group, including the three control groups. The maximum exposure to the colouring was 113 and 114 wk for males and females, respectively, in the 'original' study and 122 and 125 wk for males and females, respectively, in the 'high-dose' study. No compound-related effects were noted. The no-adverse-effect level found in this study was 5.0% in the diet providing an average intake of 2641 and 3348 mg/kg/day for male and female rats, respectively.

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, ...

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...

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.

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

Dietary and stored iron as predictors of breast cancer risk: A nested case–control study in Shanghai

Science.gov (United States)

Moore, Amber B.; Shannon, Jackilen; Chen, Chu; Lampe, Johanna W.; Ray, Roberta M.; Lewis, Sharon K.; Lin, Minggang; Stalsberg, Helge; Thomas, David B.

2009-01-01

Increases in risk of breast cancer in successive generations of migrants to the United States from China and rapid temporal changes in incidence rates in China following social and economic changes clearly implicate environmental factors in the etiology of this disease. Case–control and cohort studies have provided evidence that at least some of these factors may be dietary. Iron, an essential element necessary for cell function, has also been demonstrated to have potential carcinogenic and co-carcinogenic activities. Iron overload, which was previously uncommon, has become more common in the United States than iron deficiency and may be increasing in China concurrently with dramatic increases in meat consumption. A case–control study nested in a cohort of women in Shanghai, China, was conducted to evaluate possible associations between risk of proliferative and nonproliferative fibrocystic changes as well as breast cancer and dietary iron intake and plasma ferritin levels. Plasma ferritin levels and reported dietary iron intake were compared in 346 women with fibrocystic changes, 248 breast cancer cases and 1,040 controls. Increasing ferritin levels were significantly associated with increasing risk of nonproliferative fibrocystic changes (OR: 2.51, 95% CI: 1.16–5.45, p trend = 0.04). Similar, but weaker, trends were observed for proliferative changes and for breast cancer. Risk of breast cancer relative to the risk of fibrocystic changes was associated with dietary iron intake in women with nonproliferative fibrocystic changes (OR: 2.63, 95% CI: 1.04–6.68, p = 0.02). In conclusion, this study finds significant associations between iron (stored and dietary) and fibrocystic disease and breast cancer. PMID:19444907

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

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.

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

Dietary exposure to aflatoxin B-1, ochratoxin A and fuminisins of adults in Lao Cai province, Viet Nam: A total dietary study approach

DEFF Research Database (Denmark)

Bui, Huong Mai; Le Danh Tuyen; Do Huu Tuan

2016-01-01

Aflatoxins, fumonisins and ochratoxin A that contaminate various agricultural commodities are considered of significant toxicity and potent human carcinogens. This study took a total dietary study approach and estimated the dietary exposure of these mycotoxins for adults living in Lao Cai province...... higher than recommended provisional tolerable daily intake (PTDI) values mainly due to contaminated cereals and meat. The exposure to total fumonisins (1400 ng/kg bw/day) was typically lower than the PTDI value (2000 ng/kg bw/day). The estimated risk of liver cancer associated with exposure to aflatoxin...... B1 was 2.7 cases/100,000 person/year. Margin of exposure (MOE) of renal cancer linked to ochratoxin A and liver cancer associated with fumonisins were 1124 and 1954, respectively indicating risk levels of public health concern. Further studies are needed to evaluate the efficiency of technical...

Quantification of the neurotoxic beta-carboline harmane in barbecued/grilled meat samples and correlation with level of doneness.

Science.gov (United States)

Louis, Elan D; Zheng, Wei; Jiang, Wendy; Bogen, Kenneth T; Keating, Garrett A

2007-06-01

Harmane, one of the heterocyclic amines (HCAs), is a potent neurotoxin linked to human diseases. Dietary exposure, especially in cooked meats, is the major source of exogenous exposure for humans. However, knowledge of harmane concentrations in cooked meat samples is limited. Our goals were to (1) quantify the concentration of harmane in different types of cooked meat samples, (2) compare its concentration to that of other more well-understood HCAs, and (3) examine the relationship between harmane concentration and level of doneness. Thirty barbecued/grilled meat samples (8 beef steak, 12 hamburger, 10 chicken) were analyzed for harmane and four other HCAs (2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine [PhIP], amino-3,8-dimethylimidazo[4,5-f]quinoxaline [MeIQx], 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline [DiMeIQx], and 2-amino-1,6-dimethylfuro[3,2-e]imidazo[4,5-b]pyridine [IFP]). Mean (+/- SD) harmane concentration was 5.63 (+/- 6.63) ng/g; harmane concentration was highest in chicken (8.48 +/- 9.86 ng/g) and lowest in beef steak (3.80 +/- 3.6 ng/g). Harmane concentration was higher than that of the other HCAs and significantly correlated with PhIP concentration. Harmane concentration was associated with meat doneness in samples of cooked beef steak and hamburger, although the correlation between meat doneness and concentration was greater for PhIP than for harmane. Evidence indicates that harmane was detectable in nanograms per gram quantities in cooked meat (especially chicken) and, moreover, was more abundant than other HCAs. There was some correlation between meat doneness and harmane concentration, although this correlation was less robust than that observed for PhIP. Data such as these may be used to improve estimation of human dietary exposure to this neurotoxin.

Quantification of the Neurotoxic β-Carboline Harmane in Barbecued/Grilled Meat Samples and Correlation with Level of Doneness

Science.gov (United States)

Louis, Elan D.; Zheng, Wei; Jiang, Wendy; Bogen, Kenneth T.; Keating, Garrett A.

2016-01-01

Harmane, one of the heterocyclic amines (HCAs), is a potent neurotoxin linked to human diseases. Dietary exposure, especially in cooked meats, is the major source of exogenous exposure for humans. However, knowledge of harmane concentrations in cooked meat samples is limited. Our goals were to (1) quantify the concentration of harmane in different types of cooked meat samples, (2) compare its concentration to that of other more well-understood HCAs, and (3) examine the relationship between harmane concentration and level of doneness. Thirty barbecued/grilled meat samples (8 beef steak, 12 hamburger, 10 chicken) were analyzed for harmane and four other HCAs (2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine [PhIP], amino-3,8-dimethylimidazo[4,5-f]quinoxaline [MeIQx], 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline [DiMeIQx], and 2-amino-1,6-dimethylfuro[3,2-e]imidazo[4,5-b]pyridine [IFP]). Mean (± SD) harmane concentration was 5.63 (± 6.63) ng/g; harmane concentration was highest in chicken (8.48 ± 9.86 ng/g) and lowest in beef steak (3.80 ± 3.6 ng/g). Harmane concentration was higher than that of the other HCAs and significantly correlated with PhIP concentration. Harmane concentration was associated with meat doneness in samples of cooked beef steak and hamburger, although the correlation between meat doneness and concentration was greater for PhIP than for harmane. Evidence indicates that harmane was detectable in nanograms per gram quantities in cooked meat (especially chicken) and, moreover, was more abundant than other HCAs. There was some correlation between meat doneness and harmane concentration, although this correlation was less robust than that observed for PhIP. Data such as these may be used to improve estimation of human dietary exposure to this neurotoxin. PMID:17497412

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)

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

Null effect of dietary restriction on prostate carcinogenesis in the Wistar-Unilever rat.

Science.gov (United States)

McCormick, David L; Johnson, William D; Haryu, Todd M; Bosland, Maarten C; Lubet, Ronald A; Steele, Vernon E

2007-01-01

Chronic dietary restriction inhibits carcinogenesis in several sites in laboratory animals. To determine the effects of dietary restriction on prostate carcinogenesis, prostate cancers were induced in male Wistar-Unilever rats by a sequential regimen of cyproterone acetate (50 mg/day; 21 days); testosterone propionate (100 mg/kg/day; 3 days); N-methyl-N-nitrosourea [MNU; 30 mg/kg; single dose]; and testosterone (subcutaneous implants of 2 pellets containing 40 mg each). Dietary restriction (0% [ad libitum control], 15%, or 30%) was initiated 2 wk post-MNU, and continued until study termination at 12 mo. Dietary restriction induced a rapid suppression of body weight gain but conferred no protection against prostate carcinogenesis. 74% of carcinogen-treated ad libitum controls developed accessory sex gland cancers, versus cancer incidences of 64% and 72% in groups restricted by 15% and 30%, respectively. Similarly, 44% of dietary controls developed cancers limited to the dorsolateral/prostate, versus incidences of 45% and 53% in groups restricted by 15% and 30%. The results of the present study do not support the hypothesis that prostate carcinogenesis can be prevented by reducing caloric intake. Reducing mean body weight by up to 25% through chronic dietary restriction has no effect on the induction of prostate cancers in the Wistar-Unilever rat model.

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.

Dietary fibre, transit-time, faecal bacteria, steroids, and colon cancer in two Scandinavian populations. Report from the International Agency for Research on Cancer Intestinal Microecology Group.

Science.gov (United States)

Maclennan, R; Jensen, O M

1977-07-30

A comparison of dietary intake and faecal characteristics in population samples from two areas of Denmark and Finland with 4-fold variation in colon-cancer incidence suggests that the aetiology of colon cancer may be multifactorial and is not associated in a simple manner with dietary fat, neutral steroids, acid steroids, or their bacterial metabolites. However, meat consumption was greater in the high-incidence areas. Higher intakes of dietary fibre and milk in the low-incidence area suggest a possible protective effect, unrelated to mouth-anus transit-time. Further careful dietary and metabolic studies are needed to clarify the relationships between possible carcinogenic and protective effects of diet.

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.

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.

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

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...

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.

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

Quantitative structure activity relationship for the computational prediction of nitrocompounds carcinogenicity

International Nuclear Information System (INIS)

Morales, Aliuska Helguera; Perez, Miguel Angel Cabrera; Combes, Robert D.; Gonzalez, Maykel Perez

2006-01-01

Several nitrocompounds have been screened for carcinogenicity in rodents, but this is a lengthy and expensive process, taking two years and typically costing 2.5 million dollars, and uses large numbers of animals. There is, therefore, much impetus to develop suitable alternative methods. One possible way of predicting carcinogenicity is to use quantitative structure-activity relationships (QSARs). QSARs have been widely utilized for toxicity testing, thereby contributing to a reduction in the need for experimental animals. This paper describes the results of applying a TOPological substructural molecular design (TOPS-MODE) approach for predicting the rodent carcinogenicity of nitrocompounds. The model described 79.10% of the experimental variance, with a standard deviation of 0.424. The predictive power of the model was validated by leave-one-out validation, with a determination coefficient of 0.666. In addition, this approach enabled the contribution of different fragments to carcinogenic potency to be assessed, thereby making the relationships between structure and carcinogenicity to be transparent. It was found that the carcinogenic activity of the chemicals analysed was increased by the presence of a primary amine group bonded to the aromatic ring, a manner that was proportional to the ring aromaticity. The nitro group bonded to an aromatic carbon atom is a more important determinant of carcinogenicity than the nitro group bonded to an aliphatic carbon. Finally, the TOPS-MODE approach was compared with four other predictive models, but none of these could explain more than 66% of the variance in the carcinogenic potency with the same number of variables

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.

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.

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...

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

Chronic dietary toxicity and carcinogenicity study with potassium perfluorooctanesulfonate in Sprague Dawley rats

International Nuclear Information System (INIS)

Butenhoff, John L.; Chang, Shu-Ching; Olsen, Geary W.; Thomford, Peter J.

2012-01-01

Highlights: ► A two-year dietary toxicity and cancer bioassay was conducted with K + PFOS in rats. ► Hepatocellular hypertrophy was the main microscopic non-neoplastic finding. ► Hepatocellular adenoma was increased in males and females fed the high dose. ► Males fed high dose for 1 year had increased thyroid follicular cell adenoma. ► The latter finding is of equivocal relationship to treatment. -- Abstract: To investigate toxicity and neoplastic potential from chronic exposure to perfluorooctanesulfonate (PFOS), a two-year toxicity and cancer bioassay was conducted with potassium PFOS (K + PFOS) in male and female Sprague Dawley rats via dietary exposure at nominal K + PFOS concentrations of 0, 0.5, 2, 5, and 20 μg/g (ppm) diet for up to 104 weeks. Additional groups were fed 20 ppm for the first 52 weeks, after which they were fed control diet through study termination (20 ppm Recovery groups). Scheduled interim sacrifices occurred on Weeks 4, 14, and 53, with terminal sacrifice between Weeks 103 and 106. K + PFOS appeared to be well-tolerated, with some reductions in body weight occurring in treated rats relative to controls over certain study periods. Male rats experienced a statistically significant decreased trend in mortality with significantly increased survival to term at the two highest treatment levels. Decreased serum total cholesterol, especially in males, and increased serum urea nitrogen were consistent clinical chemistry observations that were clearly related to treatment. The principal non-neoplastic effect associated with K + PFOS exposure was in livers of males and females and included hepatocellular hypertrophy, with proliferation of endoplasmic reticulum, vacuolation, and increased eosinophilic granulation of the cytoplasm. Statistically significant increases in hepatocellular adenoma were observed in males (p = 0.046) and females (p = 0.039) of the 20 ppm treatment group, and all of these tumors were observed in rats surviving to

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

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

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.

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.

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

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.

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)

Predictors of dietary heterocyclic amine intake in three prospective cohorts.

Science.gov (United States)

Byrne, C; Sinha, R; Platz, E A; Giovannucci, E; Colditz, G A; Hunter, D J; Speizer, F E; Willett, W C

1998-06-01

Cooking meat creates heterocyclic amines (HCAs) through pyrolysis of amino acids and creatinine. Although recognized as mutagenic, the etiological role of HCA in human cancer is unclear, due to the lack of information on the effect of typical food cooking methods on HCA concentrations and on variation in HCA exposure in populations. We estimated overall daily dietary HCA intake and variation in intake between individuals, using recent data on HCA concentrations in various meats prepared by cooking methods, temperatures, and times common in United States in the 1990s. Random samples of 250 participants from each of three large prospective cohorts were mailed a questionnaire to assess frequency of consumption, cooking method, and typical outside appearance of pan-fried, broiled, and grilled or barbecued chicken, fish, hamburger, and steak; fried, microwaved, and broiled bacon; fried sausage; roast beef; and homemade gravy. The 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), and 2-amino-3,4,8-trimethylimidazo[4,5,f]quinoxaline (DiMeIQx) concentrations, measured in composite samples by solid-phase extraction and high-performance liquid chromatography, were assigned to each food, cooking method, and doneness level. The dietary reports showed approximately 30-fold relative variation in 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline intake, 20-fold for 2-amino- -methyl-6-phenylimidazo[4,5-b]pyridine, and over 110-fold for 2-amino-3,4,8-trimethylimidazo[4,5,f]quinoxaline, when the 10th and 90th percentiles of HCA intake were compared (90th/10th percentile value). These reported variations in HCA exposure among participants in these three large cohorts indicates that estimation of HCA intake and determination of association with disease risk are feasible, if additional information on meat cooking methods is obtained.

Dietary determinants for Hb-acrylamide and Hb-glycidamide adducts in Danish non-smoking women

DEFF Research Database (Denmark)

Outzen, Malene; Egeberg, Rikke; Dragsted, Lars

2011-01-01

in erythrocytes were analysed by liquid chromatography/MS/MS. Dietary determinants were evaluated by multiple linear regression analyses adjusted for age and smoking behaviour among ex-smokers. The median for Hb-AA was 35 pmol/g globin (5th percentile 17, 95th percentile 89) and for Hb-GA 21 pmol/g globin (5th......Acrylamide (AA) is a probable human carcinogen that is formed in heat-treated carbohydrate-rich foods. The validity of FFQ to assess AA exposure has been questioned. The aim of the present cross-sectional study was to investigate dietary determinants of Hb-AA and Hb-glycidamide (GA) adducts....... The study included 537 non-smoking women aged 50–65 years who participated in the Diet, Cancer and Health cohort (1993–97). At study baseline, blood samples and information on dietary and lifestyle variables obtained from self-administered questionnaires were collected. From blood samples, Hb-AA and Hb-GA...

Differences in gene expression profiles in the liver between carcinogenic and non-carcinogenic isomers of compounds given to rats in a 28-day repeat-dose toxicity study

International Nuclear Information System (INIS)

Nakayama, Koji; Kawano, Yukiko; Kawakami, Yuuki; Moriwaki, Norichika; Sekijima, Masaru; Otsuka, Masanori; Yakabe, Yoshikuni; Miyaura, Hideki; Saito, Koichi; Sumida, Kayo; Shirai, Tomoyuki

2006-01-01

Some compounds have structural isomers of which one is apparently carcinogenic, and the other not. Because of the similarity of their chemical structures, comparisons of their effects can allow gene expression elicited in response to the basic skeletons of the isomers to be disregarded. We compared the gene expression profiles of male Fischer 344 rats administered by daily oral gavage up to 28 days using an in-house oligo microarray. 2-Acetylaminofluorene (2-AAF), 2,4-diaminotoluene (2,4-DAT), 2-nitropropane (2-NP), and 2-nitro-p-phenylenediamine (2-NpP) are hepatocarcinogenic. However, their isomers, 4-acetylaminofluorene (4-AAF), 2,6-diaminotoluene (2,6-DAT), 1-nitropropane (1-NP), and 4-nitro-o-phenylenediamine (4-NoP), are non-hepatocarcinogenic. Because of the limited carcinogenicity of 2-NpP, we attempted to perform two-parametric comparison analyses with (1) a set of 4 isomers: 2-AAF, 2,4-DAT, 2-NP, and 2-NpP as 'carcinogenic', and 4-AAF, 2,6-DAT, 1-NP, and 4-NoP as 'non-carcinogenic'; and (2) a set of 3 isomers: 2-AAF, 2,4-DAT, and 2-NP, as 'carcinogenic', and 4-AAF, 2,6-DAT, and 1-NP as 'non-carcinogenic'. After ratio filtering and Welch's approximate t-test analysis, 54 and 28 genes were selected from comparisons between the sets of 3 and 4 isomers, respectively, for day 28 data. Using hierarchical clustering analysis with the 54 or 28 genes, 2-AAF, 2,4-DAT, and 2-NP clustered into a 'carcinogenic' branch. 2-NpP was in the same cluster as 4-NoP and 4-AAF. This clustering corresponded to the previous finding that 2-NpP is not carcinogenic in male Fischer 344 rats, which indicates that comparing the differences in gene expression elicited by different isomers is an effective method of developing a prediction system for carcinogenicity

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.

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...

Inhibition of carcinogen induced c-Ha-ras and c-fos proto-oncogenes expression by dietary curcumin

Directory of Open Access Journals (Sweden)

Lipigorngoson Suwiwek

2001-01-01

Full Text Available Abstract Background We investigated the chemopreventive action of dietary curcumin on 7,12-dimethylbenz(aanthracene (DMBA-initiated and 12,0-tetradecanoylphorbol-13-acetate (TPA-promoted skin tumor formation in Swiss albino mice. Curcumin, a yellow coloring matter isolated from roots of Curcuma longa Linn, is a phenolic compound possessing antioxidant, free radical scavenger, and antiinflammatory properties. It has been shown by previously reported work that TPA-induced skin tumors were inhibited by topical application of curcumin, and curcumin has been shown to inhibit a variety of biological activities of TPA. Topical application of curcumin was reported to inhibit TPA-induced c-fos, c-jun and c-myc gene expression in mouse skin. This paper reports the effects of orally administered curcumin, which was consumed as a dietary component at concentrations of 0.2 % or 1 %, in ad libitum feeding. Results Animals in which tumors had been initiated with DMBA and promoted with TPA experienced significantly fewer tumors and less tumor volume if they ingested either 0.2% or 1% curcumin diets. Also, the dietary consumption of curcumin resulted in a significantly decreased expression of ras and fos proto-oncogenes in the tumorous skin, as measured by enhanced chemiluminesence Western blotting detection system (Amersham. Conclusions Whereas earlier work demonstrated that topical application of curcumin to mouse skin inhibited TPA-induced expression of c-fos, c-jun and c-myc oncogenes, our results are the first to show that orally consumed curcumin significantly inhibited DMBA- and TPA-induced ras and fos gene expression in mouse skin.

Inhibition of carcinogen induced c-Ha-ras and c-fos proto-oncogenes expression by dietary curcumin

International Nuclear Information System (INIS)

Limtrakul, Porn-ngarm; Anuchapreeda, Songyot; Lipigorngoson, Suwiwek; Dunn, Floyd W

2001-01-01

We investigated the chemopreventive action of dietary curcumin on 7,12-dimethylbenz(a)anthracene (DMBA)-initiated and 12,0-tetradecanoylphorbol-13-acetate (TPA)-promoted skin tumor formation in Swiss albino mice. Curcumin, a yellow coloring matter isolated from roots of Curcuma longa Linn, is a phenolic compound possessing antioxidant, free radical scavenger, and antiinflammatory properties. It has been shown by previously reported work that TPA-induced skin tumors were inhibited by topical application of curcumin, and curcumin has been shown to inhibit a variety of biological activities of TPA. Topical application of curcumin was reported to inhibit TPA-induced c-fos, c-jun and c-myc gene expression in mouse skin. This paper reports the effects of orally administered curcumin, which was consumed as a dietary component at concentrations of 0.2 % or 1 %, in ad libitum feeding. Animals in which tumors had been initiated with DMBA and promoted with TPA experienced significantly fewer tumors and less tumor volume if they ingested either 0.2% or 1% curcumin diets. Also, the dietary consumption of curcumin resulted in a significantly decreased expression of ras and fos proto-oncogenes in the tumorous skin, as measured by enhanced chemiluminesence Western blotting detection system (Amersham). Whereas earlier work demonstrated that topical application of curcumin to mouse skin inhibited TPA-induced expression of c-fos, c-jun and c-myc oncogenes, our results are the first to show that orally consumed curcumin significantly inhibited DMBA- and TPA-induced ras and fos gene expression in mouse skin

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.

Comparative statistical analysis of carcinogenic and non-carcinogenic effects of uranium in groundwater samples from different regions of Punjab, India

International Nuclear Information System (INIS)

Saini, Komal; Singh, Parminder; Bajwa, Bikramjit Singh

2016-01-01

LED flourimeter has been used for microanalysis of uranium concentration in groundwater samples collected from six districts of South West (SW), West (W) and North East (NE) Punjab, India. Average value of uranium content in water samples of SW Punjab is observed to be higher than WHO, USEPA recommended safe limit of 30 µg l −1 as well as AERB proposed limit of 60 µg l −1 . Whereas, for W and NE region of Punjab, average level of uranium concentration was within AERB recommended limit of 60 µg l −1 . Average value observed in SW Punjab is around 3–4 times the value observed in W Punjab, whereas its value is more than 17 times the average value observed in NE region of Punjab. Statistical analysis of carcinogenic as well as non carcinogenic risks due to uranium have been evaluated for each studied district. - Highlights: • Uranium level in groundwater samples have been assessed in different regions of Punjab. • Comparative study of carcinogenic and non carcinogenic effects of uranium has been done. • Wide variation has been found for different geological regions. • It has been found that South west Punjab is worst affected by uranium contamination in its water. • For west and north east regions of Punjab, uranium levels in groundwater laid under recommended safe limits.

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...

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

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

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

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.

Molecular epidemiology studies of carcinogenic environmental pollutants. Effects of polycyclic aromatic hydrocarbons (PAHs) in environmental pollution on exogenous and oxidative DNA damage.

Science.gov (United States)

Farmer, Peter B; Singh, Rajinder; Kaur, Balvinder; Sram, Radim J; Binkova, Blanka; Kalina, Ivan; Popov, Todor A; Garte, Seymour; Taioli, Emanuela; Gabelova, Alena; Cebulska-Wasilewska, Antonina

2003-11-01

Exposure to high levels of environmental air pollution is known to be associated with an increased carcinogenic risk. The individual contribution to this risk derived from specific carcinogenic chemicals within the complex mixture of air pollution is less certain, but may be explored by the use of molecular epidemiological techniques. Measurements of biomarkers of exposure, of effect and of susceptibility provide information of potential benefit for epidemiological and cancer risk assessment. The application of such techniques has been mostly concerned in the past with the carcinogenic polycyclic aromatic hydrocarbons (c-PAHs) that are associated with particulate matter in air pollution, and has showed clear evidence of genotoxic effects, such as DNA adducts, chromosome aberrations (CA) and ras oncogene overexpression, in environmentally exposed Czech and Polish populations. We are currently extending these studies by an investigation of populations exposed to environmental pollution in three European countries, Czech Republic, Slovak Republic and Bulgaria. This pays particular attention to PAHs, but also investigates the extent of radically induced (oxidative) DNA damage in the exposed populations. Policemen, bus drivers and controls, who carried personal monitors to determine their exposures to PAHs have been studied, and blood and urine were collected. Antioxidant and dietary status were assessed in these populations. Stationary monitors were also used for ambient air monitoring. Amongst the parameters studied in the biological samples were: (a) exposure biomarkers, such as PAH adducts with DNA, p53 and p21(WAF1) protein levels, (b) oxidative DNA damage, (c) the biological effect of the exposure by measurement of chromosome damage by fluorescence in situ hybridisation (FISH) or conventional methods, and (d) polymorphisms in carcinogen metabolising and DNA repair enzymes. Repair ability was also measured by the Comet assay. In vitro systems are being evaluated to

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.

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...

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...

The potential contribution of dietary factors to breast cancer prevention.

Science.gov (United States)

Shapira, Niva

2017-09-01

Breast cancer (BC), the leading cancer in women, is increasing in prevalence worldwide, concurrent with western metabolic epidemics, that is, obesity, metabolic syndrome, and diabetes, and shares major risk factors with these diseases. The corresponding potential for nutritional contributions toward BC prevention is reviewed and related to critical stages in the life cycle and their implications for carcinogenic and pathometabolic trajectories. BC initiation potentially involves diet-related pro-oxidative, inflammatory, and procarcinogenic processes, that interact through combined lipid/fatty acid peroxidation, estrogen metabolism, and related DNA-adduct/depurination/mutation formation. The pathometabolic trajectory is affected by high estrogen, insulin, and growth factor cascades and resultant accelerated proliferation/progression. Anthropometric risk factors - high birth weight, adult tallness, adiposity/BMI, and weight gain - are often reflective of these trends. A sex-based nutritional approach targets women's specific risk in western obesogenic environments, associated with increasing fatness, estrogen metabolism, n-6 : n-3 polyunsaturated fatty acid ratio, and n-6 polyunsaturated fatty acid conversion to proinflammatory/carcinogenic eicosanoids, and effects of timing of life events, for example, ages at menarche, full-term pregnancy, and menopause. Recent large-scale studies have confirmed the effectiveness of the evidence-based recommendations against BC risk, emphasizing low-energy density diets, highly nutritious plant-based regimes, physical activity, and body/abdominal adiposity management. Better understanding of dietary inter-relationships with BC, as applied to food intake, selection, combination, and processing/preparation, and recommended patterns, for example, Mediterranean, DASH, plant-based, low energy density, and low glycemic load, with high nutrient/phytonutrient density, would increase public motivation and authoritative support for early

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.

Role of dietary fibers on health of the gastro-intestinal system and related types of cancer

OpenAIRE

Guiné, Raquel

2015-01-01

Dietary fibers are classified into water soluble or insoluble, and most plant foods include in their composition variable amounts of a mixture of soluble and insoluble fibers. This soluble or insoluble nature of fiber is related to its physiological effects. Insoluble fibers are characterized by high porosity, low density and the ability to increase fecal bulk, and act by facilitating intestinal transit, thus reducing the exposure to carcinogens in the colon and therefore acting as protectors...

An Assessment of Dietary Exposure to Cadmium in Residents of Guangzhou, China.

Science.gov (United States)

Zhang, Weiwei; Liu, Yungang; Liu, Yufei; Liang, Boheng; Zhou, Hongwei; Li, Yingyue; Zhang, Yuhua; Huang, Jie; Yu, Chao; Chen, Kuncai

2018-03-20

Cadmium and its compounds are human carcinogens with severe organ toxicity, and their contamination of agricultural soil in China has been frequently reported; however, the dietary exposure to cadmium in residents and the relevant health risk have seldom been reported. In this study, the concentration of cadmium in various types of food collected from 2013 to 2015 were analyzed using graphite furnace atomic absorption spectrometry, and the dietary exposure to cadmium assessed based on a dietary survey in 2976 Guangzhou residents. In total, 3074 out of 4039 food samples had cadmium levels above the limit of detection. The mean ± standard deviation (50th, 95th percentile) cadmium content in all samples was 159.0 ± 112.7 (8.6, 392.4) μg/kg, with levels ranging from 1.0 to 7830 μg/kg. Using the mean cadmium concentrations, the average monthly dietary exposure of Guangzhou residents to cadmium was 14.4 (μg/kg body weight (BW), accounting for 57.6% of the provisional tolerable monthly intake (PTMI). Rice, laver, vegetables, and live aquatic products were the main sources of cadmium intake, on average accounting for 89% of the total value. The dietary cadmium exposure in high consumers (95th percentile food consumption) was 41.0 μg/kg·BW/month, accounting for 163% of the PTMI. Additionally, dietary cadmium exposure at mean consumption but high cadmium food concentration (95th percentile) was 32.3 μg/kg·BW/month, corresponding to 129% of the PTMI. The level of dietary exposure to cadmium in most Guangzhou residents was within the safety limit, thus increased health risk from dietary cadmium exposure is low at present. However, continued efforts by local governments to monitor the levels of cadmium in the four main food categories contributing to exposure are necessary.

An Assessment of Dietary Exposure to Cadmium in Residents of Guangzhou, China

Directory of Open Access Journals (Sweden)

Weiwei Zhang

2018-03-01

Full Text Available Cadmium and its compounds are human carcinogens with severe organ toxicity, and their contamination of agricultural soil in China has been frequently reported; however, the dietary exposure to cadmium in residents and the relevant health risk have seldom been reported. In this study, the concentration of cadmium in various types of food collected from 2013 to 2015 were analyzed using graphite furnace atomic absorption spectrometry, and the dietary exposure to cadmium assessed based on a dietary survey in 2976 Guangzhou residents. In total, 3074 out of 4039 food samples had cadmium levels above the limit of detection. The mean ± standard deviation (50th, 95th percentile cadmium content in all samples was 159.0 ± 112.7 (8.6, 392.4 μg/kg, with levels ranging from 1.0 to 7830 μg/kg. Using the mean cadmium concentrations, the average monthly dietary exposure of Guangzhou residents to cadmium was 14.4 (μg/kg body weight (BW, accounting for 57.6% of the provisional tolerable monthly intake (PTMI. Rice, laver, vegetables, and live aquatic products were the main sources of cadmium intake, on average accounting for 89% of the total value. The dietary cadmium exposure in high consumers (95th percentile food consumption was 41.0 μg/kg·BW/month, accounting for 163% of the PTMI. Additionally, dietary cadmium exposure at mean consumption but high cadmium food concentration (95th percentile was 32.3 μg/kg·BW/month, corresponding to 129% of the PTMI. The level of dietary exposure to cadmium in most Guangzhou residents was within the safety limit, thus increased health risk from dietary cadmium exposure is low at present. However, continued efforts by local governments to monitor the levels of cadmium in the four main food categories contributing to exposure are necessary.

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

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....

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.

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

Four widely used in vitro assays for genetic toxicity were evaluated for their ability to predict the carcinogenicity of selected chemicals in rodents. These assays were mutagenesis in Salmonella and mouse lymphoma cells and chromosome aberrations and sister chromatid exchanges in Chinese hamster ovary cells. Seventy-three chemicals recently tested in 2-year carcinogenicity studies conducted by the National Cancer Institute and the National Toxicology Program were used in this evaluation. Test results from the four in vitro assays did not show significant differences in individual concordance with the rodent carcinogenicity results; the concordance of each assay was approximately 60 percent. Within the limits of this study there was no evidence of complementarity among the four assays, and no battery of tests constructed from these assays improved substantially on the overall performance of the Salmonella assay. The in vitro assays which represented a range of three cell types and four end points did show substantial agreement among themselves, indicating that chemicals positive in one in vitro assay tended to be positive in the other in vitro assays. To help put this project into its proper context, we emphasize certain features of the study: 1) Standard protocols were used to mimic the major use of STTs worldwide--screening for mutagens and carcinogens; no attempt was made to optimize protocols for specific chemicals. 2) The 73 NTP chemicals and their 60% incidence of carcinogenicity are probably not representative of the universe of chemicals but rather reflect the recent chemical selection process for the NTP carcinogenicity assay. 3) The small, diverse group of chemicals precludes a meaningful evaluation of the predictive utility of chemical structure information. 4) The NTP is currently testing these same 73 chemicals in two in vivo STTs for chromosomal effects. 5) Complete data for an additional group of 30 to 40 NTP chemicals will be gathered on

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.

The carcinogenic effects of aspartame: The urgent need for regulatory re-evaluation.

Science.gov (United States)

Soffritti, Morando; Padovani, Michela; Tibaldi, Eva; Falcioni, Laura; Manservisi, Fabiana; Belpoggi, Fiorella

2014-04-01

Aspartame (APM) is an artificial sweetener used since the 1980s, now present in >6,000 products, including over 500 pharmaceuticals. Since its discovery in 1965, and its first approval by the US Food and Drugs Administration (FDA) in 1981, the safety of APM, and in particular its carcinogenicity potential, has been controversial. The present commentary reviews the adequacy of the design and conduct of carcinogenicity bioassays on rodents submitted by G.D. Searle, in the 1970s, to the FDA for market approval. We also review how experimental and epidemiological data on the carcinogenic risks of APM, that became available in 2005 motivated the European Commission (EC) to call the European Food and Safety Authority (EFSA) for urgent re-examination of the available scientific documentation (including the Searle studies). The EC has further requested that, if the results of the evaluation should suggest carcinogenicity, major changes must be made to the current APM specific regulations. Taken together, the studies performed by G.D. Searle in the 1970s and other chronic bioassays do not provide adequate scientific support for APM safety. In contrast, recent results of life-span carcinogenicity bioassays on rats and mice published in peer-reviewed journals, and a prospective epidemiological study, provide consistent evidence of APM's carcinogenic potential. On the basis of the evidence of the potential carcinogenic effects of APM herein reported, a re-evaluation of the current position of international regulatory agencies must be considered an urgent matter of public health. © 2014 Wiley Periodicals, Inc.

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.

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

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

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.

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

Lack of carcinogenicity of tragacanth gum in B6C3F1 mice.

Science.gov (United States)

Hagiwara, A; Boonyaphiphat, P; Kawabe, M; Naito, H; Shirai, T; Ito, N

1992-08-01

Tragacanth gum was administered at dietary levels of 0 (control), 1.25 and 5.0% to groups of 50 male and 50 female B6C3F1 mice for 96 wk after which all animals were maintained on a basal diet without tragacanth gum for a further 10 wk. Mean body weights of females in the 5.0% and 1.25% groups were lower than those of the controls after 11 and 16 wk, respectively. However, there were no treatment-related clinical signs or adverse effects on survival rate, urinalysis, haematology, blood biochemistry and organ weight. While detailed histopathology revealed the development of squamous cell hyperplasias, papillomas and one carcinoma in the forestomach, there was no significant treatment-related increase in the incidence of any preneoplastic or neoplastic lesion. Thus, under the experimental conditions used, tragacanth gum was not carcinogenic in B6C3F1 mice of either sex.

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.

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

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

Effects of dietary antioxidants and 2-amino-3-methylimidazo[4,5-f]-quinoline (IQ) on preneoplastic lesions and on oxidative damage, hormonal status, and detoxification capacity in the rat

DEFF Research Database (Denmark)

Breinholt, Vibeke M.; Mølck, Anne-Marie; Svendsen, Gitte Winkel

2003-01-01

mechanisms were assayed in blood, liver and colon and the impact of the antioxidant administrations on putative preneoplastic changes in liver and colon was assessed. The dietary carcinogen, 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) (200 mg/kg diet) served as a pro-oxidant, genotoxicity and general...

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

Interaction Between Dietary Factors and Inflammation in Prostate Carcinogenesis

Science.gov (United States)

2008-12-01

and ducts. PIN represents the most likely precursor to many prostate cancers. Benign prostatic hyperplasia Non-cancerous enlargement consisting of...transition zone, which might enlarge considerably beyond what is shown. The inflammation found in the transition zone is associated with BPH nodules and...NH2 CH3 N H NH H N N H O O O Uric acid Charred meat PhIP Bladder Prostate Penis Heterocyclic amines Molecules that are produced as a result of cooking

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.

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.

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

Dietary behaviors related to cancer prevention among pre-adolescents and adolescents: the gap between recommendations and reality

Directory of Open Access Journals (Sweden)

White Mary C

2011-06-01

Full Text Available Abstract Background Diet is thought to play an important role in cancer risk. This paper summarizes dietary recommendations for cancer prevention and compares these recommendations to the dietary behaviors of U.S. youth ages 8-18. Methods We identified cancer prevention-related dietary recommendations from key health organizations and assessed dietary consumption patterns among youth using published statistics from the National Health and Nutrition Examination Survey, the national Youth Risk Behavior Survey, and other supplemental sources. Results Cancer prevention guidelines recommend a diet rich in fruits, vegetables, and whole grains, recommend limiting sugary foods and beverages, red and processed meats, sodium, and alcohol, and recommend avoiding foods contaminated with carcinogens. However, youth typically do not meet the daily recommendations for fruit, vegetable, or whole grain consumption and are over-consuming energy-dense, sugary and salty foods. Conclusions A large discrepancy exists between expert recommendations about diet and cancer and actual dietary practices among young people and points to the need for more research to better promote the translation of science into practice. Future research should focus on developing and evaluating policies and interventions at the community, state and national levels for aligning the diets of youth with the evolving scientific evidence regarding cancer prevention.

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.

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

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...

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 ...

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

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 

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

Optimized phases for the acquisition of J-spectra in coupled spin systems for thermally and PHIP polarized molecules.

Science.gov (United States)

Bussandri, S; Prina, I; Acosta, R H; Buljubasich, L

2018-04-01

We demonstrate that the relative phases in the refocusing pulses of multipulse sequences can compensate for pulse errors and off-resonant effects, which are commonly encountered in J-spectroscopy when CPMG is used for acquisition. The use of supercycles has been considered many times in the past, but always from the view point of time-domain NMR, that is, in an effort to lengthen the decay of the magnetization. Here we use simple spin-coupled systems, in which the quantum evolution of the system can be simulated and contrasted to experimental results. In order to explore fine details, we resort to partial J-spectroscopy, that is, to the acquisition of J-spectra of a defined multiplet, which is acquired with a suitable digital filter. We unambiguously show that when finite radiofrequency pulses are considered, the off-resonance effects on nearby multiplets affects the dynamics of the spins within the spectral window under acquisition. Moreover, the most robust phase cycling scheme for our setup consists of a 4-pulse cycle, with phases yyyy‾ or xxxx‾ for an excitation pulse with phase x. We show simulated and experimental results in both thermally polarized and PHIP hyperpolarized systems. Copyright © 2018 Elsevier Inc. All rights reserved.

Chemical carcinogenic and mutagenic agents in the workplace, Poland, 2008–2010

Directory of Open Access Journals (Sweden)

Katarzyna Konieczko

2013-04-01

Full Text Available Background: The aim of this paper is to present a concise but comprehensive information on the occurrence of carcinogenic or mutagenic agents in Polish enterprises and the number of workers exposed to those agents reported to the central register by employers. Objectives and responsibilities of the register, as well as the range and methods of data gathering are discussed. Material and Methods: Data concerning carcinogenic or mutagenic chemical substances and technological processes reported to central register in 2008-2010 were analyzed. Results: In 2008-2010 more than 300 carcinogenic or mutagenic chemical substances were reported to the register. Approximately 2500 plants reported above 150 000 per-person-exposures annually. Among all technological processes regarded as occupational carcinogens, hardwood dusts exposure (about 660 companies; 11 000-13 000 exposed workers each year and exposure to polycyclic aromatic hydrocarbons (PAHs present in coal products (117-125 plantsl 3000 exposed per year were reported. Conclusions: The most widespread carcinogenic/mutagenic substances were: benzene, chromium(VI compounds: potassium dichromate and chromate, chromium(VI trioxide and other chromium compounds, ethylene oxide, asbestos, benzo[a]pyrene and gasoline. The highest number of men was exposed to particular PAHs and benzene , and the majority of women was exposed to benzene, potassium dichromate and chromate, acrylamide, ethylene oxide and gasoline. The lack of clear-cut definitione of occupational exposure to carcinogen creates a problem faced by employers in defining the accurate number of exposed workers. Med Pr 2013;64(2:181–192

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.

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.

Inhibition of nitrobenzene-induced DNA and hemoglobin adductions by dietary constituents

Energy Technology Data Exchange (ETDEWEB)

Li Hongli; Cheng Yan; Wang Haifang; Sun Hongfang; Liu Yuanfang E-mail: yliu@pku.edu.cn; Liu Kexin; Peng Shixiang

2003-03-01

Nitrobenzene (NB), a widely used industrial chemical, is a likely human carcinogen. Many dietary constituents can suppress the DNA-adduction, acting as the inhibitors of cancer. In this study, we investigated the inhibitory effects of vitamin C (VC), vitamin E (VE), tea polyphenols (TP), garlic squeeze, curcumin, and grapestone extract on NB-DNA and NB-hemoglobin (Hb) adductions in mice using an ultrasensitive method of accelerator mass spectrometry (AMS) with {sup 14}C-labelled nitrobenzene. All of these dietary constituents showed their inhibitory effects on DNA or Hb adduction. VC, VE, TP and grapestone extract could efficaciously inhibit the adductions by 33-50%, and all of these six agents could inhibit Hb adduction by 30-64%. We also investigated resveratrol, curcumin, VC and VE as inhibitors of NB-DNA adduction in vitro using liquid scintillation counting technique. These agents in the presence of NADPH and S9 components also pronouncedly blocked DNA adduction in a dose-dependent profile. Our study suggests that these seven constituents may interrupt the process of NB-induced chemical carcinogenesis.

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...

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.

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.

Modulation of xenobiotic metabolising enzymes by anticarcinogens-focus on glutathione S-transferases and their role as targets of dietary chemoprevention in colorectal carcinogenesis

Energy Technology Data Exchange (ETDEWEB)

Pool-Zobel, Beatrice [Department of Nutritional Toxicology, Institute for Nutrition, Friedrich Schiller University Jena, 07743 Jena (Germany)]. E-mail: b8pobe@uni-jena.de; Veeriah, Selvaraju [Department of Nutritional Toxicology, Institute for Nutrition, Friedrich Schiller University Jena, 07743 Jena (Germany); Boehmer, Frank-D. [Institute of Molecular Cell Biology, University Hospital, Friedrich Schiller University Jena, 07743 Jena (Germany)

2005-12-11

There is evidence that consumption of certain dietary ingredients may favourably modulate biotransformation of carcinogens. Associated with this is the hypothesis that the risk for developing colorectal cancer could be reduced, since its incidence is related to diet. Two main groups of biotransformation enzymes metabolize carcinogens, namely Phase I enzymes, which convert hydrophobic compounds to more water-soluble moieties, and Phase II enzymes (e.g. glutathione S-transferases [GST]), which primarily catalyze conjugation reactions. The conjugation of electrophilic Phase I intermediates with glutathione, for instance, frequently results in detoxification. Several possible colon carcinogens may serve as substrates for GST isoenzymes that can have marked substrate specificity. The conjugated products could be less toxic/genotoxic if GSTs are induced, thereby reducing exposure. Thus, numerous studies have shown that the induction of GSTs by antioxidants enables experimental animals to tolerate exposure to carcinogens. One important mechanism of GST induction involves an antioxidant-responsive response element (ARE) and the transcription factor nuclear factor E2-related factor 2 (Nrf2), which is bound to the Kelch-like ECH associated protein 1 (Keap1) in the cytoplasm. Antioxidants may disrupt the Keap-Nrf2 complex, allowing Nrf2 to translocate to the nucleus and mediate expression of Phase II genes via interaction with the ARE. GSTs are also induced by butyrate, a product of gut flora-derived fermentation of plant foods, which may act via different mechanisms, e.g. by increasing histone acetylation. GSTs are expressed with high inter-individual variability in human colonocytes, which points to large differences in cellular susceptibility to xenobiotics. Enhancing expression of GSTs in human colon tissue could therefore contribute to reducing cancer risks. However, it has not been demonstrated in humans that this mechanism is associated with cancer prevention. In the

Modulation of xenobiotic metabolising enzymes by anticarcinogens-focus on glutathione S-transferases and their role as targets of dietary chemoprevention in colorectal carcinogenesis

International Nuclear Information System (INIS)

Pool-Zobel, Beatrice; Veeriah, Selvaraju; Boehmer, Frank-D.

2005-01-01

There is evidence that consumption of certain dietary ingredients may favourably modulate biotransformation of carcinogens. Associated with this is the hypothesis that the risk for developing colorectal cancer could be reduced, since its incidence is related to diet. Two main groups of biotransformation enzymes metabolize carcinogens, namely Phase I enzymes, which convert hydrophobic compounds to more water-soluble moieties, and Phase II enzymes (e.g. glutathione S-transferases [GST]), which primarily catalyze conjugation reactions. The conjugation of electrophilic Phase I intermediates with glutathione, for instance, frequently results in detoxification. Several possible colon carcinogens may serve as substrates for GST isoenzymes that can have marked substrate specificity. The conjugated products could be less toxic/genotoxic if GSTs are induced, thereby reducing exposure. Thus, numerous studies have shown that the induction of GSTs by antioxidants enables experimental animals to tolerate exposure to carcinogens. One important mechanism of GST induction involves an antioxidant-responsive response element (ARE) and the transcription factor nuclear factor E2-related factor 2 (Nrf2), which is bound to the Kelch-like ECH associated protein 1 (Keap1) in the cytoplasm. Antioxidants may disrupt the Keap-Nrf2 complex, allowing Nrf2 to translocate to the nucleus and mediate expression of Phase II genes via interaction with the ARE. GSTs are also induced by butyrate, a product of gut flora-derived fermentation of plant foods, which may act via different mechanisms, e.g. by increasing histone acetylation. GSTs are expressed with high inter-individual variability in human colonocytes, which points to large differences in cellular susceptibility to xenobiotics. Enhancing expression of GSTs in human colon tissue could therefore contribute to reducing cancer risks. However, it has not been demonstrated in humans that this mechanism is associated with cancer prevention. In the

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.

It is time to regulate carcinogenic tobacco-specific nitrosamines in cigarette tobacco

Science.gov (United States)

Hecht, Stephen S.

2014-01-01

The Family Smoking Prevention and Tobacco Control Act gives the Food and Drug Administration power to regulate tobacco products. This commentary calls for immediate regulation of the carcinogenic tobacco-specific nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N’-nitrosonornicotine (NNN) in cigarette tobacco as a logical path to cancer prevention. NNK and NNN, powerful carcinogens in laboratory animals, have been evaluated as “carcinogenic to humans” by the International Agency for Research on Cancer. NNK and NNN are present in the tobacco of virtually all marketed cigarettes; levels in cigarette smoke are directly proportional to the amounts in tobacco. The NNK metabolite NNAL, itself a strong carcinogen, is present in the urine of smokers and non-smokers exposed to secondhand smoke. Some of the highest levels of NNK and NNN are found in U.S. products. It is well established that factors such as choice of tobacco blend, agricultural conditions, and processing methods influence levels of NNK and NNN in cigarette tobacco and cigarette smoke. Therefore, it is time to control these factors and produce cigarettes with 100 ppb or less each of NNK and NNN in tobacco, which would result in an approximate 15-20 fold reduction of these carcinogens in the mainstream smoke of popular cigarettes sold in the United States. PMID:24806664

Results of screening NCI/NTP nongenotoxic carcinogens and genotoxic noncarcinogens with the k sub e test

Energy Technology Data Exchange (ETDEWEB)

Mendelsohn, M.L. (ed.); 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.

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.

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

Science.gov (United States)

Joshi, Amit D; Kim, Andre; Lewinger, Juan Pablo; Ulrich, Cornelia M; Potter, John D; Cotterchio, Michelle; Le Marchand, Loic; Stern, Mariana C

2015-06-01

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) carcinogens relevant for CRC risk. © 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

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.

Dietary exposure to aflatoxin B1, ochratoxin A and fuminisins of adults in Lao Cai province, Viet Nam: A total dietary study approach.

Science.gov (United States)

Huong, Bui Thi Mai; Tuyen, Le Danh; Tuan, Do Huu; Brimer, Leon; Dalsgaard, Anders

2016-12-01

Aflatoxins, fumonisins and ochratoxin A that contaminate various agricultural commodities are considered of significant toxicity and potent human carcinogens. This study took a total dietary study approach and estimated the dietary exposure of these mycotoxins for adults living in Lao Cai province, Vietnam. A total of 42 composite food samples representing 1134 individual food samples were prepared according to normal household practices and analysed for the three mycotoxins. Results showed that the dietary exposure to aflatoxin B1 (39.4 ng/kg bw/day) and ochratoxin A (18.7 ng/kg bw/day) were much higher than recommended provisional tolerable daily intake (PTDI) values mainly due to contaminated cereals and meat. The exposure to total fumonisins (1400 ng/kg bw/day) was typically lower than the PTDI value (2000 ng/kg bw/day). The estimated risk of liver cancer associated with exposure to aflatoxin B1 was 2.7 cases/100,000 person/year. Margin of exposure (MOE) of renal cancer linked to ochratoxin A and liver cancer associated with fumonisins were 1124 and 1954, respectively indicating risk levels of public health concern. Further studies are needed to evaluate the efficiency of technical solutions which could reduce mycotoxin contamination as well as to determine the health effects of the co-exposure to different types of mycotoxins. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

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

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.

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

Modelling of carcinogenic effects resulting from the combined action of radon and smoking

Energy Technology Data Exchange (ETDEWEB)

Ryabova, S.V.; Petin, V.G. [Medical Radiological Research Centre, Obninsk (Russian Federation)

2002-03-01

A simple mathematical model designed for the description of cell survival [1] and later developed for the evaluation of mutagenic effects [2] was proposed for the optimisation of the determination and prognosis of levels of carcinogenic effects in organisms, resulting from the combined action of different agents. The model postulates that the occurrence of synergism is to be expected as a result of additional carcinogenic damage arising from the interaction of sublesions induced by the two agents under investigation. These molecular sublesions are suggested to be non-carcinogenic, if each agent is taken separately. The main conclusion pertaining to this model is the existence of the highest level of synergistic effect. The model predicts the input values and conditions under which this level is reached. The synergistic effect appeared to decline with any deviation from the optimal value for the ratio of carcinogenic effects produced by each agent alone. These conclusions were verified by comparison with experimental data published by other researchers. (orig.)

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).

Carcinogenicity assessments of biotechnology-derived pharmaceuticals: a review of approved molecules and best practice recommendations.

Science.gov (United States)

Vahle, John L; Finch, Gregory L; Heidel, Shawn M; Hovland, David N; Ivens, Inge; Parker, Suezanne; Ponce, Rafael A; Sachs, Clifford; Steigerwalt, Ronald; Short, Brian; Todd, Marque D

2010-06-01

An important safety consideration for developing new therapeutics is assessing the potential that the therapy will increase the risk of cancer. For biotherapeutics, traditional two-year rodent bioassays are often not scientifically applicable or feasible. This paper is a collaborative effort of industry toxicologists to review past and current practice regarding carcinogenicity assessments of biotherapeutics and to provide recommendations. Publicly available information on eighty marketed protein biotherapeutics was reviewed. In this review, no assessments related to carcinogenicity or tumor growth promotion were identified for fifty-one of the eighty molecules. For the twenty-nine biotherapeutics in which assessments related to carcinogenicity were identified, various experimental approaches were employed. This review also discusses several key principles to aid in the assessment of carcinogenic potential, including (1) careful consideration of mechanism of action to identify theoretical risks, (2) careful investigation of existing data for indications of proliferative or immunosuppressive potential, and (3) characterization of any proliferative or immunosuppressive signals detected. Traditional two-year carcinogenicity assays should not be considered as the default method for assessing the carcinogenicity potential of biotherapeutics. If experimentation is considered warranted, it should be hypothesis driven and may include a variety of experimental models. Ultimately, it is important that preclinical data provide useful guidance in product labeling.

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 ...

Embryonic turkey liver: activities of biotransformation enzymes and activation of DNA-reactive carcinogens

International Nuclear Information System (INIS)

Perrone, Carmen E.; Duan, Jian Dong; Jeffrey, Alan M.; Williams, Gary M.; Ahr, Hans-Juergen; Schmidt, Ulrich; Enzmann, Harald H.

2004-01-01

Avian embryos are a potential alternative model for chemical toxicity and carcinogenicity research. Because the toxic and carcinogenic effects of some chemicals depend on bioactivation, activities of biotransformation enzymes and formation of DNA adducts in embryonic turkey liver were examined. Biochemical analyses of 22-day in ovoturkey liver post-mitochondrial fractions revealed activities of the biotransformation enzymes 7-ethoxycoumarin de-ethylase (ECOD), 7-ethoxyresorufin de-ethylase (EROD), aldrin epoxidase (ALD), epoxide hydrolase (EH), glutathione S-transferase (GST), and UDP-glucuronyltransferase (GLUT). Following the administration of phenobarbital (24 mg/egg) on day 21, enzyme activities of ECOD, EROD, ALD, EH and GLUT, but not of GST, were increased by two-fold or higher levels by day 22. In contrast, acute administration of 3-methylcholanthrene (5 mg/egg) induced only ECOD and EROD activities. Bioactivation of structurally diverse pro-carcinogens was also examined using 32 P-postlabeling for DNA adducts. In ovoexposure of turkey embryos on day 20 of gestation to 2-acetylaminofluorene (AAF), 4,4'-methylenebis(2-chloroaniline) (MOCA), benzo[a]pyrene (BaP), and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) resulted in the formation of DNA adducts in livers collected by day 21. Some of the DNA adducts had 32 P-postlabeling chromatographic migration patterns similar to DNA adducts found in livers from Fischer F344 rats exposed to the same pro-carcinogens. We conclude that 21-day embryonic turkey liver is capable of chemical biotransformation and activation of genotoxic carcinogens to form DNA adducts. Thus, turkey embryos could be utilized to investigate potential chemical toxicity and carcinogenicity. (orig.)

Embryonic turkey liver: activities of biotransformation enzymes and activation of DNA-reactive carcinogens

Energy Technology Data Exchange (ETDEWEB)

Perrone, Carmen E.; Duan, Jian Dong; Jeffrey, Alan M.; Williams, Gary M. [New York Medical College, Department of Pathology, Valhalla (United States); Ahr, Hans-Juergen; Schmidt, Ulrich [Bayer AG, Institute of Toxicology, Wuppertal (Germany); Enzmann, Harald H. [Federal Institute for Drugs and Medical Devices, Bonn (Germany)

2004-10-01

Avian embryos are a potential alternative model for chemical toxicity and carcinogenicity research. Because the toxic and carcinogenic effects of some chemicals depend on bioactivation, activities of biotransformation enzymes and formation of DNA adducts in embryonic turkey liver were examined. Biochemical analyses of 22-day in ovoturkey liver post-mitochondrial fractions revealed activities of the biotransformation enzymes 7-ethoxycoumarin de-ethylase (ECOD), 7-ethoxyresorufin de-ethylase (EROD), aldrin epoxidase (ALD), epoxide hydrolase (EH), glutathione S-transferase (GST), and UDP-glucuronyltransferase (GLUT). Following the administration of phenobarbital (24 mg/egg) on day 21, enzyme activities of ECOD, EROD, ALD, EH and GLUT, but not of GST, were increased by two-fold or higher levels by day 22. In contrast, acute administration of 3-methylcholanthrene (5 mg/egg) induced only ECOD and EROD activities. Bioactivation of structurally diverse pro-carcinogens was also examined using {sup 32}P-postlabeling for DNA adducts. In ovoexposure of turkey embryos on day 20 of gestation to 2-acetylaminofluorene (AAF), 4,4'-methylenebis(2-chloroaniline) (MOCA), benzo[a]pyrene (BaP), and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) resulted in the formation of DNA adducts in livers collected by day 21. Some of the DNA adducts had {sup 32}P-postlabeling chromatographic migration patterns similar to DNA adducts found in livers from Fischer F344 rats exposed to the same pro-carcinogens. We conclude that 21-day embryonic turkey liver is capable of chemical biotransformation and activation of genotoxic carcinogens to form DNA adducts. Thus, turkey embryos could be utilized to investigate potential chemical toxicity and carcinogenicity. (orig.)

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

OpenAIRE

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 se...

Development of quantitative structure-activity relationship (QSAR) models to predict the carcinogenic potency of chemicals

International Nuclear Information System (INIS)

Venkatapathy, Raghuraman; Wang Chingyi; Bruce, Robert Mark; Moudgal, Chandrika

2009-01-01

Determining the carcinogenicity and carcinogenic potency of new chemicals is both a labor-intensive and time-consuming process. In order to expedite the screening process, there is a need to identify alternative toxicity measures that may be used as surrogates for carcinogenic potency. Alternative toxicity measures for carcinogenic potency currently being used in the literature include lethal dose (dose that kills 50% of a study population [LD 50 ]), lowest-observed-adverse-effect-level (LOAEL) and maximum tolerated dose (MTD). The purpose of this study was to investigate the correlation between tumor dose (TD 50 ) and three alternative toxicity measures as an estimator of carcinogenic potency. A second aim of this study was to develop a Classification and Regression Tree (CART) between TD 50 and estimated/experimental predictor variables to predict the carcinogenic potency of new chemicals. Rat TD 50 s of 590 structurally diverse chemicals were obtained from the Cancer Potency Database, and the three alternative toxicity measures considered in this study were estimated using TOPKAT, a toxicity estimation software. Though poor correlations were obtained between carcinogenic potency and the three alternative toxicity (both experimental and TOPKAT) measures for the CPDB chemicals, a CART developed using experimental data with no missing values as predictor variables provided reasonable estimates of TD 50 for nine chemicals that were part of an external validation set. However, if experimental values for the three alternative measures, mutagenicity and logP are not available in the literature, then either the CART developed using missing experimental values or estimated values may be used for making a prediction

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.

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.

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...

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

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...

Cell-mediated mutagenesis and cell transformation of mammalian cells by chemical carcinogens

International Nuclear Information System (INIS)

Huberman, E.; Langenbach, R.

1977-01-01

We have developed a cell-mediated mutagenesis assay in which cells with the appropriate markers for mutagenesis are co-cultivated with either lethally irradiated rodent embryonic cells that can metabolize carcinogenic hydrocarbons or with primary rat liver cells that can metabolize chemicals carcinogenic to the liver. During co-cultivation, the reactive metabolites of the procarcinogen appear to be transmitted to the mutable cells and induce mutations in them. Assays of this type make it possible to demonstrate a relationship between carcinogenic potency of the chemicals and their ability to induce mutations in mammalian cells. In addition, by simultaneously comparing the frequencies of transformation and mutation induced in normal diploid hamster cells by benzo(a)pyrene (BP) and one of its metabolites, it is possible to estimate the genetic target size for cell transformation in vitro

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...

Identifying carcinogenic activity of methylated and non-methylated polycyclic aromatic hydrocarbons (PAHs) through electronic and topological indices

CERN Document Server

Braga, R S; Barone, P M V B

2000-01-01

Polycyclic aromatic hydrocarbons (PAHs) are a class of planar molecules, abundant in urban environment, which can induce chemical carcinogenesis. Their carcinogenic power varies in a large range, from very strong carcinogens to inactive ones. In a previous study, we proposed a methodology to identify the PAHs carcinogenic activity exploring electronic and topological indices. In the present work, we show that it is possible to simplify that methodology and expand its applicability to include methylated PAHs compounds. Using very simple rules, we can predict their carcinogenic activity with high accuracy (approx 89%).

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 ...

Carcinogenicity study of 3-monochloropropane-1, 2-diol (3-MCPD) administered by drinking water to B6C3F1 mice showed no carcinogenic potential.

Science.gov (United States)

Jeong, Jayoung; Han, Beom Seok; Cho, Wan-Seob; Choi, Mina; Ha, Chang-Su; Lee, Byoung-Seok; Kim, Yong-Bum; Son, Woo-Chan; Kim, Choong-Yong

2010-09-01

3-Monochloropropane-1, 2-diol (or 3-chloro-1,2-propanediol, 3-MCPD) is a well-known food processing contaminant found in a wide range of foods and ingredients. It has been classified as non-genotoxic carcinogen but its carcinogenic potential in the rodents has been controversial. The carcinogenicity to B6C3F1 mice by drinking water administration was assessed over a period of 104 weeks. Three groups, each comprising 50 male and 50 female mice received 3-MCPD at dosages of 30, 100 or 300 ppm up to Day 100 and 200 ppm onward (4.2, 14.3 and 33.0 mg/kg for males; 3.7, 12.2, and 31.0 mg/kg for females), were allocated. Survival was good, with at least 80% of males and 72% of females in each group surviving 104 weeks. Body weights and body weight gain were decreased in males and females receiving 200 ppm. Water and food consumptions of both sexes at 300/200 ppm were lowered. Emaciated or crouching position was observed for animals of both sexes exposed to 200 ppm. There were some differences in hematology and serum biochemistry compared with controls, although there was no histopathological evidence to support those changes. Histopathological examination did not reveal any neoplastic or non-neoplastic findings attributable to treatment with 3-MCPD. It is concluded that drinking water administration of 3-MCPD for 104 weeks revealed no evidence of carcinogenic potential.

Comparative statistical analysis of carcinogenic and non-carcinogenic effects of uranium in groundwater samples from different regions of Punjab, India.

Science.gov (United States)

Saini, Komal; Singh, Parminder; Bajwa, Bikramjit Singh

2016-12-01

LED flourimeter has been used for microanalysis of uranium concentration in groundwater samples collected from six districts of South West (SW), West (W) and North East (NE) Punjab, India. Average value of uranium content in water samples of SW Punjab is observed to be higher than WHO, USEPA recommended safe limit of 30µgl -1 as well as AERB proposed limit of 60µgl -1 . Whereas, for W and NE region of Punjab, average level of uranium concentration was within AERB recommended limit of 60µgl -1 . Average value observed in SW Punjab is around 3-4 times the value observed in W Punjab, whereas its value is more than 17 times the average value observed in NE region of Punjab. Statistical analysis of carcinogenic as well as non carcinogenic risks due to uranium have been evaluated for each studied district. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

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

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

Residential Segregation, Housing Status, and Prostate Cancer in African American and White Men

Science.gov (United States)

2008-04-01

estimated that pan frying and chicken are the cooking method and meat that comprise the primary source of dietary PhIP exposure in American men (15,28), but...of cooking temperature on the formation of heterocyclic amines in fried meat products and pan residues. Carcinogenesis 1995;16:861–7. [PubMed: 7728968...6) and stomach cancer (7), intake of fried meat increased lung cancer risk (8), and higher estimated HCA intake increased breast cancer risk (9). A

To the application of the emission Mössbauer and positron annihilation spectroscopies for detection of carcinogens

Science.gov (United States)

Bokov, A. V.; Byakov, V. M.; Kulikov, L. A.; Perfiliev, Yu. D.; Stepanov, S. V.

2017-11-01

Being the main cause of cancer, almost all chemical carcinogens are strong electrophiles, that is, they have a high affinity for the electron. We have shown that positron annihilation lifetime spectroscopy (PALS) is able to detect chemical carcinogens by their inhibition of positronium (Ps) formation in liquid media. Electrophilic carcinogens intercept thermalized track electrons, which are precursors of Ps, and as a result, when they are present Ps atom does not practically form. Available biophysical data seemingly indicate that frozen solutions model better an intracellular medium than the liquid ones. So it is reasonable to use emission Mössbauer spectroscopy (EMS) to detect chemical carcinogens, measuring the yield of 57Fe2+ions formed in reactions of Auger electrons and other secondary electrons they produced with 57Fe3+. These reactions are similar to the Ps formation process in the terminal part the positron track: e++ e- =>Ps. So EMS and PALS are complementary methods for detection of carcinogenic compounds.

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.

39-week carcinogenicity study with cyclosporin A in XPA-/- mice, wild type mice and XPA-/-.P53+/- double transgenic mice. Part of the ILSI/HESI Program on Alternative Methods for Carcinogenicity Testing

NARCIS (Netherlands)

Beems RB; Kreijl CF van; Steeg H van; LPI; LEO

2002-01-01

The objective of this study was to evaluate the carcinogenic response of cyclosporin A in XPA-/- mice having a C57BL/6 background. XPA-/- mice are deficient in nucleotide excision repair and have shown increased susceptibility to genotoxic carcinogens and uv-light. The study was part of a world-wide

Factors modifying sensitivity to carcinogens and the problem of threshold in carcinogenesis

International Nuclear Information System (INIS)

Anisimov, V.N.

1983-01-01

Maximum allowable concentrations of chemical carcinogens and dose rates of ionizing radiation have been under extensive study both experimentally and epidemiologically. The problem of the carcinogenic hazards of low-level radiation is a very difficult one: in epidemiological studies it is hard to take into account the many factors (e.g. diseases, diet, genetic peculiarities) that may affect sensitivity to radiation; in experimental studies it is hard to extrapolate with accuracy from one species to another or from the individual threshold to that of the whole population. Age, enzyme activity, sex, and DNA repair capability also modify sensitivity to radiation; when factors such as these are better understood it is expected that epidemiological studies will give a solution that allows estimation of the carcinogenic risk from low-level radiation and hence establishment of a threshold dose. (author)

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.

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.

Identification of EBP50 as a Specific Biomarker for Carcinogens Via the Analysis of Mouse Lymphoma Cellular Proteome

Science.gov (United States)

Lee, Yoen Jung; Choi, In-Kwon; Sheen, Yhun Yhong; Park, Sue Nie; Kwon, Ho Jeong

2012-01-01

To identify specific biomarkers generated upon exposure of L5178Y mouse lymphoma cells to carcinogens, 2-DE and MALDI-TOF MS analysis were conducted using the cellular proteome of L5178Y cells that had been treated with the known carcinogens, 1,2-dibromoethane and O-nitrotoluene and the noncarcinogens, emodin and D-mannitol. Eight protein spots that showed a greater than 1.5-fold increase or decrease in intensity following carcinogen treatment compared with treatment with noncarcinogens were selected. Of the identified proteins, we focused on the candidate biomarker ERM-binding phosphoprotein 50 (EBP50), the expression of which was specifically increased in response to treatment with the carcinogens. The expression level of EBP50 was determined by western analysis using polyclonal rabbit anti-EBP50 antibody. Further, the expression level of EBP50 was increased in cells treated with seven additional carcinogens, verifying that EBP50 could serve as a specific biomarker for carcinogens. PMID:22434383

Dietary broccoli sprouts protect against myocardial oxidative damage and cell death during ischemia-reperfusion.

Science.gov (United States)

Akhlaghi, Masoumeh; Bandy, Brian

2010-09-01

Cruciferous vegetables are known for antioxidant and anti-carcinogenic effects. In the current study we asked whether dietary broccoli sprouts can protect the heart from ischemia-reperfusion. Rats were fed either control diet (sham and control groups) or a diet mixed with 2% dried broccoli sprouts for 10 days. After 10 days the isolated hearts were subjected to ischemia for 20 min and reperfusion for 2 h, and evaluated for cell death, oxidative damage, and Nrf2-regulated phase 2 enzyme activities. Broccoli sprouts feeding inhibited markers of necrosis (lactate dehydrogenase release) and apoptosis (caspase-3 activity) by 78-86%, and decreased indices of oxidative stress (thiobarbituric acid reactive substances and aconitase inactivation) by 82-116%. While broccoli sprouts increased total glutathione and activities of the phase 2 enzymes glutamate cysteine ligase and quinone reductase in liver, they did not affect these in ischemic-reperfused heart. While the mechanism is not clear, the results show that a relatively short dietary treatment with broccoli sprouts can strongly protect the heart against oxidative stress and cell death caused by ischemia-reperfusion.

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

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.

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...

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.

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.

Effects of ascorbic acid on carcinogenicity and acute toxicity of nickel subsulfide, and on tumor transplants growth in gulonolactone oxidase knock-out mice and wild-type C57BL mice

Energy Technology Data Exchange (ETDEWEB)

Kasprzak, Kazimierz S. [Laboratory of Comparative Carcinogenesis, National Cancer Institute at Frederick, Frederick, MD 21702 (United States); Diwan, Bhalchandra A. [Basic Research Program, Science Applications International Corporation-Frederick, Inc., National Cancer Institute at Frederick, Frederick, MD 21702 (United States); Kaczmarek, Monika Z. [Laboratory of Comparative Carcinogenesis, National Cancer Institute at Frederick, Frederick, MD 21702 (United States); Logsdon, Daniel L. [Laboratory Animal Sciences Program, Science Applications International Corporation-Frederick, Inc., National Cancer Institute at Frederick, Frederick, MD 21702 (United States); Fivash, Mathew J. [Data Management Services, National Cancer Institute at Frederick, Frederick, MD 21702 (United States); Salnikow, Konstantin, E-mail: salnikok@mail.nih.gov [Laboratory of Comparative Carcinogenesis, National Cancer Institute at Frederick, Frederick, MD 21702 (United States)

2011-11-15

The aim of this study was to test a hypothesis that ascorbate depletion could enhance carcinogenicity and acute toxicity of nickel. Homozygous L-gulono- < gamma > -lactone oxidase gene knock-out mice (Gulo-/- mice) unable to produce ascorbate and wild-type C57BL mice (WT mice) were injected intramuscularly with carcinogenic nickel subsulfide (Ni{sub 3}S{sub 2}), and observed for the development of injection site tumors for 57 weeks. Small pieces of one of the induced tumors were transplanted subcutaneously into separate groups of Gulo-/- and WT mice and the growth of these tumors was measured for up to 3 months. The two strains of mice differed significantly with regard to (1) Ni{sub 3}S{sub 2} carcinogenesis: Gulo-/- mice were 40% more susceptible than WT mice; and (2) transplanted tumors development: Gulo-/- mice were more receptive to tumor growth than WT mice, but only in terms of a much shorter tumor latency; later in the exponential phase of growth, the growth rates were the same. And, with adequate ascorbate supplementation, the two strains were equally susceptible to acute toxicity of Ni{sub 3}S{sub 2}. Statistically significant effects of dietary ascorbate dosing levels were the following: (1) reduction in ascorbate supplementation increased acute toxicity of Ni{sub 3}S{sub 2} in Gulo-/- mice; (2) ascorbate supplementation extended the latency of transplanted tumors in WT mice. In conclusion, the lack of endogenous ascorbate synthesis makes Gulo-/- mice more susceptible to Ni{sub 3}S{sub 2} carcinogenesis. Dietary ascorbate tends to attenuate acute toxicity of Ni{sub 3}S{sub 2} and to extend the latency of transplanted tumors. The latter effects may be of practical importance to humans and thus deserve further studies. -- Highlights: Black-Right-Pointing-Pointer Ascorbate depletion enhances carcinogenicity and acute toxicity of nickel. Black-Right-Pointing-Pointer Gulo-/- mice unable to synthesize ascorbate were used in this study. Black

Effects of ascorbic acid on carcinogenicity and acute toxicity of nickel subsulfide, and on tumor transplants growth in gulonolactone oxidase knock-out mice and wild-type C57BL mice

International Nuclear Information System (INIS)

Kasprzak, Kazimierz S.; Diwan, Bhalchandra A.; Kaczmarek, Monika Z.; Logsdon, Daniel L.; Fivash, Mathew J.; Salnikow, Konstantin

2011-01-01

The aim of this study was to test a hypothesis that ascorbate depletion could enhance carcinogenicity and acute toxicity of nickel. Homozygous L-gulono- -lactone oxidase gene knock-out mice (Gulo−/− mice) unable to produce ascorbate and wild-type C57BL mice (WT mice) were injected intramuscularly with carcinogenic nickel subsulfide (Ni 3 S 2 ), and observed for the development of injection site tumors for 57 weeks. Small pieces of one of the induced tumors were transplanted subcutaneously into separate groups of Gulo−/− and WT mice and the growth of these tumors was measured for up to 3 months. The two strains of mice differed significantly with regard to (1) Ni 3 S 2 carcinogenesis: Gulo−/− mice were 40% more susceptible than WT mice; and (2) transplanted tumors development: Gulo−/− mice were more receptive to tumor growth than WT mice, but only in terms of a much shorter tumor latency; later in the exponential phase of growth, the growth rates were the same. And, with adequate ascorbate supplementation, the two strains were equally susceptible to acute toxicity of Ni 3 S 2 . Statistically significant effects of dietary ascorbate dosing levels were the following: (1) reduction in ascorbate supplementation increased acute toxicity of Ni 3 S 2 in Gulo−/− mice; (2) ascorbate supplementation extended the latency of transplanted tumors in WT mice. In conclusion, the lack of endogenous ascorbate synthesis makes Gulo−/− mice more susceptible to Ni 3 S 2 carcinogenesis. Dietary ascorbate tends to attenuate acute toxicity of Ni 3 S 2 and to extend the latency of transplanted tumors. The latter effects may be of practical importance to humans and thus deserve further studies. -- Highlights: ► Ascorbate depletion enhances carcinogenicity and acute toxicity of nickel. ► Gulo−/− mice unable to synthesize ascorbate were used in this study. ► The reduction in ascorbate levels in Gulo−/− mice increased acute toxicity induced by Ni 3 S 2 . �

Methodology in use for the assessment of carcinogenic risk. II. Radiation. Oncology overview

International Nuclear Information System (INIS)

1983-04-01

Oncology Overviews are a service of the International Cancer Research Data Bank (ICRDB) Program of the National Cancer Institute, intended to facilitate and promote the exchange of information between cancer scientists by keeping them aware of literature related to their research being published by other laboratories throughout the world. Each Oncology Overview represents a survey of the literature associated with a selected area of cancer research. It contains abstracts of articles which have been selected and organized by researchers associated with the field. Contents: Assessment of carcinogenic risk from environmental and occupational exposures to ionizing radiation; Assessment of carcinogenic risk from exposure to ionizing radiation used for medical diagnosis or treatment; Assessment of carcinogenic risk from exposure to ionizing radiation following nuclear bomb explosions; Comparison of risk from radiation sources with risk from nonradiation sources; Experimental studies to assess risk of carcinogenesis following exposure to ionizing radiation; Theoretical aspects of dose-response relationships in the assessment of carcinogenic risk from exposure to ionizing radiation; Public policy and standards for acceptable risk from exposure to ionizing radiation; General reviews on the assessment of risk from exposure to ionizing radiation

The carcinogenicity of 1-methyl-3(p-bromophenyl)-1-nitrosourea (Br-MPNU).

Science.gov (United States)

Warzok, R; Martin, J; Mendel, J; Thust, R; Schwarz, H

1983-01-01

In long-term experiments with Hooded rats the carcinogenic potential of 1-methyl-3(p-bromophenyl)-1-nitrosourea (Br-MPNU) could be demonstrated for the first time. Br-MPNU is formed also endogenously after combined administration of 1-methyl-3(p-bromophenyl)-urea (Br-MPU) and sodium nitrite. After repeated intragastric administration of 0.33 mmol Br-MPU and 0.73 mmol NaNO2 per kg b.w. papillomas and carcinomas of the forestomach developed in 83%. After repeated administration of 0.28 mmol Br-MPNU per kg b.w. these neoplasms were observed in 88%. The comparison of results obtained in similar experiments with 1-methyl-3-phenyl-1-nitrosourea shows that bromine substitution led to a reduction of the carcinogenic activity. The present paper is part of a complex program studying the interrelationships between structure, physico-chemical properties, mutagenicity and carcinogenicity of nitrosoureas.

Infectious and dietary risk factors of oral cancer.

Science.gov (United States)

Meurman, Jukka H

2010-06-01

In addition to the classic risk factors of oral cancer, namely alcohol and tobacco, other factors both infectious and environmental are thought to be associated with the development of oral malignancy. Infections in the oral cavity may be an important preventable cause of cancer. Poor oral hygiene, periodontal disease, chronic candidiasis, human papilloma virus (HPV) and herpesvirus infections link statistically with cancer but the mechanisms involved are largely unknown. Infections may trigger cell proliferation, inhibit apoptosis, interfere with cellular signaling mechanisms and up-regulate tumor promoters. In addition, several oral micro-organisms metabolize alcohol to carcinogenic acetaldehyde thus explaining the association between poor oral hygiene, alcohol consumption and carcinogenesis. With regards to dietary factors the Mediterranean-type fruit and vegetable rich diet has been shown to reduce the risk of oral cancer but the evidence is weak, the effect of individual food components and trace elements on carcinogenesis remains unclear at present. Copyright 2010 Elsevier Ltd. All rights reserved.

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.

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.

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

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

Non-genotoxic carcinogens: early effects on gap junctions, cell proliferation and apoptosis in the rat

International Nuclear Information System (INIS)

Mally, Angela; Chipman, James Kevin

2002-01-01

Non-genotoxic carcinogens are thought to induce tumour formation by disturbing the balance between cell growth and cell death. Gap junctions (GJ) contribute to the maintenance of tissue homeostasis by allowing the intercellular exchange of growth regulatory signals and potential inhibition of GJ intercellular communication through loss of connexin (Cx) plaques has been shown to be involved in the cancer process. We have investigated the time- and dose-dependent effects of the non-genotoxic hepatocarcinogens Wy-14,643, 2,3,7,8-tetrachlorodibenzo-p-dioxin, methapyrilene and hexachlorobenzene and the male rat kidney carcinogens chloroform, p-dichlorobenzene and d-limonene on gap junction plaque expression in relation to proliferation and apoptosis. With the exception of limonene, all non-genotoxic carcinogens significantly reduced the expression of GJ plaques containing Cx32 in their respective target tissue. No dose-dependent, significant effects were seen in non-target organs. Although alteration of Cx32 expression did not appear to correlate with induction of cell proliferation, out data suggest that the interaction of both processes--interference of GJ coupled with a proliferative stimulus (at the carcinogenic dose)--may be important in non-genotoxic carcinogenesis and provide a potential alert for non-genotoxic carcinogens in short-term toxicity tests

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.

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

Genotoxicity and induction of DNA damage responsive genes by food-borne heterocyclic aromatic amines in human hepatoma HepG2 cells.

Science.gov (United States)

Pezdirc, Marko; Žegura, Bojana; Filipič, Metka

2013-09-01

Heterocyclic aromatic amines (HAAs) are potential human carcinogens formed in well-done meats and fish. The most abundant are 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-Amino-3,4,8-trimethyl-3H-imidazo[4,5-f]quinoxaline (4,8-DiMeIQx) and 2-Amino-3-methyl-3H-imidazo[4,5-f]quinoline (IQ). HAAs exert genotoxic activity after metabolic transformation by CYP1A enzymes, that is well characterized, however the genomic and intervening responses are not well explored. We have examined cellular and genomic responses of human hepatoma HepG2 cells after 24h exposure to HAAs. Comet assay revealed increase in formation of DNA strand breaks by PhIP, MeIQx and IQ but not 4,8-DiMeIQx, whereas increased formation of micronuclei was not observed. The four HAAs up-regulated expression of genes encoding metabolic enzymes CYP1A1, CYP1A2 and UGT1A1 and expression of TP53 and its downstream regulated genes CDKN1A, GADD45α and BAX. Consistent with the up-regulation of CDKN1A and GADD45α the cell-cycle analysis showed arrest in S-phase by PhIP and IQ, and in G1-phase by 4,8-DiMeIQx and MeIQx. The results indicate that upon exposure to HAAs the cells respond with the cell-cycle arrest, which enables cells to repair the damage or eliminate them by apoptosis. However, elevated expression of BCL2 and down-regulation of BAX may indicate that HAAs could suppress apoptosis meaning higher probability of damaged cells to survive and mutate. Copyright © 2013 Elsevier Ltd. All rights reserved.

Preferential induction of the AhR gene battery in HepaRG cells after a single or repeated exposure to heterocyclic aromatic amines

International Nuclear Information System (INIS)

Dumont, Julie; Josse, Rozenn; Lambert, Carine; Antherieu, Sebastien; Laurent, Veronique; Loyer, Pascal; Robin, Marie-Anne; Guillouzo, Andre

2010-01-01

2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) are two of the most common heterocyclic aromatic amines (HAA) produced during cooking of meat, fish and poultry. Both HAA produce different tumor profiles in rodents and are suspected to be carcinogenic in humans. In order to better understand the molecular basis of HAA toxicity, we have analyzed gene expression profiles in the metabolically competent human HepaRG cells using pangenomic oligonucleotide microarrays, after either a single (24-h) or a repeated (28-day) exposure to 10 μM PhIP or MeIQx. The most responsive genes to both HAA were downstream targets of the arylhydrocarbon receptor (AhR): CYP1A1 and CYP1A2 after both time points and CYP1B1 and ALDH3A1 after 28 days. Accordingly, CYP1A1/1A2 induction in HAA-treated HepaRG cells was prevented by chemical inhibition or small interference RNA-mediated down-regulation of the AhR. Consistently, HAA induced activity of the CYP1A1 promoter, which contains a consensus AhR-related xenobiotic-responsive element (XRE). In addition, several other genes exhibited both time-dependent and compound-specific expression changes with, however, a smaller magnitude than previously reported for the prototypical AhR target genes. These changes concerned genes mainly related to cell growth and proliferation, apoptosis, and cancer. In conclusion, these results identify the AhR gene battery as the preferential target of PhIP and MeIQx in HepaRG cells and further support the hypothesis that intake of HAA in diet might increase human cancer risk.

Decrease of 5-Hydroxymethylcytosine in Rat Liver with Subchronic Exposure to Genotoxic Carcinogens Riddelliine and Aristolochic Acid

Science.gov (United States)

Lian, Christine Guo; Xu, Shuyun; Guo, Weimin; Yan, Jian; Frank, Maximilian Y M; Liu, Robert; Liu, Cynthia; Chen, Ying; Murphy, George F.; Chen, Tao

2018-01-01

The level of 5-hydroxymethylcytosine (5-hmC) converted by ten-eleven translocation (TET) family is decreased in cancers. However, whether 5-hmC level is perturbed in early stages of carcinogenesis caused by genotoxic carcinogens is not defined. 5-hmC levels and TET2 expression were measured in liver of rats treated with genotoxic carcinogens, riddelliine, or aristolochic acid. Levels of 5-hmC and TET2 expression decreased in the liver of the carcinogens-treated rats. Loss of 5-hmC correlates well with documented induction of genetic mutations by the carcinogens, suggesting that TET2-mediated 5-hydroxymethylation plays an epigenetic role in early state of carcinogenesis. PMID:25154389

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.

Influence of a Dietary Fiber on Development of Dimethylhydrazine-Induced Aberrant Crypt Foci and Colon Tumor Incidence in Wistar Rats

DEFF Research Database (Denmark)

Thorup, I.; Meyer, Otto A.; Kristiansen, E.

1994-01-01

Formation of aberrant crypt foci (ACF) in archived colon tissue from animals in a previous study was examined. The animals were fed a semisynthetic casein-based diet in which the carbohydrate pool was substituted with a dietary beet fiber (Fibeta) as the only source of fiber. Oral doses...... experimental data. The present state of knowledge could indicate that ACF represent true preneoplastic lesions progressing into colon tumors or that ACF and colon tumors represent two parallel independent events as a consequence of the cancer initiation (i.e., the ACF not being preneoplastic lesions per se)....... between duration of intake of high-fiber diet and number of animals with ACF, as well as the total number of ACF and number of small A CF (1-3 crypts) per affected animal. The previously reported data showed no protective effect of the dietary fiber at any stage of the colorectal carcinogenic process...

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...

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.

Inhibition of induced tumorigenesis by dietary 2-deoxy-D-Glucose in mice

International Nuclear Information System (INIS)

Singh, Saurabh; Pandey, Sanjay; Bhuria, Vikas; Bhatt, Anant Narayan; Taneja, Pankaj; Soni, Ravi; Dwarakanath, Bilikere S.; Oberoi, Raghav; Chawla, Aman Preet; Saluja, Daman

2014-01-01

Enhanced glycolysis facilitating proliferation and defence against death, besides energy production is a fundamental metabolic change exhibited by majority of the tumor types. Recent evidences support Warburg's proposition that this metabolic re-programming may also drive tumorigenesis induced by chemical carcinogens and radiation. Targeting this phenotype using the glycolytic inhibitor, 2-deoxy-D glucose (2-DG) has been shown to enhance the efficacy of radiation and chemotherapeutic drugs in experimental systems as well as clinics. 2-DG is also a potent Energy Restriction Mimetic Agent (ERMA) as an alternative to Dietary Energy Restriction (DER) for combating cancer. Since DER regimen is difficult to sustain in humans, we have hypothesized that 2-DG may impair the process of induced tumorigenesis, thereby offering an attractive chemopreventive strategy. Systematic studies have indeed shown that dietary 2-DG administration impairs the formation and growth of implanted tumor (Lewis Lung carcinoma; Ehrlich ascites carcinoma) as well as chemical (DMBA and TPA) and radiation-induced skin tumors in C57BL/6, Strain A and Swiss Albino mice respectively in the tumor implant study. Decrease in the fraction of animals bearing tumor and growth rate, besides increase in the latency period were evident. In the chemical and radiation induced tumor studies, a significant reduction in the percentage of tumor (papillomas) bearing animals (incidence), number of tumors per animal (tumor burden) and increased latency were observed. Although, mechanisms underlying cancer preventive/inhibitory potential of dietary 2-DG is not completely understood, our current findings suggests modifications of certain circulating factors (glucose and insulin), oxidative stress (LPO and GSH), immune status (CD4/CD8 and regulatory T-cells; T-regs), extracellular matrix (MMP-9) and angiogenesis (tumor associated and radiation-induced) as some of the contributing factors. Further studies are required

Site-specific induction of nuclear anomalies (apoptotic bodies and micronuclei) by carcinogens in mice

International Nuclear Information System (INIS)

Ronen, A.; Heddle, J.A.

1984-01-01

The usefulness of nuclear anomalies (NA) as a short-term test for indication of carcinogens in the mouse colon has been suggested previously by experiments in which colon-specific carcinogens induced NA in the colon, whereas non-colon carcinogens were, in general, impotent in that organ. We have extended this work to other sites in the digestive tract of female C57BL/6 mice treated with gamma-rays, 1,2-dimethylhydrazine dihydrochloride, or N-methylnitrosourea. Each agent induced NA at all of the sites examined. The frequency of NA at different times after treatment depended upon both the agent used and the site examined. 1,2-Dimethylhydrazine dihydrochloride (which is known to induce tumors predominantly in the colon) induces NA with the highest efficiency (relative to gamma-rays) in the descending colon. N-Methylnitrosourea (which induces tumors mainly in the forestomach) induces NA with the highest efficiency in the forestomach. These results further support the usefulness of the assay in that the frequency of NA produced at the various sites by 1,2-dimethylhydrazine dihydrochloride and N-methylnitrosourea correlates with that found in the carcinogenicity studies

Epithelial ovarian cancer and exposure to dietary nitrate and nitrite in the NIH-AARP Diet and Health Study.

Science.gov (United States)

Aschebrook-Kilfoy, Briseis; Ward, Mary H; Gierach, Gretchen L; Schatzkin, Arthur; Hollenbeck, Albert R; Sinha, Rashmi; Cross, Amanda J

2012-01-01

Ovarian cancer is a leading cause of cancer death among women in the United States and it has the highest mortality rate of all gynecologic cancers. Internationally, there is a five-fold variation in incidence and mortality of ovarian cancer, which suggests a role for environmental factors, including diet. Nitrate and nitrite are found in various food items and they are precursors of N-nitroso compounds, which are known carcinogens in animal models. We evaluated dietary nitrate and nitrite intake and epithelial ovarian cancer in the National Institutes of Health (NIH)-AARP Diet and Health Study, including 151 316 women aged 50-71 years at the time of the baseline questionnaire in 1995-1996. The nitrate and nitrite intake was assessed using a 124-item validated food frequency questionnaire. Through 31 December 2006, 709 incident epithelial ovarian cancer cases with complete dietary information were identified. Using Cox proportional hazards regression to estimate hazard ratios and 95% confidence intervals (CIs), women in the highest intake quintile of dietary nitrate had a 31% increased risk (95% CI: 1.01-1.68) of epithelial ovarian cancer, compared with those in the lowest intake quintile. Although there was no association for total dietary nitrite, those in the highest intake category of animal sources of nitrite had a 34% increased risk (95% CI: 1.05-1.69) of ovarian cancer. There were no clear differences in risk by histologic subtype of ovarian cancer. Our findings suggest that a role of dietary nitrate and nitrite in ovarian cancer risk should be followed in other large cohort studies.

Ochratoxin A induces rat renal carcinogenicity with limited induction of oxidative stress responses

International Nuclear Information System (INIS)

Qi, Xiaozhe; Yu, Tao; Zhu, Liye; Gao, Jing; He, Xiaoyun; Huang, Kunlun; Luo, Yunbo; Xu, Wentao

2014-01-01

Ochratoxin A (OTA) has displayed nephrotoxicity and renal carcinogenicity in mammals, however, no clear mechanisms have been identified detailing the relationship between oxidative stress and these toxicities. This study was performed to clarify the relationship between oxidative stress and the renal carcinogenicity induced by OTA. Rats were treated with 70 or 210 μg/kg b.w. OTA for 4 or 13 weeks. In the rats administrated with OTA for 13 weeks, the kidney was damaged seriously. Cytoplasmic vacuolization was observed in the outer stripe of the outer medulla. Karyomegaly was prominent in the tubular epithelium. Kidney injury molecule-1 (Kim-1) was detected in the outer stripe of the outer medulla in both low- and high-dose groups. OTA increased the mRNA levels of clusterin in rat kidneys. Interestingly, OTA did not significantly alter the oxidative stress level in rat liver and kidney. Yet, some indications related to proliferation and carcinogenicity were observed. A dose-related increase in proliferating cell nuclear antigen (PCNA) was observed at 4 weeks in both liver and kidney, but at 13 weeks, only in the kidney. OTA down-regulated reactive oxygen species (ROS) and up-regulated vimentin and lipocalin 2 in rat kidney at 13 weeks. The p53 gene was decreased in both liver and kidney at 13 weeks. These results suggest that OTA caused apparent kidney damage within 13 weeks but exerted limited effect on oxidative stress parameters. It implies that cell proliferation is the proposed mode of action for OTA-induced renal carcinogenicity. - Highlights: • We studied OTA toxicities in both the rat liver and kidney for 13 weeks. • OTA exerts limited effects on oxidative stress in the rat liver and kidney. • OTA induced renal carcinogenicity resulting from cell proliferation

Ochratoxin A induces rat renal carcinogenicity with limited induction of oxidative stress responses

Energy Technology Data Exchange (ETDEWEB)

Qi, Xiaozhe; Yu, Tao; Zhu, Liye; Gao, Jing [College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083 (China); He, Xiaoyun; Huang, Kunlun; Luo, Yunbo [College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083 (China); The Supervision, Inspection and Testing Center of Genetically Modified Organisms, Ministry of Agriculture, Beijing 100083 (China); Xu, Wentao, E-mail: xuwentao@cau.edu.cn [College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083 (China); The Supervision, Inspection and Testing Center of Genetically Modified Organisms, Ministry of Agriculture, Beijing 100083 (China)

2014-11-01

Ochratoxin A (OTA) has displayed nephrotoxicity and renal carcinogenicity in mammals, however, no clear mechanisms have been identified detailing the relationship between oxidative stress and these toxicities. This study was performed to clarify the relationship between oxidative stress and the renal carcinogenicity induced by OTA. Rats were treated with 70 or 210 μg/kg b.w. OTA for 4 or 13 weeks. In the rats administrated with OTA for 13 weeks, the kidney was damaged seriously. Cytoplasmic vacuolization was observed in the outer stripe of the outer medulla. Karyomegaly was prominent in the tubular epithelium. Kidney injury molecule-1 (Kim-1) was detected in the outer stripe of the outer medulla in both low- and high-dose groups. OTA increased the mRNA levels of clusterin in rat kidneys. Interestingly, OTA did not significantly alter the oxidative stress level in rat liver and kidney. Yet, some indications related to proliferation and carcinogenicity were observed. A dose-related increase in proliferating cell nuclear antigen (PCNA) was observed at 4 weeks in both liver and kidney, but at 13 weeks, only in the kidney. OTA down-regulated reactive oxygen species (ROS) and up-regulated vimentin and lipocalin 2 in rat kidney at 13 weeks. The p53 gene was decreased in both liver and kidney at 13 weeks. These results suggest that OTA caused apparent kidney damage within 13 weeks but exerted limited effect on oxidative stress parameters. It implies that cell proliferation is the proposed mode of action for OTA-induced renal carcinogenicity. - Highlights: • We studied OTA toxicities in both the rat liver and kidney for 13 weeks. • OTA exerts limited effects on oxidative stress in the rat liver and kidney. • OTA induced renal carcinogenicity resulting from cell proliferation.

PSA-Based Screening Outcomes, Dietary Heterocyclic Amine Exposure, and Prostate Cancer Risk in African Americans

Science.gov (United States)

2008-06-01

was conducted specifically to determine whether meat intake or meat-related mutagens, including PhIP, was associated with increased PC risk ( Cross ... Cross et al., 2005). Other intakes were not found to be associated with increased PC risk. No separate analysis was done of study results by race...369. Block G., Hartman A.M., Dresser C.M., Carroll M.D., Gannon J., and Gardner L. A data-based approach to diet questionnaire design and testing. Am

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.

Mode of carcinogenic action of pesticides inducing thyroid follicular cell tumors in rodents.

Science.gov (United States)

Hurley, P M

1998-08-01

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 acetochlor; evidence is less convincing for ethylene thiourea and etridiazole. Studies on thyroid-pituitary functioning, including indications of thyroid cell growth and/or changes in thyroxine, triiodothyronine, or thyroid-stimulating hormone levels, are available on 19 pesticides. No such antithyroid information is available for etridiazole, N-octyl bicycloheptene dicarboximide, terbutryn, triadimefon, and trifluralin. Of the studied chemicals, only bromacil lacks antithyroid activity under study conditions. Intrathyroidal and extrathyroidal sites of action are found: amitrole, ethylene thiourea, and mancozeb are thyroid peroxidase inhibitors; and acetochlor, clofentezine, fenbuconazole, fipronil, pendimethalin, pentachloronitrobenzene, prodiamine, pyrimethanil, and thiazopyr seem to enhance the hepatic metabolism and excretion of thyroid hormone. Thus, with 12 pesticides that mode of action judgments can be made, 11 disrupt thyroid-pituitary homeostasis only; no chemical is mutagenic only; and acetochlor may have both antithyroid and some mutagenic activity. More information is needed to identify other potential antithyroid modes of thyroid carcinogenic action.

[Cardiovascular risk, occupation and exposure to occupational carcinogens in a group of workers in Salamanca].

Science.gov (United States)

González-Sánchez, Jesús

2015-01-01

Identify the cardiovascular risk factors in a group of workers in the province of Salamanca, protected by external prevention services, as regards exposure to occupational carcinogens, by sector of activity and gender. An observational descriptive epidemiological study was conducted. The sample selection was by stratified random sampling in each entity. The variables collected by questionnaire were, sociodemographic characteristics, exposure to occupational carcinogens, and cardiovascular risk factors (smoking, hypertension, dyslipidemia, and diabetes), using the clinical-work histories as a source of information. Statistically significant differences were observed in cardiovascular risk according to the exposure to occupational carcinogens (p cardiovascular risk in the work place. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Temporal aspects of tumorigenic response to individual and mixed carcinogens. Progress report, October 1, 1978-September 30, 1979

International Nuclear Information System (INIS)

Albert, R.E.; Burns, F.J.; Altshuler, B.

1979-06-01

The research proposed here is designed to obtain a better understanding of the temporal kinetics of tumor induction when one or more carcinogens are present simultaneously or sequentially for prolonged periods of time. Studies done to date under this contract have shown that carcinogenesis in mouse skin by polycyclic aromatic hydrocarbon carcinogens is consistent with the induction of dependent and autonomous cell transformations by the carcinogen followed by the conversion of autonomous tumor cells into malignancies at a rate which is determined by the level of carcinogen exposure. Dependent cell transformations remain latent in the skin unless expressed by a promoting agent. Dependent neoplasia appears to follow one-hit kinetics while malignancy is a multihit endpoint. Dose-related and time-related aspects of tumor induction are separable in the initiation-promotion system of mouse skin which along with rat skin and hamster lung is being used as a model for testing hypotheses. Results to date provide the basis for a new interpretation of the linear non-threshold extrapolation model. The broad aim of the study is to provide a basis or rationale for estimating risks associated with prolonged exposures to carcinogens found in the environment and to predict how different tissues and species respond to the carcinogens, promoters, and cocarcinogens

Dietary acrylamide exposure of the French population: results of the second French Total Diet Study.

Science.gov (United States)

Sirot, Véronique; Hommet, Frédéric; Tard, Alexandra; Leblanc, Jean-Charles

2012-03-01

Acrylamide is a heat-induced carcinogen compound that is found in some foods consequently to cooking or other thermal processes. In the second French Total Diet Study (TDS), acrylamide was analysed in 192 food samples collected in mainland France to be representative of the population diet and prepared "as consumed". Highest mean concentrations were found in potato chips/crisps (954 μg/kg), French fries and other fried potatoes (724 μg/kg), and salted biscuits other than potato chips (697 μg/kg). Exposure of general adult and child populations was assessed by combining analytical results with national consumption data. Mean acrylamide exposure was assessed to be 0.43±0.33 μg/kg of body weight (bw) per day for adults and 0.69±0.58 μg/kg bw/day for children. Although the exposure assessed is lower than in previous evaluations, the calculated margins of exposure, based on benchmark dose limits defined for carcinogenic effects, remain very low especially for young children (below 100 at the 95th percentile of exposure), indicating a health concern. It is therefore advisable to continue efforts in order to reduce dietary exposure to acrylamide. Copyright © 2012 Elsevier Ltd. All rights reserved.

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

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.

Oral carcinogenicity study with nickel sulfate hexahydrate in Fischer 344 rats

International Nuclear Information System (INIS)

Heim, Katherine E.; Bates, Hudson K.; Rush, Rusty E.; Oller, Adriana R.

2007-01-01

Until now, existing data on the oral carcinogenicity of nickel substances have been inconclusive. Yet, the assessment of oral carcinogenicity of nickel has serious scientific and regulatory implications. In the present study, nickel sulfate hexahydrate was administered daily to Fischer 344 rats by oral gavage for 2 years (104 weeks) at exposure levels of 10, 30 and 50 mg NiSO 4 ·6H 2 O/kg. This treatment produced a statistically significant reduction in body weight of male and female rats, compared to controls, in an exposure-related fashion at 30 and 50 mg/kg/day. An exposure-dependent increase in mortality was observed in female rats. However, the overall study survival rate (males and females) was at least 25 animals per group (compliant with OECD guidelines) in the treated animals. Daily oral administration of nickel sulfate hexahydrate did not produce an exposure-related increase in any common tumor type or an increase in any rare tumors. One tumor type was statistically increased in a nickel sulfate-treated group compared to the study controls (keratoacanthoma in the 10 mg NiSO 4 ·6H 2 O/kg/day males), but there was no exposure-response relationship for this common tumor type. This study achieved sufficient toxicity to reach the Maximum Tolerated Dose (MTD) while maintaining a sufficiently high survival rate to allow evaluation for carcinogenicity. The present study indicated that nickel sulfate hexahydrate does not have the potential to cause carcinogenicity by the oral route of exposure in the Fischer 344 rat. Data from this and other studies demonstrate that inhalation is the only route of exposure that might cause concern for cancer in association with nickel exposures

Effects of maternal exposure to cow´s milk high or low in isoflavones on carcinogen-induced mammary tumorigenesis among rat offspring

DEFF Research Database (Denmark)

Nielsen, Tina Skau; Purup, Stig; Warri, A

2011-01-01

We investigated whether maternal exposure during pregnancy to cow's milk containing endogenous estrogens and insulin like growth factor 1 (IGF-1) and either high or low levels of isoflavones from dietary legumes (HIM and LIM, respectively) affected carcinogen-induced mammary carcinogenesis....... No differences in maternal serum estradiol (P = 0.19) and IGF-1 levels (P = 0.15) at GD 19 or birth weight among the milk and water groups were seen, but estradiol, and IGF-1 levels and birth weight were numerically higher in the LIM than in the HIM group. Puberty onset occurred earlier in the LIM offspring than...... in controls (P = 0.03). Although the high isoflavone content seemed to prevent the effect on circulating estradiol and IGF-1 levels and advanced puberty onset seen in the LIM group, HIM increased DMBA-DNA adducts in the mammary gland and tended to increase mammary tumorigenesis. In contrast, offspring exposed...

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

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

A study of tobacco carcinogenesis XLVIII. Carcinogenicity of N'-nitrosonornicotine in mink (Mustela vison).

Science.gov (United States)

Koppang, N; Rivenson, A; Reith, A; Dahle, H K; Evensen, O; Hoffmann, D

1992-11-01

During tobacco processing and smoking, nicotine and nornicotine give rise to N'-nitrosonornicotine (NNN), a highly abundant, strong carcinogen. NNN is known to exert carcinogenic activity in mice, rats and hamsters. Major target organs for NNN carcinogenicity in the rat are the esophagus and the nasal mucosa, and in the Syrian golden hamster trachea and nasal mucosa. In comparison with the rat, the mink (Mustela vison) has a markedly expanded nasal mucosa. Therefore, we explored in this study whether the mink could serve as a non-rodent model for nasal carcinogenesis using NNN as the carcinogen. Twenty random-bred mink, beginning at the age of 3 weeks, received twice weekly s.c. injections of NNN, a total dose of 11.9 mM per animal over a 38 week period. All of the 19 mink at risk developed malignant tumors of both the respiratory and the olfactory region of the nose within 3.5 years. In most animals the malignant tumors, primarily esthesioneuroepithelioma, invaded the brain. Remarkably, NNN induced no other tumors in the mink. None of the control animals developed nasal tumors nor tumors at other sites during the 3.5 years of the assay. The historical data from the farm did not reveal any spontaneous occurrence of nasal tumors in mink at any age. This study supports the concept that NNN is a proven carcinogen for multiple species of mammals and that the mink can serve as a non-rodent, non-inbred animal model for nasal carcinogenesis, especially since NNN induces only tumors in the nasal cavity in this species and not at other sites, as it does in mice, rats and hamsters.

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.

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.

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

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.

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.

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.

Asian Americans and disproportionate exposure to carcinogenic hazardous air pollutants: A national study.

Science.gov (United States)

Grineski, Sara E; Collins, Timothy W; Morales, Danielle X

2017-07-01

Studies have demonstrated disparate exposures to carcinogenic hazardous air pollutants (HAPs) in neighborhoods with high densities of Black and Hispanic residents in the US. Asians are the fastest growing racial/ethnic group in the US, yet they have been underemphasized in previous studies of environmental health and injustice. This cross-sectional study investigated possible disparities in residential exposure to carcinogenic HAPs among Asian Americans, including Asian American subgroups in the US (including all 50 states and the District of Columbia, n = 71,208 US census tracts) using National Air Toxics Assessment and US Census data. In an unadjusted analysis, Chinese and Korean Americans experience the highest mean cancer risks from HAPs, followed by Blacks. The aggregated Asian category ranks just below Blacks and above Hispanics, in terms of carcinogenic HAP risk. Multivariate models adjusting for socioeconomic status, population density, urban location, and geographic clustering show that an increase in proportion of Asian residents in census tracts is associated with significantly greater cancer risk from HAPs. Neighborhoods with higher proportions (as opposed to lower proportions) of Chinese, Korean, and South Asian residents have significantly greater cancer risk burdens relative to Whites. Tracts with higher concentrations of Asians speaking a non-English language and Asians that are US-born have significantly greater cancer risk burdens. Asian Americans experience substantial residential exposure to carcinogenic HAPs in US census tracts and in the US more generally. Copyright © 2017 Elsevier Ltd. All rights reserved.

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.

Quantification of the carcinogenic effect of polycyclic aromatic hydrocarbons in used engine oil by topical application onto the skin of mice.

Science.gov (United States)

Grimmer, G; Dettbarn, G; Brune, H; Deutsch-Wenzel, R; Misfeld, J

1982-01-01

The purpose of this investigation was to identify the substances mainly responsible for the carcinogenic effect of used engine oil from gasoline engines using topical application as a carcinogen-specific bioassay. This was performed by comparison of the tumorigenic effect of single fractions with that of an unseparated sample of the lubricating oil. The probit analysis of the results shows: 1) The used engine oil, from gasoline-driven automobiles, investigated provoked local tumors after long-term application to the dorsal skin of mice. The incidence of carcinoma depended on the dose of the oil. 2) The fraction of the polycyclic aromatic hydrocarbons (PAH) containing more than three rings accounts for about 70% of the total carcinogenicity in the case of crankcase oil. This fraction constitutes only up to 1.14% by weight of the total oil sample. 3) The content of benzo(a)pyrene (216.8 mg/kg) accounts for 18% of the total carcinogenicity of the used oil. 4) Regarding the reduced carcinogenicity of the oil sample, which was reconstituted from all fractions, it seems possible that some of the carcinogenic substances were lost due to volatility, with evaporation of the solvents from the oil-fractionation processes. 5) Regarding the small effect of the PAH-free fraction, as well as the equal carcinogenic effects of the PAH-fraction (containing more than three rings) and the reconstituted oil sample, no hints for a co-carcinogenic activity were obtained.

Chronic Dermal Toxicity of Epoxy Resins I. Skin Carcinogenic Potency and General Toxicity

Energy Technology Data Exchange (ETDEWEB)

Holland, J.M.

2001-01-16

Epoxy resins are a diverse class of chemicals that differ in structure, physical properties, and, presumably, biological activity. The purpose of these experiments was to compare the chronic dermal toxicity and carcinogenicity of selected commercial epoxy resins and to determine the potential for positive synergistic carcinogenic interactions between different resins. This work is an extension and continuation of a Department of Energy sponsored program to evaluate epoxy resins for potential occupational health risks. The materials examined were chosen on the basis of their interest to the U.S. government. They are representative of the manufacturer's production at the time, and therefore the data are completely valid only for the specific production period. Results of the experimental exposures will be reported in two parts. This report describes the test materials, their chemical and physical characteristics and the experimental design. General (systemic) toxicity will be evaluated and the skin carcinogenicity of the materials compared. A subsequent report will provide morphological descriptions of skin and significant internal pathology induced by the various treatments.

An overview of the report: Correlation between carcinogenic potency and the maximum tolerated dose: Implications for risk assessment

International Nuclear Information System (INIS)

Krewski, D.; Gaylor, D.W.; Soms, A.P.; Szyszkowicz, M.

1993-01-01

Current practice in carcinogen bioassay calls for exposure of experimental animals at doses up to and including the maximum tolerated dose (MTD). Such studies have been used to compute measures of carcinogenic potency such as the TD 50 as well as unit risk factors such as q 1 for predicting low-dose risks. Recent studies have indicated that these measures of carcinogenic potency are highly correlated with the MTD. Carcinogenic potency has also been shown to be correlated with indicators of mutagenicity and toxicity. Correlation of the MTDs for rats and mice implies a corresponding correlation in TD 50 values for these two species. The implications of these results for cancer risk assessment are examined in light of the large variation in potency among chemicals known to induce tumors in rodents. 119 refs., 2 figs., 4 tabs

Heterocyclic amines content of meat and fish cooked by Brazilian methods.

Science.gov (United States)

Iwasaki, Motoki; Kataoka, Hiroyuki; Ishihara, Junko; Takachi, Ribeka; Hamada, Gerson Shigeaki; Sharma, Sangita; Le Marchand, Loïc; Tsugane, Shoichiro

2010-02-01

Heterocyclic amine (HCA) concentrations were measured in meat and fish samples cooked by pan-frying, grilling and churrasco (Brazilian barbecue) to various levels of doneness in accordance with the cooking methods most commonly used in Brazil. HCAs were extracted by the Blue-rayon absorption method and measured by liquid chromatography-mass spectrometry. 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), and 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (4,8-DiMeIQx) were sharply increased in very well-done meats and fish. HCA levels varied somewhat across cooking methods: levels of PhIP (ng/g) in very well-done, non-marinated samples were particularly high for churrasco (31.8 in the exterior of the sample), compared to lower levels for grilled (16.3), and pan-fried beef (0.58). On comparison across foods, chicken contained higher HCA levels than other non-marinated samples. For example, PhIP levels (ng/g) in very well-done pan-fried foods were 34.6 for chicken with the skin, 0.58 for beef, 7.25 for pork, 2.28 for sardines, and 7.37 for salmon cooked with the skin. HCA levels were lower in marinated meats and fish than in non-marinated samples, except for pan-fried salmon. This study provides valuable information which will allow the estimation of dietary HCA exposure using an epidemiologic questionnaire and the investigation of the association of HCA intake with cancer risk in Brazil.

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

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

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...

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

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

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.

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

Arsenic: bioaccessibility from seaweed and rice, dietary exposure calculations and risk assessment.

Science.gov (United States)

Brandon, Esther F A; Janssen, Paul J C M; de Wit-Bos, Lianne

2014-01-01

Arsenic is a metalloid that occurs in food and the environment in different chemical forms. Inorganic arsenic is classified as a class I carcinogen. The inorganic arsenic intake from food and drinking water varies depending on the geographic arsenic background. Non-dietary exposure to arsenic is likely to be of minor importance for the general population within the European Union. In Europe, arsenic in drinking water is on average low, but food products (e.g. rice and seaweed) are imported from all over the world including from regions with naturally high arsenic levels. Therefore, specific populations living in Europe could also have a high exposure to inorganic arsenic due to their consumption pattern. Current risk assessment is based on exposure via drinking water. For a good estimation of the risks of arsenic in food, it is important to investigate if the bioavailability of inorganic arsenic from food is different from drinking water. The present study further explores the issue of European dietary exposure to inorganic arsenic via rice and seaweed and its associated health risks. The bioavailability of inorganic arsenic was measured in in vitro digestion experiments. The data indicate that the bioavailability of inorganic arsenic is similar for rice and seaweed compared with drinking water. The calculated dietary intake for specific European Union populations varied between 0.44 and 4.51 µg kg⁻¹ bw day⁻¹. The margins of exposure between the inorganic intake levels and the BMDL0.5 values as derived by JECFA are low. Decreasing the intake of inorganic arsenic via Hijiki seaweed could be achieved by setting legal limits similar to those set for rice by the Codex Alimentarius Commission in July 2014.

OSHA Confronts Carcinogens in the Workplace as Inflation Fighters Confront OSHA.

Science.gov (United States)

Heller, Ilene

1978-01-01

Discusses the apparently opposing forces of worker safety, as represented by the Occupational Safety and Health Administration (OSHA), and economic inflation spawned by expensive industrial processes needed to limit the emission of carcinogens. (CP)

Policy issues in setting de minimis standards for latent cancer risks of radiation and chemical carcinogens

International Nuclear Information System (INIS)

Spangler, M.

1984-01-01

In the fuel cycles for the development and utilization of alternative energy resources, the risk of latent cancer arises from a number of sources. Included are ionizing radiation and the carcinogenic potential of polluting chemicals present in certain fuels or in materials associated with the construction, operation, maintenance or waste treatment processes of nuclear power, fossil fuels, synfuels, biomass, and other sources of energy. One aspect of developing a carcinogen guideline policy for a consistent and effective regulatory regime to use in dealing with these assorted carcinogenic risks is the setting of de minimis quantitative standards. In this report, 11 policy issues related to the setting of such regulatory standards are identified and a brief commentary is provided. 15 references, 1 table

The utility of the guppy (Poecilia reticulata) and medaka (Oryzias latipes) in evaluation of chemicals for carcinogenicity.

Science.gov (United States)

Kissling, Grace E; Bernheim, Naomi J; Hawkins, William E; Wolfe, Marilyn J; Jokinen, Micheal P; Smith, Cynthia S; Herbert, Ronald A; Boorman, Gary A

2006-07-01

There has been considerable interest in the use of small fish models for detecting potential environmental carcinogens. In this study, both guppies (Poecilia reticulata) and medaka (Oryzias latipes) were exposed in the aquaria water to three known rodent carcinogens for up to 16 months. Nitromethane, which caused mammary gland tumors by inhalation exposure in female rats, harderian gland and lung tumors in male and female mice, and liver tumors in female mice by inhalation, failed to increase tumors in either guppies or medaka. Propanediol, which when given in the feed was a multisite carcinogen in both sexes of rats and mice, caused increased liver tumors in male guppies and male medaka. There was reduced survival in female guppies and no increased tumors in female medaka. 1,2,3-Trichloropropane, which when administered by oral gavage was a multisite carcinogen in both sexes of rats and mice, caused an increased incidence of tumors in the liver of both male and female guppies and medaka and in the gallbladder of male and female medaka. The results of this study demonstrate that for these three chemicals, under these specific exposure conditions, the fish appear less sensitive and have a narrower spectrum of tissues affected than rodents. These results suggest that fish models are of limited utility in screening unknown chemicals for potential carcinogenicity.

Persistence of sister chromatid exchanges and in vitro morphological transformation of Syrian hamster fetal cells by chemical and physical carcinogens

International Nuclear Information System (INIS)

Popescu, N.C.; Amsbaugh, S.C.; DiPaolo, J.A.

1985-01-01

The induction of neoplastic cell transformation is closely associated with DNA alterations which occur shortly after carcinogen exposure. Sister chromatid exchange (SCE) formation is a sensitive indicator of carcinogen-DNA interaction and correlates with the induction of morphological cell transformation. The persistence of lesions generating SCE produced by chemical and physical carcinogens and its relevance to the induction of morphologic transformation was evaluated in coordinated experiments with cultured Syrian hamster fetal cells (HFC). Exponentially growing HFC were exposed for 1 h to benzo[a]pyrene (BP), methyl-methanesulfonate (MMS), cis-platinum (II) diaminedichloride (cis Pt II), N-methyl-N'-nitrosourea (MNU), mitomycin C (MMC), N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), N-acetoxy-2-fluorenyl-acetamide (AcAAF) or u.v. light irradiated. SCE analysis demonstrates that for a period of 48 h after carcinogen exposure, during which time the cells undergo at least four replicative cycles, DNA damage generating SCE induced by all chemical carcinogens either persisted or was partially removed, whereas u.v.-induced lesions were completely removed. An elevated SCE frequency persisted after two additional cell cycles after treatment with BP, AcAAF or MMC without increased cell lethality as compared to other carcinogens whose lesions were completely eliminated during the same period

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.

Studies on carcinogenicity or anticarcinogenicity of isonicotinic acid hydrazide and caffeine by nine-week assay system

International Nuclear Information System (INIS)

Yun, Taik Koo; Oh, Yeong Ram; Kim, Sung Ho

1986-12-01

According to many surveys, cancer is one of the major causes of death in most developed countries and the incidence of cancer appears to be on the increase. Therefore, many studies on detection of carcinogenic or anticarcinogenic agents need urgently. The purpose of this investigation is evaluation the carcinogenic or anticarcinogenic effect of INH and caffeine, which were interpreted as showing either the presence or the absence of a carcinogenic or anticarcinogenic effect, using nine-week assay system. The non-inbred NIH(GP) newborn mice were injected subcutaneously with NIH(400,425, 450 or 480 μg/ head) or caffeine (75 or 100 μg/head) for evaluation of carcinogenicity. Caffeine (1 or 2 mg/ml of drinking water) was administered orally to the mice, which were injected subcutaneously with BP(500μg/head) at new-born, during 6 weeks after weaning for evaluation of anticarcinogenicity. Each group was killed at 9 weeks after the start of exanination. All major organs were examined grossly and histopathologically. Decreased lung adenoma incidence was observed statistically significant in mice fed with caffeine 1 mg(18.8%) or 2 mg(5.1%) per ml of drinking water compared to BP control group (41.3%). However, there was no statistical difference in the incidence of lung and other site tumor between the INH group and the normal control group or between caffeine injection group and normal control group. This result will be contribute to the prevention of cancer from the viewpoint of identifying carcinogenic or anticarcinogenic agents from the environment. (Author)

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....

Assessment of human dietary exposure to arsenic through rice.

Science.gov (United States)

Davis, Matthew A; Signes-Pastor, Antonio J; Argos, Maria; Slaughter, Francis; Pendergrast, Claire; Punshon, Tracy; Gossai, Anala; Ahsan, Habibul; Karagas, Margaret R

2017-05-15

Rice accumulates 10-fold higher inorganic arsenic (i-As), an established human carcinogen, than other grains. This review summarizes epidemiologic studies that examined the association between rice consumption and biomarkers of arsenic exposure. After reviewing the literature we identified 20 studies, among them included 18 observational and 2 human experimental studies that reported on associations between rice consumption and an arsenic biomarker. Among individuals not exposed to contaminated water, rice is a source of i-As exposure - rice consumption has been consistently related to arsenic biomarkers, and the relationship has been clearly demonstrated in experimental studies. Early-life i-As exposure is of particular concern due to its association with lifelong adverse health outcomes. Maternal rice consumption during pregnancy also has been associated with infant toenail total arsenic concentrations indicating that dietary exposure during pregnancy results in fetal exposure. Thus, the collective evidence indicates that rice is an independent source of arsenic exposure in populations around the world and highlights the importance of investigating its affect on health. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Chemical characteristic of PM2.5 emission and inhalational carcinogenic risk of domestic Chinese cooking

International Nuclear Information System (INIS)

Zhang, Nan; Han, Bin; He, Fei; Xu, Jia; Zhao, Ruojie; Zhang, Yujuan; Bai, Zhipeng

2017-01-01

To illustrate chemical characteristic of PM 2.5 emission and assess inhalational carcinogenic risk of domestic Chinese cooking, 5 sets of duplicate cooking samples were collected, using the most used 5 types of oil. The mass abundance of 14 elements, 5 water-soluble ions, organic carbon (OC), elemental carbon (EC) and 11 polycyclic aromatic hydrocarbons (PAHs) were calculated; the signature and diagnostic ratio of cooking in the domestic kitchen were analyzed; and carcinogenic risks of heavy metals and PAHs via inhalation were assessed in two scenarios. The analysis showed that OC was the primary composition in the chemical profile; Na was the most abundant element that might be due to the usage of salt; Cr and Pb, NO 3 − and SO 4 2- , Phe, FL and Pyr were the main heavy metals/water-soluble ions/PAHs, respectively. Phe and FL could be used to separate cooking and stationary sources, while diagnostic ratios of BaA/(BaA + CHR), BaA/CHR, BaP/BghiP and BaP/BeP should be applied with caution, as they were influenced by various cooking conditions. Carcinogenic risks of heavy metals and PAHs were evaluated in two scenarios, simulating the condition of cooking with no ventilation and with the range hood on, respectively. The integrated risk of heavy metals and PAHs was 2.7 × 10 −3 and 5.8 × 10 −6 , respectively, during cooking with no ventilation. While with the usage of range hood, only Cr(VI), As and Ni might induce potential carcinogenic risk. The difference in the chemical abundance in cooking sources found between this and other studies underlined the necessity of constructing locally representative source profiles under real conditions. The comparison of carcinogenic risk suggested that the potentially adverse health effects induced by inorganic compositions from cooking sources should not be ignored. Meanwhile, intervention methods, such as the operation of range hood, should be applied during cooking for health protection. - Highlights: • PM 2

A biological basis for the linear non-threshold dose-response relationship for low-level carcinogen exposure

International Nuclear Information System (INIS)

Albert, R.E.

1981-01-01

This chapter examines low-level dose-response relationships in terms of the two-stage mouse tumorigenesis model. Analyzes the feasibility of the linear non-threshold dose-response model which was first adopted for use in the assessment of cancer risks from ionizing radiation and more recently from chemical carcinogens. Finds that both the interaction of B(a)P with epidermal DNA of the mouse skin and the dose-response relationship for the initiation stage of mouse skin tumorigenesis showed a linear non-threshold dose-response relationship. Concludes that low level exposure to environmental carcinogens has a linear non-threshold dose-response relationship with the carcinogen acting as an initiator and the promoting action being supplied by the factors that are responsible for the background cancer rate in the target tissue

Effects of combined exposure of F344 rats to inhaled Plutonium-239 dioxide and a chemical carcinogen (NNK)

Energy Technology Data Exchange (ETDEWEB)

Lundgren, D.L.; Carlton, W.W. [Purdue Univ., Lafayette, IN (United States); Griffith, W.C. [and others

1995-12-01

Workers in nuclear weapons facilities have a significant potential for exposure to chemical carcinogens and to radiation from external sources or from internally deposited radionuclides such as {sup 239}Pu. Although the carcinogenic effects of inhaled {sup 239}Pu and many chemicals have been studied individually, very little information is available on their combined effects. One chemical carcinogen that workers could be exposed to via tobacco smoke is the tobacco-specific nitrosamine 4-(N-methyl-n-nitrosamino)-1-(3-pyridyl)-1(3-pyridyl)-1-butanone (NNK), a product of tobacco curing and the pyrolysis of nicotine in tobacco. NNK causes lung tumors in rats, regardless of the route of administration and to a lesser extent liver, nasal, and pancreatic tumors. From the results presented, it can be concluded that exposure to a chemical carcinogen (NNK) in combination with {alpha}-particle radiation from inhaled {sup 239}PuO{sub 2} acts in, at best, an additive manner in inducing lung cancer in rats.

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.

Role of α-Dicarbonyl Compounds in the Inhibition Effect of Reducing Sugars on the Formation of 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine.

Science.gov (United States)

Han, Zhonghui; Liu, Bing; Niu, Zhiyan; Zhang, Yan; Gao, Jianxin; Shi, Lei; Wang, Shujun; Wang, Shuo

2017-11-22

The effect of reducing sugars on formation of PhIP in fried pork was investigated, and the underlying mechanisms were revealed by studying the reaction pathways between α-dicarbonyl compounds (α-DCs) and PhIP. The addition of reducing sugars (such as glucose) greatly reduced the amount of PhIP in fried pork from 15.5 ng/g to less than 1.0 ng/g. The amount of PhIP decreased significantly with an increasing level of added α-DCs in model systems. Similarly, the addition of methylglyoxal (MGO) decreased significantly the levels of phenylalanine (Phe) and creatinine (Crn) but increased significantly the level of phenylacetaldehyde (PEA). 2-Amino-1-methyl-5-(2-oxopropylidene)-imidazol-4-one and N-(1-methyl-4-oxoimidazolidin-2-ylidene) amino propionic acids were identified in MGO/Crn and MGO/Crn/Phe model systems and fried pork with glucose. These results revealed that the degradation products of reducing sugars-α-DCs-play an important role in inhibiting formation of PhIP by reacting with key precursors of PhIP and itself.

SYN-JEM : A Quantitative Job-Exposure Matrix for Five Lung Carcinogens

NARCIS (Netherlands)

Peters, Susan; Vermeulen, Roel; Portengen, Lützen; Olsson, Ann C.; Kendzia, Benjamin; Vincent, Raymond; Savary, Barbara; LavouCrossed Sign, Jcrossed D.Signrôme; Cavallo, Domenico; Cattaneo, Andrea; Mirabelli, Dario; Plato, Nils; Fevotte, Joelle; Pesch, Beate; Brüning, Thomas; Straif, Kurt; Kromhout, Hans

2016-01-01

Objective: The use of measurement data in occupational exposure assessment allows more quantitative analyses of possible exposure-response relations. We describe a quantitative exposure assessment approach for five lung carcinogens (i.e. asbestos, chromium-VI, nickel, polycyclic aromatic

Arsenic and lead in foods: a potential threat to human health in Bangladesh.

Science.gov (United States)

Islam, Md Saiful; Ahmed, Md Kawser; Habibullah-Al-Mamun, Md; Islam, Kazi Nazrul; Ibrahim, Md; Masunaga, Shigeki

2014-01-01

The non-carcinogenic and carcinogenic risk of arsenic and lead to adults and children via daily dietary intake of food composites in Bangladesh was estimated. The target hazard quotients (THQs), hazard index (HI) and target carcinogenic risk (TR) were calculated to evaluate the non-carcinogenic and carcinogenic health risk from arsenic and lead. Most of the individual food composites contain a considerable amount of arsenic and lead. The highest mean concentrations of arsenic were found in cereals (0.254 mg kg⁻¹ fw) and vegetables (0.250 mg kg⁻¹ fw), and lead in vegetables (0.714 mg kg⁻¹ fw) and fish (0.326 mg kg⁻¹ fw). The results showed the highest THQs of arsenic in cereals and lead in vegetables for both adults and children which exceeded the safe limit (> 1) indicating that cereals and vegetables are the main food items contributing to the potential health risk. The estimated TR from ingesting dietary arsenic and lead from most of the foods exceeded 10⁻⁶, indicating carcinogenic risks for all adult people of the study area.

Assessment of Carcinogenicity of di(2-ethylhexyl) phthalate in a short-term assay using Xpa(-/-) and Xpa(-/-)/p53(+/-) mice

DEFF Research Database (Denmark)

Mortensen, Alicja; Bertram, Margareta; Aarup, V.

2002-01-01

The potential of Xpa(-/-) and Xpa(-/-)/p53(+/-) mice for short-term carcinogenicity assays was evaluated with di(2-ethylhexyl)phthalate (DEHP). Groups of 15 male and female Xpa(-/-) mice, received diets containing 0, 1,500, 3, 000, or 6,000 ppm DEHP, and wild-type (WT) and Xpa(-/-)/p53(+/-) mice 0...... 7). The negative carcinogenic response to DEHP and the positive response to p-cresidine support the expected sensitivity to genotoxic carcinogens in these transgenic models....

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.

Production of carcinogenic acetaldehyde by Candida albicans from patients with potentially malignant oral mucosal disorders.

Science.gov (United States)

Gainza-Cirauqui, M L; Nieminen, M T; Novak Frazer, L; Aguirre-Urizar, J M; Moragues, M D; Rautemaa, R

2013-03-01

Production of carcinogenic acetaldehyde by Candida has been suggested to contribute to epithelial dysplasia and oral carcinogenesis. Oral lichen planus (OLP), oral lichenoid lesion (OLL) and oral leukoplakia (OL) are potentially carcinogenic oral diseases where colonisation by Candida is common, but acetaldehyde production by Candida has not been studied. Acetaldehyde production in ethanol (11 mM), glucose (100 mM), ethanol-glucose (11 mM and 100 mM) or red wine (1200 mM ethanol) incubation by Candida albicans from patients with OLL (n = 6), OLP (n = 16), OL (n = 6) and controls (n = 6) was measured by gas chromatography. Participants completed a questionnaire regarding their smoking habits and alcohol consumption. All Candida albicans isolates produced potentially carcinogenic levels of acetaldehyde (>100 μM) in all incubations containing ethanol. The control group isolates produced the highest acetaldehyde levels. Isolates from smokers produced more acetaldehyde in all incubations than those from non-smokers. The difference was significant in ethanol-glucose incubation. Isolates from patients who were both smokers and drinkers produced the highest amounts when incubated in ethanol, ethanol-glucose and wine. Candida albicans isolated from potentially carcinogenic oral diseases can produce mutagenic amounts of acetaldehyde. Cigarette smoking and alcohol consumption may favour adaptational changes resulting in the upregulation of candidal acetaldehyde metabolism. © 2012 John Wiley & Sons A/S. All rights reserved.

SYN-JEM : A Quantitative Job-Exposure Matrix for Five Lung Carcinogens

NARCIS (Netherlands)

Peters, Susan; Vermeulen, Roel; Portengen, L??tzen; Olsson, Ann; Kendzia, Benjamin; Vincent, Raymond; Savary, Barbara; LavouCrossed Sign, Jcrossed D Signr??me; Cavallo, Domenico; Cattaneo, Andrea; Mirabelli, Dario; Plato, Nils; Fevotte, Joelle; Pesch, Beate; Br??ning, Thomas; Straif, Kurt; Kromhout, Hans

2016-01-01

OBJECTIVE The use of measurement data in occupational exposure assessment allows more quantitative analyses of possible exposure-response relations. We describe a quantitative exposure assessment approach for five lung carcinogens (i.e. asbestos, chromium-VI, nickel, polycyclic aromatic hydrocarbons

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

Aldo-keto reductase family 1 B10 protein detoxifies dietary and lipid-derived alpha, beta-unsaturated carbonyls at physiological levels

International Nuclear Information System (INIS)

Zhong, Linlin; Liu, Ziwen; Yan, Ruilan; Johnson, Stephen; Zhao, Yupei; Fang, Xiubin; Cao, Deliang

2009-01-01

Alpha, beta-unsaturated carbonyls are highly reactive mutagens and carcinogens to which humans are exposed on a daily basis. This study demonstrates that aldo-keto reductase family 1 member B10 (AKR1B10) is a critical protein in detoxifying dietary and lipid-derived unsaturated carbonyls. Purified AKR1B10 recombinant protein efficiently catalyzed the reduction to less toxic alcohol forms of crotonaldehyde at 0.90 μM, 4-hydroxynonenal (HNE) at 0.10 μM, trans-2-hexanal at 0.10 μM, and trans-2,4-hexadienal at 0.05 μM, the concentrations at or lower than physiological exposures. Ectopically expressed AKR1B10 in 293T cells eliminated immediately HNE at 1 (subtoxic) or 5 μM (toxic) by converting to 1,4-dihydroxynonene, protecting the cells from HNE toxicity. AKR1B10 protein also showed strong enzymatic activity toward glutathione-conjugated carbonyls. Taken together, our study results suggest that AKR1B10 specifically expressed in the intestine is physiologically important in protecting the host cell against dietary and lipid-derived cytotoxic carbonyls.

Dietary N-nitroso compounds and risk of colorectal cancer: a case-control study in Newfoundland and Labrador and Ontario, Canada

Science.gov (United States)

Zhu, Yun; Wang, Peizhong Peter; Zhao, Jing; Green, Roger; Sun, Zhuoyu; Roebothan, Barbara; Squires, Josh; Buehler, Sharon; Dicks, Elizabeth; Zhao, Jinhui; Cotterchio, Michelle; Campbell, Peter T.; Jain, Meera; Parfrey, Patrick S.; Mclaughlin, John R.

2015-01-01

Several N-nitroso compounds (NOC) have been shown to be carcinogenic in a variety of laboratory animals, but evidence of their carcinogenicity in humans is lacking. We aimed to examine the association between NOC intake and colorectal cancer (CRC) risk and possible effect modification by vitamins C and E and protein in a large case-control study carried out in Newfoundland and Labrador, and Ontario, Canada. A total of 1760 case patients with pathologically confirmed adenocarcinoma and 2481 population controls were asked to complete a self-administered FFQ to evaluate their dietary intakes 1 year before diagnosis (for cases) or interview (for controls). Adjusted OR and 95% CI were calculated across the quintiles of NOC (measured by N-nitrosodimethylamine (NDMA)) intake and relevant food items using unconditional logistic regression. NDMA intake was found to be associated with a higher risk of CRC (highest vs lowest quintiles, OR: 1.42; 95% CI: 1.03,1.96; p-trend=0.005), specifically for rectal carcinoma (OR: 1.61; 95% CI: 1.11,2.35; p-trend=0.01). CRC risk also increased with the consumption of NDMA-containing meats when the highest tertile was compared with the lowest tertile (OR: 1.47; 95% CI: 1.03,2.10; p-trend=0.20). There was evidence of effect modification between dietary vitamin E and NDMA. Individuals with high NDMA and low vitamin E intakes had a significantly increased risk than those with both low NDMA and vitamin E intakes (OR:3.01; 95% CI: 1.43,6.51; p-interaction=0.017). The present results support the hypothesis that NOC intake may be positively associated with CRC risk in humans. Vitamin E, which inhibits nitrosation, could modify the effect of NDMA on CRC risk. PMID:24160559

Clear Evidence of Carcinogenic Activity by a Whole-Leaf Extract of Aloe barbadensis Miller (Aloe vera) in F344/N Rats

Science.gov (United States)

Boudreau, Mary D.

2013-01-01

Aloe barbadensis Miller (Aloe vera) is an herbal remedy promoted to treat a variety of illnesses; however, only limited data are available on the safety of this dietary supplement. Drinking water exposure of F344/N rats and B6C3F1 mice to an Aloe vera whole-leaf extract (1, 2, and 3%) for 13 weeks resulted in goblet cell hyperplasia of the large intestine in both species. Based upon this observation, 2-year drinking water studies were conducted to assess the carcinogenic potential of an Aloe vera whole-leaf extract when administered to F344/N rats (48 per sex per group) at 0.5, 1, and 1.5%, and B6C3F1 mice (48 per sex per group) at 1, 2, and 3%. Compared with controls, survival was decreased in the 1.5% dose group of female rats. Treatment-related neoplasms and nonneoplastic lesions in both species were confined primarily to the large intestine. Incidences of adenomas and/or carcinomas of the ileo-cecal and cecal-colic junction, cecum, and ascending and transverse colon were significantly higher than controls in male and female rats in the 1 and 1.5% dose groups. There were no neoplasms of the large intestine in mice or in the 0 or 0.5% dose groups of rats. Increased incidences of mucosa hyperplasia of the large intestine were observed in F344/N rats, and increased incidences of goblet cell hyperplasia of the large intestine occurred in B6C3F1 mice. These results indicate that Aloe vera whole-leaf extract is an intestinal irritant in F344/N rats and B6C3F1 mice and a carcinogen of the large intestine in F344/N rats. PMID:22968693

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.

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

Lesions induced in rodent pancreas by azaserine and other pancreatic carcinogens

Energy Technology Data Exchange (ETDEWEB)

Longnecker, D.S.

1984-06-01

Focal proliferative changes in the acinar cells of the pancreas of rats have been induced by several systemically administered carcinogens including azaserine, N-nitrosobis(2-oxopropyl)amine, N-nitroso(2-hydroxypropyl) (2-oxopropyl)amine, and Ndelta-(N-methyl-N-nitrosocarbamoyl)-L-ornithine (MNCO). Foci, nodules, and adenomas induced by these carcinogens are usually made up of atypical-appearing acinar cells that maintain a high degree of differentiation, but a minority of these lesions exhibit anaplastic cellular changes that suggest the development of malignant potential. Such anaplasia may occupy the whole of smaller lesions or may occur as a secondary focal change within larger nodules or adenomas. Many foci and nodules per pancreas have been induced by single or multiple exposures to these known genotoxic carcinogens, but relatively few of them develop into carcinomas. Azaserine and MNCO have induced acinar cell carcinomas in rats. Those induced by azaserine have exhibited a broad spectrum of histologic variants, including ductlike, cystic and undifferentiated patterns. Higher doses of MNCO have induced a second pattern of change in the pancreatic lobules of rats, which includes cystic and tubular ductlike structures that have been called cystic and tubular ductal complexes. MNCO has also induced focal acinar cell lesions, cystic and tubular ductal complexes, and adenocarcinomas in the pancreas of Syrian golden hamsters. In this species, ductal complexes are much more numerous than are proliferative lesions of acinar cells, and the histologic appearance of the carcinomas is ductlike. Hyperplasia and atypical changes were also seen in the epithelium of the intralobular ducts of hamsters. 20 references, 5 figures, 1 table.

FTIR analysis and evaluation of carcinogenic and mutagenic risks of nitro-polycyclic aromatic hydrocarbons in PM1.0.

Science.gov (United States)

Schneider, Ismael Luís; Teixeira, Elba Calesso; Agudelo-Castañeda, Dayana Milena; Silva E Silva, Gabriel; Balzaretti, Naira; Braga, Marcel Ferreira; Oliveira, Luís Felipe Silva

2016-01-15

Nitro-polycyclic aromatic hydrocarbons (NPAHs) represent a group of organic compounds of significant interest due to their presence in airborne particulates of urban centers, wide distribution in the environment, and mutagenic and carcinogenic properties. These compounds, associated with atmospheric particles of size PM1.0) using infrared spectrometry. Carcinogenic and mutagenic risks of the studied NPAHs associated with PM1.0 samples were also determined for two sampling sites: Canoas and Sapucaia do Sul. The results showed that NPAH standard spectra can effectively identify NPAHs in PM1.0 samples. The transmittance and emissivity sample spectra showed broader bands and lower relative intensity than the standard NPAH spectra. The carcinogenic risk and the total mutagenic risk were calculated using the toxic equivalent factors and mutagenic potency factors, respectively. Canoas showed the highest total carcinogenic risk, while Sapucaia do Sul had the highest mutagenic risk. The seasonal analysis suggested that in the study area the ambient air is more toxic during the cold periods. These findings might of significant importance for the decision and policy making authorities.

Analysis of mutagenic and carcinogenic risks: nitrates, nitrites, N-Nitroso compounds. Comparison with radioactive risks

International Nuclear Information System (INIS)

Bittel, R.

1987-07-01

This report comes within the scope of the general studies on mutagenic and carcinogenic agents other than ionizing radiations. Through feeding, way of life and working activities, man is exposed to genotoxic risks of N-nitroso compounds (NNC). In spite of differences in the molecular modes of action, there exists some analogy between the effects of radiation exposures and those of NNC: DNA is the target in either instance. Unlike radiations, NNC are alkylating agents. The whole activation process of carcinogens arises from mechanisms leading to DNA repair [fr

Participation of IPEN in the international program of information about occupational exposure to carcinogen risks

International Nuclear Information System (INIS)

Osores, Jose; Gonzales, Susana

2014-01-01

During 2014, the Peruvian Nuclear Energy Institute participated in the mapping of risks to carcinogens due to occupational exposure for our country through CAREX program because all radioactive substances are considered by the International Agency for Research Cancer as type 1 carcinogens (high risk) and the presence of these substances in the work environment are unknown to professionals from other institutions. This occasion allowed the incorporation of Natural Occurring Radioactive Materials (NORM) as indicators in all work activities that were not considered by the Energy and Mining Sector. (authors).

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/ ).

Chemical characteristic of PM2.5 emission and inhalational carcinogenic risk of domestic Chinese cooking.

Science.gov (United States)

Zhang, Nan; Han, Bin; He, Fei; Xu, Jia; Zhao, Ruojie; Zhang, Yujuan; Bai, Zhipeng

2017-08-01

To illustrate chemical characteristic of PM 2.5 emission and assess inhalational carcinogenic risk of domestic Chinese cooking, 5 sets of duplicate cooking samples were collected, using the most used 5 types of oil. The mass abundance of 14 elements, 5 water-soluble ions, organic carbon (OC), elemental carbon (EC) and 11 polycyclic aromatic hydrocarbons (PAHs) were calculated; the signature and diagnostic ratio of cooking in the domestic kitchen were analyzed; and carcinogenic risks of heavy metals and PAHs via inhalation were assessed in two scenarios. The analysis showed that OC was the primary composition in the chemical profile; Na was the most abundant element that might be due to the usage of salt; Cr and Pb, NO 3 - and SO 4 2- , Phe, FL and Pyr were the main heavy metals/water-soluble ions/PAHs, respectively. Phe and FL could be used to separate cooking and stationary sources, while diagnostic ratios of BaA/(BaA + CHR), BaA/CHR, BaP/BghiP and BaP/BeP should be applied with caution, as they were influenced by various cooking conditions. Carcinogenic risks of heavy metals and PAHs were evaluated in two scenarios, simulating the condition of cooking with no ventilation and with the range hood on, respectively. The integrated risk of heavy metals and PAHs was 2.7 × 10 -3 and 5.8 × 10 -6 , respectively, during cooking with no ventilation. While with the usage of range hood, only Cr(VI), As and Ni might induce potential carcinogenic risk. The difference in the chemical abundance in cooking sources found between this and other studies underlined the necessity of constructing locally representative source profiles under real conditions. The comparison of carcinogenic risk suggested that the potentially adverse health effects induced by inorganic compositions from cooking sources should not be ignored. Meanwhile, intervention methods, such as the operation of range hood, should be applied during cooking for health protection. Copyright © 2017 Elsevier Ltd

Meat consumption, Cooking Practices, Meat Mutagens and Risk of Prostate Cancer

Science.gov (United States)

John, Esther M.; Stern, Mariana C.; Sinha, Rashmi; Koo, Jocelyn

2012-01-01

Consumption of red meat, particularly well done meat, has been associated with increased prostate cancer risk. High temperature cooking methods such as grilling and barbequeing may produce heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs) which are known carcinogens. We assessed the association with meat consumption and estimated HCA and PAH exposure in a population-based case-control study of prostate cancer. Newly diagnosed cases aged 40–79 years (531 advanced cases, 195 localized cases) and 527 controls were asked about dietary intake, including usual meat cooking methods and doneness levels. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariate logistic regression. For advanced prostate cancer, but not localized disease, increased risks were associated with higher consumption of hamburgers (OR=1.79. CI=1.10–2.92), processed meat (OR=1.57, CI=1.04, 2.36), grilled red meat (OR=1.63, CI=0.99–2.68), and well done red meat (OR=1.52, CI=0.93–2.46), and intermediate intake of 2-amino-1-methyl1-6-phenylimidazo[4,5-b]pyridine (PhIP) (quartile 2 vs. 1: OR=1.41, CI=0.98–2.01; quartile 3 vs. 1: OR=1.42, CI=0.98–2.04), but not for higher intake. White meat consumption was not associated with prostate cancer. These findings provide further evidence that consumption of processed meat and red meat cooked at high temperature is associated with increased risk of advanced, but not localized prostate cancer. PMID:21526454

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.

Daily dietary intake

International Nuclear Information System (INIS)

Dang, H.S.

1998-01-01

As part of study on ''Reference Asian Man'' to strengthen radiation protection, the data on the dietary consumption patterns of the Asian region were collected. Eight provided dietary data - Bangladesh, China, India, Indonesia, Japan, Pakistan, Philippines, and Viet Nam. Whereas the dietary information from Bangladesh, Indonesia, Pakistan and Viet Nam are preliminary in nature, the dietary information from China, India, Japan and Philippines, on the other hand, is quite substantial. The population of the countries from which sufficient dietary data are available represents more than 2/3 of the population of the Asian region. The details of the individual data available on dietary parameters from different Asian countries are listed below

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...

AI AND SAR APPROACHES FOR PREDICTING CHEMICAL CARCINOGENICITY: SURVEY AND STATUS REPORT

Science.gov (United States)

A wide variety of artificial intelligence (AI) and structure-activity relationship (SAR approaches have been applied to tackling the general problem of predicting rodent chemical carcinogenicity. Given the diversity of chemical structures and mechanisms relative to this endpoin...

Polybrominated diphenyl ethers: occurrence, dietary exposure, and toxicology.

Science.gov (United States)

Darnerud, P O; Eriksen, G S; Jóhannesson, T; Larsen, P B; Viluksela, M

2001-03-01

Polybrominated diphenyl ethers (PBDEs) are used as flame retardants in plastics (concentration, 5--30%) and in textile coatings. Commercial products consist predominantly of penta-, octa-, and decabromodiphenyl ether mixtures, and global PBDE production is about 40,000 tons per year. PBDEs are bioaccumulated and biomagnified in the environment, and comparatively high levels are often found in aquatic biotopes from different parts of the world. During the mid-1970--1980s there was a substantial increase in the PBDE levels with time in both sediments and aquatic biota, whereas the latest Swedish data (pike and guillemot egg) may indicate that levels are at steady state or are decreasing. However, exponentially increasing PBDE levels have been observed in mother's milk during 1972--1997. Based on levels in food from 1999, the dietary intake of PBDE in Sweden has been estimated to be 0.05 microg per day. Characteristic end points of animal toxicity are hepatotoxicity, embryotoxicity, and thyroid effects as well as maternal toxicity during gestation. Recently, behavioral effects have been observed in mice on administration of PBDEs during a critical period after birth. Based on the critical effects reported in available studies, we consider the lowest-observed-adverse-effect level (LOAEL) value of the PBDE group to be 1 mg/kg/day (primarily based on effects of pentaBDEs). In conclusion, with the scientific knowledge of today and based on Nordic intake data, the possible consumer health risk from PBDEs appears limited, as a factor of over 10(6) separates the estimated present mean dietary intake from the suggested LOAEL value. However, the presence of many and important data gaps, including those in carcinogenicity, reproduction, and developmental toxicity, as well as additional routes of exposure, make this conclusion only preliminary. Moreover, the time trend of PBDEs in human breast milk is alarming for the future.

A prospective investigation of fish, meat and cooking-related carcinogens with endometrial cancer incidence.

Science.gov (United States)

Arem, H; Gunter, M J; Cross, A J; Hollenbeck, A R; Sinha, R

2013-08-06

There are limited prospective studies of fish and meat intakes with risk of endometrial cancer and findings are inconsistent. We studied associations between fish and meat intakes and endometrial cancer incidence in the large, prospective National Institutes of Health-AARP Diet and Health Study. Intakes of meat mutagens 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) and benzo(a)pyrene (BaP) were also calculated. We used Cox proportional hazards regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). We observed no associations with endometrial cancer risk comparing the highest to lowest intake quintiles of red (HR=0.91, 95% CI 0.77-1.08), white (0.98, 0.83-1.17), processed meats (1.02, 0.86-1.21) and fish (1.10, 95% CI 0.93-1.29). We also found no associations between meat mutagen intakes and endometrial cancer. Our findings do not support an association between meat or fish intakes or meat mutagens and endometrial cancer.

Dietary risk assessment of pesticides from vegetables and drinking water in gardening areas in Burkina Faso.

Science.gov (United States)

Lehmann, Edouard; Turrero, Nuria; Kolia, Marius; Konaté, Yacouba; de Alencastro, Luiz Felippe

2017-12-01

Vegetables and water samples have been collected around the lake of Loumbila in Burkina Faso. Pesticides residues in food commodities were analyzed using a modified QuEChERS extraction method prior analysis on GC-MS and UPLC-MS/MS of 31 pesticides. Maximum Residue Limits (MRLs) were exceeded in 36% of the samples for seven pesticides: acetamiprid, carbofuran, chlorpyrifos, lambda-cyhalothrin, dieldrin, imidacloprid and profenofos. Exceedance of MRLs suggests a risk for the consumers and limits the opportunities of exportation. In order to define estimated daily intake, dietary surveys were conducted on 126 gardeners using a 24hours recall method. Single pesticide and cumulative exposure risks were assessed for children and adults. Risk was identified for: chlorpyrifos and lambda-cyhalothrin in acute and chronic exposure scenarios. Hazardous chronic exposure to the endocrine disruptor and probable carcinogen dieldrin was also detected. In the studied population, cumulative dietary exposure presented a risk (acute and chronic) for children and adults in respectively >17% and 4% of the cases when considering the worst case scenarios. Processing factor largely influenced the risk of occurrence suggesting that simple washing of vegetables with water considerably reduced the risk of hazardous exposure. Copyright © 2017 Elsevier B.V. All rights reserved.

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...

TLR2 Controls Intestinal Carcinogen Detoxication by CYP1A1

DEFF Research Database (Denmark)

Do, Khoa; Fink, Lisbeth Nielsen; Jensen, Thomas Elbenhardt

2012-01-01

of ligands for TLR2 of bacterial origin seems to be crucial for detoxication of luminal carcinogens by CYP1A1 in the intestine. This unprecedented finding indicates a complex interplay between the immune system of the host and intestinal bacteria with detoxication mechanisms. This highlights the relevance...

Determinants of dietary supplement use - healthy individuals use dietary supplements

DEFF Research Database (Denmark)

Kofoed, Christina L F; Christensen, Jane; Dragsted, Lars Ove

2015-01-01

influence the use of dietary supplements. Only few studies investigating the use of dietary supplements have been conducted in the Danish population. The present cross-sectional study is based on 54 948 Danes, aged 50-64 years, who completed self-administrated questionnaires on diet, dietary supplements...... and lifestyle between 1993 and 1997. A health index including smoking, physical activity, alcohol and diet, and a metabolic risk index including waist circumference, urinary glucose and measured hypertension were constructed. Logistic regression was used to investigate these determinants in relation...... to the intake of dietary supplements. We found that 71 % of the participants were dietary supplement users; female sex, older age groups and higher educated participants were more likely to be users of any dietary supplements. One additional point in the health index was associated with 19, 16 and 9 % higher...

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

Cancer Chemoprevention by Traditional Chinese Herbal Medicine and Dietary Phytochemicals: Targeting Nrf2-Mediated Oxidative Stress/Anti-Inflammatory Responses, Epigenetics, and Cancer Stem Cells

Directory of Open Access Journals (Sweden)

Jong Hun Lee

2013-01-01

Full Text Available Excessive oxidative stress induced by reactive oxygen species (ROS, reactive nitrogen species (RNS, and reactive metabolites of carcinogens alters cellular homeostasis, leading to genetic/epigenetic changes, genomic instability, neoplastic transformation, and cancer initiation/progression. As a protective mechanism against oxidative stress, antioxidant/detoxifying enzymes reduce these reactive species and protect normal cells from endo-/exogenous oxidative damage. The transcription factor nuclear factor-erythroid 2 p45 (NF-E2-related factor 2 (Nrf2, a master regulator of the antioxidative stress response, plays a critical role in the expression of many cytoprotective enzymes, including NAD(PH:quinine oxidoreductase (NQO1, heme oxygenase-1 (HO-1, UDP-glucuronosyltransferase (UGT, and glutathione S-transferase (GST. Recent studies demonstrated that many dietary phytochemicals derived from various vegetables, fruits, spices, and herbal medicines induce Nrf2-mediated antioxidant/detoxifying enzymes, restore aberrant epigenetic alterations, and eliminate cancer stem cells (CSCs. The Nrf2-mediated antioxidant response prevents many age-related diseases, including cancer. Owing to their fundamental contribution to carcinogenesis, epigenetic modifications and CSCs are novel targets of dietary phytochemicals and traditional Chinese herbal medicine (TCHM. In this review, we summarize cancer chemoprevention by dietary phytochemicals, including TCHM, which have great potential as a safer and more effective strategy for preventing cancer.

Research results from inquiries into the carcinogenic effects of surface active agents. On the non-hazardous nature of ABS

Energy Technology Data Exchange (ETDEWEB)

Toyama, Shinichi

1963-03-15

Although the trial-production alkylbenzene used behaved atypically and so is presumed to contain complex carcinogenic hydrocarbon-like impurity by-products, commercially available alkylbenzenes generally did not possess carcinogenic properties. These substances used in alkylbenzene sulfonate production have very small promotive characteristics comparable to croton oil. However, alkylbenzene sulfonate demonstrated no cancer producing properties. (DT)

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

Genotoxicity and carcinogenicity of diesel soot and oil shale dust, two markedly different particles with associated organic content

International Nuclear Information System (INIS)

Mauderly, J.L.; Barr, E.B.; Bechtold, W.E.

1987-01-01

Levels of DNA adducts in lungs of rats were measured by 32 P postlabeling techniques after 240-mo exposure to either diesel exhaust or oil shale dusts. Preliminary results suggest that whole-lung adduct levels from chronic inhalation exposures are not predictive for carcinogenicity. Lung tumors were observed in animals exposed to diesel exhaust. Carcinogenicity was correlated to the mutagenicity of extracts and severity of epithelial proliferation

Evaluation of carcinogenic risk to public health of the republic of Khakassia associated with consumption of drinking water

Directory of Open Access Journals (Sweden)

E.A. Pivovarov

2016-09-01

Full Text Available During the observation period for 2011–2015 in the Republic of Khakassia it has been revealed that 63.2 % of samples of drinking water contain the excess of А α due to natural radionuclides 234 U, 238 U. Within the limits of MPC the carcinogenic hazardous substances: cadmium, lead, arsenic, beryllium, chromium have been detected. Individual risks of occurrence of stochastic effects in the form of malignant tumors, caused by natural radionuclides in drinking water in different administrative territories of the Republic, vary in the range of 3.14–7.81•10 –6 cases/year; collective risks 0.013–0.288 cases/year on the corresponding amount of population. Individual cancer risks are determined by the content of carcinogenic chemicals in drinking water, in different administrative territories of the Republic it varies in the range between 5.29•10 –5 – 1.04•10 –4 cases/year; collective risks of 0.88–2.704 event/year on the corresponding amount of population. The total population carcinogenic risks caused by content of carcinogenic chemicals and PRN in drinking water, for the period of observation were as follows: Altaisky (2.903 at 26.000 of population, Beysky (1.123 at 18.500 of population, Bogradsky (0,98 at 15,000 of population, Shirinsky (2.63 at 27100 of population, Ordzhonikidzevsky (1.178 at 11900 of population, and Ust-Abakansky (2.79 at 41100 of population. The contribution of drinking water into primary ontological morbidity of population in administrative territories of the Republic was equaled to 0.5–1 %. Therefore, currently, the events aimed at reducing the carcinogenic risks caused by drinking water are not required. At the same time, due to the high seismic activity in the Republic for the last five years, the laboratory monitoring of drinking water on indicators of radiation safety and the evaluation of the carcinogenic risks continues in the prescribed amount.

Determinants of dietary supplement use--healthy individuals use dietary supplements.

Science.gov (United States)

Kofoed, Christina L F; Christensen, Jane; Dragsted, Lars O; Tjønneland, Anne; Roswall, Nina

2015-06-28

The prevalence of dietary supplement use varies largely among populations, and previous studies have indicated that it is high in the Danish population compared with other European countries. The diversity in supplement use across countries indicates that cultural and environmental factors could influence the use of dietary supplements. Only few studies investigating the use of dietary supplements have been conducted in the Danish population. The present cross-sectional study is based on 54,948 Danes, aged 50-64 years, who completed self-administrated questionnaires on diet, dietary supplements and lifestyle between 1993 and 1997. A health index including smoking, physical activity, alcohol and diet, and a metabolic risk index including waist circumference, urinary glucose and measured hypertension were constructed. Logistic regression was used to investigate these determinants in relation to the intake of dietary supplements. We found that 71 % of the participants were dietary supplement users; female sex, older age groups and higher educated participants were more likely to be users of any dietary supplements. One additional point in the health index was associated with 19, 16 and 9 % higher likelihood of being user of any, more common and less common supplements, respectively. In the metabolic risk index, one additional point was associated with 17 and 16 % lower likelihood of being user of any supplement and more common supplements, respectively. No significant association was found for less common supplement use. In conclusion, those with the healthiest lifestyle were more likely to use dietary supplements. Thus, lifestyle and dietary composition should be considered as confounders on supplement use and health outcomes.

QSAR pre-screen of 70,983 substances for genotoxic carcinogenicity, mutagenicity and developmental toxicity in the EU FP7 project ChemScreen

DEFF Research Database (Denmark)

Wedebye, Eva Bay; Dybdahl, Marianne; Nikolov, Nikolai Georgiev

2014-01-01

be performed in REACH on known genotoxic carcinogens or germ cell mutagens with appropriate risk management measures implemented, a QSAR pre-screen for genotoxic carcinogenicity, germ cell mutagenicity and (limited) developmental toxicity was included in the project. Predictions for estrogenic and anti...... algorithms were applied to combine the predictions from the individual models to reach overall predictions for genotoxic carcinogenicity, germ cell mutagenicity and developmental toxicity. Furthermore, the full list of REACH pre-registered substances (143,835) was searched for substances containing certain...

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...

Temporal aspects of tumorigenic response to individual and mixed carcinogens. Comprehensive progress report, June 1, 1975--May 31, 1978. [Mouse skin, rats, hamsters

Energy Technology Data Exchange (ETDEWEB)

Albert, R.E.; Burns, F.J.; Altshuler, B.

1978-02-01

The research proposed here is designed to obtain a better understanding of the temporal kinetics of tumor induction when one or more carcinogens are present simultaneously or sequentially for prolonged periods of time. Studies done to date under this contract have shown that carcinogenesis in mouse skin by polycyclic aromatic hydrocarbon carcinogens is consistent with the induction of dependent and autonomous cell transformations by the carcinogen followed by the conversion of autonomous tumor cells into malignancies at a rate which is determined by the level of carcinogen exposure. Dependent cell transformations remain latent in the skin unless expressed by a promoting agent. Dependent neoplasia appears to follow one-hit kinetics while malignancy is a multihit endpoint. Dose-related and time-related aspects of tumor induction are separable in the initiation-promotion system of mouse skin which along with rat skin and hamster lung is being used as a model for testing hypotheses. Results to date provide the basis for a new interpretation of the linear non-threshold extrapolation model. The broad aim of the study is to provide a basis or rationale for estimating risks associated with prolonged exposures to carcinogens found in the environment and to predict how different tissues and species respond to the same carcinogens.

Destruction of carcinogenic and mutagenic N-nitrosamides in laboratory wastes

Energy Technology Data Exchange (ETDEWEB)

Lunn, G.; Sansone, E.B.; Andrews, A.W.; Castegnaro, M.; Malaveille, C.; Michelon, J.; Brouet, I.; Keefer, L.K.

1984-01-01

The chemical degradation of five N-nitrosamides used widely for the experimental induction of cancer has been studied with the goal of identifying, and experimentally validating, reliable methods that can be recommended for the destruction of carcinogenic N-nitrosoureas and related compounds in laboratory wastes. Although data are not yet complete, preliminary evidence indicates that none of the five methods studied thus far is ideal for hazard-control purposes. Decomposition with 1 mol/L potassium hydroxide solution destroyed the N-nitrosamides, but generated diazoalkanes, which are carcinogenic, toxic and potentially explosive. Treatment with strong acid in the presence of sulfamic acid or iron filings completely decomposed all N-nitrosamides without forming diazoalkanes, but failed in the presence of solvents which were immiscible with water. Cleavage with hydrogen bromide in glacial acetic acid proceeded to a point of maximum degradation, following which gradual reformation of the N-nitrosamide was observed. Permanganate oxidation was effective in sulfuric acid solution, but was incomplete when an alcohol or dimethyl sulfoxide was present. Salmonella typhimurium tester strains TA1535, TA1530 and TA100, detected mutagenic degradation products in each of the destruction methods, with the exception of the hydrobromic acid/acetic acid procedure.

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

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

Comparison of the carcinogenic effectiveness in mouse skin of methyl- and ethylnitrosourea, nitrosourethane and nitrosonitro-guanidine and the effect of deuterium labeling

International Nuclear Information System (INIS)

Lijinsky, W.

1982-01-01

The carcinogenic activities of a number of directly acting methylating and ethylating agents have been compared by mouse skin painting in acetone solution. Nitrosomethylurethane and nitrosoethylurethane failed to induce tumors after greater than 60 weeks treatment. Nitrosomethylurea was somewhat more effective than nitrosoethylurea, as measured by the longer latent period than nitrosoethylurea, as measured Nitrosomethylnitroguanidine, by the same measure, was a weaker carcinogen than nitrosoethylnitroguanidine at both dose levels used (0.02 M and 0.008 M); the latter compound was the most potent skin carcinogen of those examined. There was no significant difference in carcinogenic effectiveness when the alkyl group of the nitrosoureas or the nitronitrosoguanidines contained deuterium instead of hydrogen, which supports the concept that alkylation of cellular macromolecules by the intact alkyl group is responsible for carcinogenesis by these compounds

Most cancer in firefighters is due to radio-frequency radiation exposure not inhaled carcinogens.

Science.gov (United States)

Milham, S

2009-11-01

Recent reviews and reports of cancer incidence and mortality in firefighters conclude that they are at an increased risk of a number of cancers. These include leukemia, multiple myeloma, non-Hodgkin's lymphoma, male breast cancer, malignant melanoma, and cancers of the brain, stomach, colon, rectum, prostate, urinary bladder, testes, and thyroid. Firefighters are exposed to a long list of recognized or probable carcinogens in combustion products and the presumed route of exposure to these carcinogens is by inhalation. Curiously, respiratory system cancers and diseases are usually not increased in firefighters as they are in workers exposed to known inhaled carcinogens. The list of cancers with increased risk in firefighters strongly overlaps the list of cancers at increased risk in workers exposed to electromagnetic fields (EMF) and radiofrequency radiation (RFR). Firefighters have increased exposure to RFR in the course of their work, from the mobile two-way radio communications devices which they routinely use while fighting fires, and at times from firehouse and fire vehicle radio transmitters. I suggest that some of the increased cancer risk in firefighters is caused by RFR exposure, and is therefore preventable. The precautionary principle should be applied to reduce the risk of cancer in firefighters, and workman's compensation rules will necessarily need to be modified.

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.

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.

Dietary adherence in the Women's Health Initiative Dietary Modification Trial.

Science.gov (United States)

2004-04-01

This article describes adherence to a low-fat dietary pattern (less than 20% energy from fat, five or more fruit/vegetable and six or more grain servings daily) in Years 1 and 5 of the Women's Health Initiative Dietary Modification Trial, which was designed to examine the effects of a low-fat dietary pattern on risk of breast and colorectal cancers and other chronic diseases in postmenopausal women. Participants were randomly assigned to a low-fat dietary intervention arm (40%, n=19,542) or a usual diet control arm (60%, n=29,294). Women in the intervention arm completed 18 group sessions during the first year, followed by quarterly annual maintenance sessions. Adherence was assessed as control minus intervention (C-I) group differences in percent total energy from fat as estimated by a food frequency questionnaire. Based on these self-reported dietary data, mean C-I was 10.9 percentage points of energy from fat at Year 1, decreasing to 9.0 at Year 5. Factors associated with poorer adherence were being older, being African American or Hispanic (compared with white), having low income, and being obese. Group session attendance was strongly associated with better dietary adherence. There are many limitations of self-reported dietary data, particularly related to social desirability and intervention-associated bias. Nonetheless, these data indicate that long-term dietary change was achieved in this clinical trial setting and reinforce the potential of the ongoing trial to answer questions of public health importance.

Toxicokinetics of chloral hydrate in ad libitum-fed, dietary-controlled, and calorically restricted male B6C3F1 mice following short-term exposure

International Nuclear Information System (INIS)

Seng, John E.; Agrawal, Nalini; Horsley, Elizabeth T.M.; Leakey, Tatiana I.; Scherer, Erin M.; Xia, Shijun; Allaben, William T.; Leakey, Julian E.A.

2003-01-01

Chloral hydrate is widely used as a sedative in pediatric medicine and is a by-product of water chlorination and a metabolic intermediate in the biotransformation of trichloroethylene. Chloral hydrate and its major metabolite, trichloroacetic acid, induce liver tumors in B6C3F 1 mice, a strain that can exhibit high rates of background liver tumor incidence, which is associated with increased body weight. This report describes the influence of diet and body weight on the acute toxicity, hepatic enzyme response, and toxickinetics of chloral hydrate as part of a larger study investigating the carcinogenicity of chloral hydrate in ad libitum-fed and dietary controlled mice. Dietary control involves moderate food restriction to maintain the test animals at an idealized body weight. Mice were dosed with chloral hydrate at 0, 50, 100, 250, 500, and 1000 mg/kg daily, 5 days/week, by aqueous gavage for 2 weekly dosing cycles. Three diet groups were used: ad libitum, dietary control, and 40% caloric restriction. Both dietary control and caloric restriction slightly reduced acute toxicity of high doses of chloral hydrate and potentiated the induction of hepatic enzymes associated with peroxisome proliferation. Chloral hydrate toxicokinetics were investigated using blood samples obtained by sequential tail clipping and a microscale gas chromatography technique. It was rapidly cleared from serum within 3 h of dosing. Trichloroacetate was the major metabolite in serum in all three diet groups. Although the area under the curve values for serum trichloroacetate were slightly greater in the dietary controlled and calorically restricted groups than in the ad libitum-fed groups, this increase did not appear to completely account for the potentiation of hepatic enzyme induction by dietary restriction

Alkylation of deoxyribonucleic acid by carcinogens dimethyl sulphate, ethyl methanesulphonate, N-ethyl-N-nitrosourea and N-methyl-N-nitrosourea

International Nuclear Information System (INIS)

Swenson, D.H.; Lawley, P.D.

1978-01-01

The ethyl phosphotriester of thymidylyl(3'-5')thymidine, dTp((Et) dT, was identified as a product from the reaction of DNA with N-ethyl-N-nitrosourea. Enzymic degradation to yield alkyl phosphotriesters from DNA alkylated by this carcinogen, and by N-methyl-N-nitrosourea, dimethyl sulphate and ethyl methanesulphonate was studied quantitatively, and the relative yields of the triesters dTp(Alk)dT were determined. The relative reactivity of the phosphodiester group dTpdT to each of the four carcinogens was thus obtained, and compared with that of DNA overall, or with that of the N-7 atom of guanine in DNA. The results are related to steric factors, and the electrophilic character of each carcinogen. (author)

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.

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

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).

Comparative evaluation of genetic toxicity patterns of carcinogens and noncarcinogens: strategies for predictive use of short-term assays

International Nuclear Information System (INIS)

Tennant, R.W.; Spalding, J.W.; Stasiewicz, S.; Caspary, W.D.; Mason, J.M.; Resnick, M.A.

1987-01-01

The results of a recent comprehensive evaluation of the relationship between four measures of in vitro genetic toxicity and the capacity of the chemicals to induce neoplasia in rodents carry some important implications. The results showed that while the Salmonella mutagenesis assay detected only about half of the carcinogenes as mutagens, the other three in vitro assays (mutagenesis in MOLY cells or induction of aberrations or SCEs in CHO cells) did not complement Salmonella since they failed to effectively discriminate between the carcinogens and noncarcinogens found negative in the Salmonella assay. The specificity of the Salmonella assay for this group of 73 chemicals was relatively high (only 4 of 29 noncarcinogens were positive). Therefore, the authors have begun to evaluate in vivo genetic toxicity assays for their ability to complement Salmonella in the identification of carcinogens

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

Surface charge-specific interactions between polymer nanoparticles and ABC transporters in Caco-2 cells

Energy Technology Data Exchange (ETDEWEB)

Bhattacharjee, Sourav, E-mail: sourav.bhattacharjee@wur.nl [Wageningen University, Laboratory of Organic Chemistry (Netherlands); Opstal, Edward J. van; Alink, Gerrit M. [Wageningen University, Division of Toxicology (Netherlands); Marcelis, Antonius T. M.; Zuilhof, Han [Wageningen University, Laboratory of Organic Chemistry (Netherlands); Rietjens, Ivonne M. C. M. [Wageningen University, Division of Toxicology (Netherlands)

2013-06-15

The surface charge-dependent transport of polymeric nanoparticles (PNPs) across Caco-2 monolayers grown on transwell culture systems as an in vitro model for intestinal transport was tested. The transport of well-characterized, monodisperse, and fluorescent tri-block copolymer nanoparticles (TCNPs/size {approx}45 nm) and polystyrene nanoparticles (PSNPs/size {approx}50 nm), with different surface charges (positive and negative), was quantified. The positive PNPs showed a higher intracellular uptake and flux across the Caco-2 monolayers than the negative PNPs. Multidrug resistance/P-glycoprotein (MDR1/P-gp), a specific ATP-binding cassette (ABC) transporter, was found to play a major role in the cellular efflux of positive PNPs, whereas the multidrug resistance protein 1 took part in the efflux of negative PNPs from Caco-2 cells. The positive PNPs also caused an increased cellular uptake and apical to basolateral transport of the carcinogen PhIP across the Caco-2 monolayer. The flavonoid quercetin, which is known to interact with ABC transporters, promoted the intracellular uptake of different PNPs and interfered with the normal distribution patterns of PNPs in the transwell system. These results indicate that PNPs display surface charge-specific interactions with ABC transporters and can even affect the bioavailability of toxic food-borne compounds (like pro-carcinogens).

Surface charge-specific interactions between polymer nanoparticles and ABC transporters in Caco-2 cells

Science.gov (United States)

Bhattacharjee, Sourav; van Opstal, Edward J.; Alink, Gerrit M.; Marcelis, Antonius T. M.; Zuilhof, Han; Rietjens, Ivonne M. C. M.

2013-06-01

The surface charge-dependent transport of polymeric nanoparticles (PNPs) across Caco-2 monolayers grown on transwell culture systems as an in vitro model for intestinal transport was tested. The transport of well-characterized, monodisperse, and fluorescent tri-block copolymer nanoparticles (TCNPs/size 45 nm) and polystyrene nanoparticles (PSNPs/size 50 nm), with different surface charges (positive and negative), was quantified. The positive PNPs showed a higher intracellular uptake and flux across the Caco-2 monolayers than the negative PNPs. Multidrug resistance/P-glycoprotein (MDR1/P-gp), a specific ATP-binding cassette (ABC) transporter, was found to play a major role in the cellular efflux of positive PNPs, whereas the multidrug resistance protein 1 took part in the efflux of negative PNPs from Caco-2 cells. The positive PNPs also caused an increased cellular uptake and apical to basolateral transport of the carcinogen PhIP across the Caco-2 monolayer. The flavonoid quercetin, which is known to interact with ABC transporters, promoted the intracellular uptake of different PNPs and interfered with the normal distribution patterns of PNPs in the transwell system. These results indicate that PNPs display surface charge-specific interactions with ABC transporters and can even affect the bioavailability of toxic food-borne compounds (like pro-carcinogens).

Surface charge-specific interactions between polymer nanoparticles and ABC transporters in Caco-2 cells

International Nuclear Information System (INIS)

Bhattacharjee, Sourav; Opstal, Edward J. van; Alink, Gerrit M.; Marcelis, Antonius T. M.; Zuilhof, Han; Rietjens, Ivonne M. C. M.

2013-01-01

The surface charge-dependent transport of polymeric nanoparticles (PNPs) across Caco-2 monolayers grown on transwell culture systems as an in vitro model for intestinal transport was tested. The transport of well-characterized, monodisperse, and fluorescent tri-block copolymer nanoparticles (TCNPs/size ∼45 nm) and polystyrene nanoparticles (PSNPs/size ∼50 nm), with different surface charges (positive and negative), was quantified. The positive PNPs showed a higher intracellular uptake and flux across the Caco-2 monolayers than the negative PNPs. Multidrug resistance/P-glycoprotein (MDR1/P-gp), a specific ATP-binding cassette (ABC) transporter, was found to play a major role in the cellular efflux of positive PNPs, whereas the multidrug resistance protein 1 took part in the efflux of negative PNPs from Caco-2 cells. The positive PNPs also caused an increased cellular uptake and apical to basolateral transport of the carcinogen PhIP across the Caco-2 monolayer. The flavonoid quercetin, which is known to interact with ABC transporters, promoted the intracellular uptake of different PNPs and interfered with the normal distribution patterns of PNPs in the transwell system. These results indicate that PNPs display surface charge-specific interactions with ABC transporters and can even affect the bioavailability of toxic food-borne compounds (like pro-carcinogens).

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.

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

Carcinogenicity and Immnotoxicity of Embedded Depleted Uranium and Heavy-Metal Tungsten Alloy in Rodents

National Research Council Canada - National Science Library

Miller, Alexandra

2002-01-01

.... We hypothesize that long-term chronic exposure to embedded DU and HMTA initiates changes in normal immune function that will eventually result in a carcinogenic response characterized by both tumor...

Biodegradation of carcinogenic textile azo dyes using bacterial isolates of mangrove sediment

Directory of Open Access Journals (Sweden)

Guru Prasad Srinivasan

2014-02-01

Full Text Available Objective: To evaluate the biodegrading property against carcinogenic azo dyes using bacterial isolates of mangrove sediment. Methods: The bacterial isolates were subjected to submerged fermentation and their growth kinetics were studied. The potential strain was characterized using 16S rDNA sequencing. Results: In the present study, dye degrading bacterial colonies were isolated from the mangrove sediment samples of Parangipettai estuarine area, Tamil Nadu. Of the 30 morphologically different strains isolated, 5 showed antagonistic property. The growth kinetics of the two strains, P1 and G1, which showed potent activity were calculated. One particular isolate (P1 showing promising dye degrading potential in the submerged fermentation was further characterized. The strain was identified as Paenibacillus sp. by 16S rDNA sequencing. Conclusions: This study reveals the less explored microflora of mangrove sediments. The novel strain may further be analyzed and used in the treatment of effluent from dye industry so as to reduce the impact of carcinogenic contaminants.

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

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.

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

Dietary Quality and Adherence to Dietary Recommendations in Patients Undergoing Hemodialysis.

Science.gov (United States)

Luis, Desiree; Zlatkis, Karyn; Comenge, Beatriz; García, Zoraida; Navarro, Juan F; Lorenzo, Victor; Carrero, Juan Jesús

2016-05-01

The multiple dietary restrictions recommended to hemodialysis patients may be difficult to achieve and, at the same time, may result in nutritional deficiencies rendering a poor dietary quality. We here assess the dietary quality and adherence to renal-specific guideline recommendations among hemodialysis patients from a single center in Canary Islands, Spain. Cross-sectional study, including 91 patients undergoing maintenance hemodialysis. Clinical data and 3-day dietary records were collected. We compared patient's reported nutrients intake with guideline recommendations. We also evaluated their alignment with current American Heart Association dietary guidelines for cardiovascular prevention. Seventy-seven percent and 50% of patients consumed less than the recommended daily energy and protein, respectively. Although half of the patients met the recommendations for dietary fat intake, this was accounted by an excess of saturated fat in 92% of them. Only 22% consumed sufficient fiber. A very small proportion of patients (less than 50%) met the requirements for vitamins and other micronutrients. Insufficient dietary intake was observed in most patients for all vitamins except for cobalamin. Similarly, inadequate dietary intake was observed for many minerals, by both excess (phosphorus, calcium, sodium, and potassium) and defect (magnesium). Most patients met the recommendations for iron and zinc in their diets. A large proportion of hemodialysis patients at our center did not meet current renal-specific dietary recommendations. The quality of the diet was considered poor and proatherogenic according to American Heart Association guidelines. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Dietary nitrate and nitrite intake and risk of colorectal cancer in the Shanghai Women's Health Study.

Science.gov (United States)

Dellavalle, Curt T; Xiao, Qian; Yang, Gong; Shu, Xiao-Ou; Aschebrook-Kilfoy, Briseis; Zheng, Wei; Lan Li, Hong; Ji, Bu-Tian; Rothman, Nathaniel; Chow, Wong-Ho; Gao, Yu-Tang; Ward, Mary H

2014-06-15

Nitrate and nitrite are precursors of endogenously formed N-nitroso compounds (NOC), known animal carcinogens. Nitrosation reactions forming NOCs can be inhibited by vitamin C and other antioxidants. We prospectively investigated the association between dietary nitrate and nitrite intake and risk of colorectal cancer in the Shanghai Women's Health Study, a cohort of 73,118 women ages 40-70 residing in Shanghai. We evaluated effect modification by factors that affect endogenous formation of NOCs: vitamin C (at or above/below median) and red meat intake (at or above/below median). Nitrate, nitrite and other dietary intakes were estimated from a 77-item food frequency questionnaire administered at baseline. Over a mean of 11 years of follow-up, we identified 619 colorectal cancer cases (n = 383, colon; n = 236, rectum). Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional hazard regression. Overall, nitrate intake was not associated with colorectal cancer risk (HR = 1.08; 95% CI: 0.73-1.59). However, among women with vitamin C intake below the median (83.9 mg day(-1) ) and hence higher potential exposure to NOCs, risk of colorectal cancer increased with increasing quintiles of nitrate intake (highest vs. lowest quintile HR = 2.45; 95% CI: 1.15-5.18; p trend = 0.02). There was no association among women with higher vitamin C intake. We found no association between nitrite intake and risk of colorectal cancer overall or by intake level of vitamin C. Our findings suggest that high dietary nitrate intake among subgroups expected to have higher exposure to endogenously formed NOCs increases risk of colorectal cancer. © 2013 UICC.

[Carcinogenic activity of ethylene oxide and its reaction products 2-chlorethanol, 2-bromoethanol, ethylene glycol and diethylene glycol. II. Testing of 2-chlorethanol and 2-bromoethanol for carcinogenic activity].

Science.gov (United States)

Dunkelberg, H

1983-04-01

The compounds 2-chloroethanol and 2-bromoethanol were administered once weekly subcutaneously to groups of 100 female NMRI mice, in the case of 2-chloroethanol in 3 dosages (3.0, 1.0 and 0.3 mg, single dosage per mouse) and 2-bromoethanol in 2 dosages (1.0 and 0.3 mg, single dosage per mouse). Tricaprylin was used as solvent. The mean total dosage per mouse was 175.9,76.3 and 23.0 for 2-chloroethanol and 72.7 and 21.0 mg for 2-bromoethanol. In addition, by intragastric treatment of rats with two dosages (single dosage 10.0 and 2.5 mg/kg body weight), 2-chloroethanol was examined for carcinogenicity. The solvent used here was salad-oil. The mean total dosage per rat amounted to 1706 or, respectively, to 434 mg/kg of body weight. No carcinogenic effect could be determined in the case of either of the test substances, 2-chloroethanol and 2-bromoethanol.

Predictive Models for Carcinogenicity and Mutagenicity: Frameworks,State-of-the-Art, and Perspectives

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 tremendou...

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.

Moving forward in carcinogenicity assessment : Report of an EURL ECVAM/ESTIV workshop

NARCIS (Netherlands)

Corvi, Raffaella; Madia, Federica; Guyton, Kathryn Z; Kasper, Peter; Rudel, Ruthann; Colacci, Annamaria; Kleinjans, Jos; Jennings, Paul

2017-01-01

There is an increased need to develop novel alternative approaches to the two-year rodent bioassay for the carcinogenicity assessment of substances where the rodent bioassay is still a basic requirement, as well as for those substances where animal use is banned or limited or where information gaps

Dietary intake of nitrate relative to antioxidant vitamin in relation to breast cancer risk: a case-control study.

Science.gov (United States)

Yang, Yoon Jung; Hwang, Se Hee; Kim, Hyun Ja; Nam, Seok-Jin; Kong, Gu; Kim, Mi Kyung

2010-01-01

Nitrate is a precursor in the endogenous formation of N-nitroso compounds, which are potent animal carcinogens, whereas antioxidant vitamins have been suggested to protect against carcinogenesis. Interestingly, nitrate and antioxidant vitamins stem from the same dietary sources. We investigated whether the intake of nitrate relative to antioxidant vitamins is associated with the risk of breast cancer. A total of 362 breast cancer cases were matched to the 362 controls by age and menopausal status. Dietary intake was assessed using a quantitative food frequency questionnaire with 121 food items by trained interviewers. The nitrate to antioxidant vitamin consumption ratio was then calculated. Conditional logistic regression analysis was used to obtain odds ratios (ORs) and corresponding 95% confidence intervals (CI). Mean intakes of nitrate for cases and controls were 421 mg/day and 424 mg/day, respectively. Intakes of nitrate, nitrate/beta-carotene, nitrate/vitamin C, and nitrate/vitamin E were not associated with breast cancer risk. However, higher breast cancer risk was observed with higher intake of nitrate/folate (OR = 2.03, 95% CI = 1.16-3.54, P for trend = 0.052). Our results suggest that lowering the ratio of nitrate to folate intake may be effective in reducing breast cancer risk.

Dietary Acculturation among Filipino Americans.

Science.gov (United States)

Vargas, Persephone; Jurado, Leo-Felix

2015-12-22

Acculturation, the subsequent changes that occur in one culture after continuous first hand contact with another culture, impacts the dietary habits and health risks of individuals. This study examines the acculturation, dietary habits and anthropometric measurements in a sample of 210 first generation Filipino American immigrants in New Jersey (NJ). Acculturation was measured using the Short Acculturation Scale for Filipino Americans (ASASFA). Dietary acculturation was measured using the Dietary Acculturation Questionnaire for Filipino Americans (DAQFA) and dietary intake was determined using the Block's Brief Food Frequency Questionnaire (BFFQ). Anthropometric measurements were obtained including weight, height and waist circumference. Acculturation had a significant negative relationship with Filipino Dietary acculturation. Western dietary acculturation was significantly correlated with caloric intake (r(208) = 0.193, p Filipino dietary acculturation, dietary intake and anthropometric measurements. The results showed that Filipino American immigrants have increased risks including increased BMI, waist circumference and increased fat intake. Over all, this research highlighted some dietary changes and their effects on dietary intake and health status.

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.

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

Extensive experience in conducting long term cancer bioassays has been gained over the past 50 years of animal testing on drugs, pesticides, industrial chemicals, food additives and consumer products. Testing protocols for the conduct of carcinogenicity studies in rodents have been developed in Guidelines promulgated by regulatory agencies, including the US EPA (Environmental Protection Agency), the US FDA (Food and Drug Administration), the OECD (Organization for Economic Co-operation and Development) for the EU member states and the MAFF (Ministries of Agriculture, Forestries and Fisheries) and MHW (Ministry of Health and Welfare) in Japan. The basis of critical elements of the study design that lead to an accepted identification of the carcinogenic hazard of substances in food and beverages is the focus of this review. The approaches used by entities well-known for carcinogenicity testing and/or guideline development are discussed. Particular focus is placed on comparison of testing programs used by the US National Toxicology Program (NTP) and advocated in OECD guidelines to the testing programs of the European Ramazzini Foundation (ERF), an organization with numerous published carcinogenicity studies. This focus allows for a good comparison of differences in approaches to carcinogenicity testing and allows for a critical consideration of elements important to appropriate carcinogenicity study designs and practices. OECD protocols serve as good standard models for carcinogenicity testing protocol design. Additionally, the detailed design of any protocol should include attention to the rationale for inclusion of particular elements, including the impact of those elements on study interpretations. Appropriate interpretation of study results is dependent on rigorous evaluation of the study design and conduct, including differences from standard practices. Important considerations are differences in the strain of animal used, diet and housing practices, rigorousness

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.

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.

Carcinogenic effects of MGP-7 and B(a)P on the Hamster Cheek Pouch

Energy Technology Data Exchange (ETDEWEB)

Brandon, J.L.; Conti, C.J.; Goldstein, L.S.; DiGiovanni, J.; Gimenez-Conti, I.B. [University of Texas MD Anderson Cancer Center, Smithville, TX (United States). Dept. of Carcinogenesis

2009-10-15

This study was performed to examine the carcinogenic effects of benzo(a)pyrene (B(a)P) and manufactured gas plant (MGP) residues on the hamster cheek pouch (HCP). Syrian hamsters were treated topically with a suspension of 2%, 10%, or 20% B(a)P or 50% or 100% MGP-7 (a mixture of residues from 7 MGP sites) in mineral oil for eight (short-term study) and sixteen, twenty, twenty-eight, and thirty-two weeks (long-term study). The short-term study showed that B(a)P induced p53 protein accumulation, indicative of genotoxic damage, as well as increased cell proliferation, hyperplasia, and inflammation, which is usually associated with promotional activity. In contrast, the MGP-7 presented only marginal p53 accumulation and induction of BrdU incorporation. In the long-term experiments, animals treated with 2% and 10% of B(a)P continued to show p53 protein accumulation as well as hyperplasia and increased cell proliferation and inflammation. By thirty weeks, all the animals treated with B(a)P had a 100% incidence of squamous cell carcinoma (SCC). Animals treated with 50% and 100% MGP-7 showed only weak hyperplasia and a low proliferation rate and accumulation of p53 protein through thirty-two weeks. Benzo(a)pyrene was highly carcinogenic when used at adequate doses. Manufactured gas plant residue, however, was not carcinogenic in this model.

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.

The Carcinogenic Agent Azoxymethane (AOM) Enhances Early Inflammation-induced Colon Crypt Pathology

DEFF Research Database (Denmark)

Venning, Freja Albjerg; Claesson, Mogens Helweg; Kissow, Hannelouise

2013-01-01

Severe combined immunodeficiency (SCID) mice transplanted with CD4+ T cells depleted of CD25+ regulatory T cells develop colitis within 2-3 weeks after the T cell transfer. In the present study we studied the effect of the carcinogen azoxymethane (AOM) on the colon crypt pathology of normal SCID...

Further improvement of genetic and cytogenetic test pattern with increased relevance predicting carcinogenic and pharmacological effects

Energy Technology Data Exchange (ETDEWEB)

Siebert, D.

1982-08-01

Testing of chemicals for their genetic activity by applying only one method has the disadvantage, that the results are of limited value. However, a combination of several test systems in such a manner that the apparent difference between the results allows additional conclusions about the pharmacokinetic properties of the substances tested, the correlation between molecular mutations and cytogenetic effects and the possible carcinogenic activity. Three nitrofuran derivatives (nitrofurantoin, carofur and FANFT) tested in six different in vitro and in vivo mutagenicity tests partly showed strong genetic activity without metabolic activation and weak cytogenetic effects. However, polycyclic hydrocarbons needed mammalian metabolism to display their mutagenicity: Dimethylbenzoanthracene and benzo(a)pyrene could be activated by liver microsomes and showed also cytogenetic effects, but phenanthrene was only active in the SCE-test. Out of nine heavy metal salts potassium chromate, potassium dichromate, calcium chromate and cis-dichloro diammine-Pt(II) were effective in at least one genetic and one cytogenetic test. The correlation between mutagenic and the known carcinogenic activity of all test substances was good in the case of the hydrocarbons and the nitrofuran derivatives; the heavy metal salts, however, are of low relevance for the carcinogenicity of the metals itself.

Development of the Tagger Microscope & Analysis of Spin Density Matrix Elements in gamma-p -> phi-p for the GlueX Experiment

Energy Technology Data Exchange (ETDEWEB)

Barnes, Alexander E. [Carnegie Mellon Univ., Pittsburgh, PA (United States); Thomas Jefferson National Accelerator Facility (TJNAF), Newport News, VA (United States)

2017-05-31

The quark model has been successful in classifying the spectrum of mesons observed since the 1960s, however, it fails to explain some of the measured bound states. Lattice QCD predictions have shown that an excited gluonic field may contribute to the quantum numbers of the bound state and form hybrid mesons, qq-bar-g, where g is a constituent gluon. It is possible for some hybrids to possess quantum numbers forbidden by the quark model and are known as \\smoking gun" hybrids due to their lack of mixing with conventional qq-bar states. The GlueX photoproduction experiment at Jefferson Lab in Newport News, VA is designed to study hybrid mesons and to map their spectrum. A 12 GeV electron beam produces 9 GeV linearly polarized photons via coherent bremsstrahlung in a diamond radiator which are incident on a liquid H2 target. In order to determine the photon energy, the use of a tagging spectrometer which measures the energy of the post-bremsstrahlung electron is required. The tagger microscope is a scintillating fiber detector designed to measure the energy of electrons corresponding to the polarized photons. The main focus of this work is the design and construction of the tagger microscope electronics as well as the calibration of the microscope within the experiment. Additionally, the analysis of the reaction gamma-p -> phi-p, where phi (1020) -> K+K-, is discussed. This analysis provides a high-level calibration for GlueX in regards to understanding the acceptance and sensitivity of the detectors to mesons with strange quark content. By studying the phi with linearly polarized photons, information on the production mechanism can be extracted. The measurement of the phi spin-density matrix elements are shown and compared with past data which are found to be in agreement.

Analysis of Carcinogenic Heavy Metals in Gallstones and its Role in Gallbladder Carcinogenesis.

Science.gov (United States)

Mondal, Bikash; Maulik, Dhrubajyoti; Mandal, Mousumi; Sarkar, Gautam Narayan; Sengupta, Sanjay; Ghosh, Debidas

2017-12-01

Gallstone is a high-risk factor for gallbladder pre-malignancy or malignancy (GB PM-M) but which substances of gallstones definitely assist to turn out in to GB PM-M, remains unclear. This study aimed to find out the presence of carcinogenic heavy metals in gallstones and to explore the aetiopathogenesis of gallbladder pre-malignancy and malignancy. Presence of elements in gallstones was detected by energy dispersive X-ray spectroscopy (EDS) with scanning electron microscopy (SEM) and then level of carcinogenic heavy metals was estimated in gallstones using atomic absorption spectroscopy (AAS). The experiment was carried out in gallstone samples of 46 patients with gallbladder pre-malignant and malignant condition (PM-M group) and 65 sex and age-matched patients with chronic cholecystitis (C-C group). Gallstones were also classified in to three types such as cholesterol stone, mixed stone, and black pigment stone. EDS analysis detected presence of mercury, lead, and cobalt elements in all types of gallstones of both PM-M and C-C groups. AAS analysis revealed significantly higher amount of mercury (p heavy metals also varied among stone types of both groups. EDS phase analysis showed 'dense deposits' of these metals in gallstones. Presence of significantly higher amount of mercury, lead, cobalt, and cadmium in gallstones may play a pivotal role as risk factors in the development of gallbladder malignancy or pre-malignancy. 'Dense deposits' of these metals in the gallstones which is the first observation, may act as crucial doses of carcinogens.

Dietary nitrate and nitrite intake and risk of colorectal cancer in the Shanghai Women’s Health Study

Science.gov (United States)

DellaValle, Curt T.; Xiao, Qian; Yang, Gong; Shu, Xiao Ou; Aschebrook-Kilfoy, Briseis; Zheng, Wei; Li, Hong Lan; Ji, Bu-Tian; Rothman, Nathaniel; Chow, Wong-Ho; Gao, Yu-Tang; Ward, Mary H.

2014-01-01

Nitrate and nitrite are precursors of endogenously formed N-nitroso compounds (NOC), known animal carcinogens. Nitrosation reactions forming NOCs can be inhibited by vitamin C and other antioxidants. We prospectively investigated the association between dietary nitrate and nitrite intake and risk of colorectal cancer in the Shanghai Women’s Health Study, a cohort of 73,118 women ages 40 to 70 residing in Shanghai. We evaluated effect modification by factors that affect endogenous formation of NOCs: vitamin C (at or above/below median) and red meat intake (at or above/below median). Nitrate, nitrite and other dietary intakes were estimated from a 77-item food frequency questionnaire administered at baseline. Over a mean of 11 years of follow-up, we identified 619 colorectal cancer cases (n=383, colon; n=236, rectum). Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional hazard regression. Overall, nitrate intake was not associated with colorectal cancer risk (HR = 1.08; 95% CI: 0.73–1.59). However, among women with vitamin C intake below the median (83.9 mg/day) and hence higher potential exposure to NOCs, risk of colorectal cancer increased with increasing quintiles of nitrate intake (highest vs. lowest quintile HR = 2.45; 95% CI: 1.15–5.18; p-trend = 0.02). There was no association among women with higher vitamin C intake. We found no association between nitrite intake and risk of colorectal cancer overall or by intake level of vitamin C. Our findings suggest that high dietary nitrate intake among subgroups expected to have higher exposure to endogenously-formed NOCs increases risk of colorectal cancer. PMID:24242755

An evaluation of the mode of action framework for mutagenic carcinogens: chromium (VI)

Science.gov (United States)

In response to the 2005 revised U.S Environmental Protection Agency’s (EPA) Cancer Guidelines, a strategy is being developed to determine whether a carcinogen operates through a mutagenic mode of action (MOA). This information is necessary for EPA to decide whether age-dependent ...

Assessment of global and gene-specific DNA methylation in rat liver and kidney in response to non-genotoxic carcinogen exposure

Energy Technology Data Exchange (ETDEWEB)

Ozden, Sibel, E-mail: stopuz@istanbul.edu.tr [Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Istanbul University, Istanbul (Turkey); Turgut Kara, Neslihan [Department of Molecular Biology and Genetics, Faculty of Science, Istanbul University, Istanbul (Turkey); Sezerman, Osman Ugur [Department of Biostatistics and Medical Informatics, Acibadem University, Istanbul (Turkey); Durasi, İlknur Melis [Biological Sciences and Bioengineering, Faculty of Engineering and Natural Sciences, Sabancı University, Istanbul (Turkey); Chen, Tao [Department of Toxicology, School of Public Health, Soochow University, Suzhou (China); Demirel, Goksun; Alpertunga, Buket [Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Istanbul University, Istanbul (Turkey); Chipman, J. Kevin [School of Biosciences, The University of Birmingham, Birmingham (United Kingdom); Mally, Angela [Department of Toxicology, University of Würzburg, Würzburg (Germany)

2015-12-01

Altered expression of tumor suppressor genes and oncogenes, which is regulated in part at the level of DNA methylation, is an important event involved in non-genotoxic carcinogenesis. This may serve as a marker for early detection of non-genotoxic carcinogens. Therefore, we evaluated the effects of non-genotoxic hepatocarcinogens, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), hexachlorobenzene (HCB), methapyrilene (MPY) and male rat kidney carcinogens, d-limonene, p-dichlorobenzene (DCB), chloroform and ochratoxin A (OTA) on global and CpG island promoter methylation in their respective target tissues in rats. No significant dose-related effects on global DNA hypomethylation were observed in tissues of rats compared to vehicle controls using LC–MS/MS in response to short-term non-genotoxic carcinogen exposure. Initial experiments investigating gene-specific methylation using methylation-specific PCR and bisulfite sequencing, revealed partial methylation of p16 in the liver of rats treated with HCB and TCDD. However, no treatment related effects on the methylation status of Cx32, e-cadherin, VHL, c-myc, Igfbp2, and p15 were observed. We therefore applied genome-wide DNA methylation analysis using methylated DNA immunoprecipitation combined with microarrays to identify alterations in gene-specific methylation. Under the conditions of our study, some genes were differentially methylated in response to MPY and TCDD, whereas d-limonene, DCB and chloroform did not induce any methylation changes. 90-day OTA treatment revealed enrichment of several categories of genes important in protein kinase activity and mTOR cell signaling process which are related to OTA nephrocarcinogenicity. - Highlights: • Studied non-genotoxic carcinogens caused no change on global DNA hypomethylation. • d-Limonene, DCB and chloroform did not show any genome-wide methylation changes. • Some genes were differentially methylated in response to MPY, TCDD and OTA. • Protein kinase activity

Assessment of global and gene-specific DNA methylation in rat liver and kidney in response to non-genotoxic carcinogen exposure

International Nuclear Information System (INIS)

Ozden, Sibel; Turgut Kara, Neslihan; Sezerman, Osman Ugur; Durasi, İlknur Melis; Chen, Tao; Demirel, Goksun; Alpertunga, Buket; Chipman, J. Kevin; Mally, Angela

2015-01-01

Altered expression of tumor suppressor genes and oncogenes, which is regulated in part at the level of DNA methylation, is an important event involved in non-genotoxic carcinogenesis. This may serve as a marker for early detection of non-genotoxic carcinogens. Therefore, we evaluated the effects of non-genotoxic hepatocarcinogens, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), hexachlorobenzene (HCB), methapyrilene (MPY) and male rat kidney carcinogens, d-limonene, p-dichlorobenzene (DCB), chloroform and ochratoxin A (OTA) on global and CpG island promoter methylation in their respective target tissues in rats. No significant dose-related effects on global DNA hypomethylation were observed in tissues of rats compared to vehicle controls using LC–MS/MS in response to short-term non-genotoxic carcinogen exposure. Initial experiments investigating gene-specific methylation using methylation-specific PCR and bisulfite sequencing, revealed partial methylation of p16 in the liver of rats treated with HCB and TCDD. However, no treatment related effects on the methylation status of Cx32, e-cadherin, VHL, c-myc, Igfbp2, and p15 were observed. We therefore applied genome-wide DNA methylation analysis using methylated DNA immunoprecipitation combined with microarrays to identify alterations in gene-specific methylation. Under the conditions of our study, some genes were differentially methylated in response to MPY and TCDD, whereas d-limonene, DCB and chloroform did not induce any methylation changes. 90-day OTA treatment revealed enrichment of several categories of genes important in protein kinase activity and mTOR cell signaling process which are related to OTA nephrocarcinogenicity. - Highlights: • Studied non-genotoxic carcinogens caused no change on global DNA hypomethylation. • d-Limonene, DCB and chloroform did not show any genome-wide methylation changes. • Some genes were differentially methylated in response to MPY, TCDD and OTA. • Protein kinase activity

Automobile tires--a potential source of highly carcinogenic dibenzopyrenes to the environment.

Science.gov (United States)

Sadiktsis, Ioannis; Bergvall, Christoffer; Johansson, Christer; Westerholm, Roger

2012-03-20

Eight tires were analyzed for 15 high molecular weight (HMW) polycyclic aromatic hydrocarbons (PAH), using pressurized fluid extraction. The variability of the PAH concentrations determined between different tires was large; a factor of 22.6 between the lowest and the highest. The relative abundance of the analytes was quite similar regardless of tire. Almost all (92.3%) of the total extractable PAH content was attributed to five PAHs: benzo[ghi]perylene, coronene, indeno[1,2,3-cd]pyrene, benzo[e]pyrene, and benzo[a]pyrene. The difference in the measured PAH content between summer and winter tires varied substantially across manufacturers, making estimates of total vehicle fleet emissions very uncertain. However, when comparing different types of tires from the same manufacturer they had significantly (p = 0.05) different PAH content. Previously, there have been no data available for carcinogenic dibenzopyrene isomers in automobile tires. In this study, the four dibenzopyrene isomers dibenzo[a,l]pyrene, dibenzo[a,e]pyrene, dibenzo[a,i]pyrene, and dibenzo[a,h]pyrene constituted tires may be a potential previously unknown source of carcinogenic dibenzopyrenes to the environment.

IDENTIFICATION OF SOME CARCINOGENIC POLYCYCLIC AROMATIC HYDROCARBONS IN BANGLADESHI VEHICLES EXHAUST TAR BY GAS CHROMATOGRAPHY-MASS SPECTROPHOTOMETER

Directory of Open Access Journals (Sweden)

M. Amzad Hossain

2010-06-01

Full Text Available A more sensitive GC-MS method has been established for the determination of some carcinogenic polycyclic aromatic hydrocarbons (PAHs in vehicles exhaust tar samples. The tar samples were extracted using dichloromethane (DMC: n-hexane solvent mixture. A multi-layer clean-up (silica gel/sodium sulphate column was used, followed by glass fiber filter (GFF paper. The method was successfully applied to determine a number of PAHs present in exhaust tar sample of different vehicles of the Atomic Energy Centre, Dhaka, Bangladesh.   Keywords: Carcinogenic polycyclic aromatic hydrocarbons, vehicles tar samples, identification, GC-MS/MS

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

NARCIS (Netherlands)

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

2006-01-01

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

Differential toxicity of heterocyclic aromatic amines and their mixture in metabolically competent HepaRG cells

International Nuclear Information System (INIS)

Dumont, Julie; Josse, Rozenn; Lambert, Carine; Antherieu, Sebastien; Le Hegarat, Ludovic; Aninat, Caroline; Robin, Marie-Anne; Guguen-Guillouzo, Christiane

2010-01-01

Human exposure to heterocyclic aromatic amines (HAA) usually occurs through mixtures rather than individual compounds. However, the toxic effects and related mechanisms of co-exposure to HAA in humans remain unknown. We compared the effects of two of the most common HAA, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), individually or in combination, in the metabolically competent human hepatoma HepaRG cells. Various endpoints were measured including cytotoxicity, apoptosis, oxidative stress and DNA damage by the comet assay. Moreover, the effects of PhIP and/or MeIQx on mRNA expression and activities of enzymes involved in their activation and detoxification pathways were evaluated. After a 24 h treatment, PhIP and MeIQx, individually and in combination, exerted differential effects on apoptosis, oxidative stress, DNA damage and cytochrome P450 (CYP) activities. Only PhIP induced DNA damage. It was also a stronger inducer of CYP1A1 and CYP1B1 expression and activity than MeIQx. In contrast, only MeIQx exposure resulted in a significant induction of CYP1A2 activity. The combination of PhIP with MeIQx induced an oxidative stress and showed synergistic effects on apoptosis. However, PhIP-induced genotoxicity was abolished by a co-exposure with MeIQx. Such an inhibitory effect could be explained by a significant decrease in CYP1A2 activity which is responsible for PhIP genotoxicity. Our findings highlight the need to investigate interactions between HAA when assessing risks for human health and provide new insights in the mechanisms of interaction between PhIP and MeIQx.

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.

Biomarkers of exposure to carcinogenic PAHs and their relationship with environmental factors

Czech Academy of Sciences Publication Activity Database

Taioli, E.; Šrám, Radim; Binková, Blanka; Kalina, I.; Popov, T. A.; Garte, S.; Farmer, P. B.

2007-01-01

Roč. 620, - (2007), s. 16-21 ISSN 0027-5107 Grant - others:EU(GB) 2000-00091 Institutional research plan: CEZ:AV0Z50390512 Source of funding: R - rámcový projekt EK Keywords : DNA adducts * air pollution * carcinogenic PAHs Subject RIV: DN - Health Impact of the Environment Quality Impact factor: 4.159, year: 2007

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.

Dietary Crude Lecithin Increases Systemic Availability of Dietary Docosahexaenoic Acid with Combined Intake in Rats.

Science.gov (United States)

van Wijk, Nick; Balvers, Martin; Cansev, Mehmet; Maher, Timothy J; Sijben, John W C; Broersen, Laus M

2016-07-01

Crude lecithin, a mixture of mainly phospholipids, potentially helps to increase the systemic availability of dietary omega-3 polyunsaturated fatty acids (n-3 PUFA), such as docosahexaenoic acid (DHA). Nevertheless, no clear data exist on the effects of prolonged combined dietary supplementation of DHA and lecithin on RBC and plasma PUFA levels. In the current experiments, levels of DHA and choline, two dietary ingredients that enhance neuronal membrane formation and function, were determined in plasma and red blood cells (RBC) from rats after dietary supplementation of DHA-containing oils with and without concomitant dietary supplementation of crude lecithin for 2-3 weeks. The aim was to provide experimental evidence for the hypothesized additive effects of dietary lecithin (not containing any DHA) on top of dietary DHA on PUFA levels in plasma and RBC. Dietary supplementation of DHA-containing oils, either as vegetable algae oil or as fish oil, increased DHA, eicosapentaenoic acid (EPA), and total n-3 PUFA, and decreased total omega-6 PUFA levels in plasma and RBC, while dietary lecithin supplementation alone did not affect these levels. However, combined dietary supplementation of DHA and lecithin increased the changes induced by DHA supplementation alone. Animals receiving a lecithin-containing diet also had a higher plasma free choline concentration as compared to controls. In conclusion, dietary DHA-containing oils and crude lecithin have synergistic effects on increasing plasma and RBC n-3 PUFA levels, including DHA and EPA. By increasing the systemic availability of dietary DHA, dietary lecithin may increase the efficacy of DHA supplementation when their intake is combined.

Dietary Acculturation among Filipino Americans

Directory of Open Access Journals (Sweden)

Persephone Vargas

2015-12-01

Full Text Available Acculturation, the subsequent changes that occur in one culture after continuous first hand contact with another culture, impacts the dietary habits and health risks of individuals. This study examines the acculturation, dietary habits and anthropometric measurements in a sample of 210 first generation Filipino American immigrants in New Jersey (NJ. Acculturation was measured using the Short Acculturation Scale for Filipino Americans (ASASFA. Dietary acculturation was measured using the Dietary Acculturation Questionnaire for Filipino Americans (DAQFA and dietary intake was determined using the Block’s Brief Food Frequency Questionnaire (BFFQ. Anthropometric measurements were obtained including weight, height and waist circumference. Acculturation had a significant negative relationship with Filipino Dietary acculturation. Western dietary acculturation was significantly correlated with caloric intake (r(208 = 0.193, p < 0.01, percentage fat intake (r(208 = 0.154, p < 0.05, percentage carbohydrate intake (r(208 = −0.172, p < 0.05, Body Mass Index (BMI (r(208 = 0.216, p < 0.01 and waist circumference (r(208 = 0.161, p < 0.01. There was no significant correlation between Filipino dietary acculturation, dietary intake and anthropometric measurements. The results showed that Filipino American immigrants have increased risks including increased BMI, waist circumference and increased fat intake. Over all, this research highlighted some dietary changes and their effects on dietary intake and health status.

[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.

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

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

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.

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.

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

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

IARC 1987 re-evaluation of carcinogenicity of mineral oils and bitumens - CONCAWE comments and interpretation

Energy Technology Data Exchange (ETDEWEB)

1988-10-01

Following the IARC response to CONCAWE comments on their 1987 re-evaluation of carcinogenicity of mineral oils and bitumens, CONCAWE decided that a revised version of Report No. 87/63 should be published in this report. The objective is to ensure that all who may be concerned with carcinogenicity classifications of these petroleum products, including national and international regulatory authorities, are aware of the reasons for the differences between the 1984 and 1987 IARC classifications and of CONCAWE's reservations concerning the revised classifications. This document reviews important differences between the new and previous evaluations, which are summarized in tabular form, and also indicates how the differences have occurred. In addition, it provides CONCAWE's interpretation of the available evidence, taking into account points discussed with IARC. 1 tab.

Foods, Nutrients, and Dietary Patterns: Interconnections and Implications for Dietary Guidelines12

Science.gov (United States)

Satija, Ambika; Hu, Frank B

2016-01-01

Dietary guidelines provide evidence-based statements on food choices to meet nutritional requirements and reduce the risk of prevailing chronic disease. They involve a substantial amount of research translation, and their implementation has important health consequences. Foods, however, are complex combinations of nutrients and other compounds that act synergistically within the food and across food combinations. In addition, the evidence base underpinning dietary guidelines accesses research that reflects different study designs, with inherent strengths and limitations. We propose a systematic approach for the review of evidence that begins with research on dietary patterns. This research will identify the combinations of foods that best protect, or appear deleterious to, health. Next, we suggest that evidence be sought from research that focuses on the effects of individual foods. Finally, nutrient-based research should be considered to explain the mechanisms by which these foods and dietary patterns exert their effects, take into account the effects of ingredients added to the food supply, and enable assessments of dietary sufficiency. The consideration of individual nutrients and food components (e.g., upper limits for saturated fat, added sugar, and sodium) provides important benchmarks for evaluating overall diet quality. The concepts of core and discretionary foods (nutrient-rich and nutrient-poor foods, respectively) enable distinctions between foods, and this has implications for the relation between food policy and food manufacturing. In summary, evidence supporting healthy dietary patterns provides the foundation for the development of dietary guidelines. Further reference to individual foods and nutrients follows from the foundation of healthy dietary patterns. PMID:27184272

The use of plants containing genotoxic carcinogens as foods and medicine.

Science.gov (United States)

Prinsloo, Gerhard; Nogemane, Noluyolo; Street, Renee

2018-04-05

In many developing countries, populations rely on traditional medicine for primary health care, which have infiltrated commercial markets globally as natural remedies are generally regarded as safe. Traditional and natural remedies are adapted and expanded in commercial products and product ranges to provide alternatives for various diseases and illnesses. These products resemble very little of the traditional use and application and adverse effects are observed in several cases. Some of the herbs and botanical formulations therefore, are not as safe as are commonly contemplated. This paper discusses some plants that are used as food or medicine. These plants are known to contain chemical components that have been identified as genotoxic carcinogens. Often contradictory results are obtained with beneficial and adverse effects reported. The concentration, biotransformation and metabolism of these compounds, as well as the matrix effect, affect the outcome of these results, therefore not providing a clear picture of the risk associated with the use and consumption of these plants. This paper focuses on plants that are accepted as healthy, however contain compounds that are genotoxic and carcinogenic. We further highlight the risks in use of these plants where thorough studies have been conducted in various food and plant products. Copyright © 2018 Elsevier Ltd. All rights reserved.

Immunogenicity of guinea pig cells transformed in culture by chemical carcinogens.

Science.gov (United States)

Ohanian, S H; McCabe, R P; Evans, C H

1981-12-01

The immunogenicity of inbred strain 2/N guinea pig fibroblasts transformed to the malignant state in vitro by chemical carcinogens was evaluated with the use of a variety of in vivo and in vitro methods including delayed-type hypersensitivity skin and tumor transplantation tests and analysis of antibody production by immunofluorescence, complement fixation, and staphylococcal protein A binding tests. Neoplastic transformation was induced by direct treatment of cells in culture with benzo[a]pyrene, 3-methylcholanthrene, or N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) or by the host-mediated method by which fetuses were exposed to diethylnitrosamine or MNNG in vivo prior to cell culture. Rabbits and syngeneic guinea pigs were inoculated with unirradiated and X-irradiated clonally derived cells. Delayed hypersensitivity skin reactions to immunizing or other cells were equivalent in immunized or control guinea pigs, and no protection to tumor outgrowth from a challenge inoculum of immunizing cells was observed. Antibody activity induced in the sera of immunized guinea pigs was cross-reactive and removed by absorption with nontumorigenic cells. Rabbit antisera after absorption with fetal guinea pig cells were nonreactive with the specific immunizing or other culture cells. Chemical carcinogen-induced neoplastic transformation of guinea pig cells can, therefore, occur without formation of detectable, individually distinct cell surface tumor-specific neoantigens.

Immunogenicity of guinea pig cells transformed in culture by chemical carcinogens

International Nuclear Information System (INIS)

Ohanian, S.H.; McCabe, R.P.; Evans, C.H.

1981-01-01

The immunogenicity of inbred strain 2/N guinea pig fibroblasts transformed to the malignant state in vitro by chemical carcinogens was evaluated with the use of a variety of in vivo and in vitro methods including delayed-type hypersensitivity skin and tumor transplantation tests and analysis of antibody production by immunofluorescence, complement fixation, and staphylococcal protein A binding tests. Neoplastic transformation was induced by direct treatment of cells in culture with benzo[a]pyrene, 3-methylcholanthrene, or N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) or by the host-mediated method by which fetuses were exposed to diethylnitrosamine or MNNG in vivo prior to cell culture. Rabbits and syngeneic guinea pigs were inoculated with unirradiated and X-irradiated clonally derived cells. Delayed hypersensitivity skin reactions to immunizing or other cells were equivalent in immunized or control guinea pigs, and no protection to tumor outgrowth from a challenge inoculum of immunizing cells was observed. Antibody activity induced in the sera of immunized guinea pigs was cross-reactive and removed by absorption with nontumorigenic cells. Rabbit anitsera after absorption with fetal guinea pig cells were nonreactive with the specific immunizing or other cultured cells. Chemical carcinogen-induced neoplastic transformation of guinea pig cells can, therefore, occur without formation of detectable, individually distinct cell surface tumor-specific neoantigens

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.

Dietary Advice on Prescription: A novel approach to dietary counseling

Directory of Open Access Journals (Sweden)

Gunnar Johansson

2011-05-01

Full Text Available This article describes a novel approach to giving dietary advice, which is called “Dietary Advice on Prescription” (DAP; Matordning på Recept [MoR] in Swedish. It is the same principle as prescription on medicine and “Physical Activity on Prescription” (PAP; Fysisk aktivitet på Recept [FaR] in Swedish. The main idea is that a written prescription will strengthen the oral advice and emphasize certain aspects of the dietary recommendation. The DAP is on the brink of being tested in a planned study.

The association of the original OSHA chemical hazard communication standard with reductions in acute work injuries/illnesses in private industry and the industrial releases of chemical carcinogens.

Science.gov (United States)

Oleinick, Arthur

2014-02-01

OSHA predicted the original chemical Hazard Communication Standard (HCS) would cumulatively reduce the lost workday acute injury/illness rate for exposure events by 20% over 20 years and reduce exposure to chemical carcinogens. JoinPoint trend software identified changes in the rate of change of BLS rates for days away from work for acute injuries/illnesses during 1992-2009 for manufacturing and nonmanufacturing industries for both chemical, noxious or allergenic injury exposure events and All other exposure events. The annual percent change in the rates was used to adjust observed numbers of cases to estimate their association with the standard. A case-control study of EPA's Toxic Release Inventory 1988-2009 data compared carcinogen and non-carcinogens' releases. The study estimates that the HCS was associated with a reduction in the number of acute injuries/illnesses due to chemical injury exposure events over the background rate in the range 107,569-459,395 (Hudson method/modified BIC model) depending on whether the HCS is treated as a marginal or sole factor in the decrease. Carcinogen releases have declined at a substantially faster rate than control non-carcinogens. The previous HCS standard was associated with significant reductions in chemical event acute injuries/illnesses and chemical carcinogen exposures. © 2013 Wiley Periodicals, Inc.

Secondary effects induced by the colon carcinogen azoxymethane in BDIX rats

DEFF Research Database (Denmark)

Kobaek-Larsen, Morten; Fenger, Claus; Ritskes-Hoitinga, Jelmera

2004-01-01

resulted in colon carcinomas with a high frequency (75-100%) and with a high reproducibility. However, some serious side effects are associated with this carcinogen treatment. In addition to the colorectal tumours, we found small intestinal tumours, hepatic lesions and a high frequency of mesenchymal renal...... the secondary effects of the induction of colon cancer by AOM, it is advisable to use male rats only and a maximum latency period of 32 weeks....

An evaluation of the mode of action framework for mutagenic carcinogens: Chromium (VI): SOT.

Science.gov (United States)

In response to the 2005 revised U.S Environmental Protection Agency’s (EPA) Cancer Guidelines, a strategy is being developed to determine whether a carcinogen operates through a mutagenic mode of action (MOA). This information is necessary for EPA to decide whether age-dependent ...

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

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

Moving forward in carcinogenicity assessment: Report of an EURL ECVAM/ESTIV workshop.

Science.gov (United States)

Corvi, Raffaella; Madia, Federica; Guyton, Kathryn Z; Kasper, Peter; Rudel, Ruthann; Colacci, Annamaria; Kleinjans, Jos; Jennings, Paul

2017-12-01

There is an increased need to develop novel alternative approaches to the two-year rodent bioassay for the carcinogenicity assessment of substances where the rodent bioassay is still a basic requirement, as well as for those substances where animal use is banned or limited or where information gaps are identified within legislation. The current progress in this area was addressed in a EURL ECVAM- ESTIV workshop held in October 2016, in Juan les Pins. A number of initiatives were presented and discussed, including data-driven, technology-driven and pathway-driven approaches. Despite a seemingly diverse range of strategic developments, commonalities are emerging. For example, providing insight into carcinogenicity mechanisms is becoming an increasingly appreciated aspect of hazard assessment and is suggested to be the best strategy to drive new developments. Thus, now more than ever, there is a need to combine and focus efforts towards the integration of available information between sectors. Such cross-sectorial harmonisation will aid in building confidence in new approach methods leading to increased implementation and thus a decreased necessity for the two-year rodent bioassay. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Enhanced replication of damaged SV40 DNA in carcinogen-treated monkey cells

International Nuclear Information System (INIS)

Maga, J.A.; Dixon, K.

1984-01-01

Treatment of mammalian cells with certain chemical or physical carcinogens prior to infection with ultraviolet-irradiated virus results in enhanced survival or reactivation of the damaged virus. To investigate the molecular basis of this enhanced reactivation (ER), Simian virus 40 DNA replication in carcinogen-treated cells was examined. Treatment of monkey kidney cells with N-acetoxy-2-acetylamino-fluorene or UV radiation 24 h prior to infection with ultraviolet-irradiated Simian virus 40 leads to enhancement of viral DNA replication measured at 36 h after infection by [ 3 H]thymidine incorporation or hybridization. The enhancement of DNA replication is observed when cells are treated from 1 to 60 h before infection or 1 to 16 h after infection. The fact that enhancement is observed also when cells are treated after infection rules out the possiblity that enhancement occurs at the level of adsorption or penetration of the virus. Measurements of the time course of viral DNA replication indicate that pretreatment of cells does not alter the time of onset of viral DNA replication. It is concluded that ER of Simain virus 40 occurs at the level of viral DNA replication. (author)

Dietary acrylamide intake and the risk of lymphatic malignancies: the Netherlands Cohort Study on diet and cancer.

Directory of Open Access Journals (Sweden)

Mathilda L Bongers

Full Text Available BACKGROUND: Acrylamide, a probable human carcinogen, is present in many everyday foods. Since the finding of its presence in foods in 2002, epidemiological studies have found some suggestive associations between dietary acrylamide exposure and the risk of various cancers. The aim of this prospective study is to investigate for the first time the association between dietary acrylamide intake and the risk of several histological subtypes of lymphatic malignancies. METHODS: The Netherlands Cohort Study on diet and cancer includes 120,852 men and women followed-up since September 1986. The number of person years at risk was estimated by using a random sample of participants from the total cohort that was chosen at baseline (n =5,000. Acrylamide intake was estimated from a food frequency questionnaire combined with acrylamide data for Dutch foods. Hazard ratios (HRs were calculated for acrylamide intake as a continuous variable as well as in categories (quintiles and tertiles, for men and women separately and for never-smokers, using multivariable-adjusted Cox proportional hazards models. RESULTS: After 16.3 years of follow-up, 1,233 microscopically confirmed cases of lymphatic malignancies were available for multivariable-adjusted analysis. For multiple myeloma and follicular lymphoma, HRs for men were 1.14 (95% CI: 1.01, 1.27 and 1.28 (95% CI: 1.03, 1.61 per 10 µg acrylamide/day increment, respectively. For never-smoking men, the HR for multiple myeloma was 1.98 (95% CI: 1.38, 2.85. No associations were observed for women. CONCLUSION: We found indications that acrylamide may increase the risk of multiple myeloma and follicular lymphoma in men. This is the first epidemiological study to investigate the association between dietary acrylamide intake and the risk of lymphatic malignancies, and more research into these observed associations is warranted.

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

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

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

A Systematic Review of Carcinogenic Outcomes and Potential Mechanisms from Exposure to 2,4-D and MCPA in the Environment

Directory of Open Access Journals (Sweden)

Katherine von Stackelberg

2013-01-01

Full Text Available Chlorophenoxy compounds, particularly 2,4-dichlorophenoxyacetic acid (2,4-D and 4-chloro-2-methylphenoxyacetic acid (MCPA, are amongst the most widely used herbicides in the United States for both agricultural and residential applications. Epidemiologic studies suggest that exposure to 2,4-D and MCPA may be associated with increased risk non-Hodgkins lymphoma (NHL, Hodgkin’s disease (HD, leukemia, and soft-tissue sarcoma (STS. Toxicological studies in rodents show no evidence of carcinogenicity, and regulatory agencies worldwide consider chlorophenoxies as not likely to be carcinogenic or unclassifiable as to carcinogenicity. This systematic review assembles the available data to evaluate epidemiologic, toxicological, pharmacokinetic, exposure, and biomonitoring studies with respect to key cellular events noted in disease etiology and how those relate to hypothesized modes of action for these constituents to determine the plausibility of an association between exposure to environmentally relevant concentrations of 2,4-D and MCPA and lymphohematopoietic cancers. The combined evidence does not support a genotoxic mode of action. Although plausible hypotheses for other carcinogenic modes of action exist, a comparison of biomonitoring data to oral equivalent doses calculated from bioassay data shows that environmental exposures are not sufficient to support a causal relationship. Genetic polymorphisms exist that are known to increase the risk of developing NHL. The potential interaction between these polymorphisms and exposures to chlorophenoxy compounds, particularly in occupational settings, is largely unknown.

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.

[To-day exposure to occupational carcinogens and their effects. The experience of the rubber industry, iron metallurgy, asphalt work and aviculture].

Science.gov (United States)

Barbieri, Pietro Gino

2009-01-01

While the progressive improvement of hygiene situations in the workplaces has taken to a reduction of chemical carcinogens exposure, in recent years in Italy the number of compensated occupational cancer resulting from carcinogens exposures of distant decades, has been increasing. Nevertheless, several experiences suggest that the proportion of occupational cancers unrecognised and not notified, as required by law, still remains important. This contribution concerns some experiences, performed between 2004-2008 by the Local Occupational Health Service (SPSAL) located in a highly industrialised province, on the working sector of rubber, iron and steel industry, the asphalt working and the poultry stock-breeders. This work concerns the following issues: - the evaluation of carcinogens exposure; - technical preventive measures and personal protection; - the level of workers' information and formation and the registration of exposed workers; - the characterization of work-related cancer. The results of the 5 years of activity allow us to underline that, in the most of 49 plants involved in the study, the carcinogens exposure evaluation and the prevention and protection measures were lacking. Information of workers was largely deficient and the registration of exposed workers was absent. A major attention to detect and to evaluate the work-related cancer has allowed us to recognize 50 new cases in the iron-steel industries and 21 new cases in a rubber industry. Although this experience concerns only few occupational fields, it provides the basis to call for a greater commitment of SPSAL addressed to companies and general practitioners to both, the promotion and surveillance of the correct procedures of carcinogens exposure evaluation and his prevention, and the active detection of occupational cancer, still missing.

The expression of xenobiotic-metabolizing enzymes in human prostate and in prostate epithelial cells (PECs) derived from primary cultures.

Science.gov (United States)

Al-Buheissi, S Z; Cole, K J; Hewer, A; Kumar, V; Bryan, R L; Hudson, D L; Patel, H R; Nathan, S; Miller, R A; Phillips, D H

2006-06-01

Dietary heterocyclic amines (HCAs) are carcinogenic in rodent prostate requiring activation by enzymes such as cytochrome P450 (CYP) and N-acetyltransferase (NAT). We investigated by Western blotting and immunohistochemistry the expression of CYP1A1, CYP1A2, and NAT1 in human prostate and in prostate epithelial cells (PECs) derived from primary cultures and tested their ability to activate the dietary carcinogen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and its N-hydroxy metabolite (N-OH-IQ) to DNA-damaging moieties. Western blotting identified CYP1A1, CYP1A2, and NAT1. Immunohistochemistry localized NAT1 to the cytoplasm of PECs. Inter-individual variation was observed in the expression levels of CYP1A1, 1A2, and NAT1 (11, 75, and 35-fold, respectively). PECs expressed CYP1A1 and NAT1 but not CYP1A2. When incubated with IQ or N-OH-IQ, PECs formed DNA adducts indicating their ability to metabolically activate these compounds. Prostate cells possess the capacity to activate dietary carcinogens. PECs may provide a useful model system to study their role in prostate carcinogenesis.

On the contribution of polycyclic aromatic hydrocarbons to the carcinogenic impact of automobile exhaust condensate evaluated by local application onto mouse skin.

Science.gov (United States)

Grimmer, G; Brune, H; Deutsch-Wenzel, R; Naujack, K W; Misfeld, J; Timm, J

1983-11-01

The objective of this investigation was to identify the substances chiefly responsible for the carcinogenicity of automobile exhaust condensate using topical application onto the skin of mice. This was performed by comparing the carcinogenic effect of various fractions with that of an unseparated sample of automobile exhaust condensate, tested in 3 different doses. The probit and Weibull analysis of the result shows: (a) The condensate, emitted from a gasoline-driven automobile provokes local tumors after long-term application to the dorsal skin of mice. The tumor incidence demonstrates a clear cut dose-response relationship. (b) The fraction of polycyclic aromatic hydrocarbons (PAH) containing more than 3 rings accounts for about 84-91% of the total carcinogenicity of automobile exhaust condensate. This fraction represents only about 3.5% by wt of the condensate. (c) The content of benzo[a]pyrene (BaP) (0.414 mg/g) accounts for 6-7.6% of the total carcinogenicity of automobile exhaust condensate, 15 selected PAHs for about 41%. (d) Regarding the minor effect of the PAH-free fraction (about 83% by wt), no hints for a cocarcinogenic activity were observed.

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.

Protection by caffeine against oxic radiation damage and chemical carcinogens : mechanistic considerations

International Nuclear Information System (INIS)

Kesavan, P.C.

1992-01-01

There is little doubt that caffeine administered after exposure to UV light enhances the damage to cells and organisms by inhibiting photoreactivation, excision and/or recombinational repair. However, when already present in the system, it affords remarkable protection not only against O 2 -dependent component of radiation damage, but also against chemical carcinogens that require metabolic activation. Possible mechanistic aspects are discussed briefly. (author). 81 refs

Influence of dietary fiber from coconut kernel (Cocos nucifera) on the 1,2-dimethylhydrazine-induced lipid peroxidation in rats.

Science.gov (United States)

Pillai, M G; Thampi, B S; Menon, V P; Leelamma, S

1999-09-01

The influence of dietary fiber from coconut kernel isolated by the neutral detergent fiber method on the antioxidant status in rats treated with the colon specific carcinogen 1,2-dimethylhydrazine (DMH) was studied in rats fed a high-fat diet for 15 weeks. The DMH-treated fiber group showed higher levels of lipid peroxides than the control group treated with DMH at the preneoplastic and neoplastic stages. Free fatty acid levels were found to decrease significantly in the DMH-treated control group, whereas it was near normal in the fiber groups. Superoxide dismutase and catalase activity also were found to be increased in the liver, intestine, proximal colon, and distal colon. Glutathione levels in all the tissues studied showed significant decreases in the fiber group. The results suggest that coconut kernel fiber can protect cells from loss of oxidative capacity with the administration of the procarcinogen DMH.

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.

Polycyclic aromatic hydrocarbons in cigarette sidestream smoke particulates from a Taiwanese brand and their carcinogenic relevance.

Science.gov (United States)

Lee, Hui-Ling; Hsieh, Dennis P H; Li, Lih-Ann

2011-01-01

Polycyclic aromatic hydrocarbons (PAHs) adsorbed on cigarette sidestream smoke particulates (CSSPs) have been regarded as important contributors to lung carcinogenesis in never smokers. However, limited information is available on PAH levels in cigarette sidestream smoke. Here we determine the concentrations of 22 PAHs, including 16 US EPA priority PAHs, in CSSPs generated from a high market-share domestic brand in Taiwan. Five of the 22 PAHs are undetectable. The remaining 17 PAHs constitute about 0.022% of the total mass of CSSPs. Near one fifth of the PAH mass come from IARC group 1 and group 2 carcinogens. Carcinogenic potency is equivalent to 144 ng benzo[a]pyrene per cigarette converted according to potency equivalency factors (PEFs). The CSSP condensate could activate AhR activity and induce AhR target gene expression. High concentrations of CSSPs also exhibited AhR-independent cytotoxicity. However, mixing the 17 PAHs as the composition in the CSSP condensate could not reconstitute either capacity. Since AhR activation and cytotoxicity are important mechanisms underlying carcinogenic potency, the results suggest that other component compounds play a more active role in carcinogenesis. The approach of individual PAH profiling plus PEF conversion commonly used in risk assessment is likely to underestimate the risk caused by environmental cigarette smoke exposure. Copyright © 2010 Elsevier Ltd. All rights reserved.

Modulatory role of dietary Chlorella vulgaris powder against arsenic-induced immunotoxicity and oxidative stress in Nile tilapia (Oreochromis niloticus).

Science.gov (United States)

Zahran, Eman; Risha, Engy

2014-12-01

Arsenic intoxicant have long been regarded as an impending carcinogenic, genotoxic, and immunotoxic heavy metal to human and animals as well. In this respect, we evaluated biomarkers of the innate immune response and oxidative stress metabolism in gills and liver of Nile tilapia (Oreochromis niloticus) after arsenic exposure, and the protective role of Chlorella vulgaris (Ch) dietary supplementation were elucidated. Protective role of C. vulgaris (Ch), as supplementary feeds (5% and 10% of the diet) was studied in Nile tilapia (O. niloticus) against arsenic induced toxicity (NaAsO2 at 7 ppm) for 21 days exposure period. A significant down-regulation in innate immune response; including, respiratory burst, lysozyme, and bactericidal activity followed due to deliberately As(+3) exposure. Similarly, oxidative stress response; like nitric oxide (NO), catalase (CAT), glutathione (GSH), glutathione peroxidase (GPx), malondialdehyde (MDA) and hydrogen peroxide (H2O2) levels were significantly decreased. Combined treatment of Ch and As(+3) significantly enhanced the innate immune response and antioxidant activity. Strikingly, Ch supplementation at 10% has been considered the optimum for Nile tilapia since it exhibited enhancement of innate immune response and antioxidant activity over the level 5%, and even better than that of control level. Thus, our results concluded that dietary Ch supplementation could protect Nile tilapia against arsenic induced immunosuppression and oxidative stresses. Copyright © 2014 Elsevier Ltd. All rights reserved.

Carcinogens, Teratogens and Mutagens: Their Impact on Occupational Health, Particularly for Women in Veterinary Medicine.

Science.gov (United States)

Milligan, J. E.; And Others

1983-01-01

Pregnant women, especially those working in veterinary medicine, face occupational health/disease risks from mutagens, teratogens, and carcinogens. These hazards can be placed into three categories: physical, chemical, and biological. Each of these hazards is discussed with examples. (Author/JN)

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

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

Different mechanisms of modulation of gap junction communication by non-genotoxic carcinogens in rat liver in vivo

International Nuclear Information System (INIS)

Cowles, C.; Mally, A.; Chipman, J.K.

2007-01-01

This is a comparative study of the mechanisms by which three different rodent non-genotoxic carcinogens modulate connexin-mediated gap junction intercellular communication in male rat liver in vivo. In the case of the peroxisome proliferating agent Wy-14,643, a non-hepatotoxic dose of 50 mg/kg led to a marked loss of inter-hepatocyte dye transfer associated with a loss of both Cx32 and Cx26 protein expression. In contrast, p,p'-dichlorodiphenyltrichloroethane (DDT) at a non-hepatotoxic dose (25 mg/kg) was not found to alter Cx32 or Cx26 expression or to produce a measurable Cx32 serine phosphorylation but did give a small, significant reduction of cell communication. Carbon tetrachloride (CCl 4 ) did not affect cell communication (despite a small significant reduction of Cx32 content) at a non-hepatotoxic dose. Both loss of communication and Cx32 expression was observed only at a dose that caused hepatocyte toxicity as evidenced by increased serum alanine aminotransferase activity. Overall, the findings emphasise that loss of gap junctional communication in vivo can contribute to carcinogenesis by non-genotoxic carcinogens through different primary mechanism. In contrast to Wy-14,643 and DDT, the results with CCl 4 are consistent with a requirement for hepatotoxicity in its carcinogenic action

TRANSCRIPTOMIC ANALYSIS OF F344 RAT NASAL EPITHELIUM SUGGESTS THAT THE LACK OF CARCINOGENIC RESPONSE TO GLUTARALDEHYDE IS DUE TO ITS GREATER TOXICITY COMPARED TO FORMALDEHYDE

Science.gov (United States)

Formaldehyde is cytotoxic and carcinogenic to the rat nasal respiratory epithelium inducing tumors after 12 months. Glutaraldehyde is also cytotoxic but is not carcinogenic to nasal epithelium even after 24 months. Both aldehydes induce similar acute and subchronic histopathology...

Dietary modulation of the biotransformation and genotoxicity of aflatoxin B1

International Nuclear Information System (INIS)

Gross-Steinmeyer, Kerstin; Eaton, David L.

2012-01-01

Diet and its various components are consistently identified as among the most important ‘risk factors’ for cancer worldwide, yet great uncertainty remains regarding the relative contribution of nutritive (e.g., vitamins, calories) vs. non-nutritive (e.g., phytochemicals, fiber, contaminants) factors in both cancer induction and cancer prevention. Among the most potent known human dietary carcinogens is the mycotoxin, aflatoxin B 1 (AFB). AFB and related aflatoxins are produced as secondary metabolites by the molds Aspergillus flavus and Aspergillus parasiticus that commonly infect poorly stored foods including peanuts, pistachios, corn, and rice. AFB is a potent hepatocarcinogenic agent in numerous animal species, and has been implicated in the etiology of human hepatocellular carcinoma. Recent research has shown that many diet-derived factors have great potential to influence AFB biotransformation, and some efficiently protect from AFB-induced genotoxicity. One key mode of action for reducing AFB-induced carcinogenesis in experimental animals was shown to be the induction of detoxification enzymes such as certain glutathione-S-transferases that are regulated through the Keap1–Nrf2–ARE signaling pathway. Although initial studies utilized the dithiolthione drug, oltipraz, as a prototypical inducer of antioxidant response, dietary components such as suforaphane (SFN) are also effective inducers of this pathway in rodent models. However, human GSTs in general do not appear to be extensively induced by SFN, and GSTM1 – the only human GST with measurable catalytic activity toward aflatoxin B 1 -8,9-epoxide (AFBO; the genotoxic metabolite of AFB), does not appear to be induced by SFN, at least in human hepatocytes, even though its expression in human liver cells does appear to offer considerable protection against AFB–DNA damage. Although induction of detoxification pathways has served as the primary mechanistic focus of chemoprevention studies, protective

Marketing dietary supplements in the United States: A review of the requirements for new dietary ingredients

International Nuclear Information System (INIS)

Noonan, Chris; Patrick Noonan, W.

2006-01-01

Since the passage of the Dietary Supplement Health and Education Act in 1994, the marketplace for dietary supplements has experienced dramatic growth. New products have redefined the entire marketplace, and new ingredients are introduced to consumers at lightning speed. As part of this act, laws were passed to ensure the safety of new dietary ingredients introduced into the United States marketplace. But more than 11 years later, these laws are frequently misunderstood, and more frequently ignored. This article reviews the regulatory landscape of new dietary ingredients and defines the issues manufacturers must contend with to legally market dietary supplements with new dietary ingredients in the U.S

Ochratoxin A Dietary Exposure of Ten Population Groups in the Czech Republic: Comparison with Data over the World.

Science.gov (United States)

Ostry, Vladimir; Malir, Frantisek; Dofkova, Marcela; Skarkova, Jarmila; Pfohl-Leszkowicz, Annie; Ruprich, Jiri

2015-09-10

Ochratoxin A is a nephrotoxic and renal carcinogenic mycotoxin and is a common contaminant of various food commodities. Eighty six kinds of foodstuffs (1032 food samples) were collected in 2011-2013. High-performance liquid chromatography with fluorescence detection was used for ochratoxin A determination. Limit of quantification of the method varied between 0.01-0.2 μg/kg depending on the food matrices. The most exposed population is children aged 4-6 years old. Globally for this group, the maximum ochratoxin A dietary exposure for "average consumer" was estimated at 3.3 ng/kg bw/day (lower bound, considering the analytical values below the limit of quantification as 0) and 3.9 ng/kg bw/day (middle bound, considering the analytical values below the limit of quantification as 1/2 limit of quantification). Important sources of exposure for this latter group include grain-based products, confectionery, meat products and fruit juice. The dietary intake for "high consumers" in the group 4-6 years old was estimated from grains and grain-based products at 19.8 ng/kg bw/day (middle bound), from tea at 12.0 ng/kg bw/day (middle bound) and from confectionery at 6.5 ng/kg bw/day (middle bound). For men aged 18-59 years old beer was the main contributor with an intake of 2.60 ng/kg bw/day ("high consumers", middle bound). Tea and grain-based products were identified to be the main contributors for dietary exposure in women aged 18-59 years old. Coffee and wine were identified as a higher contributor of the OTA intake in the population group of women aged 18-59 years old compared to the other population groups.

Transformation assay in Bhas 42 cells: a model using initiated cells to study mechanisms of carcinogenesis and predict carcinogenic potential of chemicals.

Science.gov (United States)

Sasaki, Kiyoshi; Umeda, Makoto; Sakai, Ayako; Yamazaki, Shojiro; Tanaka, Noriho

2015-01-01

Transformation assays using cultured cells have been applied to the study of carcinogenesis. Although various cell systems exist, few cell types such as BALB/c 3T3 subclones and Syrian hamster embryo cells have been used to study chemically induced two-stage carcinogenesis. Bhas 42 cells were established as a clone by the transfection with the v-Ha-ras gene into mouse BALB/c 3T3 A31-1-1 cells and their subsequent selection based on their sensitivity to 12-O-tetradecanoylphorbol-13-acetate. Using Bhas 42 cells, transformed foci were induced by the treatment with nongenotoxic carcinogens, most of which act as tumor promoters. Therefore, Bhas 42 cells were considered to be a model of initiated cells. Subsequently, not only nongenotoxic carcinogens but also genotoxic carcinogens, most of which act as tumor initiators, were found to induce transformed foci by the modification of the protocol. Furthermore, transformation of Bhas 42 cells was induced by the transfection with genes of oncogenic potential. We interpret this high sensitivity of Bhas 42 cells to various types of carcinogenic stimuli to be related to the multistage model of carcinogenesis, as the transfection of v-Ha-ras gene further advances the parental BALB/c 3T3 A31-1-1 cells toward higher transforming potential. Thus, we propose that Bhas 42 cells are a novel and sensitive cell line for the analysis of carcinogenesis and can be used for the detection of not only carcinogenic substances but also gene alterations related to oncogenesis. This review will address characteristics of Bhas 42 cells, the transformation assay protocol, validation studies, and the various chemicals tested in this assay.

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.

Dietary patterns and colorectal cancer

OpenAIRE

Tayyem, Reema F.; Bawadi, Hiba A.; Shehadah, Ihab; Agraib, Lana M.; AbuMweis, Suhad S.; Al-Jaberi, Tareq; Al-Nusairr, Majed; Bani-Hani, Kamal E.; Heath, Dennis D.

2016-01-01

Summary Background & aimsDietary pattern and lifestyle have been reported to be important risk factors in the development of colorectal cancer (CRC). However, the mechanism of action of dietary factors in CRC disease is unclear. The aim of this study is the examination of several dietary choices and their potential association with the risk of developing CRC. MethodsDietary data was collected from 220 subjects who were previously diagnosed with CRC, and 281 control subjects (matched by age, g...

A novel approach: chemical relational databases, and the role of the ISSCAN database on assessing chemical carcinogenicity.

Science.gov (United States)

Benigni, Romualdo; Bossa, Cecilia; Richard, Ann M; Yang, Chihae

2008-01-01

Mutagenicity and carcinogenicity databases are crucial resources for toxicologists and regulators involved in chemicals risk assessment. Until recently, existing public toxicity databases have been constructed primarily as "look-up-tables" of existing data, and most often did not contain chemical structures. Concepts and technologies originated from the structure-activity relationships science have provided powerful tools to create new types of databases, where the effective linkage of chemical toxicity with chemical structure can facilitate and greatly enhance data gathering and hypothesis generation, by permitting: a) exploration across both chemical and biological domains; and b) structure-searchability through the data. This paper reviews the main public databases, together with the progress in the field of chemical relational databases, and presents the ISSCAN database on experimental chemical carcinogens.

Assessing patients' attitudes towards dietary supplements.

Science.gov (United States)

Wierzejska, Regina; Jarosz, Mirosław; Siuba, Magdalena; Rambuszek, Michał

2014-01-01

There is currently many over the counter products on the market that exert nutritional or physiological effects on the human body. The differences between dietary supplements and non-prescription drugs are however poorly understood by the average consumer and may thus affect their expectations as to the desired effect produced on the body. To evaluate patients' knowledge and attitudes towards dietary supplements as compared to non-prescription drugs. Subjects were 335 patients of the Mazowiecki Voivodeship Hospital in Warsaw, Poland. The data were collected from a face-to-face interview using a single and multiple choice questionnaire with 10 questions on dietary supplements. Statistical analysis used the Chi-square (χ2) test. The majority of respondents were found to be familiar with the term 'dietary supplements', but had difficulties in classifying these products into appropriate categories. Over 55% do not consider dietary supplements to be foodstuffs and more than 40% considered such products to be drugs. Most respondents thought that the main purpose of taking dietary supplements is to improve nutrition, but over one third expected them to also treat disease. Over 70% declared taking notice to which category the non-prescription products they bought belongs to ie. whether non-prescription drugs (medicinal products) or dietary supplements. Many patients mistakenly believe that dietary supplements are drugs and can be used to treat disease and health disorders. dietary supplements, opinion on dietary supplements, nutrition, dietary supplement vs. medicinal product.

Dietary Antioxidants Effectiveness on Carbon Tetrachloride-Induced Hepatotoxicity in Adult Female Albino Rats

International Nuclear Information System (INIS)

EI-Sherbiny, E.M.; EI-Mahdy, A.A.

2008-01-01

Hepatic toxicity through carbon tetrachloride (CCI 4 ) induced lipid peroxidation was extensively used in experimental models to understand the cellular mechanisms behind oxidative damage and to evaluate the therapeutic potential of drugs and dietary antioxidants. The ameliorative effect of Aloe vera juice and carrot supplementation on hepato carcinogenesis induced by carbon tetrachloride in adult female albino rats was investigated. The carcinogenic process was determined by measuring gamma-glutamyl transpeptidase (GGT), ornithine carbamyl transferase (OCT), thiobarbituric acid reactive substances (TBARs), representing levels of lipid peroxides, and carcinoembryonic antigen (CEA) in the sera of female albino rats. Carbon tetrachloride significantly elevated the serum GGT, OCT activities and the level of TBARs. Administration of Aloe vera leaf juice filtrate after CCl 4 treatment resulted in a non-significant modification in GGT, OCT activities and significantly improved the level of TBARs in comparison with control. Supplementation of carrot to CCI 4 treated animals led to a great amelioration in OCT activity and TBARs level, whereas GGT activity was ameliorated but statistically changed compared to control. There was a non-significant alteration in the level of CEA in all treated groups compared to normal control one

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

Acculturation and dietary patterns among residents of Surinamese origin in the Netherlands: the HELIUS dietary pattern study.

Science.gov (United States)

Sturkenboom, Suzanne M; Dekker, Louise H; Lamkaddem, Majda; Schaap, Laura A; de Vries, Jeanne H M; Stronks, Karien; Nicolaou, Mary

2016-03-01

Insight into the role of acculturation in dietary patterns is important to inform the development of nutrition programmes that target ethnic minority groups. Therefore, the present study aimed to investigate how the adherence to dietary patterns within an ethnic minority population in the Netherlands varies by acculturation level compared with the host population. Cross-sectional study using data of the HELIUS study. Dietary patterns were assessed with an ethnic-specific FFQ. Acculturation was operationalized using unidimensional proxies (residence duration, age at migration and generation status) as well as on the basis of the bidimensional perspective, defined by four distinct acculturation strategies: assimilation, integration, separation and marginalization. Amsterdam, the Netherlands. Participants of Dutch (n 1370) and Surinamese (n 1727) origin. Three dietary patterns were identified: (i) 'noodle/rice dishes and white meat' (traditional Surinamese pattern); (ii) 'red meat, snacks and sweets'; and (iii) 'vegetables, fruit and nuts'. Surinamese-origin respondents adhered more to the traditional Surinamese pattern than the other dietary patterns. Neither the unidimensional proxies nor the bidimensional acculturation strategies demonstrated consistent associations with dietary patterns. The lack of consistent association between acculturation and dietary patterns in the present study indicates that dietary patterns are quite robust. Understanding the continued adherence to traditional dietary patterns when developing dietary interventions in ethnic minority groups is warranted.

Structure alerts for carcinogenicity, and the Salmonella assay system: a novel insight through the chemical relational databases technology.

Science.gov (United States)

Benigni, Romualdo; Bossa, Cecilia

2008-01-01

In the past decades, chemical carcinogenicity has been the object of mechanistic studies that have been translated into valuable experimental (e.g., the Salmonella assays system) and theoretical (e.g., compilations of structure alerts for chemical carcinogenicity) models. These findings remain the basis of the science and regulation of mutagens and carcinogens. Recent advances in the organization and treatment of large databases consisting of both biological and chemical information nowadays allows for a much easier and more refined view of data. This paper reviews recent analyses on the predictive performance of various lists of structure alerts, including a new compilation of alerts that combines previous work in an optimized form for computer implementation. The revised compilation is part of the Toxtree 1.50 software (freely available from the European Chemicals Bureau website). The use of structural alerts for the chemical biological profiling of a large database of Salmonella mutagenicity results is also reported. Together with being a repository of the science on the chemical biological interactions at the basis of chemical carcinogenicity, the SAs have a crucial role in practical applications for risk assessment, for: (a) description of sets of chemicals; (b) preliminary hazard characterization; (c) formation of categories for e.g., regulatory purposes; (d) generation of subsets of congeneric chemicals to be analyzed subsequently with QSAR methods; (e) priority setting. An important aspect of SAs as predictive toxicity tools is that they derive directly from mechanistic knowledge. The crucial role of mechanistic knowledge in the process of applying (Q)SAR considerations to risk assessment should be strongly emphasized. Mechanistic knowledge provides a ground for interaction and dialogue between model developers, toxicologists and regulators, and permits the integration of the (Q)SAR results into a wider regulatory framework, where different types of

Short Tools to Assess Young Children's Dietary Intake: A Systematic Review Focusing on Application to Dietary Index Research

Directory of Open Access Journals (Sweden)

Lucinda K. Bell

2013-01-01

Full Text Available Dietary indices evaluate diet quality, usually based on current dietary guidelines. Indices can therefore contribute to our understanding of early-life obesity-risk dietary behaviours. Yet indices are commonly applied to dietary data collected by onerous methods (e.g., recalls or records. Short dietary assessment instruments are an attractive alternative to collect data from which to derive an index score. A systematic review of studies published before April 2013 was conducted to identify short (≤50 items tools that measure whole-of-diet intake of young children (birth-five years and are applicable to dietary indices, in particular screening obesogenic dietary behaviours. The search identified 3686 papers of which 16, reporting on 15 tools (n=7, infants and toddlers birth-24 months; n=8, preschoolers 2–5 years, met the inclusion criteria. Most tools were food frequency questionnaires (n=14, with one innovative dietary questionnaire identified. Seven were tested for validity or reliability, and one was tested for both. Six tools (n=2, infants and toddlers; n=4, preschoolers are applicable for use with current dietary indices, five of which screen obesogenic dietary behaviours. Given the limited number of brief, valid and reliable dietary assessment tools for young children to which an index can be applied, future short tool development is warranted, particularly for screening obesogenic dietary behaviours.

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

Preferential binding of growth inhibitory prostaglandins by the target protein of a carcinogen

Energy Technology Data Exchange (ETDEWEB)

Khan, S.H.; Sorof, S. (Fox Chase Cancer Center, Philadelphia, PA (United States))

1990-12-01

Liver fatty acid binding protein (L-FABP) is the principal target protein of the hepatic carcinogen N-(2-fluorenyl)acetamide (2-acetylaminofluorene) in rat liver. In addition, the cyclopentenone prostaglandins (PG), PGA, PGJ{sub 2}, and {Delta}{sup 12}-PGJ{sub 2}, inhibit the growth of many cell types in vitro. This report describes the preferential binding of the growth inhibitory prostaglandins by L-FABP and the reversible inhibition of thymidine incorporation into DNA by PGA{sub 2} and {Delta}{sup 12}-PGJ{sub 2} in primary cultures of purified rat hepatocytes. As a model ligand, ({sup 3}H)PGA{sub 1} bound to L-FABP specifically, reversibly, rapidly, and with high affinity. Its dissociation constants were 134 nM (high affinity) and 3.6 {mu}M (low affinity). The high-affinity finding of ({sup 3}H)PGA{sup 1} correlated with their growth inhibitory activities reported previously and here. The in vitro actions of L-FABP are compatible with those of a specific and dissociable carrier of growth inhibitory prostaglandins in rat hepatocytes and suggest that the carcinogen may usurp the cellular machinery of the growth inhibitory prostaglandins.

Potency of carcinogens derived from covalent DNA binding and stimulation of DNA synthesis in rat liver

International Nuclear Information System (INIS)

Lutz, W.K.; Buesser, M.T.; Sagelsdorff, P.

1984-01-01

In order to investigate the role of the stimulation of cell division for the initiation (and possibly promotion) of liver tumors by chemical carcinogens, the incorporation of radiolabelled thymidine into liver DNA was determined in male rats. Single doses of various levels of aflatoxin B1, benzidine and carbon tetrachloride (all known to be genotoxic via DNA binding) did not affect cell division, whereas several hepatocarcinogens known not to bind to DNA (alpha-HCH, clofibrate, and 2,3,7,8-tetrachlorodibenzo-p-dioxin) gave rise to a dose-dependent stimulation of liver DNA synthesis within 24 h. An equation combining the influences of mitotic stimulation, expressed as dose required to double the control level of DNA synthesis, and DNA binding potency, expressed as the Covalent Binding Index, correlated well with the carcinogenic potency for both classes of hepatocarcinogens

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.

Lack of adverse health effects following 30-weeks of dietary exposure to acrylamide at low doses in male F344 rats

Directory of Open Access Journals (Sweden)

Jayadev Raju

Full Text Available Understanding the health hazards following exposure to food-borne acrylamide, especially at low levels typified by human diets, is an ongoing food safety issue. We recently published results from a study that aimed to understand the effects of acrylamide short-term exposure at doses known to cause tumors in rodents, demonstrating that a number of key toxicological end points were altered by acrylamide exposure. Additionally, we reported that at much lower doses for 30 weeks of exposure, dietary acrylamide was ‘not a complete carcinogen’ to the colon in an organ-specific rodent carcinogenesis study but acted as a co-carcinogen along with azoxymethane (AOM, a colon-specific carcinogen. Here, we present toxicological data from a sub-set of this long-term exposure study from animals that received saline (instead of AOM. Briefly, male F344 rats were randomized to receive acrylamide at 0.5, 1.0 and 2.0 mg/kg diet (∼0.02, 0.04, and 0.09 mg/kg BW/day, respectively or no acrylamide (control, for 30 weeks; all rats were then euthanized and their tissues harvested and processed for toxicological evaluation. We report that at the doses tested, acrylamide did not cause any changes in general well-being, body weight or food intake. Similarly, acrylamide did not cause any biologically relevant change in parameters associated with immunophenotyping, serum biochemistry or hematology. Histopathology assessment of tissues showed no changes except in the testis, where non-specific mild lesions were observed in all the groups, inclusive of the controls. No neuropathological effects of acrylamide were observed in the brain and nerve tissues. Together, these results suggest that acrylamide administered to rats through the diet at low doses for 30 weeks did not cause any toxicologically relevant changes. Given that the doses of acrylamide in the current study are low and are comparable to human dietary exposure, this null-effect study provides data that

Environmental Carcinogen Releases and Lung Cancer Mortality in Rural-Urban Areas of the United States

Science.gov (United States)

Luo, Juhua; Hendryx, Michael

2011-01-01

Purpose: Environmental hazards are unevenly distributed across communities and populations; however, little is known about the distribution of environmental carcinogenic pollutants and lung cancer risk across populations defined by race, sex, and rural-urban setting. Methods: We used the Toxics Release Inventory (TRI) database to conduct an…

Carcinogenic agents present in the atmosphere and incidence of primary lung tumors in mice

Energy Technology Data Exchange (ETDEWEB)

Campbell, J A

1939-01-01

Exposure of mice to suspended benzene extracts of exhaust pipe soot from engine burning heavy oil for once/hr, 6 hr/day, for a lifetime, produced a slight increase in lung tumors whereas chimney soot had no effect. Conversely, chimney soot extract painted on skin was judged carcinogenic, whereas exhaust soot did not produce cancer.

Determination of potentially carcinogenic compounds in food : trace analysis of vinylchloride, vinylidenechloride, acrylonitrile, epichlorohydrin and diethylpyrocarbonate

NARCIS (Netherlands)

Lierop, van J.B.H.

1979-01-01

Toxicological evidence shows that some monomers present in packaging materials may be carcinogenic. These monomers, notably vinylchloride, vinylidenechloride, acrylonitrile and epichlorohydrin, may migrate from the packaging material into the food. Therefore, severe limits are set to the contents of

The effect of substituents in the aromatic ring on carcinogenicity of N-nitrosomethylaniline in F344 rats.

Science.gov (United States)

Kroeger-Koepke, M B; Reuber, M D; Iype, P T; Lijinsky, W; Michejda, C J

1983-01-01

N-Nitroso-N-methylaniline (NMA) and N-nitroso-N-methyl-4-fluoroaniline (p-F-NMA), both non-mutagenic in Salmonella typhimurium and N-nitroso-N-methyl-4-nitroaniline (p-NO2-NMA), a potent mutagen, were tested for carcinogenicity in F344 rats. NMA was shown to induce a high level of tumors in the upper gastrointestinal tract, particularly in the esophagus. Male rats treated with NMA died with tumors at a slightly higher rate than females, although the final tumor yield was the same. Most of the rats treated with p-F-NMA also developed tumors of the esophagus, but they died less rapidly than the NMA treated rats, indicating that p-F-NMA is a slightly weaker carcinogen than NMA. The powerful, directly acting mutagen, p-NO2-NMA did not appear to induce tumors at all since its tumor spectrum was essentially identical to that of the untreated control rats. Thus, the carcinogenic activities of NMA and its substituted analogs do not appear to correlate with bacterial mutagenesis assays. Additionally, NMA, p-F-NMA and N-nitroso-N-methyl-4-bromoaniline, the last a strong mutagen in S. typhimurium, were shown not to induce sister chromatid exchanges in CHO cells and in a clone of a CHO:liver cell hybrid which had previously been shown to be sensitive to chemical agents which require metabolic activation.

Dietary fat content modulates the hypolipidemic effect of dietary inulin in rats.

Science.gov (United States)

Han, Kyu-Ho; Yamamoto, Aiko; Shimada, Ken-Ichiro; Kikuchi, Hiroto; Fukushima, Michihiro

2017-08-01

Dietary fat content (low versus high fat) may modulate the serum lipid-lowering effect of high-performance (HP)-inulin. This study investigated the effect of dietary HP-inulin on metabolism in rats fed a low- or high-fat diet. Rats were fed a diet of 5% fat with 5% cellulose or 5% HP-inulin (average degree of polymerization = 24) (low-fat diet) or of 20% fat with 5% cellulose or 5% HP-inulin (high-fat diet) for 28 days. Total, HDL, and non-HDL cholesterols, and triglyceride concentrations in the serum were measured along with total lipid content of liver and feces. Hepatic triglyceride and cholesterol, and fecal neutral and acidic sterol concentrations in total lipid were assessed. In addition, cecum SCFA levels and bacterial profiles were determined. The hypolipidemic effect of HP-inulin differed depending on dietary fat content (5% versus 20%). Specifically, 5% inulin instead of cellulose in a semi-purified diet significantly reduced serum lipid levels in rats fed a high-fat diet, which was strongly associated with increased total lipid and neutral sterol excretion. Dietary fat content modulates the hypolipidemic effect of dietary inulin. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

Dietary Intake of Competitive Bodybuilders.

Science.gov (United States)

Spendlove, Jessica; Mitchell, Lachlan; Gifford, Janelle; Hackett, Daniel; Slater, Gary; Cobley, Stephen; O'Connor, Helen

2015-07-01

Competitive bodybuilders are well known for extreme physique traits and extremes in diet and training manipulation to optimize lean mass and achieve a low body fat. Although many of the dietary dogmas in bodybuilding lack scientific scrutiny, a number, including timing and dosing of high biological value proteins across the day, have more recently been confirmed as effective by empirical research studies. A more comprehensive understanding of the dietary intakes of bodybuilders has the potential to uncover other dietary approaches, deserving of scientific investigation, with application to the wider sporting, and potential health contexts, where manipulation of physique traits is desired. Our objective was to conduct a systematic review of dietary intake practices of competitive bodybuilders, evaluate the quality and currency of the existing literature, and identify research gaps to inform future studies. A systematic search of electronic databases was conducted from the earliest record until March 2014. The search combined permutations of the terms 'bodybuilding', 'dietary intake', and 'dietary supplement'. Included studies needed to report quantitative data (energy and macronutrients at a minimum) on habitual dietary intake of competitive bodybuilders. The 18 manuscripts meeting eligibility criteria reported on 385 participants (n = 62 women). Most studies were published in the 1980-1990s, with three published in the past 5 years. Study methodological quality was evaluated as poor. Energy intake ranged from 10 to 24 MJ/day for men and from 4 to 14 MJ/day for women. Protein intake ranged from 1.9 to 4.3 g/kg for men and from 0.8 to 2.8 g/kg for women. Intake of carbohydrate and fat was 6 months from competition) or immediate post-competition period and lowest during competition preparation (≤6 months from competition) or competition week. The most commonly reported dietary supplements were protein powders/liquids and amino acids. The studies failed to provide

A one-electron oxidation of carcinogenic nonaminoazo dye Sudan I by horseradish peroxidase

Czech Academy of Sciences Publication Activity Database

Semanská, M.; Dračínský, Martin; Martínek, V.; Hudeček, J.; Hodek, P.; Frei, E.; Stiborová, M.

2008-01-01

Roč. 29, č. 5 (2008), s. 712-716 ISSN 0172-780X Grant - others:GA MŠk(CZ) 1M0505; GA ČR(CZ) GA203/06/0329 Program:1M Institutional research plan: CEZ:AV0Z40550506 Keywords : carcinogen * Sudan I * peroxidase * NMR spectroscopy * mechanism of oxidation Subject RIV: CC - Organic Chemistry Impact factor: 1.359, year: 2008 http://node.nel.edu

Effects of dietary beef, pork, chicken and salmon on intestinal carcinogenesis in A/J Min/+ mice.

Directory of Open Access Journals (Sweden)

Christina Steppeler

Full Text Available The International Agency for Research on Cancer has classified red meat as "probably carcinogenic to humans" (Group 2A. In mechanistic studies exploring the link between intake of red meat and CRC, heme iron, the pigment of red meat, is proposed to play a central role as a catalyzer of luminal lipid peroxidation and cytotoxicity. In the present work, the novel A/J Min/+ mouse was used to investigate the effects of dietary beef, pork, chicken, or salmon (40% muscle food (dry weight and 60% powder diet on Apc-driven intestinal carcinogenesis, from week 3-13 of age. Muscle food diets did not differentially affect carcinogenesis in the colon (flat ACF and tumors. In the small intestine, salmon intake resulted in a lower tumor size and load than did meat from terrestrial animals (beef, pork or chicken, while no differences were observed between the effects of white meat (chicken and red meat (pork and beef. Additional results indicated that intestinal carcinogenesis was not related to dietary n-6 polyunsaturated fatty acids, intestinal formation of lipid peroxidation products (thiobarbituric acid reactive substances, TBARS, or cytotoxic effects of fecal water on Apc-/+ cells. Notably, the amount of heme reaching the colon appeared to be relatively low in this study. The greatest tumor load was induced by the reference diet RM1, underlining the importance of the basic diets in experimental CRC. The present study in A/J Min/+ mice does not support the hypothesis of a role of red meat in intestinal carcinogenesis.

78 FR 4419 - Draft Report on Carcinogens Monographs for 1-Bromopropane and Cumene; Availability of Documents...

Science.gov (United States)

2013-01-22

... Monographs for 1-Bromopropane and Cumene; Availability of Documents; Request for Comments; Notice of Meeting SUMMARY: Peer review meeting of the Draft Report on Carcinogens (RoC) Monographs for 1-Bromopropane and... monographs will be available by January [[Page 4420