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Sample records for multi-organ carcinogenesis bioassay

  1. Alpha-linolenic acid-enriched diacylglycerol oil does not promote tumor development in tongue and gastrointestinal tract tissues in a medium-term multi-organ carcinogenesis bioassay using male F344 rat.

    Science.gov (United States)

    Honda, Hiroshi; Kawamoto, Taisuke; Doi, Yuko; Matsumura, Shoji; Ito, Yuichi; Imai, Norio; Ikeda, Naohiro; Mera, Yukinori; Morita, Osamu

    2017-08-01

    Alpha-linolenic acid (ALA)-enriched diacylglycerol (DAG) oil is an edible oil enriched with DAG (>80%) and ALA (>50%). The present study investigated whether ALA-DAG oil promotes tumorigenesis in the tongue and gastrointestinal tract, using a rat medium-term multi-organ carcinogenesis bioassay model. Rats were treated with five genotoxic carcinogens to induce multi-organ tumorigenesis until week 4, and from 1 week after withdrawal, fed a semi-synthetic diet (AIN-93G) containing ALA-DAG oil at concentrations of 0, 13,750, 27,500, and 55,000 ppm. Rats fed AIN-93G containing 55,000 ppm ALA-triacylglycerol or a standard basal diet served as reference and negative control groups, respectively. Animals were euthanized at week 30. ALA-DAG oil was shown to have no effects on survival, general condition, body weight, food consumption, or organ weight. More discolored spots were observed in the stomachs of the 13,750- and 55,000-ppm ALA-DAG groups than in those of the control groups; however, there were no differences in the frequency of histopathological findings across groups. There were no meaningful increases in the incidence of pre-neoplastic and neoplastic lesions in the tongue and gastrointestinal tract among the groups. We therefore conclude that ALA-DAG oil does not promote tumor development in the digestive system. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Effects of X-irradiation on N-methyl-N-nitrosourea-induced multi-organ carcinogenesis in rats

    International Nuclear Information System (INIS)

    Morishita, Yukiko; Tanaka, Takuji; Mori, Hideki; Sasaki, Shunsaku.

    1993-01-01

    The effects of X-irradiation on N-methyl-N-nitrosourea (MNU)-induced multi-organ carcinogenesis were examined in both sexes of ACI/N rats. At 6 weeks of age, rats in groups 1 (25 males, 25 females) and 3 (24 males, 23 females) received a single intraperitoneal injection of MNU (25 mg/kg body weight), while those in groups 2 (25 males, 26 females) and 4 (25 males, 25 females) were administered the carcinogen at a dose of 50 mg/kg body weight. At 10 weeks of age, group 3 and group 4 were X-irradiated at dose of 3 Gy. Group 5 (24 males, 24 females) received X-irradiation alone. Group 6 (21 males, 21 females) served as an untreated control. As a result, neoplasms developed mainly in the digestive tract, kidney, uterus, and hematopoietic organ in groups 1-5. The incidences of adenocarcinoma in small and large intestines of male rats of group 4 (50 mg/kg MNU and X-irradiation) (small intestine: 48%, large intestine: 32%) were significantly higher than those of group 2 (50 mg/kg MNU) (small intestine: 17%, p<0.05; large intestine: 8%, p<0.05), and also the frequency of adenocarcinoma in the large intestine of males of group 3 (25 mg/kg MNU and X-irradiation) (22%) was significantly greater than that of group 1 (25 mg/kg MNU) (0%, p<0.05). These results indicated that X-irradiation enhanced the development of intestinal neoplasms induced by MNU in male ACI/N rats. (author)

  3. Effects of X-irradiation on N-methyl-N-nitrosourea-induced multi-organ carcinogenesis in rats

    Energy Technology Data Exchange (ETDEWEB)

    Morishita, Yukiko; Tanaka, Takuji; Mori, Hideki (Gifu Univ. (Japan). Faculty of Medicine); Sasaki, Shunsaku

    1993-01-01

    The effects of X-irradiation on N-methyl-N-nitrosourea (MNU)-induced multi-organ carcinogenesis were examined in both sexes of ACI/N rats. At 6 weeks of age, rats in groups 1 (25 males, 25 females) and 3 (24 males, 23 females) received a single intraperitoneal injection of MNU (25 mg/kg body weight), while those in groups 2 (25 males, 26 females) and 4 (25 males, 25 females) were administered the carcinogen at a dose of 50 mg/kg body weight. At 10 weeks of age, group 3 and group 4 were X-irradiated at dose of 3 Gy. Group 5 (24 males, 24 females) received X-irradiation alone. Group 6 (21 males, 21 females) served as an untreated control. As a result, neoplasms developed mainly in the digestive tract, kidney, uterus, and hematopoietic organ in groups 1-5. The incidences of adenocarcinoma in small and large intestines of male rats of group 4 (50 mg/kg MNU and X-irradiation) (small intestine: 48%, large intestine: 32%) were significantly higher than those of group 2 (50 mg/kg MNU) (small intestine: 17%, p<0.05; large intestine: 8%, p<0.05), and also the frequency of adenocarcinoma in the large intestine of males of group 3 (25 mg/kg MNU and X-irradiation) (22%) was significantly greater than that of group 1 (25 mg/kg MNU) (0%, p<0.05). These results indicated that X-irradiation enhanced the development of intestinal neoplasms induced by MNU in male ACI/N rats. (author).

  4. Chemically induced immunotoxicity in a medium-term multiorgan bioassay for carcinogenesis with Wistar rats

    International Nuclear Information System (INIS)

    Spinardi-Barbisan, Ana Lucia Tozzi; Kaneno, Ramon; Barbisan, Luis Fernando; Viana de Camargo, Joao Lauro; Rodrigues, Maria Aparecida Marchesan

    2004-01-01

    A variety of chemicals can adversely affect the immune system and influence tumor development. The modifying potential of chemical carcinogens on the lymphoid organs and cytokine production of rats submitted to a medium-term initiation-promotion bioassay for carcinogenesis was investigated. Male Wistar rats were sequentially initiated with N-nitrosodiethylamine (DEN), N-methyl-N-nitrosourea (MNU), N-butyl-N-(4hydroxybutyl)nitrosamine (BBN), dihydroxy-di-n-propylnitrosamine (DHPN), and 1,2-dimethylhydrazine (DMH) during 4 weeks. Two initiated groups received phenobarbital (PB) or 2-acetylaminofluorene (2-AAF) for 25 weeks and two noninitiated groups received only PB or 2-AAF. A nontreated group was used as control. Lymphohematopoietic organs, liver, kidneys, lung, intestines, and Zymbal's gland were removed for histological analysis. Interleukin (IL)-2, IL-12, interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), IL-10, and transforming growth factor beta1 (TGF-β1) levels were determined by ELISA in spleen cell culture supernatants. At the fourth week, exposure to the initiating carcinogens resulted in cell depletion of the thymus, spleen and bone marrow, and impairment of IL-2, IL-12, and IFN-γ production. However, at the 30th week, no important alterations were observed both in lymphoid organs and cytokine production in the different groups. The results indicate that the initiating carcinogens used in the present protocol exert toxic effects on the lymphoid organs and affect the production of cytokines at the initiation step of carcinogenesis. This early and reversible depression of the immune surveillance may contribute to the survival of initiated cells facilitating the development of future neoplasia

  5. Expression Patterns of Cancer Stem Cell Markers During Specific Celecoxib Therapy in Multistep Rat Colon Carcinogenesis Bioassays.

    Science.gov (United States)

    Salim, Elsayed I; Hegazi, Mona M; Kang, Jin Seok; Helmy, Hager M

    2016-01-01

    The purpose of this study was to investigate the role of colon cancer stem cells (CSCs) during chemicallyinduced rat multi-step colon carcinogenesis with or without the treatment with a specific cyclooxygenase-2 inhibitor drug (celecoxib). Two experiments were performed, the first, a short term 12 week colon carcinogenesis bioassay in which only surrogate markers for colon cancer, aberrant crypt foci (ACF) lesions, were formed. The other experiment was a medium term colon cancer rat assay in which tumors had developed after 32 weeks. Treatment with celecoxib lowered the numbers of ACF, as well as the tumor volumes and multiplicities after 32 weeks. Immunohistochemical proliferating cell nuclear antigen (PCNA) labeling indexes LI (%) were downregulated after treatment by celecoxib. Also different cell surface antigens known to associate with CSCs such as the epithelial cell adhesion molecule (EpCAM), CD44 and CD133 were compared between the two experiments and showed differential expression patterns depending on the stage of carcinogenesis and treatment with celecoxib. Flow cytometric analysis demonstrated that the numbers of CD133 cells were increased in the colonic epithelium after 12 weeks while those of CD44 but not CD133 cells were increased after 32 weeks. Moreover, aldehyde dehydrogenase-1 activity levels in the colonic epithelium (a known CSC marker) detected by ELISA assay were found down-regulated after 12 weeks, but were up-regulated after 32 weeks. The data have also shown that the protective effect of celecoxib on these specific markers and populations of CSCs and on other molecular processes such as apoptosis targeted by this drug may vary depending on the genetic and phenotypic stages of carcinogenesis. Therefore, uncovering these distinction roles of CSCs during different phases of carcinogenesis and during specific treatment could be useful for targeted therapy.

  6. Enhancement of preneoplastic lesion yield by Chios Mastic Gum in a rat liver medium-term carcinogenesis bioassay

    International Nuclear Information System (INIS)

    Doi, Kenichiro; Wei, Min; Kitano, Mitsuaki; Uematsu, Naomi; Inoue, Masayo; Wanibuchi, Hideki

    2009-01-01

    The mastic (Pistacia lentiscus var. chia) tree is native throughout the Mediterranean region and has long proved a source of food additives and medical treatments. To investigate the modifying effects of Chios Mastic Gum on rat liver carcinogenesis, 6-week-old male F344 rats were subjected to the established rat liver medium-term carcinogenesis bioassay (Ito-test). At the commencement, rats (groups 1-4) were intraperitoneally injected with 200 mg/kg body weight of diethylnitrosamine (DEN). After two weeks, mastic was added to CRF (Charles River Formula)-1 powdered basal diet at doses of 0, 0.01, 0.1 and 1% in groups 1-4, respectively. At week 3, all rats were underwent two-thirds partial hepatectomy. The experiment was terminated at week 8. As results show, liver weights were significantly increased in a mastic dose-dependent manner among groups 1-4. The numbers (/cm 2 ) and the areas (mm 2 /cm 2 ) of glutathione S-transferase placental form (GST-P)-positive cell foci (≥ 0.2 mm in diameter) were significantly increased in the DEN-1% group compared to the DEN-alone group, along with the average areas per foci and larger-sized foci (≥ 0.4 mm). 5-Bromo-2'-deoxyuridine (BrdU) + GST-P double-immunohistochemistry showed the highest BrdU-labeling indices within GST-P foci in the DEN-1% group. 8-hydroxydeoxyguanosine (8-OHdG) levels in liver DNA did not vary, while real-time quantitative polymerase chain reaction (PCR) analysis of livers revealed many up- or down-regulated genes in the DEN-1% group. In conclusion, this is the first report to display a promotion potential of Chios Mastic Gum on the formation of preneoplastic lesions in the established rat liver medium-term carcinogenesis bioassay

  7. Carcinogenesis

    International Nuclear Information System (INIS)

    Anon.

    1976-01-01

    Progress is reported on studies at the molecular, biochemical, and immunological level of carcinogenesis induced in mice by viruses, radiation, or environmental chemicals alone or in combinations. Emphasis was placed on the identification and assessments of cocarcinogens and studies on their mechanisms of action. Data are included on mechanisms of carcinogenesis in the liver, thyroid, Harderian glands, skin, and lungs. The effects of the food additive butylated hydroxytoluene (BHT), phenobarbitol, DDT, uv irradiation, the herbicide 3-amino-1,2,4-triazole(AT), the pituitary hormone prolactin, topically applied 8-methoxypsoralen (8-MOP), and benzo(a) pyrene(BaP) on tumor induction or enhancement were studied

  8. Predictive values of traditional animal bioassay studies for human perinatal carcinogenesis risk determination

    International Nuclear Information System (INIS)

    Anderson, Lucy M.

    2004-01-01

    The many physiological, biochemical, and structure differences between rodents and humans, especially with regard to gestation and fetal development, invite questions as to the utility of rodent models for the prediction of risk of perinatal carcinogenesis in humans and for extrapolation of mechanistic studies. Here, the relevance of basic generalities, derived from rodent perinatal studies, to human contexts is considered. The cross-species usefulness of these generalities was upheld by the example of carcinogen activation and detoxification as determining factors. These have been established in rodent studies and recently indicted in humans by investigations of genetic polymorphisms in cytochromes P450, N-acetyltransferase, myeloperoxidase, quinone reductase, and glutathione S-transferase. Also, published data have been analyzed comparatively for diethylstilbestrol and irradiation, the two known human transplacental carcinogenic agents. At similar doses to those experienced by humans, both diethylstilbestrol and X- and gamma-irradiation in rodents and dogs yielded increased tumors at rates similar to those for humans. In rodents, there was a clearly negative relationship between total diethylstilbestrol dose and tumors per dose unit, and a similar pattern was suggested for radiation. Diethylstilbestrol had transgenerational effects that did not diminish over three generations. Overall, this analysis of the published literature indicates that there are basic qualitative and quantitative similarities in the responsiveness of human and rodent fetuses to carcinogens, and that dose effects may be complex and in need of further investigation

  9. Carcinogenesis

    International Nuclear Information System (INIS)

    Fry, R.J.M.

    1975-01-01

    The long-term aims are concerned with various aspects of the natural history and biology of cancer, the mechanism of induction and of the advancement of time of appearance of tumors, the development of systems suitable for the assay of oncogenesis and cocarcinogenesis, and the elucidation of some of the factors important to the problem of extrapolation of estimates of risk made in experimental systems to the estimate of risk in man. It is necessary to have a number of test systems in order to study the various factors related to cocarcinogenesis; some of these are clearly tissue specific. The liver tumor system is clearly useful for certain compounds, and the liver is an excellent tissue for the study of the mechanisms of cocarcinogenesis. This year we report on the relatively rapid induction of what appears histologically to be carcinoma of the thyroid by aminotriazole. In a collaborative study with the Neutron and Gamma-Ray Toxicity Group, we have established a new example of synergism in carcinogenesis, namely between radiation and pituitary hormone(s) in the production of Harderian gland tumors. Not only does a synergistic effect on incidence occur, but also on the degree of malignancy of the tumor induced. We thus have three different model systems for the study of various aspects of cocarcinogenesis: various chemicals, including nononcogenic polycyclic hydrocarbons, in liver tumorigenesis; ionizing radiation and aminotriazole in thyroid tumorigenesis; and in conjunction with the JANUS Program, the interaction of radiation and hormones in the production of Harderian gland, mammary gland, and other tumors

  10. Aberrant crypt foci and colon cancer: comparison between a short- and medium-term bioassay for colon carcinogenesis using dimethylhydrazine in Wistar rats

    Directory of Open Access Journals (Sweden)

    Rodrigues M.A.M.

    2002-01-01

    Full Text Available Aberrant crypt foci (ACF in the colon of carcinogen-treated rodents are considered to be the earliest hallmark of colon carcinogenesis. In the present study the relationship between a short-term (4 weeks and medium-term (30 weeks assay was assessed in a model of colon carcinogenesis induced by dimethylhydrazine (DMH in the rat. Six-week-old male Wistar rats were given subcutaneous injections of DMH (40 mg/kg twice a week for 2 weeks and killed at the end of the 4th or 30th week. ACF were scored for number, distribution pattern along the colon and crypt multiplicity in 0.1% methylene-blue whole-mount preparations. ACF were distinguished from normal crypts by their larger size and elliptical shape. The incidence, distribution and morphology of colon tumors were recorded. The majority of ACF were present in the middle and distal colon of DMH-treated rats and their number increased with time. By the 4th week, 91.5% ACF were composed of one or two crypts and 8.5% had three or more crypts, while by the 30th week 46.9% ACF had three or more crypts. Thus, a progression of ACF consisting of multiple crypts was observed from the 4th to the 30th week. Nine well-differentiated adenocarcinomas were found in 10 rats by the 30th week. Seven tumors were located in the distal colon and two in the middle colon. No tumor was found in the proximal colon. The present data indicate that induction of ACF by DMH in the short-term (4 weeks assay was correlated with development of well-differentiated adenocarcinomas in the medium-term (30 weeks assay.

  11. Bioassay Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — The Bioassay Laboratory is an accredited laboratory capable of conducting standardized and innovative environmental testing in the area of aquatic ecotoxicology. The...

  12. Radiation carcinogenesis

    International Nuclear Information System (INIS)

    1978-01-01

    The Cancergram deals with all aspects of radiation carcinogenesis. The term radiation here includes U-V radiation and the entire electromagnetic spectrum, electron and other charged particle beams, neutrons, and alpha and beta radiation from radioactive substances. Abstracts included concern relationships between radiation and carcinogenesis in humans, experimental induction of tumors in animals by irradiation, studies on the mechanism of radiation carcinogenesis at the cellular level, studies of RBE, dose response or dose threshold in relation to radiation carcinogenesis, and methods and policies for control of radiation exposure in the general population. In general, this Cancergram excludes abstracts on radio-therapy, radiologic diagnosis, radiation pathology, and radiation biology, where these articles have no bearing on radiation carcinogenesis

  13. Radiation carcinogenesis

    International Nuclear Information System (INIS)

    Adams, G.E.

    1987-01-01

    In this contribution about carcinogenesis induced by ionizing radiation some radiation dose-response relationships are discussed. Curves are shown of the relation between cell survival and resp. low and high LET radiation. The difference between both curves can be ascribed to endogenous repair mechanisms in the cell. The relation between single-gen mutation frequency and the surviving fractions of irradiated cells indicates that these repairing mechanisms are not error free. Some examples of reverse dose-response relationships are presented in which decreasing values of dose-rate (LET) correspond with increasing radiation induced cell transformation. Finally some molecular aspects of radiation carcinogenesis are discussed. (H.W.). 22 refs.; 4 figs

  14. Protective effects of lemongrass (Cymbopogon citratus STAPF) essential oil on DNA damage and carcinogenesis in female Balb/C mice.

    Science.gov (United States)

    Bidinotto, Lucas T; Costa, Celso A R A; Salvadori, Daisy M F; Costa, Mirtes; Rodrigues, Maria A M; Barbisan, Luís F

    2011-08-01

    This study investigated the protective effect of oral treatment with lemongrass (Cymbopogon citratus STAPF) essential oil (LGEO) on leukocyte DNA damage induced by N-methyl-N-nitrosurea (MNU). Also, the anticarcinogenic activity of LGEO was investigated in a multi-organ carcinogenesis bioassay induced by 7,12-dimethylbenz(a)antracene, 1,2-dimethylhydrazine and N-butyl-N-(4-hydroxibuthyl)nitrosamine in Balb/C female Balb/c mice (DDB-initiated mice). In the short-term study, the animals were allocated into three groups: vehicle group (negative control), MNU group (positive control) and LGEO 500 mg kg⁻¹ (five times per week for 5 weeks) plus MNU group (test group). Blood samples were collected to analyze leukocyte DNA damage by comet assay 4 h after each MNU application at the end of weeks 3 and 5. The LGEO 500 mg kg⁻¹ treated group showed significantly lower (P lemongrass essential oil provided protective action against MNU-induced DNA damage and a potential anticarcinogenic activity against mammary carcinogenesis in DDB-initiated female Balb/C mice. Copyright © 2010 John Wiley & Sons, Ltd.

  15. Cadmium carcinogenesis

    International Nuclear Information System (INIS)

    Waalkes, Michael P.

    2003-01-01

    Cadmium is a heavy metal of considerable environmental and occupational concern. Cadmium compounds are classified as human carcinogens by several regulatory agencies. The most convincing data that cadmium is carcinogenic in humans comes from studies indicating occupational cadmium exposure is associated with lung cancer. Cadmium exposure has also been linked to human prostate and renal cancer, although this linkage is weaker than for lung cancer. Other target sites of cadmium carcinogenesis in humans, such as liver, pancreas and stomach, are considered equivocal. In animals, cadmium effectively induces cancers at multiple sites and by various routes. Cadmium inhalation in rats induces pulmonary adenocarcinomas, in accord with its role in human lung cancer. Cadmium can induce tumors and/or preneoplastic lesions within the rat prostate after ingestion or injection. At relatively high doses, cadmium induces benign testicular tumors in rats, but these appear to be due to early toxic lesions and loss of testicular function, rather than from a specific carcinogenic effect of cadmium. Like many other metals, cadmium salts will induce mesenchymal tumors at the site of subcutaneous (s.c.) or intramuscular (i.m.) injections, but the human relevance of these is dubious. Other targets of cadmium in rodents include the liver, adrenal, pancreas, pituitary, and hematopoietic system. With the exception of testicular tumors in rodents, the mechanisms of cadmium carcinogenesis are poorly defined. Cadmium can cause any number of molecular lesions that would be relevant to oncogenesis in various cellular model systems. Most studies indicate cadmium is poorly mutagenic and probably acts through indirect or epigenetic mechanisms, potentially including aberrant activation of oncogenes and suppression of apoptosis

  16. Cadmium carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Waalkes, Michael P

    2003-12-10

    Cadmium is a heavy metal of considerable environmental and occupational concern. Cadmium compounds are classified as human carcinogens by several regulatory agencies. The most convincing data that cadmium is carcinogenic in humans comes from studies indicating occupational cadmium exposure is associated with lung cancer. Cadmium exposure has also been linked to human prostate and renal cancer, although this linkage is weaker than for lung cancer. Other target sites of cadmium carcinogenesis in humans, such as liver, pancreas and stomach, are considered equivocal. In animals, cadmium effectively induces cancers at multiple sites and by various routes. Cadmium inhalation in rats induces pulmonary adenocarcinomas, in accord with its role in human lung cancer. Cadmium can induce tumors and/or preneoplastic lesions within the rat prostate after ingestion or injection. At relatively high doses, cadmium induces benign testicular tumors in rats, but these appear to be due to early toxic lesions and loss of testicular function, rather than from a specific carcinogenic effect of cadmium. Like many other metals, cadmium salts will induce mesenchymal tumors at the site of subcutaneous (s.c.) or intramuscular (i.m.) injections, but the human relevance of these is dubious. Other targets of cadmium in rodents include the liver, adrenal, pancreas, pituitary, and hematopoietic system. With the exception of testicular tumors in rodents, the mechanisms of cadmium carcinogenesis are poorly defined. Cadmium can cause any number of molecular lesions that would be relevant to oncogenesis in various cellular model systems. Most studies indicate cadmium is poorly mutagenic and probably acts through indirect or epigenetic mechanisms, potentially including aberrant activation of oncogenes and suppression of apoptosis.

  17. Bioassay guideline 2: guidelines for tritium bioassay

    International Nuclear Information System (INIS)

    1983-01-01

    This guideline is one of a series under preparation by the Federal-Provincial Working Group on Bioassay and In Vivo Monitoring Criteria. In this report tritium compounds have been grouped into four categories for the purpose of calculating Annual Limits on Intake and Investigation Levels: tritium gas, tritiated water, tritium-labelled compounds and nucleic acid precursors

  18. Chemical Carcinogenesis of the Gastrointestinal Tract in Rodents: An Overview with Emphasis on NTP Carcinogenesis Bioassays

    OpenAIRE

    Chandra, Sundeep A.; Nolan, Michael W.; Malarkey, David E.

    2009-01-01

    Cancers of the stomach and large intestine (LI) are the second and fourth leading causes of human cancer mortality. A review of the National Toxicology Program (NTP) database and the Carcinogenic Potency Database (CPDB) reveals that chemically induced neoplasms of the gastrointestinal tract (GIT) are relatively common. Within the GIT, epithelial tumors of the forestomach in mice and rats and LI of the rat are most common. Generally, there is a high species concordance for forestomach with at ...

  19. Mechanisms of radiation carcinogenesis

    International Nuclear Information System (INIS)

    Bekkum, D.W. van

    1975-01-01

    This speculative review on radiation carcinogenesis deals mainly with its immunological aspects. It need not be emphasized that the role of immunology in carcinogenesis is not yet well understood. Immunological aspects of radiation carcinogenesis comprise a large number of different parameters on the part of the host as well as on the part of the tumor itself. Only two aspects, both related to radiation, will be discussed here. One is the way in which the carcinogenic exposure to ionizing radiation may affect the immune reactivity of the irradiated organism, thereby perhaps changing its responses against the malignant cells. The second aspect is the immunological properties of cells transformed by ionizing irradiation, which may provide the targets for a host-anti-tumor reaction

  20. Radiation carcinogenesis, laboratory studies

    International Nuclear Information System (INIS)

    Shellabarger, C.J.

    1974-01-01

    Laboratory studies on radioinduced carcinogenesis are reviewed. Some topics discussed are: radioinduced neoplasia in relation to life shortening; dose-response relationships; induction of skin tumors in rats by alpha particles and electrons; effects of hormones on tumor response; effects of low LET radiations delivered at low dose-rates; effects of fractionated neutron radiation; interaction of RBE and dose rate effects; and estimates of risks for humans from animal data. (U.S.)

  1. Bioassay guideline 1: general guidlines for bioassay programs

    International Nuclear Information System (INIS)

    1980-01-01

    This guideline is the first of a series of documents which elaborate criteria for bioassay programs, to be presented as recommendations to the Atomic Energy Control Board. It specifies which workers require routine bioassays, the accuracy and frequency of measurements, the dose levels at which specific actions must be taken, and the documentation required

  2. Microfluidic-Based Multi-Organ Platforms for Drug Discovery

    Directory of Open Access Journals (Sweden)

    Ahmad Rezaei Kolahchi

    2016-09-01

    Full Text Available Development of predictive multi-organ models before implementing costly clinical trials is central for screening the toxicity, efficacy, and side effects of new therapeutic agents. Despite significant efforts that have been recently made to develop biomimetic in vitro tissue models, the clinical application of such platforms is still far from reality. Recent advances in physiologically-based pharmacokinetic and pharmacodynamic (PBPK-PD modeling, micro- and nanotechnology, and in silico modeling have enabled single- and multi-organ platforms for investigation of new chemical agents and tissue-tissue interactions. This review provides an overview of the principles of designing microfluidic-based organ-on-chip models for drug testing and highlights current state-of-the-art in developing predictive multi-organ models for studying the cross-talk of interconnected organs. We further discuss the challenges associated with establishing a predictive body-on-chip (BOC model such as the scaling, cell types, the common medium, and principles of the study design for characterizing the interaction of drugs with multiple targets.

  3. Carcinogenesis. Genetics and circumstances

    International Nuclear Information System (INIS)

    Hino, Okio

    2005-01-01

    Described are the author's study and aspect concerning carcinogenesis and radiation carcinogenesis, where he thinks cancer is not automatic, has a process and takes time. For radiation carcinogenic studies, he has used a model of the rat with genetically determined kidney cancer which is highly radiosensitive. That is, mutation by the so-called 2nd-hit of the causal gene (tumor suppressing gene Tsc2) is studied in the animal where the 1st-hit has been done by retrotransposon insertion, with and without exposure to radiations (X-ray, heavy particle beam and cosmic ray) for elucidating the mutation spectrum of the causal gene, the carcinogenic target, for the ultimate aim to prevent human cancer. He discusses the drama-type molecular mechanisms leading to cancer, gene abnormality and disease crisis, discontinuity in continuity in cancer formation, and importance of the timely diagnosis and appropriate therapy, and concludes the present age is becoming such one as that the nature of cancer even if genetic can be controlled by circumstances like timely and appropriate intervention. (S.I.)

  4. Radiation and multistage carcinogenesis

    International Nuclear Information System (INIS)

    Day, N.E.

    1984-01-01

    Epidemiological data are insufficient at present to define with much precision the shape of the dose-response curve for radiation carcinogenesis at low or moderate dose levels, for different organs. The available data have to be supplemented with theoretical models for the mode of action. These models, however, often seem not to take into account the complex nature of the process of carcinogenesis. They relate more to mutational events, rather than the long process of cancer induction. In addition, they ignore the fact that in the human situation radiation is one among a large number of exposures, and even the basic form of the dose response may be dependent on the presence or absence of other factors. Information on modes of action usually comes from experimental results, where the requisite combination of exposures can be chosen in advance. Epidemiology, however, also provides information on mechanisms. The purpose of this paper is to consider some of the information that epidemiology provides on the role of radiation in increasing cancer risk in humans

  5. Bioassay programs for radiation protection

    International Nuclear Information System (INIS)

    1979-01-01

    This report discusses the rationale for the establishment of bioassay programs as a means of protection for radiation workers in the nuclear industry. The bioassay program of the Radiation Protection Bureau is described for the years 1966-1978 and plans for future changes are outlined. (auth)

  6. External radiation carcinogenesis

    International Nuclear Information System (INIS)

    Fry, R.J.M.; Storer, J.B.

    1987-01-01

    There have been many reviews of the subject of radiation carcinogenesis in general and of specific radiation-induced cancers. The aim of this article is not to give an exhaustive, and perhaps exhausting, review of all that has been published since the thorough treatise of Walburg in volume 4 of this series but rather to concentrate on the questions that still remain of importance and recent contributions to the answers. In the years since 1974 a vast amount of information has been reported, and the authors assess what gain there has been in knowledge. For example, it is in the 13 years since the last review that the great majority of data for the carcinogenic effects of neutrons has appeared. It is over 50 years since the discovery of the neutron, and yet knowledge of the carcinogenic effects of neutrons is far from adequate

  7. 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.

  8. Fluorescence lifetime based bioassays

    Science.gov (United States)

    Meyer-Almes, Franz-Josef

    2017-12-01

    Fluorescence lifetime (FLT) is a robust intrinsic property and material constant of fluorescent matter. Measuring this important physical indicator has evolved from a laboratory curiosity to a powerful and established technique for a variety of applications in drug discovery, medical diagnostics and basic biological research. This distinct trend was mainly driven by improved and meanwhile affordable laser and detection instrumentation on the one hand, and the development of suitable FLT probes and biological assays on the other. In this process two essential working approaches emerged. The first one is primarily focused on high throughput applications employing biochemical in vitro assays with no requirement for high spatial resolution. The second even more dynamic trend is the significant expansion of assay methods combining highly time and spatially resolved fluorescence data by fluorescence lifetime imaging. The latter approach is currently pursued to enable not only the investigation of immortal tumor cell lines, but also specific tissues or even organs in living animals. This review tries to give an actual overview about the current status of FLT based bioassays and the wide range of application opportunities in biomedical and life science areas. In addition, future trends of FLT technologies will be discussed.

  9. contribution to carcinogenesis

    Directory of Open Access Journals (Sweden)

    Aneta Białkowska

    2014-01-01

    Full Text Available The centrosomes are subcellular organelles composed of two centrioles surrounded by a pericentriolar material. In animal cells they are responsible for the organization of the interphase microtubule cytoskeleton including microtubule nucleation and elongation, their attachment and release. The centrosomes are also involved in the construction of the mitotic spindle and chromosome segregation. More than a century ago it was suggested that these structures might be involved in human diseases, including cancer. Cancer cells show a high frequency of centrosome aberrations, especially amplification. Centrosome defects may increase the incidence of multipolar mitoses that lead to chromosomal segregation abnormalities and aneuploidy, which is the predominant type of genomic instability found in human solid tumors. The number of these organelles in cells is strictly controlled and is dependent on the proper process of centrosome duplication. Multiple genes that are frequently found mutated in cancers encode proteins which participate in the regulation of centrosome duplication and the numeral integrity of centrosomes. In recent years there has been growing interest in the potential participation of centrosomes in the process of carcinogenesis, especially because centrosome abnormalities are observed in premalignant stages of cancer development. The common presence of abnormal centrosomes in cancer cells and the role these organelles play in the cells suggest that the factors controlling the number of centrosomes may be potential targets for cancer therapy.

  10. Gene amplification in carcinogenesis

    Directory of Open Access Journals (Sweden)

    Lucimari Bizari

    2006-01-01

    Full Text Available Gene amplification increases the number of genes in a genome and can give rise to karyotype abnormalities called double minutes (DM and homogeneously staining regions (HSR, both of which have been widely observed in human tumors but are also known to play a major role during embryonic development due to the fact that they are responsible for the programmed increase of gene expression. The etiology of gene amplification during carcinogenesis is not yet completely understood but can be considered a result of genetic instability. Gene amplification leads to an increase in protein expression and provides a selective advantage during cell growth. Oncogenes such as CCND1, c-MET, c-MYC, ERBB2, EGFR and MDM2 are amplified in human tumors and can be associated with increased expression of their respective proteins or not. In general, gene amplification is associated with more aggressive tumors, metastases, resistance to chemotherapy and a decrease in the period during which the patient stays free of the disease. This review discusses the major role of gene amplification in the progression of carcinomas, formation of genetic markers and as possible therapeutic targets for the development of drugs for the treatment of some types of tumors.

  11. Platelets and Multi-Organ Failure in Sepsis

    Directory of Open Access Journals (Sweden)

    Elisabetta Greco

    2017-10-01

    Full Text Available Platelets have received increasing attention for their role in the pathophysiology of infectious disease, inflammation, and immunity. In sepsis, a low platelet count is a well-known biomarker for disease severity and more recently authors have focused their attention on the active role of platelets in the pathogenesis of multi-organ failure. Septic shock is characterised by a dysregulated inflammatory response, which can impair the microcirculation and lead to organ injury. Being at the crossroads between the immune system, clotting cascade, and endothelial cells, platelets seem to be an appealing central mediator and possible therapeutic target in sepsis. This review focuses on the pathogenic role of platelets in septic organ dysfunction in humans and animal models.

  12. Platelets and Multi-Organ Failure in Sepsis.

    Science.gov (United States)

    Greco, Elisabetta; Lupia, Enrico; Bosco, Ornella; Vizio, Barbara; Montrucchio, Giuseppe

    2017-10-20

    Platelets have received increasing attention for their role in the pathophysiology of infectious disease, inflammation, and immunity. In sepsis, a low platelet count is a well-known biomarker for disease severity and more recently authors have focused their attention on the active role of platelets in the pathogenesis of multi-organ failure. Septic shock is characterised by a dysregulated inflammatory response, which can impair the microcirculation and lead to organ injury. Being at the crossroads between the immune system, clotting cascade, and endothelial cells, platelets seem to be an appealing central mediator and possible therapeutic target in sepsis. This review focuses on the pathogenic role of platelets in septic organ dysfunction in humans and animal models.

  13. Applied in vitro radio bioassay

    International Nuclear Information System (INIS)

    Gaburo, J.C.G.; Sordi, G.M.A.A.

    1992-11-01

    The aim of this publication is to show the concepts and in vitro bioassay techniques as well as experimental procedures related with internal contamination evaluation. The main routes of intake, metabolic behavior, and the possible types of bioassay samples that can be collected for radionuclides analysis are described. Both biological processes and the chemical and physical behavior of the radioactive material of interest are considered and the capabilities of analytical techniques to detect and quantify the radionuclides are discussed. Next, the need of quality assurance throughout procedures are considered and finally a summary of the techniques applied to the internal routine monitoring of IPEN workers is given. (author)

  14. Epigenetic mechanism of radiation carcinogenesis

    International Nuclear Information System (INIS)

    Niwa, Ohtsura

    1995-01-01

    Carcinogenic action of radiations has long been thought to be due to its mutagenic activity. Since DNA damage is induced and distributes in a stochastic fashion, radiation induction of cancers was also assumed to follow a stochastic kinetics. However, recent progress in radiation research has revealed that some features of radiation carcinogenesis are not explainable by the simple action of radiation as a DNA damaging and mutagenic agent. Firstly, frequencies of radiation-induced transformation in vitro and radiation-induced mammary cancers in rats are too high to be accounted for by the frequency of radiation-induced mutation. Secondly, trans-generation carcinogenesis among F1 mice born to irradiated parents occurs also much more frequently than to be predicted by the frequency of radiation induced germline mutation. Thirdly, multistage carcinogenesis theory predicts that carcinogens give hits to the target cells so as to shorten the latency of cancers. However, latencies of radiation induced solid cancers among atomic bomb survivors are similar to those of the control population. Fourthly, although radiation elevates the frequency of cancers, the induced cancers seem to share the same spectrum of cancer types as in the unirradiated control populations. This suggests that radiation induces cancer by enhancement of the spontaneous carcinogenesis process. These data suggest that the first step of radiation carcinogenesis may not be the direct induction of mutation. Radiation may induce genetic instability which increases the spontaneous mutation rate in the cells to produce carcinogenic mutations. Growth stimulatory effect of radiation may also contribute to the process. Thus, epigenetic, but not genetic effect of radiation might better contribute in the process of carcinogenesis. (author)

  15. 77 FR 14837 - Bioassay at Uranium Mills

    Science.gov (United States)

    2012-03-13

    ... NUCLEAR REGULATORY COMMISSION [NRC-2012-0057] Bioassay at Uranium Mills AGENCY: Nuclear Regulatory..., ``Bioassay at Uranium Mills.'' This guide describes a bioassay program acceptable to the NRC staff for uranium mills and applicable portions of uranium conversion facilities where the possibility of exposure...

  16. Experimental radiation carcinogenesis is studies at NIRS

    International Nuclear Information System (INIS)

    Sado, Toshihiko

    1992-01-01

    Experimental radiation carcinogenesis studies conducted during the past decade at NIRS are briefly reviewed. They include the following: 1) Age dependency of susceptibility to radiation carcinogenesis. 2) Radiation-induced myeloid leukemia. 3) Mechanism of fractionated X-irradiation (FX) induced thymic lymphomas. 4) Significance of radiation-induced immunosuppression in radiation carcinogenesis in vivo. 5) Other ongoing studies. (author)

  17. Radiation carcinogenesis: radioprotectors and photosensitizers

    International Nuclear Information System (INIS)

    Fry, R.J.M.

    1982-01-01

    This paper outlines 1) some of the salient features of radiation carcinogenesis that are pertinent to the questions of how the carcinogenic effects might be influenced, 2) the effects of radioprotectors on ionizing radiation-induced cancer, and 3) the effect of photosensitizers on UVR-induced skin cancer

  18. Radiation carcinogenesis: radioprotectors and photosensitizers

    Energy Technology Data Exchange (ETDEWEB)

    Fry, R.J.M.

    1982-01-01

    This paper outlines 1) some of the salient features of radiation carcinogenesis that are pertinent to the questions of how the carcinogenic effects might be influenced, 2) the effects of radioprotectors on ionizing radiation-induced cancer, and 3) the effect of photosensitizers on UVR-induced skin cancer.

  19. Studies on Erythropoietin Bioassay Method

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Kyoung Sam; Ro, Heung Kyu; Lee, Mun Ho [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1975-09-15

    It is the purpose of this paper to design the most preferable method of erythropoietin bioassay in Korea. Bioassay utilizing polycythemic mice are currently in general use for the indirect determination of erythropoietin. Assay animals are usually prepared either by transfusion or by exposure to reduced oxygen tension in specially constructed chamber. We prepared the polycythemic mice by the specially constructed hypobaric chamber. We observed weights and hematocrits of the mice in the hypobaric chamber, then hematocrits and 72 hours {sup 59}Fe red cell uptake ratio of the polycythemic mice induced by hypoxia after removal from the hypobaric chamber. We designed the method of erythropoietin bioassay according to the results obtained by above experiments. Then we measured the 72 hours {sup 59}Fe red cell uptake ratio of the polycythemic mice with normal saline, normal plasma and anemic plasma according to the method we designed. The results are followed:1) The hematocrits of the mice in hypobaric chamber increased to 74% in 11 days. It is preferable to maintain the pressure of the chamber to 400 mmHg for first 4 days then 300 mmHg for last 10 days to reduce the death rate and time consuming in hypobaric chamber. 2) After removal from the hypobaric chamber, the 72 hours {sup 59}Fe red cell uptake ratio decreased rapidly and maintained the lowest level from the fourth day to tenth day. 3) We design the method of erythropoietin bioassay according to the results of above experiment and to the half life of erythropoietin. 4) The Korean product {sup 59}Fe is mixture of {sup 55}Fe and {sup 59}Fe. And the {sup 59}Fe red cell uptake ratio in normal mice was far less with Korean product {sup 59}Fe than with pure {sup 59}Fe of foreign product. So it is desirable to use pure {sup 59}Fe in this method of erythropoietin bioassay. 5) Considering the cost, the technique, the time consuming and the sensitivity it is the most preferable method of erythropoietin bioassay in Korea

  20. Radiation carcinogenesis in scid mice

    Energy Technology Data Exchange (ETDEWEB)

    Ishii, Hiroko; Nishimura, Mayumi; Kobayashi, Shigeru; Tsuji, Hideo; Shimada, Yoshiya; Ogiu, Toshiaki [National Inst. of Radiological Sciences, Chiba (Japan); Suzuki, Fumio; Sado, Toshihiko

    1999-06-01

    Scid mice which have the defect of DNA-dependent protein kinase catalitic subunit, exhibit the limited activities of repair from DNA double strand breaks, and are sensitive to ionizing radiation. In order to study the relationship between repair capacity for DNA double strand breaks and carcinogenesis, the effects of ionizing radiation were studied using scid homozygotes (scid/scid), scid heterozygotes (scid/+) and CB-17 (+/+) mice. Both the Scid bone marrow cells and fibroblast cell lines from Scid embryos were highly sensitivity to acute effects of ionizing radiation. Carcinogenesis experiments showed the high incidence of thymic lymphomas (80 to 90%) in 1 to 3 Gy {sup 137}Cs-{gamma}-ray-irradiated Scid mice. (author)

  1. Exposure dose assessment using bioassay

    International Nuclear Information System (INIS)

    Suga, Shinichi

    1994-01-01

    Bioassay involves following steps: sampling, pre-treatment, chemical separation and counting of radioactivity. As bioassay samples, urines are usually used, although faecal analysis may be required in some occasions for example to assess intake of non-transferable radioactive materials. Nasal smear is a useful indicator of an inhalation case. Exhalation air is used to estimate the intake of tritiated water. Sample pre-treatment includes evaporation for concentration, wet ashing, dry ashing and co-precipitation. After adding small amount of nitric acid, the sample can be concentrated by 1/10 of initial volume, which may be used to identify γ-emitters. As the pre-treatment of urine, wet ashing is used for example for analysis of Pu, and co-precipitation is used for example for analysis of Sr. Dry ashing by electric furnace is usually adopted for faecal samples. Methods of chemical separation depend on the radionuclide(s) to be analysed. The detection limit depends also on radionuclide, and for example typical detection limits are 0.4Bq / l (volume of urine sample) for 89 Sr or 90 Sr, and 0.01 Bq / l with urine and 0.01 Bq per sample with faeces for 238 Pu, 239 Pu or 241 Am. Simpler methods can be used for some radionuclides: For example, radioactivity concentration of tritium can be determined by liquid scintillation counting of urine or condensed water from exhaled air, and natural uranium in urine can be quantified by using fluorometric method. In some circumstances, gross-α or gross-β analyses are useful for quick estimation. To estimate intakes by inhalation or by ingestion from bioassay results and to assess the committed dose equivalent, commonly available bases are the relevant publications by the ICRP and domestic guides and manuals that conform to the radiation protection regulations. (author)

  2. Radiogenic cell transformation and carcinogenesis

    Science.gov (United States)

    Yang, T. C.; Georgy, K. A.; Mei, M.; Durante, M.; Craise, L. M.

    1995-01-01

    Radiation carcinogenesis is one of the major biological effects considered important in the risk assessment for space travel. Various biological model systems, including both cultured cells and animals, have been found useful for studying the carcinogenic effects of space radiations, which consist of energetic electrons, protons and heavy ions. The development of techniques for studying neoplastic cell transformation in culture has made it possible to examine the cellular and molecular mechanisms of radiation carcinogenesis. Cultured cell systems are thus complementary to animal models. Many investigators have determined the oncogenic effects of ionizing and nonionizing radiation in cultured mammalian cells. One of the cell systems used most often for radiation transformation studies is mouse embryonic cells (C3H10T1/2), which are easy to culture and give good quantitative dose-response curves. Relative biological effectiveness (RBE) for heavy ions with various energies and linear energy transfer (LET) have been obtained with this cell system. Similar RBE and LET relationship was observed by investigators for other cell systems. In addition to RBE measurements, fundamental questions on repair of sub- and potential oncogenic lesions, direct and indirect effect, primary target and lesion, the importance of cell-cell interaction and the role of oncogenes and tumor suppressor genes in radiogenic carcinogenesis have been studied, and interesting results have been found. Recently several human epithelial cell systems have been developed, and ionizing radiation have been shown to transform these cells. Oncogenic transformation of these cells, however, requires a long expression time and/or multiple radiation exposures. Limited experimental data indicate high-LET heavy ions can be more effective than low-LET radiation in inducing cell transformation. Cytogenetic and molecular analyses can be performed with cloned transformants to provide insights into basic genetic

  3. Development of Carcinogenesis Bioassay Models: Response of Small Fish Species to Various Classes of Carcinogens

    Science.gov (United States)

    1991-12-20

    series by precision liquid dispensing syringe pumps (PLD-II, Hamilton Company, Reno, NV) and delivered through microbore tubing to a maximum of six...In a parallel study, inIwhich acrylonitrile was administered by stomach tube (olive oil carrier, 5 mg/kg, once daily, 3 times weekly, 52 weeks) no...actually are combinations of solute and microfine particulate test compound. These particulates can vary in both size distribution and quantity so

  4. Bioassay of carcinogenesis: effects on the epithelial cell complement of rat tracheae maintained in vitro

    International Nuclear Information System (INIS)

    Lindsay, D.W.; Jones, J.R.; Higgins, W.J.; Brown, P.W.

    1974-01-01

    The effects on the epithelium of suckling rat tracheae in organ cultures of three polycyclic hydrocarbons, 7,12-dimethylben(a)anthracene and benzo(a)pyrene which are carcinogenic and pyrene which is not carcinogenic, of diethylnitrosamine and of cigarette smoke condensates prepared from two types of cigarettes were studied. The changes found in the epithelial cell complement were analyzed by differential cell counts which revealed the relative numbers of undifferentiated, normally differentiated and abnormally differentiated cells present. It was found that the same general pattern of change, involving a reduction in the proportion of differentiated cells at low concentrations of test material and an increasing proportion of abnormally differentiated cells at higher concentrations was found with all the carcinogens and the cigarette smoke condensates but not with the noncarcinogen. Some evidence suggesting that this constant pattern of change was induced in a different manner by different materials was found. The total cell number per unit length of epithelium was also recorded and it was found that all of the active materials caused an increase in total cell number except in the case of 7,12-dimethylben(a)anthracene which was markedly toxic and reduced cell number at relatively low concentrations

  5. Interpretation of thorium bioassay data

    International Nuclear Information System (INIS)

    Juliao, L.M.Q.C.; Azeredo, A.M.G.F.; Santos, M.S.; Melo, D.R.; Dantas, B.M.; Lipsztein, J.L.

    1994-01-01

    A comparison have been made between bioassay data of thorium-exposed workers from two different facilities. The first of these facilities is a monazite sand extraction plant. Isotopic equilibrium between 232 Th and 238 Th was not observed in excreta samples of these workers. The second facility is a gas mantle factory. An isotopic equilibrium between 232 Th and 228 Th was observed in extra samples. Whole body counter measurements have indicated a very low intake of thorium through inhalation. As the concentration of thorium in feces was very high it was concluded that the main pathway of entrance of the nuclide was ingestion, mainly via contamination through dirty hands. The comparison between the bioassay results of workers from the two facilities shows that the lack of Th isotopic equilibrium observed in the excretion from the workers at the monazite sand plant possibly occurred due to an additional Th intake by ingestion of contaminated fresh food. This is presumably because 228 Ra is more efficiently taken up from the soil by plants, in comparison to 228 Th or 232 Th, and subsequently, 228 Th grows in from its immediate parent, 228 Ra. (author) 5 refs.; 3 tabs

  6. Carcinogenesis

    International Nuclear Information System (INIS)

    Reilly, C.A. Jr.

    1979-01-01

    This section contains summaries of research in the following areas: use of liver for mechanistic studies of multistage hepatocarcinogenesis and for screening of environmental contaminants for tumor initiating and promoting activity; molecular properties of rat liver ornithine aminotransferase; regulation of gene expression in rat liver; methods of tumor detection; mechanisms of radiation and viral oncogenesis; biphenyl metabolism by rat liver microsomes; and studies on aryl hydrocarbon hydroxylase activity

  7. Carcinogenesis

    International Nuclear Information System (INIS)

    Buess, E.M.; Cerny, E.A.; Chan, E.W.

    1977-01-01

    The first section deals with the assessment of carcinogens and cocarcinogens and the underlying mechanisms of their actions. The second concerns cancer induction by bone-seeking radionuclides and seeks to provide a firm foundation for estimating cancer risks to human populations in the event of accidental incorporation of radionuclides. The third is aimed at defining the role of oncornavirus activation in tumor induction by radiation and other environmental pollutants. The other two sections describe the new studies, one dealing with the development of an in vitro cell system (murine teratocarcinoma cells) to screen chemicals rapidly for carcinogenic and mutagenic capacity, and the other investigating the potential use of plasma isozymes as indicators of mutagenesis in mammals. Accomplishments and projections for each of these studies follow

  8. Liver Development, Regeneration, and Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Janet W. C. Kung

    2010-01-01

    Full Text Available The identification of putative liver stem cells has brought closer the previously separate fields of liver development, regeneration, and carcinogenesis. Significant overlaps in the regulation of these processes are now being described. For example, studies in embryonic liver development have already provided the basis for directed differentiation of human embryonic stem cells and induced pluripotent stem cells into hepatocyte-like cells. As a result, the understanding of the cell biology of proliferation and differentiation in the liver has been improved. This knowledge can be used to improve the function of hepatocyte-like cells for drug testing, bioartificial livers, and transplantation. In parallel, the mechanisms regulating cancer cell biology are now clearer, providing fertile soil for novel therapeutic approaches. Recognition of the relationships between development, regeneration, and carcinogenesis, and the increasing evidence for the role of stem cells in all of these areas, has sparked fresh enthusiasm in understanding the underlying molecular mechanisms and has led to new targeted therapies for liver cirrhosis and primary liver cancers.

  9. Mutagenesis and carcinogenesis resulting from environment pollution

    International Nuclear Information System (INIS)

    Dimitrov, B.

    2001-01-01

    The paper reviews different ways of environmental contamination with natural and artificial harmful substances (chemical and radioactive) and their role in the processes of mutagenesis and carcinogenesis. The recent studies of the mechanism of mutagenesis and carcinogenesis due to environmental pollution are discussed

  10. Mutiple simultaneous event model for radiation carcinogenesis

    International Nuclear Information System (INIS)

    Baum, J.W.

    1979-01-01

    Theoretical Radiobiology and Risk Estimates includes reports on: Multiple Simultaneous Event Model for Radiation Carcinogenesis; Cancer Risk Estimates and Neutron RBE Based on Human Exposures; A Rationale for Nonlinear Dose Response Functions of Power Greater or Less Than One; and Rationale for One Double Event in Model for Radiation Carcinogenesis

  11. Rapid bioassay for oil-contaminated soil

    Energy Technology Data Exchange (ETDEWEB)

    Ashworth, J. [ALS Environmental, Edmonton, AB (Canada); Oosterbroek, L. [HydroQual, Calgary, AB (Canada)

    2010-07-01

    This PowerPoint presentation described a study conducted to develop a rapid bioassay for soils contaminated with oil. The bioassay method was designed for a weight of evidence (WoE) approach and eco-contact guideline derivation protocol. Microtox bioassays were conducted on cyclodextrin extracts of soil quantified by solvent extraction and gas chromatography. The method was demonstrated using straight {beta}-cyclodextrin soil extracts and activated {beta}-cyclodextrin soil extracts. An analysis of the methods showed that the activation step weakens or breaks the cyclodextrin and polycyclic hydrocarbon (PHC) inclusion complex. The released PHC became toxic to the microtox organism. Results from the bioassays were then correlated with earthworm reproduction bioassay results. tabs., figs.

  12. Investigation of independence in inter-animal tumor-type occurrences within the NTP rodent-bioassay database

    Energy Technology Data Exchange (ETDEWEB)

    Bogen, K.T. [Lawrence Livermore National Lab., CA (United States); Seilkop, S. [Analytical Sciences, Inc., Durham, NC (United States)

    1993-05-01

    Statistically significant elevation in tumor incidence at multiple histologically distinct sites is occasionally observed among rodent bioassays of chemically induced carcinogenesis. If such data are to be relied on (as they have, e.g., by the US EPA) for quantitative cancer potency assessment, their proper analysis requires a knowledge of the extent to which multiple tumor-type occurrences are independent or uncorrelated within individual bioassay animals. Although difficult to assess in a statistically rigorous fashion, a few significant associations among tumor-type occurrences in rodent bioassays have been reported. However, no comprehensive studies of animal-specific tumor-type occurrences at death or sacrifice have been conducted using the extensive set of available NTP rodent-bioassay data, on which most cancer-potency assessment for environmental chemicals is currently based. This report presents the results of such an analysis conducted on behalf of the National Research Council`s Committee on Risk Assessment for Hazardous Air Pollutants. Tumor-type associations among individual animals were examined for {approximately}2500 to 3000 control and {approximately}200 to 600 treated animals using pathology data from 62 B6C3F1 mouse studies and 61 F/344N rat studies obtained from a readily available subset of the NTP carcinogenesis bioassay database. No evidence was found for any large correlation in either the onset probability or the prevalence-at-death or sacrifice of any tumor-type pair investigated in control and treated rats and niece, although a few of the small correlations present were statistically significant. Tumor-type occurrences were in most cases nearly independent, and departures from independence, where they did occur, were small. This finding is qualified in that tumor-type onset correlations were measured only indirectly, given the limited nature of the data analyzed.

  13. Environmental carcinogenesis and genetic variability

    International Nuclear Information System (INIS)

    Knudsen, A.G. Jr

    1977-01-01

    It was found that carcinogenesis in man may involve the interaction of genetic and environmental forces, and that mutation, whether germinal or somatic, seems to be involved in the origin of many, perhaps all cancers. The cancers of man may be visualized as occurring in four groups of individuals according to whether (1) neither genetic nor environmental factors are dominant, i.e. 'background' or 'spontaneous' cancer, (2) heredity alone is dominant, (3) environment alone is important, or (4) both are operating (Knudsen, 1977). The last two groups together are widely thought to contribute 70-80% of cancer cases in the United States; the relative contribution of each group is a major question to be answered

  14. Time factors in radiation carcinogenesis

    International Nuclear Information System (INIS)

    Sasaki, Shunsaku

    1995-01-01

    Results of experiments using B6C3F 1 female mice were made subject of analysis on the time factors in radiation carcinogenesis. In the experiment for examination of influence of age at irradiation on the lifetime risk and on distribution of ages at death, mice were irradiated at day 12, 14 or 17 of the prenatal period, or day 0, 7, 35, 105, 240 or 365 of the postnatal period with doses ranging from 0.48 to 5.7 Gy gamma-rays from 137 Cs. In the experiment to examine the reduction factor for carcinogenic effect by multiple fractionation of gamma-rays dose 1.9 or 3.8 Gy was divided into 10 fractions, which were delivered once a week during period from 5 to 15 weeks of age. All mice were allowed to live out their life spans under a specific pathogen free condition. The cumulative relative risk for mortality from all causes except lymphoma and leukemia was shown to decrease with age when mice were irradiated at the fetal, neonatal, suckling, adolescent or young adult period, whereas, the decrease in the cumulative relative risk was very little when gamma-rays were given at the intermediate adult period. The lifetime risk for the increase in mortality and for the induction of solid tumors was highest in mice irradiated during neonatal, suckling or adolescent period. Age-dependence of susceptibility to radiation carcinogenesis was different for each type of neoplasm. However, the most susceptible period for induction of each type of neoplasm concentrated in the age from neonatal to adolescent period. Radiation-induced late effects were apparently reduced by multiple fractionation of radiation dose, but the reduction factor for the increase in the long-term mortality did not exceed 2.0. (author)

  15. Tea polyphenols EGCG and TF restrict tongue and liver carcinogenesis simultaneously induced by N-nitrosodiethylamine in mice

    Energy Technology Data Exchange (ETDEWEB)

    Sur, Subhayan, E-mail: subhayansur18@gmail.com [Dept. of Oncogene Regulation, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata 700 026, West Bengal (India); Pal, Debolina; Roy, Rituparna; Barua, Atish [Dept. of Oncogene Regulation, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata 700 026, West Bengal (India); Roy, Anup [North Bengal Medical College and Hospital, West Bengal (India); Saha, Prosenjit [Dept. of Oncogene Regulation, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata 700 026, West Bengal (India); Panda, Chinmay Kumar, E-mail: ckpanda.cnci@gmail.com [Dept. of Oncogene Regulation, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata 700 026, West Bengal (India)

    2016-06-01

    The aim of this study is to understand the molecular mechanisms of N-nitrosodiethylamine (NDEA) induced multi-organ carcinogenesis in tongue and liver of the same mouse and restriction of carcinogenesis by Epigallocatechin gallate (EGCG) and Theaflavin (TF), if any. For that purpose, cellular proliferation/apoptosis, prevalence of CD44 positive stem cell population and expressions of some key regulatory genes of self renewal Wnt and Hedgehog (Hh) pathways and some of their associated genes were analyzed in the NDEA induced tongue and liver lesions in absence or presence of EGCG/TF. Chronic NDEA exposure in oral cavity could decrease mice body weights and induce tongue and liver carcinogenesis with similar histological stages (severe dysplasia up to 30th weeks of NDEA administration). Increasing mice body weights were seen in continuous and post EGCG/TF treated groups. EGCG/TF treatment could restrict both the carcinogenesis at similar histological stages showing potential chemopreventive effect in continuous treated groups (mild dysplasia) followed by pre treatment (moderate dysplasia) and therapeutic efficacy in post treated groups (mild dysplasia) up to 30th week. The mechanism of carcinogenesis by NDEA and restriction by the EGCG/TF in both tongue and liver were similar and found to be associated with modulation in cellular proliferation/apoptosis and prevalence of CD44 positive population. The up-regulation of self renewal Wnt/β-catenin, Hh/Gli1 pathways and their associated genes Cyclin D1, cMyc and EGFR along with down regulation of E-cadherin seen during the carcinogenesis processes were found to be modulated during the restriction processes by EGCG/TF. - Highlights: • Simultaneous tongue and liver carcinogenesis in mice by oral NDEA administration • Restriction of both carcinogenesis by EGCG and TF at early pre-malignant stages • The mechanisms of carcinogenesis and restriction were similar in both the organs. • Changes in proliferation

  16. Tea polyphenols EGCG and TF restrict tongue and liver carcinogenesis simultaneously induced by N-nitrosodiethylamine in mice

    International Nuclear Information System (INIS)

    Sur, Subhayan; Pal, Debolina; Roy, Rituparna; Barua, Atish; Roy, Anup; Saha, Prosenjit; Panda, Chinmay Kumar

    2016-01-01

    The aim of this study is to understand the molecular mechanisms of N-nitrosodiethylamine (NDEA) induced multi-organ carcinogenesis in tongue and liver of the same mouse and restriction of carcinogenesis by Epigallocatechin gallate (EGCG) and Theaflavin (TF), if any. For that purpose, cellular proliferation/apoptosis, prevalence of CD44 positive stem cell population and expressions of some key regulatory genes of self renewal Wnt and Hedgehog (Hh) pathways and some of their associated genes were analyzed in the NDEA induced tongue and liver lesions in absence or presence of EGCG/TF. Chronic NDEA exposure in oral cavity could decrease mice body weights and induce tongue and liver carcinogenesis with similar histological stages (severe dysplasia up to 30th weeks of NDEA administration). Increasing mice body weights were seen in continuous and post EGCG/TF treated groups. EGCG/TF treatment could restrict both the carcinogenesis at similar histological stages showing potential chemopreventive effect in continuous treated groups (mild dysplasia) followed by pre treatment (moderate dysplasia) and therapeutic efficacy in post treated groups (mild dysplasia) up to 30th week. The mechanism of carcinogenesis by NDEA and restriction by the EGCG/TF in both tongue and liver were similar and found to be associated with modulation in cellular proliferation/apoptosis and prevalence of CD44 positive population. The up-regulation of self renewal Wnt/β-catenin, Hh/Gli1 pathways and their associated genes Cyclin D1, cMyc and EGFR along with down regulation of E-cadherin seen during the carcinogenesis processes were found to be modulated during the restriction processes by EGCG/TF. - Highlights: • Simultaneous tongue and liver carcinogenesis in mice by oral NDEA administration • Restriction of both carcinogenesis by EGCG and TF at early pre-malignant stages • The mechanisms of carcinogenesis and restriction were similar in both the organs. • Changes in proliferation

  17. Bioassay for uranium mill tailings

    International Nuclear Information System (INIS)

    Tschaeche, A.N.

    1986-01-01

    Uranium mill tailings are composed of fine sand that contains, among other things, some uranium (U/sup 238/ primarily), and all of the uranium daughters starting with /sup 230/Th that are left behind after the usable uranium is removed in the milling process. Millions of pounds of tailings are and continue to be generated at uranium mills around the United States. Discrete uranium mill tailings piles exist near the mills. In addition, the tailings materials were used in communities situated near mill sites for such purposes as building materials, foundations for buildings, pipe runs, sand boxes, gardens, etc. The Uranium Mill Tailings Remedial Action Project (UMTRAP) is a U.S. Department of Energy Program designed with the intention of removing or stabilizing the mill tailings piles and the tailings used to communities so that individuals are not exposed above the EPA limits established for such tailings materials. This paper discusses the bioassay programs that are established for workers who remove tailings from the communities in which they are placed

  18. Recent progress in nickel carcinogenesis. [Cornybacterium; E. coli; S. typhimurium; B. subtillis

    Energy Technology Data Exchange (ETDEWEB)

    Sunderman, F.W. Jr.

    1984-01-01

    Research on nickel carcinogenesis from 1979 to 1983 is reviewed. Epidemiological studies have strengthened the evidence that workers in nickel refineries have increased risks of lung and sinonasal cancers, but have not substantiated increased risks of respiratory cancers in other nickel-exposed workers. Carcinogenesis bioassays have demonstrated carcinogenicity of certain nickel sulfide, hydroxide, selenide, arsenide, antimonide, and telluride compounds following parenteral administration to rodents. Positive bacterial mutagenesis tests have been obtained with Ni(II) in Cornybacterium, but not in E. coli, S. typhimurium, or B. subtilis. Transformation assays of several soluble and crystalline Ni compounds have been positive in Syrian hamster embryo cells. Ni(II) binds to DNA, RNA, and nucleoproteins, and becomes localized in nucleoli. Genotoxic effects of Ni include: (a) chromosomal aberrations, including sister-chromatid exchanges, (b) DNA strandbreaks and DNA-protein cross-links, (c) inhibition of DNA and RNA synthesis, (d) infidelity of DNA transcription, and (e) mutations at the HGPRTase locus in Chinese hamster cells and the TK locus in mouse lymphoma cells. These findings are consistent with somatic mutation as the mechanism for initiation of nickel carcinogenesis. Ni compounds cause reversible transition of double-stranded poly(dG-dC) DNA from the right-handed B-helix to the left-handed Z-helix, suggesting a mechanism whereby nickel might modulate oncogene expression. 99 references, 6 tables.

  19. Free radicals in chemical carcinogenesis.

    Science.gov (United States)

    Clemens, M R

    1991-12-15

    During the past decade, remarkable progress has been made in our understanding of cancer-causing agents, mechanisms of cancer formation and the behavior of cancer cells. Cancer is characterized primarily by an increase in the number of abnormal cells derived from a given normal tissue, invasion of adjacent tissues by these abnormal cells, and lymphatic or blood-borne spread of malignant cells to regional lymph nodes and to distant sites (metastasis). It has been estimated that about 75-80% of all human cancers are environmentally induced, 30-40% of them by diet. Only a small minority, possibly no more than 2% of all cases, result purely from inherent genetic changes. Several lines of evidence confirm that the fundamental molecular event or events that cause a cell to become malignant occur at the level of the DNA and a variety of studies indicate that the critical molecular event in chemical carcinogenesis is the interaction of the chemical agent with DNA. The demonstration that DNA isolated from tumor cells can transfect normal cells and render them neoplastic provides direct proof that an alteration of the DNA is responsible for cancer. The transforming genes, or oncogenes, have been identified by restriction endonuclease mapping. One of the characteristics of tumor cells generated by transformation with viruses, chemicals, or radiation is their reduced requirement for serum growth factors. A critical significance of electrophilic metabolites of carcinogenes in chemical carcinogenesis has been demonstrated. A number of "proximate" and "ultimate" metabolites, especially those of aromatic amines, were described. The "ultimate" forms of carcinogens actually interact with cellular constituents to cause neoplastic transformation and are the final metabolic products in most pathways. Recent evidence indicates that free radical derivatives of chemical carcinogens may be produced both metabolically and nonenzymatically during their metabolism. Free radicals carry no

  20. Bioassay criteria for environmental restoration workers

    International Nuclear Information System (INIS)

    Carbaugh, E.H.; Bihl, D.E.

    1993-01-01

    Environmental restoration (ER) work at the U. S. Department of Energy Hanford Site posed questions concerning when to perform bioassay monitoring of workers for potential intakes of radioactivity. Application of criteria originally developed for use inside radionuclide processing facilities to ER work resulted in overly restrictive bioassay requirements. ER work typically involves site characterization or, excavating large quantities of potentially contaminated soil, rather than working with concentrated quantities of radioactivity as in a processing facility. An improved approach, tailored to ER work, provided soil contamination concentrations above which worker bioassay would be required. Soil concentrations were derived assuming acute or chronic intakes of 2% of an Annual Limit on Intake (ALI), or a potential committed effective dose equivalent of 100 mrem, and conservative dust loading of air from the work. When planning ER work, the anticipated soil concentration and corresponding need for bioassay could be estimated from work-site historical records. Once site work commenced, soil sampling and work-place surveys could be used to determine bioassay needs. This approach substantially reduced the required number of bioassay samples with corresponding reductions in analytical costs, schedules, and more flexible work-force management. (Work supported by the US Department of Energy under contract DOE-AC06-76RLO 1830.)

  1. Statistical modeling and extrapolation of carcinogenesis data

    International Nuclear Information System (INIS)

    Krewski, D.; Murdoch, D.; Dewanji, A.

    1986-01-01

    Mathematical models of carcinogenesis are reviewed, including pharmacokinetic models for metabolic activation of carcinogenic substances. Maximum likelihood procedures for fitting these models to epidemiological data are discussed, including situations where the time to tumor occurrence is unobservable. The plausibility of different possible shapes of the dose response curve at low doses is examined, and a robust method for linear extrapolation to low doses is proposed and applied to epidemiological data on radiation carcinogenesis

  2. Understanding Carcinogenesis for Fighting Oral Cancer

    OpenAIRE

    Tanaka, Takuji; Ishigamori, Rikako

    2011-01-01

    Oral cancer is one of the major global threats to public health. Oral cancer development is a tobacco-related multistep and multifocal process involving field cancerization and carcinogenesis. The rationale for molecular-targeted prevention of oral cancer is promising. Biomarkers of genomic instability, including aneuploidy and allelic imbalance, are able to measure the cancer risk of oral premalignancies. Understanding of the biology of oral carcinogenesis will give us important advances for...

  3. Recent progress in nickel carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Sunderman, F.W. Jr.

    1984-01-01

    Positive bacterial mutagenesis tests have been obtained with Ni(II) in Corynybacterium, but not in E. coli, S. typhimurium, or B. subtilis. Transformation assays of several soluble and crystalline Ni compounds have been positive in Syrian hamster embryo cells. Ni(II) binds to DNA, RNA, and nucleoproteins, and becomes localized in nucleoli. Genotoxic effects of Ni include: (a) chromosomal aberrations, including sister-chromatid exchanges, (b) DNA strandbreaks and DNA-protein crosslinks, (c) inhibition of DNA and RNA synthesis, (d) infidelity of DNA transcription, and (e) mutations at the HGPRTase locus in Chinese hamster cells and the TK locus in mouse lymphoma cells. These findings are consistent with somatic mutation as the mechanism for initiation of nickel carcinogenesis. Ni compounds cause reversible transition of double-stranded poly(dG-dC) DNA from the right-handed B-helix to the left-handed Z-helix, suggesting a mechanism whereby nickel might modulate oncogene expression. 99 references, 4 tables.

  4. Australian perioperative nurses' experiences of assisting in multi-organ procurement surgery: a grounded theory study.

    Science.gov (United States)

    Smith, Zaneta; Leslie, Gavin; Wynaden, Dianne

    2015-03-01

    Multi-organ procurement surgical procedures through the generosity of deceased organ donors, have made an enormous impact on extending the lives of recipients. There is a dearth of in-depth knowledge relating to the experiences of perioperative nurses working closely with organ donors undergoing multi-organ procurement surgical procedures. The aim of this study was to address this gap by describing the perioperative nurses experiences of participating in multi-organ procurement surgical procedures and interpreting these findings as a substantive theory. This qualitative study used grounded theory methodology to generate a substantive theory of the experiences of perioperative nurses participating in multi-organ procurement surgery. Recruitment of participants took place after the study was advertised via a professional newsletter and journal. The study was conducted with participants from metropolitan, rural and regional areas of two Australian states; New South Wales and Western Australia. Thirty five perioperative nurse participants with three to 39 years of professional nursing experience informed the study. Semi structured in-depth interviews were undertaken from July 2009 to April 2010 with a mean interview time of 60 min. Interview data was transcribed verbatim and analysed using the constant comparative method. The study results draw attention to the complexities that exist for perioperative nurses when participating in multi-organ procurement surgical procedures reporting a basic social psychological problem articulated as hiding behind a mask and how they resolved this problem by the basic social psychological process of finding meaning. This study provides a greater understanding of how these surgical procedures impact on perioperative nurses by providing a substantive theory of this experience. The findings have the potential to guide further research into this challenging area of nursing practice with implications for clinical initiatives, management

  5. Role of bacteria in oral carcinogenesis

    Directory of Open Access Journals (Sweden)

    R Rajeev

    2012-01-01

    Full Text Available Oral cancer is the most common cancer diagnosed in Indian men and is the leading cause of cancer deaths. It is considered as a multistep and multifactorial disease. Besides accumulation of genetic mutations, numerous other carcinogens are involved. In this category, viral and chemical carcinogens are well studied and documented. However, in the oral cavity, the role of microbiota in carcinogenesis is not known. Microbial populations on mouth mucosa differ between healthy and malignant sites, and certain oral bacterial species have been linked with malignancies, but the evidence is still weak in this respect. Nevertheless, oral microorganisms inevitably up-regulate cytokines and other inflammatory mediators that affect the complex metabolic pathways, and may thus be involved in carcinogenesis. Poor oral health associates statistically with prevalence of many types of cancer such as pancreatic and gastrointestinal cancer. This review presents possible carcinogenesis pathway involved in bacterial carcinogenesis, commonly implicated bacteria in oral carcinogenesis, and their role in cancer therapeutics as well.

  6. Transplacental arsenic carcinogenesis in mice

    International Nuclear Information System (INIS)

    Waalkes, Michael P.; Liu, Jie; Diwan, Bhalchandra A.

    2007-01-01

    Our work has focused on the carcinogenic effects of in utero arsenic exposure in mice. Our data show that a short period of maternal exposure to inorganic arsenic in the drinking water is an effective, multi-tissue carcinogen in the adult offspring. These studies have been reproduced in three temporally separate studies using two different mouse strains. In these studies pregnant mice were treated with drinking water containing sodium arsenite at up to 85 ppm arsenic from days 8 to 18 of gestation, and the offspring were observed for up to 2 years. The doses used in all these studies were well tolerated by both the dam and offspring. In C3H mice, two separate studies show male offspring exposed to arsenic in utero developed liver carcinoma and adrenal cortical adenoma in a dose-related fashion during adulthood. Prenatally exposed female C3H offspring show dose-related increases in ovarian tumors and lung carcinoma and in proliferative lesions (tumors plus preneoplastic hyperplasia) of the uterus and oviduct. In addition, prenatal arsenic plus postnatal exposure to the tumor promoter, 12-O-tetradecanoyl phorbol-13-acetate (TPA) in C3H mice produces excess lung tumors in both sexes and liver tumors in females. Male CD1 mice treated with arsenic in utero develop tumors of the liver and adrenal and renal hyperplasia while females develop tumors of urogenital system, ovary, uterus and adrenal and hyperplasia of the oviduct. Additional postnatal treatment with diethylstilbestrol or tamoxifen after prenatal arsenic in CD1 mice induces urinary bladder transitional cell proliferative lesions, including carcinoma and papilloma, and enhances the carcinogenic response in the liver of both sexes. Overall this model has provided convincing evidence that arsenic is a transplacental carcinogen in mice with the ability to target tissues of potential human relevance, such as the urinary bladder, lung and liver. Transplacental carcinogenesis clearly occurs with other agents in humans

  7. Modeling Multiple Causes of Carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Jones, T D

    1999-01-24

    multiple causes of carcinogenesis and shifts the risk-assessment logic to considerations of "what dose does?" in contrast to the current process of the substance-specific question of "what dose is?" Whether reactive oxygen is the proximate or contributing cause of disease or simply a better estimate of biologically effective dose, it has enormous advantages for improved risk- and policy-based decisions. Various estimates of immune system modulation will be given based on radiobiology.

  8. Bacterionomics and vironomics in carcinogenesis

    Directory of Open Access Journals (Sweden)

    Pratiwi Sudarmono

    2017-02-01

    Full Text Available Virus and bacteria are microbes which are very common cause human infection. Most of the bacterial infection can be eradicated by antibiotics and infection symptoms disappear. But for virus infection, once infected, the virus will persistently stay in the host, even undergo not only a lytic cycle but also integrated into host genome. Nowadays, at least 6 virus type are consistently related to human cancer, such as EBV,HPV,HTLV,HBV,HCV,HKSV, and the new one Merkel Virus (MCV. Although not every infected people will get cancer, but around 20% of the whole cancer in human are caused by viral oncogene. Class one oncogenic bacterial is Helicobacter pylori. Infection with this bacteria can cause persistent gastro duodenal inflammation which cause some alteration in gastric cell growth into transformation. Expression of Cag gene and Vac gene and some expression of OMP protein usually link to gastric cancer. Molecular mechanisms of carcinogenesis for every virus which cause infection  is a very complex , which include several processes caused by cell transformation. Besides, other host and environmental factors are also play a significant role in cancer development. Some scientist put a Hallmark analysis as a model to quickly summarize what pathobiology process will happen and what gene or protein caused the process. The Hallmark analysis comprise of several process which may happen simultaneously because some of the Hallmark is caused by the same protein. The Hallmark consists of various virus strategies in oncogenesis such as promoting angiogenesis, avoiding immune destruction, genome instability and mutation, deregulating cellular energetic, resisting cell death, sustaining proliferative signaling, evading growth suppressors, enabling cellular immortality, promoting inflammation and activation metastasis. For example, infection by HPV, will cause low grade dysplasia which can continue to invasive cervical cancer. After host cell transformation, in

  9. Multi-Organ toxicity demonstration in a functional human in vitro system composed of four organs.

    Science.gov (United States)

    Oleaga, Carlota; Bernabini, Catia; Smith, Alec S T; Srinivasan, Balaji; Jackson, Max; McLamb, William; Platt, Vivien; Bridges, Richard; Cai, Yunqing; Santhanam, Navaneetha; Berry, Bonnie; Najjar, Sarah; Akanda, Nesar; Guo, Xiufang; Martin, Candace; Ekman, Gail; Esch, Mandy B; Langer, Jessica; Ouedraogo, Gladys; Cotovio, Jose; Breton, Lionel; Shuler, Michael L; Hickman, James J

    2016-02-03

    We report on a functional human model to evaluate multi-organ toxicity in a 4-organ system under continuous flow conditions in a serum-free defined medium utilizing a pumpless platform for 14 days. Computer simulations of the platform established flow rates and resultant shear stress within accepted ranges. Viability of the system was demonstrated for 14 days as well as functional activity of cardiac, muscle, neuronal and liver modules. The pharmacological relevance of the integrated modules were evaluated for their response at 7 days to 5 drugs with known side effects after a 48 hour drug treatment regime. The results of all drug treatments were in general agreement with published toxicity results from human and animal data. The presented phenotypic culture model exhibits a multi-organ toxicity response, representing the next generation of in vitro systems, and constitutes a step towards an in vitro "human-on-a-chip" assay for systemic toxicity screening.

  10. Demonstration of SLUMIS: a clinical database and management information system for a multi organ transplant program.

    OpenAIRE

    Kurtz, M.; Bennett, T.; Garvin, P.; Manuel, F.; Williams, M.; Langreder, S.

    1991-01-01

    Because of the rapid evolution of the heart, heart/lung, liver, kidney and kidney/pancreas transplant programs at our institution, and because of a lack of an existing comprehensive database, we were required to develop a computerized management information system capable of supporting both clinical and research requirements of a multifaceted transplant program. SLUMIS (ST. LOUIS UNIVERSITY MULTI-ORGAN INFORMATION SYSTEM) was developed for the following reasons: 1) to comply with the reportin...

  11. Increased Dicarbonyl Stress as a Novel Mechanism of Multi-Organ Failure in Critical Illness

    Directory of Open Access Journals (Sweden)

    Bas C. T. van Bussel

    2017-02-01

    Full Text Available Molecular pathological pathways leading to multi-organ failure in critical illness are progressively being unravelled. However, attempts to modulate these pathways have not yet improved the clinical outcome. Therefore, new targetable mechanisms should be investigated. We hypothesize that increased dicarbonyl stress is such a mechanism. Dicarbonyl stress is the accumulation of dicarbonyl metabolites (i.e., methylglyoxal, glyoxal, and 3-deoxyglucosone that damages intracellular proteins, modifies extracellular matrix proteins, and alters plasma proteins. Increased dicarbonyl stress has been shown to impair the renal, cardiovascular, and central nervous system function, and possibly also the hepatic and respiratory function. In addition to hyperglycaemia, hypoxia and inflammation can cause increased dicarbonyl stress, and these conditions are prevalent in critical illness. Hypoxia and inflammation have been shown to drive the rapid intracellular accumulation of reactive dicarbonyls, i.e., through reduced glyoxalase-1 activity, which is the key enzyme in the dicarbonyl detoxification enzyme system. In critical illness, hypoxia and inflammation, with or without hyperglycaemia, could thus increase dicarbonyl stress in a way that might contribute to multi-organ failure. Thus, we hypothesize that increased dicarbonyl stress in critical illness, such as sepsis and major trauma, contributes to the development of multi-organ failure. This mechanism has the potential for new therapeutic intervention in critical care.

  12. Diet, lifestyle, and molecular alterations that drive colorectal carcinogenesis

    NARCIS (Netherlands)

    Diergaarde, B.

    2004-01-01

    Environmental factors have been repeatedly implicated in the etiology of colorectal cancer, and much is known about the molecular events involved in colorectal carcinogenesis. The relationships between environmental risk factors and the molecular alterations that drive colorectal carcinogenesis are

  13. A specific bioassay for the inhibition of flowering.

    Science.gov (United States)

    Blake, J

    1972-06-01

    A bioassay for the inhibition of flowering involving the in vitro culture of excised, partially-induced, apices of Viscaria candida is described. This bioassay has been used to detect flowering inhibition in extracts from Kalanchoe blossfeldiana.

  14. Deficiency of CCAAT/enhancer binding protein family DNA binding prevents malignant conversion of adenoma to carcinoma in NNK-induced lung carcinogenesis in the mouse

    Directory of Open Access Journals (Sweden)

    Kimura Shioko

    2012-12-01

    Full Text Available Abstract Background The CCAAT/enhancer binding proteins (C/EBPs play important roles in carcinogenesis of many tumors including the lung. Since multiple C/EBPs are expressed in lung, the combinatorial expression of these C/EBPs on lung carcinogenesis is not known. Methods A transgenic mouse line expressing a dominant negative A-C/EBP under the promoter of lung epithelial Clara cell secretory protein (CCSP gene in doxycycline dependent fashion was subjected to 4-(methylnitrosamino-1-(3-pyridyl-1-butanone (NNK-induced lung carcinogenesis bioassay in the presence and absence of doxycycline, and the effect of abolition of DNA binding activities of C/EBPs on lung carcinogenesis was examined. Results A-C/EBP expression was found not to interfere with tumor development; however, it suppressed the malignant conversion of adenoma to carcinoma during NNK-induced lung carcinogenesis. The results suggested that Ki67 may be used as a marker for lung carcinomas in mouse. Conclusions The DNA binding of C/EBP family members can be used as a potential molecular target for lung cancer therapy.

  15. 7 Vascular Hydrophytes for Bioassay.cdr

    African Journals Online (AJOL)

    Administrator

    4 water (see Table 1). tool. The greater extension growth of macrophyte shoots in water from downstream of STWs (Fig. 1) was supported by both chemical analysis, which showed increased phosphate concentration (Table 1), and by conventional Selenastrum bioassay in which higher cell concentrations were achieved.

  16. Bioassay of naturally occurring allelochemicals for phytotoxicity.

    Science.gov (United States)

    Leather, G R; Einhellig, F A

    1988-10-01

    The bioassay has been one of the most widely used tests to demonstrate allelopathic activity. Often, claims that a particular plant species inhibits the growth of another are based entirely on the seed germination response to solvent extracts of the suspected allelopathic plant; few of these tests are of value in demonstrating allelopathy under natural conditions. The veracity of the bioassay for evaluating naturally occurring compounds for phytotoxicity depends upon the physiological and biochemical response capacity of the bioassay organism and the mechanism(s) of action of the allelochemicals. The possibility that more than one allelochemical, acting in concert at very low concentrations, may be responsible for an observed allelopathic effect makes it imperative that bioassays be extremely sensitive to chemical growth perturbation agents. Among the many measures of phytotoxicity of allelochemicals, the inhibition (or stimulation) of seed germination, radicle elongation, and/or seedling growth have been the parameters of choice for most investigations. Few of these assays have been selected with the view towards the possible mechanism of the allelopathic effect.

  17. Micro-organism distribution sampling for bioassays

    Science.gov (United States)

    Nelson, B. A.

    1975-01-01

    Purpose of sampling distribution is to characterize sample-to-sample variation so statistical tests may be applied, to estimate error due to sampling (confidence limits) and to evaluate observed differences between samples. Distribution could be used for bioassays taken in hospitals, breweries, food-processing plants, and pharmaceutical plants.

  18. Radiation carcinogenesis and related radiobiology. Special listing

    International Nuclear Information System (INIS)

    1980-01-01

    The special listing of Current Cancer Research Projects is a publication of the International Cancer Research Data Bank (ICRDB) Program of the National Cancer Institute. Each Listing contains descriptions of ongoing projects in one selected cancer research area. The research areas include: Human cancer and exposure to radiation; Experimental radiation carcinogenesis and radiation biology

  19. Experimental radiation carcinogenesis: what have we learned

    Energy Technology Data Exchange (ETDEWEB)

    Fry, R.J.M.

    1980-01-01

    The author reviews the need for animal experiments in development of a biological model for radioinduced carcinogenesis. He concludes they are vital for: (1) study of mechanisms; (2) establishment of generalizations; (3) elucidation of dose-response and time-dose relationships; and (4) determination of dose-distributions and their results, particularly for radionuclides. (PSB)

  20. Experimental radiation carcinogenesis: what have we learned

    International Nuclear Information System (INIS)

    Fry, R.J.M.

    1980-01-01

    The author reviews the need for animal experiments in development of a biological model for radioinduced carcinogenesis. He concludes they are vital for: (1) study of mechanisms; (2) establishment of generalizations; (3) elucidation of dose-response and time-dose relationships; and (4) determination of dose-distributions and their results, particularly for radionuclides

  1. Molecular mechanisms in radiation carcinogenesis: introduction

    International Nuclear Information System (INIS)

    Setlow, R.B.

    1975-01-01

    Molecular studies of radiation carcinogenesis are discussed in relation to theories for extrapolating from cellular and animal models to man. Skin cancer is emphasized because of sunlight-induced photochemical damage to DNA. It is emphasized that cellular and animal models are needed as well as molecular theories for quantitative evaluation of hazardous environmental agents. (U.S.)

  2. In vitro studies of human lung carcinogenesis.

    Science.gov (United States)

    Harris, C C; Lechner, J F; Yoakum, G H; Amstad, P; Korba, B E; Gabrielson, E; Grafstrom, R; Shamsuddin, A; Trump, B F

    1985-01-01

    Advances in the methodology to culture normal human lung cells have provided opportunities to investigate fundamental problems in biomedical research, including the mechanism(s) of carcinogenesis. Using the strategy schematically shown in Figure 1, we have initiated studies of the effects of carcinogens on the normal progenitor cells of the human cancers caused by these carcinogens. Extended lifespans and aneuploidy were found after exposure of mesothelial cells to asbestos and bronchial epithelial cells to nickel sulfate. These abnormal cells may be considered to be preneoplastic and at an intermediate position in the multistage process of carcinogenesis. Human bronchial epithelial cells can also be employed to investigate the role of specific oncogenes in carcinogenesis and tumor progression. Using the protoplast fusion method for high frequency gene transfection, vHa-ras oncogene initiates a cascade of events in the normal human bronchial cells leading to their apparent immortality, aneuploidy, and tumorigenicity in athymic nude mice. These results suggest that oncogenes may play an important role in human carcinogenesis.

  3. A Case Against Fancy Decorated Drinks: Multi-Organ Failure After Drinking a Mojito Cocktail

    Directory of Open Access Journals (Sweden)

    Simon Bac

    2016-09-01

    Full Text Available We present the first case of gastro-intestinal perforation caused by a mint twig decorating a cocktail drink. A 76-year-old man was enjoying his Mojito cocktail on a cruise ship near Mexico when he accidently swallowed a mint twig, resulting in ileum perforation. This led to a cascade of events, eventually resulting in life-threatening multi-organ failure. Given this rare but potentially severe complication and the increasing popularity of decorated drinks, a less ‘fancy’ presentation for cocktails and similar drinks may be warranted.

  4. Strawberry Phytochemicals Inhibit Azoxymethane/Dextran Sodium Sulfate-Induced Colorectal Carcinogenesis in Crj: CD-1 Mice

    Directory of Open Access Journals (Sweden)

    Ni Shi

    2015-03-01

    Full Text Available Human and experimental colon carcinogenesis are enhanced by a pro-inflammatory microenvironment. Pharmacologically driven chemopreventive agents and dietary variables are hypothesized to have future roles in the prevention of colon cancer by targeting these processes. The current study was designed to determine the ability of dietary lyophilized strawberries to inhibit inflammation-promoted colon carcinogenesis in a preclinical animal model. Mice were given a single i.p. injection of azoxymethane (10 mg kg−1 body weight. One week after injection, mice were administered 2% (w/v dextran sodium sulfate in drinking water for seven days and then an experimental diet containing chemically characterized lyophilized strawberries for the duration of the bioassay. Mice fed control diet, or experimental diet containing 2.5%, 5.0% or 10.0% strawberries displayed tumor incidence of 100%, 64%, 75% and 44%, respectively (p < 0.05. The mechanistic studies demonstrate that strawberries reduced expression of proinflammatory mediators, suppressed nitrosative stress and decreased phosphorylation of phosphatidylinositol 3-kinase, Akt, extracellular signal-regulated kinase and nuclear factor kappa B. In conclusion, strawberries target proinflammatory mediators and oncogenic signaling for the preventive efficacies against colon carcinogenesis in mice. This works supports future development of fully characterized and precisely controlled functional foods for testing in human clinical trials for this disease.

  5. Tissue misrepair hypothesis for radiation carcinogenesis

    International Nuclear Information System (INIS)

    Kondo, Sohei

    1991-01-01

    Dose-response curves for chronic leukemia in A-bomb survivors and liver tumors in patients given Thorotrast (colloidal thorium dioxide) show large threshold effects. The existence of these threshold effects can be explained by the following hypothesis. A high dose of radiation causes a persistent wound in a cellrenewable tissue. Disorder of the injured cell society partly frees the component cells from territorial restraints on their proliferation, enabling them to continue development of their cellular functions toward advanced autonomy. This progression might be achieved by continued epigenetic and genetic changes as a result of occasional errors in the otherwise concerted healing action of various endogeneous factors recruited for tissue repair. Carcinogenesis is not simply a single-cell problem but a cell-society problem. Therefore, it is not warranted to estimate risk at low doses by linear extrapolation from cancer data at high doses without knowledge of the mechanism of radiation carcinogenesis. (author) 57 refs

  6. Inflammatory and redox reactions in colorectal carcinogenesis.

    Science.gov (United States)

    Guina, Tina; Biasi, Fiorella; Calfapietra, Simone; Nano, Mario; Poli, Giuseppe

    2015-03-01

    It has been established that there is a relationship between chronic inflammation and cancer development. The constant colonic inflammation typical of inflammatory bowel diseases is now considered a risk factor for colorectal carcinoma (CRC) development. The inflammatory network of signaling molecules is also required during the late phases of carcinogenesis, to enable cancer cells to survive and to metastasize. Oxidative reactions are an integral part of the inflammatory response, and are generally associated with CRC development. However, when the malignant phenotype is acquired, increased oxidative status induces antioxidant defenses in cancer cells, favoring their aggressiveness. This contradictory behavior of cancer cells toward redox status is of great significance for potential anticancer therapies. This paper summarizes the essential background information relating to the molecules involved in regulating oxidative stress and inflammation during carcinogenesis. Understanding more of their function in CRC stages might provide the foundation for future developments in CRC treatment. © 2015 New York Academy of Sciences.

  7. Introduction to Genetic Mechanisms of Carcinogenesis

    International Nuclear Information System (INIS)

    Yang, W.K.

    1983-01-01

    Recent technical advances in nucleic acid research and molecular biology have made it possible to explore the complicated genetic systems of eukaryotic cells. One of the fields showing rapid progress concerns genes and gene regulatory functions related to neoplastic processes. Thus, the 35th Annual Conference of the Biology Division of Oak Ridge National Laboratory, held at Gatlinburg, April 12-15, 1982, was organized with the intention to bring together investigators working on seemingly diverse fields of cancer research to discuss and exchange their views on the genetic mechanisms of carcinogenesis. The meeting was attended by workers from chemical, physical as well as biological carcinogenesis fields, by classical geneticists as well as by molecular biologists, and by researchers interested in experimental as well as in human cancers. Included in this volume are papers by the invited speakers of the symposium as well as by those presenting poster papers at the meeting

  8. Lymphotoxin prevention of diethylnitrosamine carcinogenesis in vivo

    International Nuclear Information System (INIS)

    Ransom, J.H.; Evans, C.H.; DiPaolo, J.A.

    1982-01-01

    Development of intervention measures to control cancer would be facilitated by being able to monitor in vivo carcinogenesis by in vitro quantitation of early indices of neoplastic transformation to assess the in vivo effectiveness of preventive-therapeutic measures. Pregnant Syrian golden hamsters were used in an in vivo-in vitro transplacental model of carcinogenesis to determine the extent that in vivo administration of immunologic hormone preparations along with chemical carcinogen would prevent morphologic transformation assessed in vitro. Pregnant hamsters at 10-11 days of gestation were given injections ip of 3 mg diethylnitrosamine (DENA)/100 g body weight and were killed 2 days later when fetal cells were seeded for colony formation. The frequency of morphologically transformed colonies was assessed after 7 days of growth. Cloning efficiency and mean transformation frequency after DENA exposure were 3.6% and 1 X 10(-4) per cell seeded, respectively. The ip injection of an immunologic hormone preparation reduced the transformation frequency by 46%. The hormone preparation, containing 10,000 U of lymphotoxin but no detectable interferon, was the ultrafiltered lymphokines (greater than 10,000 mol wt) from phytohemagglutinin-stimulated hamster peritoneal leukocytes. The effect of lymphotoxin on cocarcinogenic exposure of fetal cells to DENA in vivo followed by X-irradiation in vitro was also determined. Cells exposed to 250 rad in vitro had a cloning efficiency of 0.5% and a transformation frequency of 0.4 X 10(-4) per cell seeded. After DENA injection and X-irradiation, the transformation frequency increased to 1 X 10(-4) and was inhibited 64% by lymphotoxin in vivo. Thus immunologic hormones (e.g., lymphotoxin) can prevent carcinogenesis in vivo. Furthermore, in vitro quantitation of transformation is a rapid means for evaluating therapeutic and autochthonous effector mechanisms for their ability to prevent or otherwise modulate carcinogenesis in vivo

  9. Radiation carcinogenesis and related radiobiology. Special listing

    International Nuclear Information System (INIS)

    1978-01-01

    This Special Listing of Current Cancer Research Projects is a service of the International Cancer Research Data Bank (ICRDB) program of the National Cancer Institute. Each listing contains descriptions of ongoing projects in one selected cancer research area. The descriptions are provided by cancer scientists in about 50 different countries. Research areas covered in this listing are: Human cancer and exposure to radiation; experimental radiation carcinogenesis and radiation biology

  10. Genetic alterations during radiation-induced carcinogenesis

    International Nuclear Information System (INIS)

    Kodama, Seiji

    1995-01-01

    This paper reviews radiation-induced genetic alterations and its carcinogenesis, focusing on the previous in vitro assay outcome. A colony formation assay using Syrian hamster fetal cells and focus formation assay using mouse C3H10T1/2 cells are currently available to find malignant transformation of cells. Such in vitro assays has proposed the hypothesis that radiation-induced carcinogenesis arises from at least two-stage processes; i.e., that an early step induced by irradiation plays an important role in promoting the potential to cause the subsequent mutation. A type of genetic instability induced by radiation results in a persistently elevated frequency of spontaneous mutations, so-called the phenomenon of delayed reproductive death. One possible mechanism by which genetic instability arises has been shown to be due to the development of abnormality in the gene group involved in the maintenance mechanism of genome stability. Another possibility has also been shown to stem from the loss of telomere (the extremities of a chromosome). The importance of search for radiation-induced genetic instability is emphasized in view of the elucidation of carcinogenesis. (N.K.)

  11. Lemierre's Syndrome - A rare cause of disseminated sepsis requiring multi-organ support.

    Science.gov (United States)

    Rae, John; Misselbrook, Katie

    2017-11-01

    Lemierre's syndrome is a rare complication of acute pharyngitis characterised by septicaemia with infective thrombophlebitis of the internal jugular vein, most commonly due to Fusobacterium necrophorum . It characteristically affects healthy young adults causing persistent pyrexia and systemic sepsis presenting several days after an initial pharyngitis. Septic emboli seed via the bloodstream to distant sites including the lung, joints, skin, liver, spleen and brain. Prolonged antimicrobial therapy is required and admission to intensive care common. This once rare condition is increasing in incidence but awareness amongst clinicians is low. We present a classic case in a young man who developed multi-organ failure requiring intensive care support and describe the epidemiology, pathophysiology, microbiology, clinical features and management of the disease.

  12. The ICRP working party on bioassay interpretation

    International Nuclear Information System (INIS)

    Fry, F.A.; Lipsztein, J.L.; Birchall, A.

    2003-01-01

    In recent years there have been many developments in modelling the behaviour of radionuclides in the human body. The current generation of models are designed to be more 'realistic' than the previous generation of simple compartment models. The International Commission on Radiological Protection (ICRP) uses these models to produce dose coefficients and recognises that there is a need to give more guidance on how these models can be used to interpret bioassay data. A working party has been set up to address the issue. This paper describes some of the problems, some approaches to solving the problems and the progress of the ICRP working party. (author)

  13. 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...

  14. 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...

  15. Bioassay method for Uranium in urine by Delay Neutron counting

    International Nuclear Information System (INIS)

    Suratman; Purwanto; Sukarman-Aminjoyo

    1996-01-01

    A bioassay method for uranium in urine by neutron counting has been studied. The aim of this research is to obtain a bioassay method for uranium in urine which is used for the determination of internal dose of radiation workers. The bioassay was applied to the artificially uranium contaminated urine. The weight of the contaminant was varied. The uranium in the urine was irradiated in the Kartini reactor core, through pneumatic system. The delayed neutron was counted by BF3 neutron counter. Recovery of the bioassay was between 69.8-88.8 %, standard deviation was less than 10 % and the minimum detection was 0.387 μg

  16. Application of evolutionary games to modeling carcinogenesis.

    Science.gov (United States)

    Swierniak, Andrzej; Krzeslak, Michal

    2013-06-01

    We review a quite large volume of literature concerning mathematical modelling of processes related to carcinogenesis and the growth of cancer cell populations based on the theory of evolutionary games. This review, although partly idiosyncratic, covers such major areas of cancer-related phenomena as production of cytotoxins, avoidance of apoptosis, production of growth factors, motility and invasion, and intra- and extracellular signaling. We discuss the results of other authors and append to them some additional results of our own simulations dealing with the possible dynamics and/or spatial distribution of the processes discussed.

  17. Mechanisms of carcinogenesis prevention by flavonoids

    Directory of Open Access Journals (Sweden)

    G. A. Belitsky

    2014-01-01

    Full Text Available The mechanisms of anticancerogenic effects of flavanoids and isocyanates from the plants widely consumed in the midland belt of Russia were reviewed. Data of studies both in vitro and in vivo were analyzed. Special attention was paid to inhibition of targets responsible for carcinogen metabolic activation, carcinogenesis promotion and tumor progression as well as neoangiogenesis. Besides that the antioxidant properties of flavonoids and their effects on cell cycle regulation, apoptosis initiation and cell mobility were considered.

  18. Bioassay method for Uranium in urine by Delay Neutron counting; Metoda Bioassay Uranium dalam urin dengan pencacahan Netron Kasip

    Energy Technology Data Exchange (ETDEWEB)

    Suratman,; Purwanto,; Sukarman-Aminjoyo, [Yogyakarta Nuclear Research Centre, National Atomic Energy Agency, Yogyakarta (Indonesia)

    1996-04-15

    A bioassay method for uranium in urine by neutron counting has been studied. The aim of this research is to obtain a bioassay method for uranium in urine which is used for the determination of internal dose of radiation workers. The bioassay was applied to the artificially uranium contaminated urine. The weight of the contaminant was varied. The uranium in the urine was irradiated in the Kartini reactor core, through pneumatic system. The delayed neutron was counted by BF3 neutron counter. Recovery of the bioassay was between 69.8-88.8 %, standard deviation was less than 10 % and the minimum detection was 0.387 {mu}g.

  19. Urine sample collection protocols for bioassay samples

    Energy Technology Data Exchange (ETDEWEB)

    MacLellan, J.A.; McFadden, K.M.

    1992-11-01

    In vitro radiobioassay analyses are used to measure the amount of radioactive material excreted by personnel exposed to the potential intake of radioactive material. The analytical results are then used with various metabolic models to estimate the amount of radioactive material in the subject`s body and the original intake of radioactive material. Proper application of these metabolic models requires knowledge of the excretion period. It is normal practice to design the bioassay program based on a 24-hour excretion sample. The Hanford bioassay program simulates a total 24-hour urine excretion sample with urine collection periods lasting from one-half hour before retiring to one-half hour after rising on two consecutive days. Urine passed during the specified periods is collected in three 1-L bottles. Because the daily excretion volume given in Publication 23 of the International Commission on Radiological Protection (ICRP 1975, p. 354) for Reference Man is 1.4 L, it was proposed to use only two 1-L bottles as a cost-saving measure. This raised the broader question of what should be the design capacity of a 24-hour urine sample kit.

  20. Urine sample collection protocols for bioassay samples

    Energy Technology Data Exchange (ETDEWEB)

    MacLellan, J.A.; McFadden, K.M.

    1992-11-01

    In vitro radiobioassay analyses are used to measure the amount of radioactive material excreted by personnel exposed to the potential intake of radioactive material. The analytical results are then used with various metabolic models to estimate the amount of radioactive material in the subject's body and the original intake of radioactive material. Proper application of these metabolic models requires knowledge of the excretion period. It is normal practice to design the bioassay program based on a 24-hour excretion sample. The Hanford bioassay program simulates a total 24-hour urine excretion sample with urine collection periods lasting from one-half hour before retiring to one-half hour after rising on two consecutive days. Urine passed during the specified periods is collected in three 1-L bottles. Because the daily excretion volume given in Publication 23 of the International Commission on Radiological Protection (ICRP 1975, p. 354) for Reference Man is 1.4 L, it was proposed to use only two 1-L bottles as a cost-saving measure. This raised the broader question of what should be the design capacity of a 24-hour urine sample kit.

  1. Bioassay of procoagulant albumin in human plasma.

    Science.gov (United States)

    Grosset, A; Liu, L; Parker, C J; Rodgers, G M

    1994-09-01

    Procoagulant albumin (P-Al) is present in normal human plasma and increases monocyte and endothelial cell expression of tissue factor activity. To develop a bioassay for P-Al, we partially purified plasma from healthy volunteers and several patient groups using BaCl2 and (NH4)2SO4 precipitation. The samples were assayed for tissue factor (TF) inducing activity, expressed as a percentage increase compared to a serum-free media control. Over six months, the assay was reproducible in stored samples and in serial samples from normal volunteers. The plasma P-Al activities of 35 volunteers averaged 141 +/- 8.2% (SEM). There was no diurnal variation. There was no difference in the P-Al activity after a 12 hour fast and 2 hours after a large meal in 4 healthy volunteers. There was no increase in activity (r = 0.16) with the subject's age. The average activity from 16 poorly-controlled diabetics was 131 +/- 11% (SEM). No alteration in activity was seen with samples from patients with uremia, liver dysfunction, hemophilia, thrombotic events, or adenocarcinoma. These results indicate that P-Al activity can be bioassayed in individual patient samples; however, pathologic states associated with abnormal P-Al-induced tissue factor activity presently remain unidentified.

  2. Curcumin: the spicy modulator of breast carcinogenesis.

    Science.gov (United States)

    Banik, Urmila; Parasuraman, Subramani; Adhikary, Arun Kumar; Othman, Nor Hayati

    2017-07-19

    Worldwide breast cancer is the most common cancer in women. For many years clinicians and the researchers are examining and exploring various therapeutic modalities for breast cancer. Yet the disease has remained unconquered and the quest for cure is still going on. Present-day strategy of breast cancer therapy and prevention is either combination of a number of drugs or a drug that modulates multiple targets. In this regard natural products are now becoming significant options. Curcumin exemplifies a promising natural anticancer agent for this purpose. This review primarily underscores the modulatory effect of curcumin on the cancer hallmarks. The focus is its anticancer effect in the complex pathways of breast carcinogenesis. Curcumin modulates breast carcinogenesis through its effect on cell cycle and proliferation, apoptosis, senescence, cancer spread and angiogenesis. Largely the NFkB, PI3K/Akt/mTOR, MAPK and JAK/STAT are the key signaling pathways involved. The review also highlights the curcumin mediated modulation of tumor microenvironment, cancer immunity, breast cancer stem cells and cancer related miRNAs. Using curcumin as a therapeutic and preventive agent in breast cancer is perplexed by its diverse biological activity, much of which remains inexplicable. The information reviewed here should point toward potential scope of future curcumin research in breast cancer.

  3. Radiation carcinogenesis: Epidemiology and biological significance

    International Nuclear Information System (INIS)

    Boice, J.D.; Fraumeni, J.F.

    1984-01-01

    Epidemiologic studies of populations exposed to radiation have led to the identification of a preventable cause of cancer, but in the long run perhaps the most important contribution of radiation studies will be to provide insights into the basic processes of human carcinogenesis. In this volume, key investigators of major epidemiologic projects summarize their observations to date, including information to help assess the effects of low-level exposures. Experimentalists and theorists emphasize the relevance of laboratory and epidemiologic data in elucidating carcinogenic risks and mechanisms in man. This volume was prepared with several objectives in mind: (a) organize and synthesize knowledge on radiation carcinogenesis through epidemiologic and experimental approaches; (b) illustrate and explore ways of utilizing this information to gain insights into the fundamental mechanisms of cancer development; (c) stimulate the formation of hypotheses suited to experimental or epidemiologic testing, theoretical modeling, and multidisciplinary approaches; and (d) identify recent advances that clarify dose-response relationships and the influence of low-dose exposures, provide leads to carcinogenic mechanisms and host-environmental interactions, and suggest strategies for future research and preventive action

  4. Are bioassays useful tools to assess redox processes and biodegradation?

    DEFF Research Database (Denmark)

    Albrechtsen, Hans-Jørgen; Pedersen, Philip Grinder; Ludvigsen, L.

    2002-01-01

    sensitive hydrochemical or geochemical parameters, levels of hydrogen, and redox potential. However, all these approaches have to be evaluated against TEAP-bioassays as the most direct measure. We assessed successfully ongoing microbial-mediated redox processes by TEAP-bioassays in degradation studies...... of aromatic and chlorinated aliphatic compounds in landfill leachate plumes, and of pesticides in aquifers with various redox conditions....

  5. Initiation-promotion skin carcinogenesis and immunological competence.

    Science.gov (United States)

    Curtis, G L; Stenbäck, F; Ryan, W L

    1975-10-01

    The immune competence of mice during initiation-promotion skin carcinogenesis was determined by skin allograft rejection and lymphocyte mitogenesis. The carcinogen 7, 12-dimethylbenzanthracene inhibited the cellular immune competence of mice while lymphocytes from croton oil treated mice had enhanced PWM response. Chlorphenesin, a stimulator of cellular immunity, was found to inhibit tumorigenesis in initiation-promotion skin carcinogenesis when injected during promotion.

  6. Multi-organ dysfunction in bodybuilding possibly caused by prolonged hypercalcemia due to multi-substance abuse

    DEFF Research Database (Denmark)

    Schäfer, Carolyn; Guldager, Helle Skov; Jørgensen, H L

    2011-01-01

    and chronic ulcers due to paraffin-oil injections in both upper arms one year before. Over the course of the next few hours, the patient developed signs of multi-organ dysfunction, including pancreatitis, hemorrhagic gastritis, nephropathy with temporary anuria, and respiratory insufficiency...

  7. Circular Bioassay Platforms for Applications in Microwave-Accelerated Techniques.

    Science.gov (United States)

    Mohammed, Muzaffer; Clement, Travis C; Aslan, Kadir

    2014-12-02

    In this paper, we present the design of four different circular bioassay platforms, which are suitable for homogeneous microwave heating, using theoretical calculations (i.e., COMSOL™ multiphysics software). Circular bioassay platforms are constructed from poly(methyl methacrylate) (PMMA) for optical transparency between 400-800 nm, has multiple sample capacity (12, 16, 19 and 21 wells) and modified with silver nanoparticle films (SNFs) to be used in microwave-accelerated bioassays (MABs). In addition, a small monomode microwave cavity, which can be operated with an external microwave generator (100 W), for use with the bioassay platforms in MABs is also developed. Our design parameters for the circular bioassay platforms and monomode microwave cavity during microwave heating were: (i) temperature profiles, (ii) electric field distributions, (iii) location of the circular bioassay platforms inside the microwave cavity, and (iv) design and number of wells on the circular bioassay platforms. We have also carried out additional simulations to assess the use of circular bioassay platforms in a conventional kitchen microwave oven (e.g., 900 W). Our results show that the location of the circular bioassay platforms in the microwave cavity was predicted to have a significant effect on the homogeneous heating of these platforms. The 21-well circular bioassay platform design in our monomode microwave cavity was predicted to offer a homogeneous heating pattern, where inter-well temperature was observed to be in between 23.72-24.13°C and intra-well temperature difference was less than 0.21°C for 60 seconds of microwave heating, which was also verified experimentally.

  8. Plasmonically amplified fluorescence bioassay with microarray format

    Science.gov (United States)

    Gogalic, S.; Hageneder, S.; Ctortecka, C.; Bauch, M.; Khan, I.; Preininger, Claudia; Sauer, U.; Dostalek, J.

    2015-05-01

    Plasmonic amplification of fluorescence signal in bioassays with microarray detection format is reported. A crossed relief diffraction grating was designed to couple an excitation laser beam to surface plasmons at the wavelength overlapping with the absorption and emission bands of fluorophore Dy647 that was used as a label. The surface of periodically corrugated sensor chip was coated with surface plasmon-supporting gold layer and a thin SU8 polymer film carrying epoxy groups. These groups were employed for the covalent immobilization of capture antibodies at arrays of spots. The plasmonic amplification of fluorescence signal on the developed microarray chip was tested by using interleukin 8 sandwich immunoassay. The readout was performed ex situ after drying the chip by using a commercial scanner with high numerical aperture collecting lens. Obtained results reveal the enhancement of fluorescence signal by a factor of 5 when compared to a regular glass chip.

  9. Immune thrombocytopenia with multi-organ dysfunction syndrome as a rare presentation of scrub typhus: a case report.

    Science.gov (United States)

    Ittyachen, Abraham M; Abraham, Saramma P; Krishnamoorthy, Smitha; Vijayan, Anuroopa; Kokkat, Jayamohan

    2017-10-06

    Scrub typhus is an acute infectious illness caused by Orientia tsutsugamushi. It is endemic to a part of the world known as the "tsutsugamushi triangle". Humans are accidental hosts in this zoonotic disease. About a third of patients admitted with scrub typhus have evidence of multi-organ dysfunction. Multi-organ dysfunction secondary to scrub typhus carries a high mortality rate. We report a 65-year old lady who was admitted in a Tertiary Care Center in the state of Kerala in India, with 7 day history of fever, myalgia and reduced urine output. Head to foot examination revealed the presence of an eschar on her chest. One week prior to the onset of her illness she had gone trekking through a hilly forest area. She was clinically suspected to have scrub typhus, which was later confirmed with laboratory tests. She developed multi-organ dysfunction syndrome secondary to this illness. Though there was an improvement in the multi-organ dysfunction, thrombocytopenia alone failed to improve. Bone marrow study was done which was suggestive of immune thrombocytopenia. Patient was given a course of steroids with which the thrombocytopenia improved. Failure of platelet count to normalize even after there has been a general improvement of other markers of multi-organ dysfunction in scrub typhus should prompt the clinician to consider other potential causes of thrombocytopenia. An unusual finding as this calls for further research to understand the molecular mechanisms behind such an event. Further, considering the close similarity in clinical presentation of several tropical illnesses, meticulous history taking and a detailed physical examination needs to be emphasized.

  10. Multi-organ damage induced by anabolic steroid supplements: a case report and literature review

    Directory of Open Access Journals (Sweden)

    Samaha Ali A

    2008-10-01

    Full Text Available Abstract Introduction The use of anabolic supplements and other related drugs for body building and to enhance athletic performance is nowadays widespread and acutely pervasive all around the world. This alarming increase in the use of anabolic and amino acid supplements has been linked to a diverse array of pathologies. As previously reported, the abuse of androgenic steroids is not without severe physiological, psychiatric and physical costs. The case we report here describes multi-organ damage resulting from the abuse and uncontrolled use of anabolic steroid supplements, mainly testosterone. Case presentation A 24-year-old white man presented with abdominal pain concomitant with nausea and vomiting. Laboratory analysis revealed hypercalcemia, elevated liver enzymes and high levels of amylase, lipase and creatine protein kinase. Conclusion Amino acid as well as anabolic supplements may lead to abnormal functioning of many organs, which could be fatal in some instances. This mandates worldwide and concerted efforts to educate the public, especially the youth, about the dangers of these increasingly abused drugs.

  11. Multi Organ Failure Following Intravenous Gasoline for Suicide: A Case Report

    Directory of Open Access Journals (Sweden)

    Hadi Hamishehkar

    2012-12-01

    Full Text Available Hydrocarbons are ubiquitous in daily life and include plant and animal fats, alcohols, solvents, natural gas, petroleum derivates. Majority of intoxication reports of hydrocarbons are due to inhalation or ingestion, but there is few reports about intravenous injection of gasoline. We report a 58 year-old man who injected gasoline intravenously for suicide. He developed soft tissue necrosis of forearm and bilateral pulmonary infiltration. He underwent fasciotomy and extensive debridement of necrotic tissues, at the operation room. He was intubated and mechanically ventilated because of acute lung injury. He developed acute kidney injury after 2 days. These symptoms seem to be due to extravasation of gasoline from vessels which lead to inflammation, cell damage and organ failure. The patient developed multi organ failure which unfortunately did not respond to our treatment and he died at day 21. Management of gasoline intoxication depends on the rout of exposure. Like other types of toxications, intravenous toxication has pulmonary involvement, however in this case we had multiple organ involvement. It seems that in such cases we should consider early end organ targeted therapy to stop the future organ failure

  12. Multi organ failure following intravenous gasoline for suicide: a case report.

    Science.gov (United States)

    Mahmoodpoor, Ata; Soleimanpour, Hassan; Hamishehkar, Hadi

    2012-01-01

    Hydrocarbons are ubiquitous in daily life and include plant and animal fats, alcohols, solvents, natural gas, petroleum derivates. Majority of intoxication reports of hydrocarbons are due to inhalation or ingestion, but there is few reports about intravenous injection of gasoline. We report a 58 year-old man who injected gasoline intravenously for suicide. He developed soft tissue necrosis of forearm and bilateral pulmonary infiltration. He underwent fasciotomy and extensive debridement of necrotic tissues, at the operation room. He was intubated and mechanically ventilated because of acute lung injury. He developed acute kidney injury after 2 days. These symptoms seem to be due to extravasation of gasoline from vessels which lead to inflammation, cell damage and organ failure. The patient developed multi organ failure which unfortunately did not respond to our treatment and he died at day 21. Management of gasoline intoxication depends on the rout of exposure. Like other types of toxications, intravenous toxication has pulmonary involvement, however in this case we had multiple organ involvement. It seems that in such cases we should consider early end organ targeted therapy to stop the future organ failure. © 2012 Tehran University of Medical Sciences. All rights reserved.

  13. Information dynamics in carcinogenesis and tumor growth.

    Science.gov (United States)

    Gatenby, Robert A; Frieden, B Roy

    2004-12-21

    The storage and transmission of information is vital to the function of normal and transformed cells. We use methods from information theory and Monte Carlo theory to analyze the role of information in carcinogenesis. Our analysis demonstrates that, during somatic evolution of the malignant phenotype, the accumulation of genomic mutations degrades intracellular information. However, the degradation is constrained by the Darwinian somatic ecology in which mutant clones proliferate only when the mutation confers a selective growth advantage. In that environment, genes that normally decrease cellular proliferation, such as tumor suppressor or differentiation genes, suffer maximum information degradation. Conversely, those that increase proliferation, such as oncogenes, are conserved or exhibit only gain of function mutations. These constraints shield most cellular populations from catastrophic mutator-induced loss of the transmembrane entropy gradient and, therefore, cell death. The dynamics of constrained information degradation during carcinogenesis cause the tumor genome to asymptotically approach a minimum information state that is manifested clinically as dedifferentiation and unconstrained proliferation. Extreme physical information (EPI) theory demonstrates that altered information flow from cancer cells to their environment will manifest in-vivo as power law tumor growth with an exponent of size 1.62. This prediction is based only on the assumption that tumor cells are at an absolute information minimum and are capable of "free field" growth that is, they are unconstrained by external biological parameters. The prediction agrees remarkably well with several studies demonstrating power law growth in small human breast cancers with an exponent of 1.72+/-0.24. This successful derivation of an analytic expression for cancer growth from EPI alone supports the conceptual model that carcinogenesis is a process of constrained information degradation and that malignant

  14. (Radiation carcinogenesis in the whole body system)

    Energy Technology Data Exchange (ETDEWEB)

    Fry, R.J.M.

    1990-12-14

    The objectives of the trip were: to take part in and to give the summary of a Symposium on Radiation Carcinogenesis at Tokyo, and to give a talk at the National Institute of Radiological Sciences at Chiba. The breadth of the aspects considered at the conference was about as broad as is possible, from effects at the molecular level to human epidemiology, from the effects of tritium to cancer induction by heavy ions. The events induced by cancer that lead to cancer and the events that are secondary are beginning to come into better focus but much is still not known. Interest in suppressor genes is increasing rapidly in the studies of human tumors and many would predict that the three or four suppressor genes associated with cancer are only the first sighting of a much larger number.

  15. Radiation carcinogenesis in mouse thymic lymphomas

    International Nuclear Information System (INIS)

    Kominami, Ryo; Niwa, Ohtsura

    2006-01-01

    Ionizing radiation is a well-known carcinogen for various human tissues and a complete carcinogen that is able to initiate and promote neoplastic progression. Studies of radiation-induced mouse thymic lymphomas, one of the classic models in radiation carcinogenesis, demonstrated that even the unirradiated thymus is capable of developing into full malignancy when transplanted into the kidney capsule or subcutaneous tissue of irradiated mice. This suggests that radiation targets tissues other than thymocytes to allow expansion of cells with tumorigenic potential in the thymus. The idea is regarded as the ''indirect mechanism'' for tumor development. This paper reviews the indirect mechanism and genes affecting the development of thymic lymphomas that we have analyzed. One is the Bcl11b/Rit1 tumor suppressor gene and the other is Mtf-1 gene affecting tumor susceptibility. (author)

  16. Parasite Infection, Carcinogenesis and Human Malignancy

    Directory of Open Access Journals (Sweden)

    Hoang van Tong

    2017-02-01

    Full Text Available Cancer may be induced by many environmental and physiological conditions. Infections with viruses, bacteria and parasites have been recognized for years to be associated with human carcinogenicity. Here we review current concepts of carcinogenicity and its associations with parasitic infections. The helminth diseases schistosomiasis, opisthorchiasis, and clonorchiasis are highly carcinogenic while the protozoan Trypanosoma cruzi, the causing agent of Chagas disease, has a dual role in the development of cancer, including both carcinogenic and anticancer properties. Although malaria per se does not appear to be causative in carcinogenesis, it is strongly associated with the occurrence of endemic Burkitt lymphoma in areas holoendemic for malaria. The initiation of Plasmodium falciparum related endemic Burkitt lymphoma requires additional transforming events induced by the Epstein-Barr virus. Observations suggest that Strongyloides stercoralis may be a relevant co-factor in HTLV-1-related T cell lymphomas. This review provides an overview of the mechanisms of parasitic infection-induced carcinogenicity.

  17. Dysregulation of Autophagy Contributes to Anal Carcinogenesis.

    Directory of Open Access Journals (Sweden)

    Evie H Carchman

    Full Text Available Autophagy is an intracellular catabolic process that removes and recycles unnecessary/dysfunctional cellular components, contributing to cellular health and survival. Autophagy is a highly regulated cellular process that responds to several intracellular signals, many of which are deregulated by human papillomavirus (HPV infection through the expression of HPV-encoded oncoproteins. This adaptive inhibitory response helps prevent viral clearance. A strong correlation remains between HPV infection and the development of squamous cell carcinoma (SCC of the anus, particularly in HIV positive and other immunosuppressed patients. We hypothesize that autophagy is inhibited by HPV-encoded oncoproteins thereby promoting anal carcinogenesis (Fig 1.HPV16 transgenic mice (K14E6/E7 and non-transgenic mice (FVB/N, both of which do not spontaneously develop anal tumors, were treated topically with the chemical carcinogen, 7,12-Dimethylbenz[a]anthracene (DMBA, to induce anal cancer. The anuses at different time points of treatment (5, 10, 15 and 20 weeks were analyzed using immunofluorescence (IF for two key autophagy marker proteins (LC3β and p62 in addition to histological grading. The anuses from the K14E6/E7 mice were also analyzed for visual evidence of autophagic activity by electron microscopy (EM. To see if there was a correlation to humans, archival anal specimens were assessed histologically for grade of dysplasia and then analyzed for LC3β and p62 protein content. To more directly examine the effect of autophagic inhibition on anal carcinogenesis, nontransgenic mice that do not develop anal cancer with DMBA treatment were treated with a known pharmacologic inhibitor of autophagy, chloroquine, and examined for tumor development and analyzed by IF for autophagic proteins.Histologically, we observed the progression of normal anoderm to invasive SCC with DMBA treatment in K14E6/E7 mice but not in nontransgenic, syngeneic FVB/N background control mice

  18. Role of retinoic receptors in lung carcinogenesis

    Directory of Open Access Journals (Sweden)

    Renyi-Vamos Ferenc

    2008-07-01

    Full Text Available Abstract Several in vitro and in vivo studies have examined the positive and negative effects of retinoids (vitamin A analogs in premalignant and malignant lesions. Retinoids have been used as chemopreventive and anticancer agents because of their pleiotropic regulator function in cell differentiation, growth, proliferation and apoptosis through interaction with two types of nuclear receptors: retinoic acid receptors and retinoid X receptors. Recent investigations have gradually elucidated the function of retinoids and their signaling pathways and may explain the failure of earlier chemopreventive studies. In this review we have compiled basic and recent knowledge regarding the role of retinoid receptors in lung carcinogenesis. Sensitive and appropriate biological tools are necessary for screening the risk population and monitoring the efficacy of chemoprevention. Investigation of retinoid receptors is important and may contribute to the establishment of new strategies in chemoprevention for high-risk patients and in the treatment of lung cancer.

  19. Effect of complex polyphenols on colon carcinogenesis.

    Science.gov (United States)

    Caderni, G; Remy, S; Cheynier, V; Morozzi, G; Dolara, P

    1999-06-01

    Complex polyphenols and tannins from wine (WCPT) are being considered increasingly as potential cancer chemopreventive agents, since epidemiological studies suggest that populations consuming a high amount of polyphenols in the diet may have a lower incidence of some types of cancer. We studied the effect of WCPT on a series of parameters related to colon carcinogenesis in rats. WCPT were administered to F344 rats at a dose of 14 or 57 mg/kg/d, mixed with the diet. The higher dose is about ten times the exposure to polyphenols of a moderate drinker of red wine. In rats treated with WCPT, we measured fecal bile acids and long chain fatty acids, colon mucosa cell proliferation, apoptosis and, after administration of colon carcinogens, the number and size of aberrant crypt foci (ACF) and nuclear aberrations. Colon mucosa proliferation was not varied by chronic administration (90 d) of WCPT (14 or 57 mg/kg/d). The highest dose of WCPT decreased the number of cells in the colon crypts, but did not increase apoptosis. WCPT (57 mg/kg) administered before or after the administration of azoxymethane (AOM) did not vary the number or multiplicity of ACF in the colon. The number of nuclear aberrations (NA) in colon mucosa was studied after administration of 1,2-dimethylhydrazine (DMH) and 2-amino-3-methylimidazo (4,5-f)quinoline (IQ), colon-specific carcinogens which require metabolic activation. The effect of DMH and IQ was not varied by pre-feeding WCPT (57 mg/kg) for 10 d. Similarly, the levels of total, secondary bile acids and long chain fatty acids did not varied significantly in animals fed WCPT for 90 d. WCPT administration does not influence parameters related to colon carcinogenesis in the rat.

  20. Radiation-induced mammary carcinogenesis in rodent models. What's different from chemical carcinogenesis?

    International Nuclear Information System (INIS)

    Imaoka, Tatsuhiko; Nishimura, Mayumi; Iizuka, Daisuke; Daino, Kazuhiro; Takabatake, Takashi; Okamoto, Mieko; Kakinuma, Shizuko; Shimada, Yoshiya

    2009-01-01

    Ionizing radiation is one of a few well-characterized etiologic factors of human breast cancer. Laboratory rodents serve as useful experimental models for investigating dose responses and mechanisms of cancer development. Using these models, a lot of information has been accumulated about mammary gland cancer, which can be induced by both chemical carcinogens and radiation. In this review, we first list some experimental rodent models of breast cancer induction. We then focus on several topics that are important in understanding the mechanisms and risk modification of breast cancer development, and compare radiation and chemical carcinogenesis models. We will focus on the pathology and natural history of cancer development in these models, genetic changes observed in induced cancers, indirect effects of carcinogens, and finally risk modification by reproductive factors and age at exposure to the carcinogens. In addition, we summarize the knowledge available on mammary stem/progenitor cells as a potential target of carcinogens. Comparison of chemical and radiation carcinogenesis models on these topics indicates certain similarities, but it also indicates clear differences in several important aspects, such as genetic alterations of induced cancers and modification of susceptibility by age and reproductive factors. Identification of the target cell type and relevant translational research for human risk management may be among the important issues that are addressed by radiation carcinogenesis models. (author)

  1. Collection and control of tritium bioassay samples at Pantex

    International Nuclear Information System (INIS)

    Fairrow, N.L.; Ivie, W.E.

    1992-01-01

    Pantex is the final assembly/disassembly point for US nuclear weapons. The Pantex internal dosimetry section monitors radiation workers once a month for tritium exposure. In order to manage collection and control of the bioassay specimens efficiently, a bar code system for collection of samples was developed and implemented to speed up the process and decrease the number of errors probable when transferring data. In the past, all the bioassay data from samples were entered manually into a computer database. Transferring the bioassay data from the liquid scintillation counter to each individual's dosimetry record required as much as two weeks of concentrated effort

  2. Bioassays for the determination of nitrification inhibition

    Energy Technology Data Exchange (ETDEWEB)

    Grunditz, Camilla

    1999-07-01

    Requirements for nitrogen reduction in wastewater treatment plants were introduced in Sweden in the early 1990's. This was a governmental move to reduce the nitrogen discharges to the Baltic and Kattegat in order to prevent eutrophication. The nitrification process in wastewater treatment plants is performed by nitrifying bacteria. These are susceptible to inhibition and it is of great importance that the influent water does not contain toxic compounds. Therefore, there is a need for assays for the determination of nitrification inhibition. This thesis describes the development and applications of such bioassays. Pure cultures of Nitrosomonas sp. and Nitrobacter sp. were isolated from activated sludge of a wastewater treatment plant. These cultures were used as test organisms in the development of bioassays for nitrification inhibition measurements. The assays are based on two different principles; cell suspensions of the bacteria, performed in test tubes, and mediated amperometric biosensors with the bacteria immobilised. Ammonia oxidation and nitrite oxidation are studied separately without interference from other organisms, which makes it easier to interpret the results. The cell suspension assays were applied to samples of industrial and municipal wastewater. The Nitrosomonas and Nitrobacter assays showed to have different inhibition patterns. A large percentage of the Swedish municipal wastewater treatment plants were found to receive inhibitory influent water, but the inhibition level was generally low. Compared to an assay based on activated sludge, the screening method, the pure culture assays found more samples of influent water strongly inhibitory or stimulating. The highest correlation was found between the screening method and the Nitrosomonas assay. The Nitrobacter assay was found to be the most sensitive method. Assessment of toxicity of a number of chemical substances was studied using the biosensors, together with the cell suspension assays

  3. Allometric Scaling and Cell Ratios in Multi-Organ in vitro Models of Human Metabolism

    International Nuclear Information System (INIS)

    Ucciferri, Nadia; Sbrana, Tommaso; Ahluwalia, Arti

    2014-01-01

    Intelligent in vitro models able to recapitulate the physiological interactions between tissues in the body have enormous potential as they enable detailed studies on specific two-way or higher order tissue communication. These models are the first step toward building an integrated picture of systemic metabolism and signaling in physiological or pathological conditions. However, the rational design of in vitro models of cell–cell or cell–tissue interaction is difficult as quite often cell culture experiments are driven by the device used, rather than by design considerations. Indeed, very little research has been carried out on in vitro models of metabolism connecting different cell or tissue types in a physiologically and metabolically relevant manner. Here, we analyze the physiological relationship between cells, cell metabolism, and exchange in the human body using allometric rules, downscaling them to an organ-on-a-plate device. In particular, in order to establish appropriate cell ratios in the system in a rational manner, two different allometric scaling models (cell number scaling model and metabolic and surface scaling model) are proposed and applied to a two compartment model of hepatic-vascular metabolic cross-talk. The theoretical scaling studies illustrate that the design and hence relevance of multi-organ models is principally determined by experimental constraints. Two experimentally feasible model configurations are then implemented in a multi-compartment organ-on-a-plate device. An analysis of the metabolic response of the two configurations demonstrates that their glucose and lipid balance is quite different, with only one of the two models recapitulating physiological-like homeostasis. In conclusion, not only do cross-talk and physical stimuli play an important role in in vitro models, but the numeric relationship between cells is also crucial to recreate in vitro interactions, which can be extrapolated to the in vivo reality.

  4. Allometric scaling and cell ratios in multi-organ in vitro models of human metabolism

    Directory of Open Access Journals (Sweden)

    Nadia eUcciferri

    2014-12-01

    Full Text Available Intelligent in vitro models able to recapitulate the physiological interactions between tissues in the body have enormous potential as they enable detailed studies on specific two-way or higher order tissue communication. These models are the first step towards building an integrated picture of systemic metabolism and signalling in physiological or pathological conditions. However the rational design of in vitro models of cell-cell or cell-tissue interaction is difficult as quite often cell culture experiments are driven by the device used, rather than by design considerations. Indeed very little research has been carried out on in vitro models of metabolism connecting different cell or tissue types in a physiologically and metabolically relevant manner. Here we analyse the physiologic relationship between cells, cell metabolism and exchange in the human body using allometric rules, downscaling them to an organ-on-a plate device. In particular, in order to establish appropriate cell ratios in the system in a rational manner, two different allometric scaling models (Cell Number Scaling Model, CNSM, and Metabolic and Surface Scaling model, MSSM are proposed and applied to a two compartment model of hepatic-vascular metabolic cross-talk. The theoretical scaling studies illustrate that the design and hence relevance of multi-organ models is principally determined by experimental constraints. Two experimentally feasible model configurations are then implemented in a multi-compartment organ-on-a plate device. An analysis of the metabolic response of the two configurations demonstrates that their glucose and lipid balance is quite different, with only one of the two models recapitulating physiological-like homeostasis. In conclusion, not only do cross-talk and physical stimuli play an important role in in vitro models, but the numeric relationship between cells is also crucial to recreate in vitro interactions which can be extrapolated to the in vivo

  5. Allometric Scaling and Cell Ratios in Multi-Organ in vitro Models of Human Metabolism.

    Science.gov (United States)

    Ucciferri, Nadia; Sbrana, Tommaso; Ahluwalia, Arti

    2014-01-01

    Intelligent in vitro models able to recapitulate the physiological interactions between tissues in the body have enormous potential as they enable detailed studies on specific two-way or higher order tissue communication. These models are the first step toward building an integrated picture of systemic metabolism and signaling in physiological or pathological conditions. However, the rational design of in vitro models of cell-cell or cell-tissue interaction is difficult as quite often cell culture experiments are driven by the device used, rather than by design considerations. Indeed, very little research has been carried out on in vitro models of metabolism connecting different cell or tissue types in a physiologically and metabolically relevant manner. Here, we analyze the physiological relationship between cells, cell metabolism, and exchange in the human body using allometric rules, downscaling them to an organ-on-a-plate device. In particular, in order to establish appropriate cell ratios in the system in a rational manner, two different allometric scaling models (cell number scaling model and metabolic and surface scaling model) are proposed and applied to a two compartment model of hepatic-vascular metabolic cross-talk. The theoretical scaling studies illustrate that the design and hence relevance of multi-organ models is principally determined by experimental constraints. Two experimentally feasible model configurations are then implemented in a multi-compartment organ-on-a-plate device. An analysis of the metabolic response of the two configurations demonstrates that their glucose and lipid balance is quite different, with only one of the two models recapitulating physiological-like homeostasis. In conclusion, not only do cross-talk and physical stimuli play an important role in in vitro models, but the numeric relationship between cells is also crucial to recreate in vitro interactions, which can be extrapolated to the in vivo reality.

  6. Allometric Scaling and Cell Ratios in Multi-Organ in vitro Models of Human Metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Ucciferri, Nadia [CNR Institute of Clinical Physiology, Pisa (Italy); Interdepartmental Research Center “E. Piaggio”, University of Pisa, Pisa (Italy); Sbrana, Tommaso [Interdepartmental Research Center “E. Piaggio”, University of Pisa, Pisa (Italy); Ahluwalia, Arti, E-mail: arti.ahluwalia@unipi.it [CNR Institute of Clinical Physiology, Pisa (Italy); Interdepartmental Research Center “E. Piaggio”, University of Pisa, Pisa (Italy)

    2014-12-17

    Intelligent in vitro models able to recapitulate the physiological interactions between tissues in the body have enormous potential as they enable detailed studies on specific two-way or higher order tissue communication. These models are the first step toward building an integrated picture of systemic metabolism and signaling in physiological or pathological conditions. However, the rational design of in vitro models of cell–cell or cell–tissue interaction is difficult as quite often cell culture experiments are driven by the device used, rather than by design considerations. Indeed, very little research has been carried out on in vitro models of metabolism connecting different cell or tissue types in a physiologically and metabolically relevant manner. Here, we analyze the physiological relationship between cells, cell metabolism, and exchange in the human body using allometric rules, downscaling them to an organ-on-a-plate device. In particular, in order to establish appropriate cell ratios in the system in a rational manner, two different allometric scaling models (cell number scaling model and metabolic and surface scaling model) are proposed and applied to a two compartment model of hepatic-vascular metabolic cross-talk. The theoretical scaling studies illustrate that the design and hence relevance of multi-organ models is principally determined by experimental constraints. Two experimentally feasible model configurations are then implemented in a multi-compartment organ-on-a-plate device. An analysis of the metabolic response of the two configurations demonstrates that their glucose and lipid balance is quite different, with only one of the two models recapitulating physiological-like homeostasis. In conclusion, not only do cross-talk and physical stimuli play an important role in in vitro models, but the numeric relationship between cells is also crucial to recreate in vitro interactions, which can be extrapolated to the in vivo reality.

  7. Reporter gene bioassays in environmental analysis.

    Science.gov (United States)

    Köhler, S; Belkin, S; Schmid, R D

    2000-01-01

    In parallel to the continuous development of increasingly more sophisticated physical and chemical analytical technologies for the detection of environmental pollutants, there is a progressively more urgent need also for bioassays which report not only on the presence of a chemical but also on its bioavailability and its biological effects. As a partial fulfillment of that need, there has been a rapid development of biosensors based on genetically engineered bacteria. Such microorganisms typically combine a promoter-operator, which acts as the sensing element, with reporter gene(s) coding for easily detectable proteins. These sensors have the ability to detect global parameters such as stress conditions, toxicity or DNA-damaging agents as well as specific organic and inorganic compounds. The systems described in this review, designed to detect different groups of target chemicals, vary greatly in their detection limits, specificity, response times and more. These variations reflect on their potential applicability which, for most of the constructs described, is presently rather limited. Nevertheless, present trends promise that additional improvements will make microbial biosensors an important tool for future environmental analysis.

  8. Annotating Human P-Glycoprotein Bioassay Data.

    Science.gov (United States)

    Zdrazil, Barbara; Pinto, Marta; Vasanthanathan, Poongavanam; Williams, Antony J; Balderud, Linda Zander; Engkvist, Ola; Chichester, Christine; Hersey, Anne; Overington, John P; Ecker, Gerhard F

    2012-08-01

    Huge amounts of small compound bioactivity data have been entering the public domain as a consequence of open innovation initiatives. It is now the time to carefully analyse existing bioassay data and give it a systematic structure. Our study aims to annotate prominent in vitro assays used for the determination of bioactivities of human P-glycoprotein inhibitors and substrates as they are represented in the ChEMBL and TP-search open source databases. Furthermore, the ability of data, determined in different assays, to be combined with each other is explored. As a result of this study, it is suggested that for inhibitors of human P-glycoprotein it is possible to combine data coming from the same assay type, if the cell lines used are also identical and the fluorescent or radiolabeled substrate have overlapping binding sites. In addition, it demonstrates that there is a need for larger chemical diverse datasets that have been measured in a panel of different assays. This would certainly alleviate the search for other inter-correlations between bioactivity data yielded by different assay setups.

  9. Bioassay Phantoms Using Medical Images and Computer Aided Manufacturing

    International Nuclear Information System (INIS)

    Xu, X. Geroge

    2011-01-01

    A radiation bioassay program relies on a set of standard human phantoms to calibrate and assess radioactivity levels inside a human body for radiation protection and nuclear medicine imaging purposes. However, the methodologies in the development and application of anthropomorphic phantoms, both physical and computational, had mostly remained the same for the past 40 years. We herein propose a 3-year research project to develop medical image-based physical and computational phantoms specifically for radiation bioassay applications involving internally deposited radionuclides. The broad, long-term objective of this research was to set the foundation for a systematic paradigm shift away from the anatomically crude phantoms in existence today to realistic and ultimately individual-specific bioassay methodologies. This long-term objective is expected to impact all areas of radiation bioassay involving nuclear power plants, U.S. DOE laboratories, and nuclear medicine clinics.

  10. In vivo cell kinetics in breast carcinogenesis

    International Nuclear Information System (INIS)

    Bai, Maria; Agnantis, Niki J; Kamina, Sevasti; Demou, Asimina; Zagorianakou, Panayiota; Katsaraki, Aphroditi; Kanavaros, Panayiotis

    2001-01-01

    Disruption of the balance between apoptosis and proliferation is considered to be an important factor in the development and progression of tumours. In the present study we determined the in vivo cell kinetics along the spectrum of apparently normal epithelium, hyperplasia, preinvasive lesions and invasive carcinoma, in breast tissues affected by fibrocystic changes in which preinvasive and/or invasive lesions developed, as a model of breast carcinogenesis. A total of 32 areas of apparently normal epithelium and 135 ductal proliferative and neoplastic lesions were studied. More than one epithelial lesion per case were analyzed. The apoptotic index (AI) and the proliferative index (PI) were expressed as the percentage of TdT-mediated dUTP-nick end-labelling (TUNEL) and Ki-67-positive cells, respectively. The PI/AI (P/A index) was calculated for each case. The AIs and PIs were significantly higher in hyperplasia than in apparently normal epithelium (P = 0.04 and P = 0.0005, respectively), in atypical hyperplasia than in hyperplasia (P = 0.01 and P = 0.04, respectively) and in invasive carcinoma than in in situ carcinoma (P < 0.001 and P < 0.001, respectively). The two indices were similar in atypical hyperplasia and in in situ carcinoma. The P/A index increased significantly from normal epithelium to hyperplasia (P = 0.01) and from preinvasive lesions to invasive carcinoma (P = 0.04) whereas it was decreased (non-significantly) from hyperplasia to preinvasive lesions. A strong positive correlation between the AIs and the PIs was found (r = 0.83, P < 0.001). These findings suggest accelerating cell turnover along the continuum of breast carcinogenesis. Atypical hyperplasias and in situ carcinomas might be kinetically similar lesions. In the transition from normal epithelium to hyperplasia and from preinvasive lesions to invasive carcinoma the net growth of epithelial cells results from a growth imbalance in favour of proliferation. In the transition from hyperplasia

  11. The Dose Response Relationship for Radiation Carcinogenesis

    Science.gov (United States)

    Hall, Eric

    2008-03-01

    Recent surveys show that the collective population radiation dose from medical procedures in the U.S. has increased by 750% in the past two decades. It would be impossible to imagine the practice of medicine today without diagnostic and therapeutic radiology, but nevertheless the widespread and rapidly increasing use of a modality which is a known human carcinogen is a cause for concern. To assess the magnitude of the problem it is necessary to establish the shape of the dose response relationship for radiation carcinogenesis. Information on radiation carcinogenesis comes from the A-bomb survivors, from occupationally exposed individuals and from radiotherapy patients. The A-bomb survivor data indicates a linear relationship between dose and the risk of solid cancers up to a dose of about 2.5 Sv. The lowest dose at which there is a significant excess cancer risk is debatable, but it would appear to be between 40 and 100 mSv. Data from the occupation exposure of nuclear workers shows an excess cancer risk at an average dose of 19.4 mSv. At the other end of the dose scale, data on second cancers in radiotherapy patients indicates that cancer risk does not continue to rise as a linear function of dose, but tends towards a plateau of 40 to 60 Gy, delivered in a fractionated regime. These data can be used to estimate the impact of diagnostic radiology at the low dose end of the dose response relationship, and the impact of new radiotherapy modalities at the high end of the dose response relationship. In the case of diagnostic radiology about 90% of the collective population dose comes from procedures (principally CT scans) which involve doses at which there is credible evidence of an excess cancer incidence. While the risk to the individual is small and justified in a symptomatic patient, the same is not true of some screening procedures is asymptomatic individuals, and in any case the huge number of procedures must add up to a potential public health problem. In the

  12. A data-driven modeling approach to identify disease-specific multi-organ networks driving physiological dysregulation.

    Directory of Open Access Journals (Sweden)

    Warren D Anderson

    2017-07-01

    Full Text Available Multiple physiological systems interact throughout the development of a complex disease. Knowledge of the dynamics and connectivity of interactions across physiological systems could facilitate the prevention or mitigation of organ damage underlying complex diseases, many of which are currently refractory to available therapeutics (e.g., hypertension. We studied the regulatory interactions operating within and across organs throughout disease development by integrating in vivo analysis of gene expression dynamics with a reverse engineering approach to infer data-driven dynamic network models of multi-organ gene regulatory influences. We obtained experimental data on the expression of 22 genes across five organs, over a time span that encompassed the development of autonomic nervous system dysfunction and hypertension. We pursued a unique approach for identification of continuous-time models that jointly described the dynamics and structure of multi-organ networks by estimating a sparse subset of ∼12,000 possible gene regulatory interactions. Our analyses revealed that an autonomic dysfunction-specific multi-organ sequence of gene expression activation patterns was associated with a distinct gene regulatory network. We analyzed the model structures for adaptation motifs, and identified disease-specific network motifs involving genes that exhibited aberrant temporal dynamics. Bioinformatic analyses identified disease-specific single nucleotide variants within or near transcription factor binding sites upstream of key genes implicated in maintaining physiological homeostasis. Our approach illustrates a novel framework for investigating the pathogenesis through model-based analysis of multi-organ system dynamics and network properties. Our results yielded novel candidate molecular targets driving the development of cardiovascular disease, metabolic syndrome, and immune dysfunction.

  13. Effect of Dendrobium officinale Extraction on Gastric Carcinogenesis in Rats

    Directory of Open Access Journals (Sweden)

    Yi Zhao

    2016-01-01

    Full Text Available Dendrobium officinale (Tie Pi Shi Hu in Chinese has been widely used to treat different diseases in China. Anticancer effect is one of the important effects of Dendrobium officinale. However, the molecular mechanism of its anticancer effect remains unclear. In the present study, gastric carcinogenesis in rats was used to evaluate the effect of Dendrobium officinale on cancer, and its pharmacological mechanism was explored. Dendrobium officinale extracts (4.8 and 2.4 g/kg were orally administered to the rats of the gastric carcinogenesis model. Compared with the cancer model group, the high dose of Dendrobium officinale extracts significantly inhibited the rate of carcinogenesis. Further analysis revealed that Dendrobium officinale extracts could regulate the DNA damage, oxidative stress, and cytokines related with carcinogenesis and induce cell apoptosis in order to prevent gastric cancer.

  14. Application of Bioassays for the Ecotoxicity Assessment of Contaminated Soils

    Science.gov (United States)

    Fernández, María D.; Babín, Mar; Tarazona, José V.

    The use of bioassays for soil characterization is receiving significant attention as a complementary tool to chemical analysis. Bioassays consist of direct toxicity assays of environmental samples that are transferred to the laboratory and analyzed for toxicity against selected organisms. Such soil samples contain the combination of the different pollutants present in situ and enable factors such as the bioavailability of contaminants or the interactions (synergic and antagonic) between them to be simultaneously studied.

  15. Oral Carcinogenesis and Oral Cancer Chemoprevention: A Review

    OpenAIRE

    Tanaka, Takuji; Tanaka, Mayu; Tanaka, Takahiro

    2011-01-01

    Oral cancer is one of the major global threats to public health. The development of oral cancer is a tobacco-related multistep and multifocal process involving field cancerization and carcinogenesis. The rationale for molecular-targeted prevention of oral cancer is promising. Biomarkers of genomic instability, including aneuploidy and allelic imbalance, are possible to measure the cancer risk of oral premalignancies. Understanding of the biology of oral carcinogenesis will yield important adv...

  16. Comfrey (Symphytum officinale. L. and Experimental Hepatic Carcinogenesis: A Short-Term Carcinogenesis Model Study

    Directory of Open Access Journals (Sweden)

    Maria Fernanda Pereira Lavieri Gomes

    2010-01-01

    Full Text Available Comfrey or Symphytum officinale (L. (Boraginaceae is a very popular plant used for therapeutic purposes. Since the 1980s, its effects have been studied in long-term carcinogenesis studies, in which Comfrey extract is administered at high doses during several months and the neoplastic hepatic lesions are evaluated. However, the literature on this topic is very poor considering the studies performed under short-term carcinogenesis protocols, such as the ‘resistant hepatocyte model’ (RHM. In these studies, it is possible to observe easily the phenomena related to the early phases of tumor development, since pre-neoplastic lesions (PNLs rise in about 1–2 months of chemical induction. Herein, the effects of chronic oral treatment of rats with 10% Comfrey ethanolic extract were evaluated in a RHM. Wistar rats were sequentially treated with N-nitrosodiethylamine (ip and 2-acetilaminofluorene (po, and submitted to hepatectomy to induce carcinogenesis promotion. Macroscopic/microscopic quantitative analysis of PNL was performed. Non-parametric statistical tests (Mann–Whitney and χ2 were used, and the level of significance was set at P ≤ 0.05. Comfrey treatment reduced the number of pre-neoplastic macroscopic lesions up to 1 mm (P ≤ 0.05, the percentage of oval cells (P = 0.0001 and mitotic figures (P = 0.007, as well as the number of Proliferating Cell Nuclear Antigen (PCNA positive cells (P = 0.0001 and acidophilic pre-neoplastic nodules (P = 0.05. On the other hand, the percentage of cells presenting megalocytosis (P = 0.0001 and vacuolar degeneration (P = 0.0001 was increased. Scores of fibrosis, glycogen stores and the number of nucleolus organizing regions were not altered. The study indicated that oral treatment of rats with 10% Comfrey alcoholic extract reduced cell proliferation in this model.

  17. Comfrey (Symphytum Officinale. l.) and Experimental Hepatic Carcinogenesis: A Short-term Carcinogenesis Model Study.

    Science.gov (United States)

    Gomes, Maria Fernanda Pereira Lavieri; de Oliveira Massoco, Cristina; Xavier, José Guilherme; Bonamin, Leoni Villano

    2010-06-01

    Comfrey or Symphytum officinale (L.) (Boraginaceae) is a very popular plant used for therapeutic purposes. Since the 1980s, its effects have been studied in long-term carcinogenesis studies, in which Comfrey extract is administered at high doses during several months and the neoplastic hepatic lesions are evaluated. However, the literature on this topic is very poor considering the studies performed under short-term carcinogenesis protocols, such as the 'resistant hepatocyte model' (RHM). In these studies, it is possible to observe easily the phenomena related to the early phases of tumor development, since pre-neoplastic lesions (PNLs) rise in about 1-2 months of chemical induction. Herein, the effects of chronic oral treatment of rats with 10% Comfrey ethanolic extract were evaluated in a RHM. Wistar rats were sequentially treated with N-nitrosodiethylamine (ip) and 2-acetilaminofluorene (po), and submitted to hepatectomy to induce carcinogenesis promotion. Macroscopic/microscopic quantitative analysis of PNL was performed. Non-parametric statistical tests (Mann-Whitney and χ(2)) were used, and the level of significance was set at P ≤ 0.05. Comfrey treatment reduced the number of pre-neoplastic macroscopic lesions up to 1 mm (P ≤ 0.05), the percentage of oval cells (P = 0.0001) and mitotic figures (P = 0.007), as well as the number of Proliferating Cell Nuclear Antigen (PCNA) positive cells (P = 0.0001) and acidophilic pre-neoplastic nodules (P = 0.05). On the other hand, the percentage of cells presenting megalocytosis (P = 0.0001) and vacuolar degeneration (P = 0.0001) was increased. Scores of fibrosis, glycogen stores and the number of nucleolus organizing regions were not altered. The study indicated that oral treatment of rats with 10% Comfrey alcoholic extract reduced cell proliferation in this model.

  18. Carcinogenesis induced by low-dose radiation

    Directory of Open Access Journals (Sweden)

    Piotrowski Igor

    2017-11-01

    Full Text Available Although the effects of high dose radiation on human cells and tissues are relatively well defined, there is no consensus regarding the effects of low and very low radiation doses on the organism. Ionizing radiation has been shown to induce gene mutations and chromosome aberrations which are known to be involved in the process of carcinogenesis. The induction of secondary cancers is a challenging long-term side effect in oncologic patients treated with radiation. Medical sources of radiation like intensity modulated radiotherapy used in cancer treatment and computed tomography used in diagnostics, deliver very low doses of radiation to large volumes of healthy tissue, which might contribute to increased cancer rates in long surviving patients and in the general population. Research shows that because of the phenomena characteristic for low dose radiation the risk of cancer induction from exposure of healthy tissues to low dose radiation can be greater than the risk calculated from linear no-threshold model. Epidemiological data collected from radiation workers and atomic bomb survivors confirms that exposure to low dose radiation can contribute to increased cancer risk and also that the risk might correlate with the age at exposure.

  19. Dysbiosis of the microbiome in gastric carcinogenesis.

    Science.gov (United States)

    Castaño-Rodríguez, Natalia; Goh, Khean-Lee; Fock, Kwong Ming; Mitchell, Hazel M; Kaakoush, Nadeem O

    2017-11-21

    The gastric microbiome has been proposed as an etiological factor in gastric carcinogenesis. We compared the gastric microbiota in subjects presenting with gastric cancer (GC, n = 12) and controls (functional dyspepsia (FD), n = 20) from a high GC risk population in Singapore and Malaysia. cDNA from 16S rRNA transcripts were amplified (515F-806R) and sequenced using Illumina MiSeq 2 × 250 bp chemistry. Increased richness and phylogenetic diversity but not Shannon's diversity was found in GC as compared to controls. nMDS clustered GC and FD subjects separately, with PERMANOVA confirming a significant difference between the groups. H. pylori serological status had a significant impact on gastric microbiome α-diversity and composition. Several bacterial taxa were enriched in GC, including Lactococcus, Veilonella, and Fusobacteriaceae (Fusobacterium and Leptotrichia). Prediction of bacterial metabolic contribution indicated that serological status had a significant impact on metabolic function, while carbohydrate digestion and pathways were enriched in GC. Our findings highlight three mechanisms of interest in GC, including enrichment of pro-inflammatory oral bacterial species, increased abundance of lactic acid producing bacteria, and enrichment of short chain fatty acid production pathways.

  20. Pulmonary carcinogenesis from plutonium-containing particles

    International Nuclear Information System (INIS)

    Thomas, R.G.; Smith, D.M.; Anderson, E.C.

    1980-01-01

    Induction of lung tumors by various types of radiation is of paramount concern to the nuclear industry. The data presented were obtained by exposing the pulmonary system of Syrian hamsters to particles of zirconium oxide containing various amounts of either plutonium-238 or -239 as the alpha radiation source. These particles were injected intravenously and lodged permanently in the capillary bed of the lung. When less than 20% of the lung tissue was irradiated, simulating the ''hot particle'' mode, tumors were not evident with lung burdens up to 500 nCi plutonium. More diffuse irradiation significantly increased the tumor incidence, with lung burdens of 50 to 150 nCi. When plutonium-laden microspheres were administered intratracheally, tumor production was considerably increased and the addition of 3 mg of iron oxide intratracheally further increased the incidence. Using the zirconium oxide matrix for the carrier of plutonium in aerosol particles produced tumor incidences of up to 50% in Syrian hamsters exposed by inhalation. Initial pulmonary (alveolar) burdens reached 100 nCi of plutonium. Similar inhalation studies using plutonium dioxide alone (no matrix) failed to produce any increase in lung tumorigenesis. The results are discussed in terms of possible mechanisms necessary for lung carcinogenesis. (H.K.)

  1. Parasite Infection, Carcinogenesis and Human Malignancy.

    Science.gov (United States)

    van Tong, Hoang; Brindley, Paul J; Meyer, Christian G; Velavan, Thirumalaisamy P

    2017-02-01

    Cancer may be induced by many environmental and physiological conditions. Infections with viruses, bacteria and parasites have been recognized for years to be associated with human carcinogenicity. Here we review current concepts of carcinogenicity and its associations with parasitic infections. The helminth diseases schistosomiasis, opisthorchiasis, and clonorchiasis are highly carcinogenic while the protozoan Trypanosoma cruzi, the causing agent of Chagas disease, has a dual role in the development of cancer, including both carcinogenic and anticancer properties. Although malaria per se does not appear to be causative in carcinogenesis, it is strongly associated with the occurrence of endemic Burkitt lymphoma in areas holoendemic for malaria. The initiation of Plasmodium falciparum related endemic Burkitt lymphoma requires additional transforming events induced by the Epstein-Barr virus. Observations suggest that Strongyloides stercoralis may be a relevant co-factor in HTLV-1-related T cell lymphomas. This review provides an overview of the mechanisms of parasitic infection-induced carcinogenicity. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  2. Molecular epidemiology of radiation-induced carcinogenesis

    International Nuclear Information System (INIS)

    Trosko, J.E.

    1996-01-01

    The role of ionizing radiation in carcinogenesis is discussed. Every cell contains proto-oncogenes, which if damaged may lead to cell transformation. Every cell also contains tumor suppressor genes, which guard against transformation. Thus, transformation would seem to require a double injury to the DNA in a cell. Ionizing radiation is known to be a relatively weak mutagen, but a good clastogen (inducer of chromosome breaks, deletions and rearrangements). Ionizing radiation may therefore be a 'promoter' of cancer, i.e. a stimulant of the clonal expansion of transformed cells, if it kills enough cells to induce compensatory hyperplasia - i.e. rapid growth of cells. Ionizing radiation may be a 'progressor', if it deactivates tumor suppressor genes tending to suppress the growth of existing clones of transformed cells resulting from any of numerous causes. It may therefore be an oversimplification to say that radiation causes cancer; rather, it seems to be a weak initiator, an indirect promoter, and a late-stage progressor. 2 figs

  3. Experimental carcinogenesis induced by incorporated plutonium

    International Nuclear Information System (INIS)

    Oghiso, Yoichi

    1999-01-01

    The carcinogenic effects of an alpha-emitter, 239 Pu, were investigated by animal experiments as focused on both pulmonary tumors after inhalation exposures to insoluble oxide aerosols and tumor spectra induced by injection of soluble citrate. The life-span study using Wistar strain rats exposed to Pu dioxide aerosols has shown differential dose-related responses of malignancies and histopathological phenotypes of lung tumors, suggesting a threshold dose around 1.0 Gy of the lung dose. As abnormality of tumor-related genes could be supposed for the background of pulmonary carcinogenesis, the mutations of p53 tumor suppressor gene were examined by PCR-SSCP analysis using DNA fragments extracted from lung tumors. While mutations were detected in 23 cases (about 28%) among 82 lung tumors, their relations to either malignancies, histological phenotypes, dose, or oncogenesis are not yet to be elucidated. The life-span study using C3H strain mice injected with Pu citrate has shown contrast dose responses between osteosarcomas and lymphoid tumors around 10 Gy of the skeletal dose, and further indicated specific tumor spectra differed from low LET radiation exposures as shown by much more frequency of B cell type leukemic lymphomas and none of myeloid leukemias. (author)

  4. Radiation carcinogenesis from a membrane perspective

    Energy Technology Data Exchange (ETDEWEB)

    Petkau, A

    1980-01-01

    Radiation damage in phospholipid membranes involves free radical chain reactions which propagate on their own. These reactions oxidize the constituent fatty acids (LH) to alkyl radicals (L) which upon oxygenation, form lipid hydroperoxides (LOOH), some of which absorb light at 232 nm. The response (R) of these membranes to irradiation from tritium (/sup 3/H) in tritiated water increases with dose (D) in accordance with R = aD/sup m/, where m = 1.44 +- 0.30 in the absence of superoxide dismutase and 0.80 +- 0.14 in its presence. The parameter a is expressible in terms of dose rate (..delta..D/..delta..t) by a = c (..delta..D/..delta..t)/sup -n/, where n = 1.18 +- 0.05 in the absence of superoxide dismutase and 0.82 +- 0.02 in its presence. Thus, R = cD/sup m/..delta..D/..delta..t)/sup -n/ where the values of m, n depend on the presence or absence of the free radical scavenger, superoxide dismutase. From this composite relationship, the response per annum for 100 to 250 millirem/y is calculable and found to differ qualitatively, that is, in the absence of superoxide dismutase the response increases whereas in the enzyme's presence it decreases. The latter trend is reminiscent of the correlation between radiation dose rate and the per annum malignant mortality rate in humans. This coincidence is interesting in that LOOH are linked in the literature to several forms of carcinogenesis.

  5. Inflammation, oxidative DNA damage, and carcinogenesis

    International Nuclear Information System (INIS)

    Lewis, J.G.; Adams, D.O.

    1987-01-01

    Inflammation has long been associated with carcinogenesis, especially in the promotion phase. The mechanism of action of the potent inflammatory agent and skin promoter 12-tetradecanoyl phorbol-13-acetate (TPA) is unknown. It is though that TPA selectively enhances the growth of initiated cells, and during this process, initiated cells progress to the preneoplastic state and eventually to the malignant phenotype. The authors and others have proposed that TPA may work, in part, by inciting inflammation and stimulating inflammatory cells to release powerful oxidants which then induce DNA damage in epidermal cells. Macrophages cocultured with target cells and TPA induce oxidized thymine bases in the target cells. This process is inhibited by both catalase and inhibitors of lipoxygenases, suggesting the involvement of both H 2 O 2 and oxidized lipid products. In vivo studies demonstrated that SENCAR mice, which are sensitive to promotion by TPA, have a more intense inflammatory reaction in skin that C57LB/6 mice, which are resistant to promotion by TPA. In addition, macrophages from SENCAR mice release more H 2 O 2 and metabolites of AA, and induce more oxidative DNA damage in cocultured cells than macrophages from C57LB/6 mice. These data support the hypothesis that inflammation and the release of genotoxic oxidants may be one mechanism whereby initiated cells receive further genetic insults. They also further complicate risk assessment by suggesting that some environmental agents may work indirectly by subverting host systems to induce damage rather than maintaining homeostasis

  6. Hypoxia and Angiogenesis in Endometrioid Endometrial Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Nicole Horrée

    2007-01-01

    Full Text Available Background: Hypoxia-inducible factor 1α (HIF-1α plays an essential role in the adaptive response of cells to hypoxia, triggering biologic events associated with aggressive tumor behavior. Methods: Expression of HIF-1α and proteins in the HIF-1α pathway (Glut-1, CAIX, VEGF in paraffin-embedded specimens of normal (n = 17, premalignant (n = 17 and endometrioid endometrial carcinoma (n = 39 was explored by immunohistochemistry, in relation to microvessel density (MVD. Results: HIF-1α overexpression was absent in inactive endometrium but present in hyperplasia (61% and carcinoma (87%, with increasing expression in a perinecrotic fashion pointing to underlying hypoxia. No membranous expression of Glut-1 and CAIX was noticed in inactive endometrium, in contrast with expression in hyperplasia (Glut-1 0%, CAIX 61%, only focal and diffuse and carcinoma (Glut-1 94.6%, CAIX 92%, both mostly perinecrotically. Diffuse HIF-1α was accompanied by activation of downstream targets. VEGF was significantly higher expressed in hyperplasias and carcinomas compared to inactive endometrium. MVD was higher in hyperplasias and carcinomas than in normal endometrium (p < 0.001. Conclusion: HIF-1α and its downstream genes are increasingly expressed from normal through premalignant to endometrioid adenocarcinoma of the endometrium, paralleled by activation of its downstream genes and increased angiogenesis. This underlines the potential importance of hypoxia and its key regulator HIF-1α in endometrial carcinogenesis.

  7. Collective studies on carcinogenesis due to exposure to radiation

    International Nuclear Information System (INIS)

    Yamashita, Hisao

    1980-01-01

    Carcinogenesis was found in 150 of 25,692 patients who had received radiotherapy for benign diseases. Of primary diseases subjected to radiotherapy, skin diseases were the most. Carcinogenesis was found in 26 of 7,230 patients with skin diseases (0.36%) and 18 in 2286 patients with tuberculous cervical lymphadenitis (0.79%). The sites of carcinogenesis was the skin in 51 patients, the hypopharynx in 43, and the larynx in 18. Carcinogenesis was also found in 140 of 220,361 patients who had received radiotherapy for malignant tumors. As primary cancer, cancer of the cervix uteri was found in 59 of 48,662 patients, and breast cancer was found in 20 of 27,967 patients. As radiation-induced cancer, leukemia was found in 18 patients, soft tissue sarcoma in 18, skin cancer in 10, osteosarcoma in 6, cancer of the hypopharynx in 6, and cancer of the cervical esophagus in 6. It is necessary to differentiate cancer due to exposure to radiation from delayed recurrent cancer and double cancer. Irradiation fields should be restricted as small as possible in order to reduce carcinogenesis. As leukemia and carcinoma were found in a-bomb survivors exposed to very small dose of a-bomb radiation, carcinogenic mechanisms by chromosome aberrations, carcinogenic rates from a viewpoint of epidemiology, and other factors which influenced carcinogenesis are being investigated. (Tsunoda, M.)

  8. Implications of tyrosine phosphoproteomics in cervical carcinogenesis

    Directory of Open Access Journals (Sweden)

    DeFord James

    2008-01-01

    Full Text Available Abstract Background Worldwide cervical cancer remains a leading cause of mortality from gynecologic malignancies. The link between cervical cancer and persistent infection with HPV has been established. At a molecular level little is known about the transition from the precancerous state to invasive cancer. To elucidate this process, cervical biopsies from human specimens were obtained from precancerous state to stage III disease. Methods Cervical biopsies were obtained from patients with a diagnosis of cervical cancer undergoing definitive surgery or staging operation. Biopsies were obtained from patients with precancerous lesions at the time of their excisional procedure. Control samples were obtained from patients undergoing hysterectomy for benign conditions such as fibroids. Samples were subjected to proteomic profiling using two dimensional gel electrophoresis with subsequent trypsin digestion followed by MALDI-TOF protein identification. Candidate proteins were then further studied using western blotting, immunoprecipitation and immunohistochemistry. Results Annexin A1 and DNA-PKcs were found to be differentially expressed. Phosphorylated annexin A1 was up regulated in diseased states in comparison to control and its level was strongly detected in the serum of cervical cancer patients compared to controls. DNA-PKcs was noted to be hyperphosphorylated and fragmented in cancer when compared to controls. By immunohistochemistry annexin A1 was noted in the vascular environment in cancer and certain precancerous samples. Conclusion This study suggests a probable role for protein tyrosine phosphorylation in cervical carcinogenesis. Annexin A1 and DNA-PK cs may have synergistic effects with HPV infection. Precancerous lesions that may progress to cervical cancer may be differentiated from lesions that will not base on similar immunohistochemical profile to invasive squamous cell carcinoma.

  9. [Investigation on pattern and methods of quality control for Chinese materia medica based on dao-di herbs and bioassay - bioassay for Coptis chinensis].

    Science.gov (United States)

    Yan, Dan; Xiao, Xiao-he

    2011-05-01

    Establishment of bioassay methods is the technical issues to be faced with in the bioassay of Chinese materia medica. Taking the bioassay of Coptis chinensis Franch. as an example, the establishment process and application of the bioassay methods (including bio-potency and bio-activity fingerprint) were explained from the aspects of methodology, principle of selection, experimental design, method confirmation and data analysis. The common technologies were extracted and formed with the above aspects, so as to provide technical support for constructing pattern and method of the quality control for Chinese materia medica based on the dao-di herbs and bioassay.

  10. Automatic abdominal multi-organ segmentation using deep convolutional neural network and time-implicit level sets.

    Science.gov (United States)

    Hu, Peijun; Wu, Fa; Peng, Jialin; Bao, Yuanyuan; Chen, Feng; Kong, Dexing

    2017-03-01

    Multi-organ segmentation from CT images is an essential step for computer-aided diagnosis and surgery planning. However, manual delineation of the organs by radiologists is tedious, time-consuming and poorly reproducible. Therefore, we propose a fully automatic method for the segmentation of multiple organs from three-dimensional abdominal CT images. The proposed method employs deep fully convolutional neural networks (CNNs) for organ detection and segmentation, which is further refined by a time-implicit multi-phase evolution method. Firstly, a 3D CNN is trained to automatically localize and delineate the organs of interest with a probability prediction map. The learned probability map provides both subject-specific spatial priors and initialization for subsequent fine segmentation. Then, for the refinement of the multi-organ segmentation, image intensity models, probability priors as well as a disjoint region constraint are incorporated into an unified energy functional. Finally, a novel time-implicit multi-phase level-set algorithm is utilized to efficiently optimize the proposed energy functional model. Our method has been evaluated on 140 abdominal CT scans for the segmentation of four organs (liver, spleen and both kidneys). With respect to the ground truth, average Dice overlap ratios for the liver, spleen and both kidneys are 96.0, 94.2 and 95.4%, respectively, and average symmetric surface distance is less than 1.3 mm for all the segmented organs. The computation time for a CT volume is 125 s in average. The achieved accuracy compares well to state-of-the-art methods with much higher efficiency. A fully automatic method for multi-organ segmentation from abdominal CT images was developed and evaluated. The results demonstrated its potential in clinical usage with high effectiveness, robustness and efficiency.

  11. The effect of pesticide residue on caged mosquito bioassays.

    Science.gov (United States)

    Barber, J A S; Greer, Mike; Coughlin, Jamie

    2006-09-01

    Wind tunnel experiments showed that secondary pickup of insecticide residue by mosquitoes in cage bioassays had a significant effect on mortality. Cage bioassays using adult Ochlerotatus taeniorhynchus (Wiedemann) investigated the effect of exposure time to a contaminated surface. Cages were dosed in a wind tunnel using the LC50 for naled (0.124 mg a.i./ml) and an LC25 (0.0772 mg a.i./ml) for naled. Half of the bioassay mosquitoes were moved directly into clean cages with the other half remaining in the sprayed, hence contaminated, cage. Treatment mortality was assessed at 8, 15, 30, 60, 120, 240, and 1,440 min postapplication. Cage contamination had a significant effect on mosquito mortality for both the LC25 and LC50 between 15 and 30 min postapplication.

  12. Internal dosimetry performing dose assessments via bioassay measurements

    International Nuclear Information System (INIS)

    Bailey, K.M.

    1993-01-01

    The Internal Dosimetry Department at the Y-12 Plant maintains a state-of-the-art bioassay program managed under the guidance and regulations of the Department of Energy. The two major bioassay techniques currently used at Y-12 are the in vitro (urinalysis) and in vivo (lung counting) programs. Fecal analysis (as part of the in vitro program) is another alternative; however, since both urine and fecal analysis provide essentially the same capabilities for detecting exposures to uranium, the urinalysis is the main choice primarily for aesthetic reasons. The bioassay frequency is based on meeting NCRP 87 objectives which are to monitor the accumulation of radioactive material in exposed individuals, and to ensure that significant depositions are detected

  13. Bioassays for risk assessment of coal conversion products

    Energy Technology Data Exchange (ETDEWEB)

    Schacht, S.; Sinder, C.; Pfeifer, F.; Klein, J. [DMT-Gesellschaft fuer Forschung und Pruefung mbH, Essen (Germany)

    1999-07-01

    Traditional as well as biotechnological processing coal leads to complex mixtures of products. Besides chemical and physical characterization, which provides the information for product application, there is a need for bioassays to monitor properties that are probably toxic, mutagenic or cancerogenic. Investigations carried out focused on the selection, adaptation and validation of bioassays for the sensitive estimation of toxic effects. Organisms like bacteria, Daphnia magna and Scenedesmus subspicatus, representing different complexities in the biosphere, were selected as test systems for ecotoxicological and mutagenicity studies. The results obtained indicate that bioassays are, in principle, suitable tools for characterization and evaluation of coal-derived substances and bioconversion products. Using coal products, coal-relevant model compounds and bioconversion products, data for risk assessment are presented. (orig.)

  14. Experimental, statistical, and biological models of radon carcinogenesis

    International Nuclear Information System (INIS)

    Cross, F.T.

    1991-09-01

    Risk models developed for underground miners have not been consistently validated in studies of populations exposed to indoor radon. Imprecision in risk estimates results principally from differences between exposures in mines as compared to domestic environments and from uncertainties about the interaction between cigarette-smoking and exposure to radon decay products. Uncertainties in extrapolating miner data to domestic exposures can be reduced by means of a broad-based health effects research program that addresses the interrelated issues of exposure, respiratory tract dose, carcinogenesis (molecular/cellular and animal studies, plus developing biological and statistical models), and the relationship of radon to smoking and other copollutant exposures. This article reviews experimental animal data on radon carcinogenesis observed primarily in rats at Pacific Northwest Laboratory. Recent experimental and mechanistic carcinogenesis models of exposures to radon, uranium ore dust, and cigarette smoke are presented with statistical analyses of animal data. 20 refs., 1 fig

  15. Colorectal Carcinogenesis: Role of Oxidative Stress and Antioxidants.

    Science.gov (United States)

    Carini, Francesco; Mazzola, Margherita; Rappa, Francesca; Jurjus, Abdo; Geagea, Alice Gerges; Al Kattar, Sahar; Bou-Assi, Tarek; Jurjus, Rosalyn; Damiani, Provvidenza; Leone, Angelo; Tomasello, Giovanni

    2017-09-01

    One of the contributory causes of colon cancer is the negative effect of reactive oxygen species on DNA repair mechanisms. Currently, there is a growing support for the concept that oxidative stress may be an important etiological factor for carcinogenesis. The purpose of this review is to elucidate the role of oxidative stress in promoting colorectal carcinogenesis and to highlight the potential protective role of antioxidants. Several studies have documented the importance of antioxidants in countering oxidative stress and preventing colorectal carcinogenesis. However, there are conflicting data in the literature concerning its proper use in humans, since these studies did not yield definitive results and were performed mostly in vitro on cell populations, or in vivo in experimental animal models. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  16. Initiator of carcinogenesis selectively and stably inhibits stem cell differentiation: a concept that initiation of carcinogenesis involves multiple phases

    International Nuclear Information System (INIS)

    Scott, R.E.; Maercklein, P.B.

    1985-01-01

    A concept of carcinogenesis was recently devised in our laboratory that suggests the development of defects in the control of cell differentiation is associated with an early phase of carcinogenesis. To test this proposal directly, the effects of an initiator of carcinogenesis (i.e., UV irradiation) on proadipocyte stem cell differentiation and proliferation was assayed. In this regard, 3T3 T proadipocytes represent a nontransformed mesenchymal stem cell line that possesses the ability to regulate its differentiation at a distinct state in the G 1 phase of the cell cycle as well as the ability to regulate its proliferation at two additional G 1 states. The results establish that a slow dosage of 254 nm UV irradiation selectivity and stably inhibits the differentiation of a high percentage of proadipocyte stem cells without significantly altering their ability to regulate cellular proliferation in growth factor-deficient or nutrient-deficient culture conditions. Differentiation-defect proadipocyte stem cells are demonstrated not to be completely transformed but to show an increased spontaneous transformation rate, as evidenced by the formation of type III foci in high density cell cultures. These data support the role of defects in the control of differentiation in the inhibition of carcinogenesis. These observations support a concept that the initiation of carcinogenesis involves multiple phases

  17. Manual on theory and practical aspects of bioassay

    International Nuclear Information System (INIS)

    Nuraini Hambali.

    1985-06-01

    This manual is set to provide necessary basic guidance on theory and practical aspects of bioassay specially for the newcomer in this field and the man in the laboratory. The first part is a brief information on the entry of radionuclides into the body, the metabolism and the programs of bioassay. All other factors to be considered in assessing internal contamination in man have also been brought up. In the second part, various procedures of radiochemical separations, detection and measurements are abstracted from journals and other revisions. Some methods have been attempted and to be followed where appropriate. (author)

  18. An examination of the analysis of radiostrontiums in bioassay applications

    International Nuclear Information System (INIS)

    Linauskas, S.H.; Leon, J.W.

    1993-05-01

    Radiostrontiums are among the most radiologically significant radionuclides in the nuclear reactor environment due to their relatively high fission yield, long physical half-life, volatility and mobility in the workplace, and long retention times in tissues such as bone. Effective bioassay programs include analytical processes that consider prospective monitoring requirements provided by screening measurements, as well as the retrospective monitoring requirements provided by screening measurements following an intake. Chromatography using crown ethers as well as the use of spectrometry techniques with advanced liquid-scintillation counters or solid-state surface-barrier detectors appear to have significant benefits for Sr bioassay programs. (author). 90 refs., 2 tabs., 3 figs

  19. An examination of the analysis of radiostrontiums in bioassay applications

    Energy Technology Data Exchange (ETDEWEB)

    Linauskas, S H; Leon, J W

    1993-05-01

    Radiostrontiums are among the most radiologically significant radionuclides in the nuclear reactor environment due to their relatively high fission yield, long physical half-life, volatility and mobility in the workplace, and long retention times in tissues such as bone. Effective bioassay programs include analytical processes that consider prospective monitoring requirements provided by screening measurements, as well as the retrospective monitoring requirements provided by screening measurements following an intake. Chromatography using crown ethers as well as the use of spectrometry techniques with advanced liquid-scintillation counters or solid-state surface-barrier detectors appear to have significant benefits for Sr bioassay programs. (author). 90 refs., 2 tabs., 3 figs.

  20. μOrgano: A Lego®-Like Plug & Play System for Modular Multi-Organ-Chips.

    Directory of Open Access Journals (Sweden)

    Peter Loskill

    Full Text Available Human organ-on-a-chip systems for drug screening have evolved as feasible alternatives to animal models, which are unreliable, expensive, and at times erroneous. While chips featuring single organs can be of great use for both pharmaceutical testing and basic organ-level studies, the huge potential of the organ-on-a-chip technology is revealed by connecting multiple organs on one chip to create a single integrated system for sophisticated fundamental biological studies and devising therapies for disease. Furthermore, since most organ-on-a-chip systems require special protocols with organ-specific media for the differentiation and maturation of the tissues, multi-organ systems will need to be temporally customizable and flexible in terms of the time point of connection of the individual organ units. We present a customizable Lego®-like plug & play system, μOrgano, which enables initial individual culture of single organ-on-a-chip systems and subsequent connection to create integrated multi-organ microphysiological systems. As a proof of concept, the μOrgano system was used to connect multiple heart chips in series with excellent cell viability and spontaneously physiological beat rates.

  1. μOrgano: A Lego®-Like Plug & Play System for Modular Multi-Organ-Chips.

    Science.gov (United States)

    Loskill, Peter; Marcus, Sivan G; Mathur, Anurag; Reese, Willie Mae; Healy, Kevin E

    2015-01-01

    Human organ-on-a-chip systems for drug screening have evolved as feasible alternatives to animal models, which are unreliable, expensive, and at times erroneous. While chips featuring single organs can be of great use for both pharmaceutical testing and basic organ-level studies, the huge potential of the organ-on-a-chip technology is revealed by connecting multiple organs on one chip to create a single integrated system for sophisticated fundamental biological studies and devising therapies for disease. Furthermore, since most organ-on-a-chip systems require special protocols with organ-specific media for the differentiation and maturation of the tissues, multi-organ systems will need to be temporally customizable and flexible in terms of the time point of connection of the individual organ units. We present a customizable Lego®-like plug & play system, μOrgano, which enables initial individual culture of single organ-on-a-chip systems and subsequent connection to create integrated multi-organ microphysiological systems. As a proof of concept, the μOrgano system was used to connect multiple heart chips in series with excellent cell viability and spontaneously physiological beat rates.

  2. Initial sample extract stock concentration affects in vitro bioassay-based toxicological risk characterization

    NARCIS (Netherlands)

    Montano, M.; Loffmann, L.; Murk, A.J.; Gutleb, A.C.

    2014-01-01

    Purpose Bioassays have become an alternative for sediment risk profiling, including potential compliance with sediment quality criteria (SQC). In vitro functional bioassays have evolved through standardization and validation towards a confident toxicological hazard estimate of sediments. Sample

  3. A statistical treatment of bioassay pour fractions

    Science.gov (United States)

    Barengoltz, Jack; Hughes, David

    A bioassay is a method for estimating the number of bacterial spores on a spacecraft surface for the purpose of demonstrating compliance with planetary protection (PP) requirements (Ref. 1). The details of the process may be seen in the appropriate PP document (e.g., for NASA, Ref. 2). In general, the surface is mechanically sampled with a damp sterile swab or wipe. The completion of the process is colony formation in a growth medium in a plate (Petri dish); the colonies are counted. Consider a set of samples from randomly selected, known areas of one spacecraft surface, for simplicity. One may calculate the mean and standard deviation of the bioburden density, which is the ratio of counts to area sampled. The standard deviation represents an estimate of the variation from place to place of the true bioburden density commingled with the precision of the individual sample counts. The accuracy of individual sample results depends on the equipment used, the collection method, and the culturing method. One aspect that greatly influences the result is the pour fraction, which is the quantity of fluid added to the plates divided by the total fluid used in extracting spores from the sampling equipment. In an analysis of a single sample’s counts due to the pour fraction, one seeks to answer the question: What is the probability that if a certain number of spores are counted with a known pour fraction, that there are an additional number of spores in the part of the rinse not poured. This is given for specific values by the binomial distribution density, where detection (of culturable spores) is success and the probability of success is the pour fraction. A special summation over the binomial distribution, equivalent to adding for all possible values of the true total number of spores, is performed. This distribution when normalized will almost yield the desired quantity. It is the probability that the additional number of spores does not exceed a certain value. Of course

  4. Changes in chemical composition and bioassay assessment of ...

    African Journals Online (AJOL)

    Changes in chemical composition and bioassay assessment of nutritional potentials of almond fruit waste as an alternative feedstuff for livestock. ... AFW using day-old cockerels and considering performance parameters showed that treated AFW improved feed intake, body weight gain and feed conversion ratio even better ...

  5. Preliminary results of testing bioassay analytical performance standards

    International Nuclear Information System (INIS)

    Fisher, D.R.; Robinson, A.V.; Hadley, R.T.

    1983-08-01

    The analytical performance of both in vivo and in vitro bioassay laboratories is being studied to determine the capability of these laboratories to meet the minimum criteria for accuracy and precision specified in the draft ANSI Standard N13.30, Performance Criteria for Radiobioassay. This paper presents preliminary results of the first round of testing

  6. US Army Radiological Bioassay and Dosimetry: The RBD software package

    International Nuclear Information System (INIS)

    Eckerman, K.F.; Ward, R.C.; Maddox, L.B.

    1993-01-01

    The RBD (Radiological Bioassay and Dosimetry) software package was developed for the U. S. Army Material Command, Arlington, Virginia, to demonstrate compliance with the radiation protection guidance 10 CFR Part 20 (ref. 1). Designed to be run interactively on an IBM-compatible personal computer, RBD consists of a data base module to manage bioassay data and a computational module that incorporates algorithms for estimating radionuclide intake from either acute or chronic exposures based on measurement of the worker's rate of excretion of the radionuclide or the retained activity in the body. In estimating the intake,RBD uses a separate file for each radionuclide containing parametric representations of the retention and excretion functions. These files also contain dose-per-unit-intake coefficients used to compute the committed dose equivalent. For a given nuclide, if measurements exist for more than one type of assay, an auxiliary module, REPORT, estimates the intake by applying weights assigned in the nuclide file for each assay. Bioassay data and computed results (estimates of intake and committed dose equivalent) are stored in separate data bases, and the bioassay measurements used to compute a given result can be identified. The REPORT module creates a file containing committed effective dose equivalent for each individual that can be combined with the individual's external exposure

  7. Soil bioassays as tools for sludge compost quality assessment

    International Nuclear Information System (INIS)

    Domene, Xavier; Sola, Laura; Ramirez, Wilson; Alcaniz, Josep M.; Andres, Pilar

    2011-01-01

    Composting is a waste management technology that is becoming more widespread as a response to the increasing production of sewage sludge and the pressure for its reuse in soil. In this study, different bioassays (plant germination, earthworm survival, biomass and reproduction, and collembolan survival and reproduction) were assessed for their usefulness in the compost quality assessment. Compost samples, from two different composting plants, were taken along the composting process, which were characterized and submitted to bioassays (plant germination and collembolan and earthworm performance). Results from our study indicate that the noxious effects of some of the compost samples observed in bioassays are related to the low organic matter stability of composts and the enhanced release of decomposition endproducts, with the exception of earthworms, which are favored. Plant germination and collembolan reproduction inhibition was generally associated with uncomposted sludge, while earthworm total biomass and reproduction were enhanced by these materials. On the other hand, earthworm and collembolan survival were unaffected by the degree of composting of the wastes. However, this pattern was clear in one of the composting procedures assessed, but less in the other, where the release of decomposition endproducts was lower due to its higher stability, indicating the sensitivity and usefulness of bioassays for the quality assessment of composts.

  8. Assessment of acrylamide toxicity using a battery of standardised bioassays.

    Science.gov (United States)

    Zovko, Mira; Vidaković-Cifrek, Željka; Cvetković, Želimira; Bošnir, Jasna; Šikić, Sandra

    2015-12-01

    Acrylamide is a monomer widely used as an intermediate in the production of organic chemicals, e.g. polyacrylamides (PAMs). Since PAMs are low cost chemicals with applications in various industries and waste- and drinking water treatment, a certain amount of non-polymerised acrylamide is expected to end up in waterways. PAMs are non-toxic but acrylamide induces neurotoxic effects in humans and genotoxic, reproductive, and carcinogenic effects in laboratory animals. In order to evaluate the effect of acrylamide on freshwater organisms, bioassays were conducted on four species: algae Desmodesmus subspicatus and Pseudokirchneriella subcapitata, duckweed Lemna minor and water flea Daphnia magna according to ISO (International Organization for Standardisation) standardised methods. This approach ensures the evaluation of acrylamide toxicity on organisms with different levels of organisation and the comparability of results, and it examines the value of using a battery of low-cost standardised bioassays in the monitoring of pollution and contamination of aquatic ecosystems. These results showed that EC50 values were lower for Desmodesmus subspicatus and Pseudokirchneriella subcapitata than for Daphnia magna and Lemna minor, which suggests an increased sensitivity of algae to acrylamide. According to the toxic unit approach, the values estimated by the Lemna minor and Daphnia magna bioassays, classify acrylamide as slightly toxic (TU=0-1; Class 1). The results obtained from algal bioassays (Desmodesmus subspicatus and Pseudokirchneriella subcapitata) revealed the toxic effect of acrylamide (TU=1-10; Class 2) on these organisms.

  9. Microplate Bioassay for Determining Substrate Selectivity of "Candida rugosa" Lipase

    Science.gov (United States)

    Wang, Shi-zhen; Fang, Bai-shan

    2012-01-01

    Substrate selectivity of "Candida rugosa" lipase was tested using "p"-nitrophenyl esters of increasing chain length (C[subscript 1], C[subscript 7], C[subscript 15]) using the high-throughput screening method. A fast and easy 96-well microplate bioassay was developed to help students learn and practice biotechnological specificity screen. The…

  10. Soil plate bioassay: an effective method to determine ecotoxicological risks.

    Science.gov (United States)

    Boluda, R; Roca-Pérez, L; Marimón, L

    2011-06-01

    Heavy metals have become one of the most serious anthropogenic stressors for plants and other living organisms. Having efficient and feasible bioassays available to assess the ecotoxicological risks deriving from soil pollution is necessary. This work determines pollution by Cd, Co, Cr, Cu, Ni, Pb, V and Zn in two soils used for growing rice from the Albufera Natural Park in Valencia (Spain). Both were submitted to a different degree of anthropic activity, and their ecotoxicological risk was assessed by four ecotoxicity tests to compare their effectiveness: Microtox test, Zucconi test, pot bioassay (PB) and soil plate bioassay (SPB). The sensitivity of three plant species (barley, cress and lettuce) was also assessed. The results reveal a different degree of effectiveness and level of inhibition in the target organisms' growth depending on the test applied, to such an extent that the one-way analysis of variance showed significant differences only for the plate bioassay results, with considerable inhibition of root and shoot elongation in seedlings. Of the three plant species selected, lettuce was the most sensitive species to toxic effects, followed by cress and barley. Finally, the results also indicate that the SPB is an efficient, simple and economic alternative to other ecotoxicological assays to assess toxicity risks deriving from soil pollution. Copyright © 2011 Elsevier Ltd. All rights reserved.

  11. Horseradish extract promotes urinary bladder carcinogenesis when administered to F344 rats in drinking water.

    Science.gov (United States)

    Cho, Young-Man; Hasumura, Mai; Imai, Toshio; Takami, Shigeaki; Nishikawa, Akiyoshi; Ogawa, Kumiko

    2017-07-01

    Horseradish extract (HRE), consisting mainly of a mixture of allyl isothiocyanate and other isothiocyanates, has been used as a food additive. To evaluate the potential hazards of HRE, a 104-week chronic study, a 2-week analysis of cell proliferation in the urinary bladder and a medium-term promotion bioassay of HRE were conducted with administration at concentrations of up to 0.04% HRE in the drinking water to male F344 rats. In the 104-week chronic study with 32 male rats per group, no treatment-related increases in the incidences of neoplastic lesions in any organ, including urinary bladder, were observed, except for simple hyperplasia in the urinary bladder in rats treated with HRE at concentrations of more than 0.01% (5.0 mg kg -1 body weight day -1 ). In the promotion study, HRE treatment after N-butyl-N-(4-hydroxybutyl)nitrosamine initiation caused a clear increase in papillary or nodular hyperplasia, papilloma, and urothelial carcinoma of the urinary bladder in the groups given HRE for 13 weeks at doses higher than 0.005%, 0.01%, and 0.04% (2.7, 5.4 and 20.5 mg kg -1 body weight day -1 ), respectively. In the 2-week cell proliferation analysis, treatment with HRE at concentrations greater than 0.005% (3.9 mg kg -1 body weight day -1 ) caused transient increases in 5-bromo-2'-deoxyuridine labeling indices in the urothelium. Although clear tumor induction was not observed, administration of relatively low-dose HRE increased cell proliferation in the urothelium and exerted obvious promoting effects on rat urinary bladder carcinogenesis. Further studies are needed to elucidate the mode of action of HRE in the rat urinary bladder to facilitate data extrapolation from the present study and provide insights into risk assessment. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  12. Towards a systemic paradigm in carcinogenesis: linking epigenetics and genetics.

    Science.gov (United States)

    Burgio, Ernesto; Migliore, Lucia

    2015-04-01

    For at least 30 years cancer has been defined as a genetic disease and explained by the so-called somatic mutation theory (SMT), which has dominated the carcinogenesis field. Criticism of the SMT has recently greatly increased, although still not enough to force all SMT supporters to recognize its limits. Various researchers point out that cancer appears to be a complex process concerning a whole tissue; and that genomic mutations, although variably deleterious and unpredictably important in determining the establishment of the neoplastic phenotype, are not the primary origin for a malignant neoplasia. We attempt to describe the inadequacies of the SMT and demonstrate that epigenetics is a more logical cause of carcinogenesis. Many previous models of carcinogenesis fall into two classes: (i) in which some biological changes inside cells alone lead to malignancy; and (ii) requiring changes in stroma/extracellular matrix. We try to make clear that in the (ii) model genomic instability is induced by persistent signals coming from the microenvironment, provoking epigenetic and genetic modifications in tissue stem cells that can lead to cancer. In this perspective, stochastic mutations of DNA are a critical by-product rather then the primary cause of cancer. Indirect support for such model of carcinogenesis comes from the in vitro and vivo experiments showing apparent 'reversion' of cancer phenotypes obtained via physiological factors of cellular differentiation (cytokines and other signaling molecules) or drugs, even if the key mutations are not 'reversed'.

  13. A challenge to mutation theory of radiation carcinogenesis

    International Nuclear Information System (INIS)

    Watanabe, Masami

    2006-01-01

    This paper presents an objection against the commonly accepted mutation theory in radiation carcinogenesis. First, author's studies of X-ray irradiated syrian hamster embryo (SHE) cells on malignant morphological changes and mutational change of HGPRT gene showed that the changing patterns were quite different, and as well, other studies in mice gave the essentially similar results. Thus radiation-induced carcinogenesis in cells does not simply occur by an accumulation of radiation-induced mutation. Second, as cultured cells usually used for oncogenesis studies already have the infinitively proliferative ability, the author used the primary cell culture obtained from the rodent embryo. Even those cells became immortal to be cancerous after repeated culture passage with the higher frequency of 10 3 -10 4 relative to somatic cell mutation. Cells thus seem to be easily changeable to cancerous ones. Bystander effect can cause transformation in non-irradiated cells and genetic instability by radiation can form the potentially unstable chromatin region, which induces telomere instability. The author has found that, while short-lived radicals yielded by X-ray irradiation attack DNA to induce cell death and chromosome aberration, long-lived radicals in biomolecules do not, but can cause mutation and carcinogenesis, which are reduced by vitamine C supplementation. The author concludes that the primary target in the radiation carcinogenesis in cells and even in the whole individuals is conceivably protein and not DNA. (T.I.)

  14. Ultraviolet radiation-induced carcinogenesis: mechanisms and experimental models

    International Nuclear Information System (INIS)

    Ramasamy, Karthikeyan; Shanmugam, Mohana; Balupillai, Agilan; Govindhasamy, Kanimozhi; Gunaseelan, Srithar; Muthusamy, Ganesan; Robert, Beualah Mary; Nagarajan, Rajendra Prasad

    2017-01-01

    Ultraviolet radiation (UVR) is a very prominent environmental toxic agent. UVR has been implicated in the initiation and progression of photocarcinogenesis. UVR exposure elicits numerous cellular and molecular events which include the generation of inflammatory mediators, DNA damage, epigenetic modifications, and oxidative damages mediated activation of signaling pathways. UVR-initiated signal transduction pathways are believed to be responsible for tumor promotion effects. UVR-induced carcinogenic mechanism has been well studied using various animal and cellular models. Human skin-derived dermal fibroblasts, epidermal keratinocytes, and melanocytes served as excellent cellular model systems for the understanding of UVR-mediated carcinogenic events. Apart from this, scientists developed reconstituted three-dimensional normal human skin equivalent models for the study of UVR signaling pathways. Moreover, hairless mice such as SKH-1, devoid of Hr gene, served as a valuable model for experimental carcinogenesis. Scientists have also used transgenic mice and dorsal portion shaved Swiss albino mice for UVR carcinogenesis studies. In this review, we have discussed the current progress in the study on ultraviolet B (UVB)-mediated carcinogenesis and outlined appropriate experimental models for both ultraviolet A- and UVB-mediated carcinogenesis. (author)

  15. Chronology of p53 protein accumulation in gastric carcinogenesis

    NARCIS (Netherlands)

    Craanen, M. E.; Blok, P.; Dekker, W.; Offerhaus, G. J.; Tytgat, G. N.

    1995-01-01

    p53 Protein accumulation in early gastric carcinoma was studied in relation to the histological type (Lauren classification) and the type of growth pattern, including the chronology of p53 protein accumulation during carcinogenesis. Forty five, paraffin embedded gastrectomy specimens from early

  16. Carcinogenesis related to intense pulsed light and UV exposure

    DEFF Research Database (Denmark)

    Hedelund, L; Lerche, C; Wulf, H C

    2006-01-01

    This study examines whether intense pulsed light (IPL) treatment has a carcinogenic potential itself or may influence ultraviolet (UV)-induced carcinogenesis. Secondly, it evaluates whether UV exposure may influence IPL-induced side effects. Hairless, lightly pigmented mice (n=144) received three...

  17. Hypoxia and cell cycle deregulation in endometrial carcinogenesis

    NARCIS (Netherlands)

    Horrée, N.

    2007-01-01

    Because uterine endometrial carcinoma is the most common malignancy of the female genital tract and 1 of every 5 patients dies of this disease, understanding the mechanisms of carcinogenesis and progression of endometrial carcinoma is important. In general, this thesis can be summarized as a study

  18. Bioassay for aquatic ecosystems review and classification; Rassegna dei principali test di ecotossicologia acquatica

    Energy Technology Data Exchange (ETDEWEB)

    Sanci, Antonella; Rosa, Silvia [ENEA, Centro Ricerche Casaccia, Rome (Italy). Dipt. Ambiente

    1997-09-01

    Bioassay play a crucial role in assessing the actual or potential impacts of anthropogenic agents on the natural environment. In this technical report, literature on bioassays for aquatic ecosystems has been reviewed and classified. Problems associated with the choice and application of bioassays are discussed.

  19. Breast cancer as heterogeneous disease: contributing factors and carcinogenesis mechanisms.

    Science.gov (United States)

    Kravchenko, Julia; Akushevich, Igor; Seewaldt, Victoria L; Abernethy, Amy P; Lyerly, H Kim

    2011-07-01

    The observed bimodal patterns of breast cancer incidence in the U.S. suggested that breast cancer may be viewed as more than one biological entity. We studied the factors potentially contributing to this phenomenon, specifically focusing on how disease heterogeneity could be linked to breast carcinogenesis mechanisms. Using empirical analyses and population-based biologically motivated modeling, age-specific patterns of incidence of ductal and lobular breast carcinomas from the SEER registry (1990-2003) were analyzed for heterogeneity and characteristics of carcinogenesis, stratified by race, stage, grade, and estrogen (ER)/progesterone (PR) receptor status. The heterogeneity of breast carcinoma age patterns decreased after stratification by grade, especially for grade I and III tumors. Stratification by ER/PR status further reduced the heterogeneity, especially for ER(+)/PR(-) and ER(-)/(-) tumors; however, the residual heterogeneity was still observed. The number of rate-limiting events of carcinogenesis and the latency of ductal and lobular carcinomas differed, decreasing from grade I to III, with poorly differentiated tumors associated with the least number of carcinogenesis stages and the shortest latency. Tumor grades play important role in bimodal incidence of breast carcinoma and have distinct mechanisms of carcinogenesis. Race and cancer subtype could play modifying role. ER/PR status contributes to the observed heterogeneity, but is subdominant to tumor grade. Further studies on sources of "remaining" heterogeneity of population with breast cancer (such as genetic/epigenetic characteristics) are necessary. The results of this study could suggest stratification rather than unification of breast cancer prevention strategies, risk assessment, and treatment.

  20. Oxidative stress and inflammation in liver carcinogenesis

    Directory of Open Access Journals (Sweden)

    Natalia Olaya

    2007-02-01

    series of transcription factors. Moreover, in addition to direct production of ROS by these pathogens, liver infiltration by activated phagocytic cells provides an additional source of ROS production that promotes oxidative stress via interleukin or NO production that can damage proteins, lipids and DNA.

    Nuclear MSI was demonstrated first in familial hereditary colorectal cancer (HNPCC and then in sporadic cancers, primarily digestive tract cancers such as colorectal, gastric and pancreatic cancers.In HCC, although nuclear MSI has been shown in some studies (15,18, there is as yet no direct evidence of alteration of the MMR genes and the biological and the clinicopathological significance of the lowlevel MSI seen in HCC is unclear. MSI has also been shown to occur in inflammatory tissues such as chronic hepatitis and cirrhosis as well as in ulcerative colitis, chronic pancreatitis and in non digestive inflammatory diseases such as rheumatoid arthritis.

    Recently, the role of mitochondria in carcinogenesis has been under numerous investigation, in part because their prominent role in apoptosis, ROS production and other aspects of tumour biology. The mitochondrial genome is particularly susceptible to mutations because of the high level of ROS generation in this organelle, coupled with a relatively low level of DNA repair. Somatic mutations of mitochondrial DNA (mtDNA have been shown in HCC as was also observed MSI. These findings suggest a potential role for mitochondrial genome instability in the early steps of tumorigenesis.

    Ischemia-reperfusion injury can occur in several situations and is a major cause of cell damage during surgery. Cells and tissues subjected to hypoxia by prolonged ischemia become acidic

  1. Abdominal multi-organ CT segmentation using organ correlation graph and prediction-based shape and location priors.

    Science.gov (United States)

    Okada, Toshiyuki; Linguraru, Marius George; Hori, Masatoshi; Summers, Ronald M; Tomiyama, Noriyuki; Sato, Yoshinobu

    2013-01-01

    The paper addresses the automated segmentation of multiple organs in upper abdominal CT data. We propose a framework of multi-organ segmentation which is adaptable to any imaging conditions without using intensity information in manually traced training data. The features of the framework are as follows: (1) the organ correlation graph (OCG) is introduced, which encodes the spatial correlations among organs inherent in human anatomy; (2) the patient-specific organ shape and location priors obtained using OCG enable the estimation of intensity priors from only target data and optionally a number of untraced CT data of the same imaging condition as the target data. The proposed methods were evaluated through segmentation of eight abdominal organs (liver, spleen, left and right kidney, pancreas, gallbladder, aorta, and inferior vena cava) from 86 CT data obtained by four imaging conditions at two hospitals. The performance was comparable to the state-of-the-art method using intensity priors constructed from manually traced data.

  2. Multi-organ sarcoidosis treatment with fumaric acid esters: a case report and review of the literature.

    Science.gov (United States)

    Zouboulis, Christos C; Lippert, Undine; Karagiannidis, Ioannis

    2014-01-01

    Sarcoidosis is a rare, systemic disease that is characterized by the formation of granulomas in various organs, including the skin. As the etiology remains unknown, the treatment of sarcoidosis is challenging. We present a 47-year-old female patient with progressive, multi-organ sarcoidosis who had a complete clinical improvement of the skin lesions, a moderate reduction in pulmonary opacities on chest X-ray, a marked subjective improvement in general status and pulmonary efficiency and a marked reduction in serum angiotensin-converting enzyme and soluble interleukin-2 receptor after 6 months of therapy with fumaric acid esters. The present case and similar reports in the literature highlight the probable efficacy of fumaric acid esters in the treatment of sarcoidosis and other non-infectious, granulomatous diseases. © 2014 S. Karger AG, Basel.

  3. Bioassay-based risk assessment of hazardous waste

    Energy Technology Data Exchange (ETDEWEB)

    Donnelly, K.C.; Brown, K.W.; He, L.Y. [Texas A and M Univ., College Station, TX (United States)

    1994-12-31

    Microbial bioassays have been used to assess the genotoxic hazard at more than 30 different hazardous waste sites. Environmental samples were extracted with dichloromethane and methanol, and the resulting residue tested using GC/MS analysis as well as the Salmonella Microsomal and E. coli Prophage Induction assays. At a munitions wastewater contaminated site, there was no correlation between mutagenicity in bacteria, and the risk as estimated from chemical analysis data of trinitrotoluene. Samples 202 and 204 from a coal gasification site contained 72 mg/kg and 9 mg/kg benzo(a)pyrene, whereas the mutagenic responses of these samples were 231 net revertants/mg and 902 revertants/mg, respectively. The data suggest that microbial bioassays provide a valuable tool for monitoring the interactions of the components of a complex mixture.

  4. Improving global laboratory capabilities for emergency radionuclide bioassay

    International Nuclear Information System (INIS)

    Li, C.; Jourdain, J.; Kramer, G. H.

    2012-01-01

    During a radiological or nuclear emergency, first-responders and the general public may be internally contaminated with the radionuclide(s) involved. A timely radionuclide bioassay provides important information about contamination, for subsequent dose assessment and medical management. Both technical and operational gaps are discussed in this paper. As many people may need to be assessed in a short period of time, any single laboratory may find its capabilities insufficient. Laboratories from other regions or other countries may be called upon for assistance. This paper proposes a road-map to improve global capabilities in emergency radionuclide bioassay, suggesting a phased approach for establishing a global laboratory network. Existing international collaboration platforms could provide the base on which to build such a network. (authors)

  5. A Rapid and Simple Bioassay Method for Herbicide Detection

    Directory of Open Access Journals (Sweden)

    Xiu-Qing Li

    2008-01-01

    Full Text Available Chlamydomonas reinhardtii, a unicellular green alga, has been used in bioassay detection of a variety of toxic compounds such as pesticides and toxic metals, but mainly using liquid culture systems. In this study, an algal lawn--agar system for semi-quantitative bioassay of herbicidal activities has been developed. Sixteen different herbicides belonging to 11 different categories were applied to paper disks and placed on green alga lawns in Petri dishes. Presence of herbicide activities was indicated by clearing zones around the paper disks on the lawn 2-3 days after application. The different groups of herbicides induced clearing zones of variable size that depended on the amount, mode of action, and chemical properties of the herbicides applied to the paper disks. This simple, paper-disk-algal system may be used to detect the presence of herbicides in water samples and act as a quick and inexpensive semi-quantitative screening for assessing herbicide contamination.

  6. The use of cultivars of Raphanus sativus for cytokinin bioassay

    Directory of Open Access Journals (Sweden)

    Dorota Kubowicz

    2013-12-01

    Full Text Available Six cultivars of radish (Raphanus sativus were tested for their usefulness in radish cytokinin bioassay by the method of Letham (1971. The best cultivar was found to be 'Sopel Lodu' which responds well to both zeatin and 2iP over a wide range of concentrations. The fresh weight of cotyledons increased at most by 71.5% (if treated with zeatin or 101.0% (if treated with 2iP compared to untreated cotyledons. This cultivar is also sensitive to the partially purified cytokinin-like fraction isolated from the pine (Pinus silvestris cambial region. The cultivar 'Sopel Lodu' is therefore proposed to be a suitable plant for cytokinin bioassays.

  7. The IMBA suite: integrated modules for bioassay analysis

    Energy Technology Data Exchange (ETDEWEB)

    Birchall, A.; Jarvis, N.S.; Peace, M.S.; Riddell, A.E.; Battersby, W.P

    1998-07-01

    The increasing complexity of models representing the biokinetic behaviour of radionuclides in the body following intake poses problems for people who are required to implement these models. The problem is exacerbated by the current paucity of suitable software. In order to remedy this situation, a collaboration between British Nuclear Fuels, Westlakes Research Institute and the National Radiological Protection Board has started with the aim of producing a suite of modules for estimating intakes and doses from bioassay measurements using the new ICRP models. Each module will have a single purpose (e.g. to calculate respiratory tract deposition) and will interface with other software using data files. The elements to be implemented initially are plutonium, uranium, caesium, iodine and tritium. It is intended to make the software available to other parties under terms yet to be decided. This paper describes the proposed suite of integrated modules for bioassay analysis, IMBA. (author)

  8. Log bioassay of residual effectiveness of insecticides against bark beetles

    Science.gov (United States)

    Richard H. Smith

    1982-01-01

    Residual effectiveness of nine insecticides applied to bark was tested against western, mountain, and Jeffrey pine beetles. Ponderosa and Jeffrey pine trees were treated and logs cut from them 2 to 13 months later, and bioassayed with the three beetles. The insecticides were sprayed at the rate of 1 gal (3.8 l) per 40- or 80-ft² (3.6 or 7.2 m²) bark surface at varying...

  9. Eubacterium brachy - Reactivity in In Vitro Bone Resorptive Bioassay,

    Science.gov (United States)

    1983-02-10

    Center Washington, D. C . 20307 If Eubacterium brachy - Reactivity in In Vitro Bone Resorptive Bioassay 1. ABSTRACT Recent studies have demonstrated an...Relative distribution of bacteria at clinically healthy and periodontally diseased sites in humans. J Clin Periodontal 5:115, 1978. 3. Evian, C ...applied foreign protein into rat gingiva. J Periodont Res 6:89, 1971. 21. Gaffer, A., Coleman, E.J., and Marcussen, H.W.: Penetration of dental plaque

  10. Activities of Jatropha curcas phorbol esters in various bioassays.

    Science.gov (United States)

    Devappa, Rakshit K; Rajesh, Sanjay K; Kumar, Vikas; Makkar, Harinder P S; Becker, Klaus

    2012-04-01

    Jatropha curcas seeds contain 30-35% oil, which can be converted to high quality biodiesel. However, Jatropha oil is toxic, ascribed to the presence of phorbol esters (PEs). In this study, isolated phorbol ester rich fraction (PEEF) was used to evaluate the activity of PEs using three aquatic species based bioassays (snail (Physa fontinalis), brine shrimp (Artemeia salina), daphnia (Daphnia magna)) and microorganisms. In all the bioassays tested, increase in concentration of PEs increased mortality with an EC(50) (48 h) of 0.33, 26.48 and 0.95 mg L(-1) PEs for snail, artemia and daphnia, respectively. The sensitivity of various microorganisms for PEs was also tested. Among the bacterial species tested, Streptococcus pyogenes and Proteus mirabilis were highly susceptible with a minimum inhibitory concentration (MIC) of 215 mg L(-1) PEs; and Pseudomonas putida were also sensitive with MIC of 251 mg L(-1) PEs. Similarly, Fusarium species of fungi exhibited EC(50) of 58 mg L(-1) PEs, while Aspergillus niger and Curvularia lunata had EC(50) of 70 mg L(-1). The snail bioassay was most sensitive with 100% snail mortality at 1 μg of PEs mL(-1). In conclusion, snail bioassay could be used to monitor PEs in Jatropha derived products such as oil, biodiesel, fatty acid distillate, kernel meal, cake, glycerol or for contamination in soil or other environmental matrices. In addition, PEs with molluscicidal/antimicrobial activities could be utilized for agricultural and pharmaceutical applications. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. BioAssay templates for the semantic web

    Directory of Open Access Journals (Sweden)

    Alex M. Clark

    2016-05-01

    Full Text Available Annotation of bioassay protocols using semantic web vocabulary is a way to make experiment descriptions machine-readable. Protocols are communicated using concise scientific English, which precludes most kinds of analysis by software algorithms. Given the availability of a sufficiently expressive ontology, some or all of the pertinent information can be captured by asserting a series of facts, expressed as semantic web triples (subject, predicate, object. With appropriate annotation, assays can be searched, clustered, tagged and evaluated in a multitude of ways, analogous to other segments of drug discovery informatics. The BioAssay Ontology (BAO has been previously designed for this express purpose, and provides a layered hierarchy of meaningful terms which can be linked to. Currently the biggest challenge is the issue of content creation: scientists cannot be expected to use the BAO effectively without having access to software tools that make it straightforward to use the vocabulary in a canonical way. We have sought to remove this barrier by: (1 defining a BioAssay Template (BAT data model; (2 creating a software tool for experts to create or modify templates to suit their needs; and (3 designing a common assay template (CAT to leverage the most value from the BAO terms. The CAT was carefully assembled by biologists in order to find a balance between the maximum amount of information captured vs. low degrees of freedom in order to keep the user experience as simple as possible. The data format that we use for describing templates and corresponding annotations is the native format of the semantic web (RDF triples, and we demonstrate some of the ways that generated content can be meaningfully queried using the SPARQL language. We have made all of these materials available as open source (http://github.com/cdd/bioassay-template, in order to encourage community input and use within diverse projects, including but not limited to our own

  12. Effectiveness of Bioactive Food Components in Experimental Colon Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Emília Hijová

    2009-01-01

    Full Text Available The aim of the present study was the evaluation of possible protective effects of selected bioactive food components in experimental N,N-dimethylhydrazine (DMH-induced colon carcinogenesis. Wistar albino rats (n = 92 were fed a high fat diet or conventional laboratory diet. Two weeks after the beginning of the trial, DMH injections were given to six groups of rats at the dose of 20 mg/kg b.w. twice weekly. The activity of bacterial enzymes in faeces and serum bile acid concentrations were determined. High fat diet, DMH injections, and their combination significantly increased the activies of β-galactosidase, β-glucuronidase, and α-glucosidase (p p < 0.001, as well as the bile acid concentration compared to the group at the highest risk. The protective effects of selected bioactive food components in experimentally induced colon carcinogenesis allow for their possible use in cancer prevention or treatment.

  13. Experimental Hepatic Carcinogenesis: Oxidative Stress and Natural Antioxidants

    Directory of Open Access Journals (Sweden)

    Velid Unsal

    2017-08-01

    Full Text Available Hepatocellular carcinoma is one of the most common cancers in the world, and it is influenced by agents such as DEN, 2-AAF, phenobarbital, alcohol, aflatoxin B1 metabolite or hepatitis viruses (B and C. Oxidative stress is becoming recognized as a key factor in the progression of hepatocarcinogenesis. Reactive oxygen species can play a leading role in initiation and promotion of hepatic carcinogenesis. The metabolites of DEN Diethylnitrosamine (DEN mediate the binding of tumour promoters by covalently binding to the DNA with one or two oxidation-providing electrons. 2-AAF is the inducer of DEN, and it is involved in tumour formation in the bladder and liver. Reactive Oxygen species (ROS; carbohydrates, lipids, DNA and enzymes, such as affect all important structures. Additionally, an excessive amount of ROS is highly toxic to cells. Antioxidants are protects against ROS, toxic substances, carcinogens. This review focuses on the literature on studies of Hepatic Carcinogenesis, oxidative stress and antioxidant therapy.

  14. The 10th Annual Bioassays and Bioanalytical Method Development Conference.

    Science.gov (United States)

    Ma, Mark; Tudan, Christopher; Koltchev, Dolly

    2015-01-01

    The 10th Annual Bioassays and Bioanalytical Method Development Conference was hosted in Boston, MA, USA on 20-22 October 2014. This meeting brought together scientists from the biopharmaceutical and life sciences industries, the regulatory agency and academia to share and discuss current trends in cell-based assays and bioanalysis, challenges and ideas for the future of the bioassays and bioanalytical method development. The experiences associated with new and innovative technologies were evaluated as well as their impact on the current bioassays methodologies and bioanalysis workflow, including quality, feasibility, outsourcing strategies and challenges, productivity and compliance. Several presentations were also provided by members of the US FDA, sharing both scientific and regulatory paradigms including a most recent update on the position of the FDA with specific aspects of the draft Bioanalytical Method Validation guidance following its review of the industry's responses. The meeting was jointly coincided with the 15th Annual Immunogenicity for Biotherapeutics meeting, allowing for attendees to also familiarize themselves with new and emerging approaches to overcome the effect of immunogenicity, in addition to investigative strategies.

  15. A Bioassay System Using Bioelectric Signals from Small Fish

    Science.gov (United States)

    Terawaki, Mitsuru; Soh, Zu; Hirano, Akira; Tsuji, Toshio

    Although the quality of tap water is generally examined using chemical assay, this method cannot be used for examination in real time. Against such a background, the technique of fish bioassay has attracted attention as an approach that enables constant monitoring of aquatic contamination. The respiratory rhythms of fish are considered an efficient indicator for the ongoing assessment of water quality, since they are sensitive to chemicals and can be indirectly measured from bioelectric signals generated by breathing. In order to judge aquatic contamination accurately, it is necessary to measure bioelectric signals from fish swimming freely as well as to stably discriminate measured signals, which vary between individuals. However, no bioassay system meeting the above requirements has yet been established. This paper proposes a bioassay system using bioelectric signals generated from small fish in free-swimming conditions. The system records signals using multiple electrodes to cover the extensive measurement range required in a free-swimming environment, and automatically discriminates changes in water quality from signal frequency components. This discrimination is achieved through an ensemble classification method using probability neural networks to solve the problem of differences between individual fish. The paper also reports on the results of related validation experiments, which showed that the proposed system was able to stably discriminate between water conditions before and after bleach exposure.

  16. Experimental gastric carcinogenesis in Cebus apella nonhuman primates.

    Directory of Open Access Journals (Sweden)

    Joana de Fátima Ferreira Borges da Costa

    Full Text Available The evolution of gastric carcinogenesis remains largely unknown. We established two gastric carcinogenesis models in New-World nonhuman primates. In the first model, ACP03 gastric cancer cell line was inoculated in 18 animals. In the second model, we treated 6 animals with N-methyl-nitrosourea (MNU. Animals with gastric cancer were also treated with Canova immunomodulator. Clinical, hematologic, and biochemical, including C-reactive protein, folic acid, and homocysteine, analyses were performed in this study. MYC expression and copy number was also evaluated. We observed that all animals inoculated with ACP03 developed gastric cancer on the 9(th day though on the 14(th day presented total tumor remission. In the second model, all animals developed pre-neoplastic lesions and five died of drug intoxication before the development of cancer. The last surviving MNU-treated animal developed intestinal-type gastric adenocarcinoma observed by endoscopy on the 940(th day. The level of C-reactive protein level and homocysteine concentration increased while the level of folic acid decreased with the presence of tumors in ACP03-inoculated animals and MNU treatment. ACP03 inoculation also led to anemia and leukocytosis. The hematologic and biochemical results corroborate those observed in patients with gastric cancer, supporting that our in vivo models are potentially useful to study this neoplasia. In cell line inoculated animals, we detected MYC immunoreactivity, mRNA overexpression, and amplification, as previously observed in vitro. In MNU-treated animals, mRNA expression and MYC copy number increased during the sequential steps of intestinal-type gastric carcinogenesis and immunoreactivity was only observed in intestinal metaplasia and gastric cancer. Thus, MYC deregulation supports the gastric carcinogenesis process. Canova immunomodulator restored several hematologic measurements and therefore, can be applied during/after chemotherapy to increase the

  17. Effect of Dendrobium officinale Extraction on Gastric Carcinogenesis in Rats

    OpenAIRE

    Zhao, Yi; Liu, Yan; Lan, Xi-Ming; Xu, Guo-Liang; Sun, You-Zhi; Li, Fei; Liu, Hong-Ning

    2016-01-01

    Dendrobium officinale (Tie Pi Shi Hu in Chinese) has been widely used to treat different diseases in China. Anticancer effect is one of the important effects of Dendrobium officinale. However, the molecular mechanism of its anticancer effect remains unclear. In the present study, gastric carcinogenesis in rats was used to evaluate the effect of Dendrobium officinale on cancer, and its pharmacological mechanism was explored. Dendrobium officinale extracts (4.8 and 2.4 g/kg) were orally adminis...

  18. Biologically based modelling and simulation of carcinogenesis at low doses

    International Nuclear Information System (INIS)

    Ouchi, Noriyuki B.

    2003-01-01

    The process of the carcinogenesis is studied by computer simulation. In general, we need a large number of experimental samples to detect mutations at low doses, but in practice it is difficult to get such a large number of data. To satisfy the requirements of the situation at low doses, it is good to study the process of carcinogenesis using biologically based mathematical model. We have mainly studied it by using as known as 'multi-stage model'; the model seems to get complicated, as we adopt the recent new findings of molecular biological experiments. Moreover, the basic idea of the multi-stage model is based on the epidemiologic data of log-log variation of cancer incidence with age, it seems to be difficult to compare with experimental data of irradiated cell culture system, which has been increasing in recent years. Taking above into consideration, we concluded that we had better make new model with following features: 1) a unit of the target system is a cell, 2) the new information of the molecular biology can be easily introduced, 3) having spatial coordinates for checking a colony formation or tumorigenesis. In this presentation, we will show the detail of the model and some simulation results about the carcinogenesis. (author)

  19. The relevance of cell transformation to carcinogenesis in vivo

    International Nuclear Information System (INIS)

    Little, J.B.

    1989-01-01

    Despite the caveats concerning rodent as opposed to human cell transformation systems, the author concludes there are several areas in which cell transformation studies with rodent cells have shown clear relevance to carcinogenesis in vivo, especially studies of carcinogenic effects of high LET radiation, particularly dependence on dose rate. In vitro studies firmly established the generality of promotion by phorbol esters tumour promotors. Initial studies on suppression of transformation, notably by protease inhibitors, has led to the confirmation of this phenomenon in in vivo carcinogenesis; development of inhibitor preparations from natural sources suitable for long-term supplementation in human diet, is under investigation. The potential importance of these modifiers is further emphasized by mechanistic studies suggesting that radiation may initiate a large fraction of exposed cell population, and expression of transformation may be controlled to a large extent by environmental conditions including the presence of promoting or suppressing agents. Finally, cell transformation systems offer the opportunity for mechanistic studies of the initial stages of carcinogenesis. Provocative results have arisen in several areas consistent with findings in experimental animals. (author)

  20. Cellular adaptation as an important response during chemical carcinogenesis

    International Nuclear Information System (INIS)

    Farber, E.

    1992-01-01

    Since disease processes are largely expressions of how living organisms react and respond to perturbations in the external and internal environments, adaptive or protective responses and their modulations and mechanisms are of the greatest concern in fundamental studies of disease pathogenesis. Such considerations are also of the greatest relevance in toxicology, including how living organisms respond to low levels of single and multiple xenobiotics and radiations. As the steps and mechanisms during cancer development are studied in greater depth, phenomena become apparent that suggest that adaptive reactions and responses may play important or even critical roles in the process of carcinogenesis. The question becomes whether the process of carcinogenesis is fundamentally an adversarial one (i.e., an abnormal cell in a vulnerable host), or is it more in the nature of a physiological selection or differentiation, which has survival value for the host as an adaptive phenomena? The very early initial interactions of mutagenic chemical carcinogens, radiations and viruses with DNA prejudice most to consider the adversarial 'abnormal' view as the appropriate one. Yet, the unusually common nature of the earliest altered rare cells that appear during carcinogenesis, their unusually bland nature, and their spontaneous differentiation to normal-appearing adult liver should be carefully considered

  1. Multi-Organ Damage in Human Dipeptidyl Peptidase 4 Transgenic Mice Infected with Middle East Respiratory Syndrome-Coronavirus.

    Directory of Open Access Journals (Sweden)

    Guangyu Zhao

    Full Text Available The Middle East Respiratory Syndrome Coronavirus (MERS-CoV causes severe acute respiratory failure and considerable extrapumonary organ dysfuction with substantial high mortality. For the limited number of autopsy reports, small animal models are urgently needed to study the mechanisms of MERS-CoV infection and pathogenesis of the disease and to evaluate the efficacy of therapeutics against MERS-CoV infection. In this study, we developed a transgenic mouse model globally expressing codon-optimized human dipeptidyl peptidase 4 (hDPP4, the receptor for MERS-CoV. After intranasal inoculation with MERS-CoV, the mice rapidly developed severe pneumonia and multi-organ damage, with viral replication being detected in the lungs on day 5 and in the lungs, kidneys and brains on day 9 post-infection. In addition, the mice exhibited systemic inflammation with mild to severe pneumonia accompanied by the injury of liver, kidney and spleen with neutrophil and macrophage infiltration. Importantly, the mice exhibited symptoms of paralysis with high viral burden and viral positive neurons on day 9. Taken together, this study characterizes the tropism of MERS-CoV upon infection. Importantly, this hDPP4-expressing transgenic mouse model will be applicable for studying the pathogenesis of MERS-CoV infection and investigating the efficacy of vaccines and antiviral agents designed to combat MERS-CoV infection.

  2. Brucellosis With Multi-Organ Involvement in a Patient With History of Composite Aortic Graft and Hepatitis B.

    Science.gov (United States)

    Dehghan Manshadi, Seyed Ali; Rezahosseini, Omid; Abdi Liaei, Zahra

    2016-11-01

    The brucellosis with multi-organ involvement in a patient with a history of the composite aortic graft (Bentall procedure) and Hepatitis B infection is rare. A 35-year-old man presented to us with fever and loss of consciousness. Four years ago, he was IDU and underwent cardiac surgery because of endocarditis. Recently lumbar spondylodiscitis was diagnosed. The Wright (1/320) and Coombs Wright tests (1/640) were positive. After CNS imaging, lumbar puncture was done. The CSF pleocytosis was lymphocyte dominant. In cardiac echocardiography, large vegetation on prosthetic aortic valve leaflets was seen. The brain MRI was reported abnormal. Treatment of brucellosis started with Ceftriaxone, Doxycycline, Rifampin and Gentamycin. After 4 days, he became oriented, and fever was disappeared then we continued the treatment for 16 days. The patient discharged and followed by daily phone calls. As symptoms of abdominal pain and jaundice were presented on the fifth day, he re-admitted. The patient expired because of hepatorenal and cardiac insufficiency. Drug side effects, activation of Hepatitis B and embolism of cardiac vegetation to other organs were suspected causes of death. We do not suggest medical therapy without cardiac surgery in such cases. When combination therapy is necessary for brucellosis in an HBsAg-positive patient, hepatitis virus activity should be assess by HBV-DNA PCR and the dose of drugs with known hepatotoxic effects such as rifampin and co-trimoxazole should be adjust. Combination therapy with quinolones instead of hepatoxic drugs is one of our suggustions.

  3. Fluorescence-Based Bioassays for the Detection and Evaluation of Food Materials

    OpenAIRE

    Nishi, Kentaro; Isobe, Shin-Ichiro; Zhu, Yun; Kiyama, Ryoiti

    2015-01-01

    We summarize here the recent progress in fluorescence-based bioassays for the detection and evaluation of food materials by focusing on fluorescent dyes used in bioassays and applications of these assays for food safety, quality and efficacy. Fluorescent dyes have been used in various bioassays, such as biosensing, cell assay, energy transfer-based assay, probing, protein/immunological assay and microarray/biochip assay. Among the arrays used in microarray/biochip assay, fluorescence-based mi...

  4. Comparison of five bioassay techniques for assessing sediment-bound contaminants

    OpenAIRE

    Ahlf, Wolfgang; Calmano, Wolfgang; Erhard, Judith; Förstner, Ulrich

    1989-01-01

    Biological response could not be predicted based on chemical concentration of the sediment contaminants. Bioassays integrate the response of test organisms to contaminants and nutrients. Comparative results of five acute bioassays indicated that Neubauer phytoassay was the most sensitive. The mircobial biomass and algal growth tests indicated a response to the availability of contaminants and nutrients. These results suggest the usefulness of a diversity of bioassays in toxicity testing of se...

  5. Comparison of solid-phase bioassays and ecoscores to evaluate the toxicity of contaminated soils.

    OpenAIRE

    Lors , Christine; Ponge , Jean-François; Martínez Aldaya , Maite; Damidot , Denis

    2010-01-01

    International audience; Five bioassays (inhibition of lettuce germination and growth, earthworm mortality, inhibition of springtail population growth, avoidance by springtails) were compared, using four coke factory soils contaminated by PAHs and trace elements, before and after biotreatment. For each bioassay, several endpoints were combined in an 'ecoscore', a measure of test sensitivity. Ecoscores pooled over all tested bioassays revealed that most organisms were highly sensitive to the co...

  6. Fluorescent bioassays for toxic metals in milk and yoghurt

    Science.gov (United States)

    2012-01-01

    Background From a human health viewpoint, contaminated milk and its products could be a source of long-term exposure to toxic metals. Simple, inexpensive, and on-site assays would enable constant monitoring of their contents. Bioassays that can measure toxic metals in milk or yoghurt might reduce the risk. For this purpose, the green fluorescent protein (GFP)-tagged trans factors, ArsR-GFP and CadC-GFP, together with their cis elements were used to develop such bioassays. Results ArsR-GFP or CadC-GFP, which binds either toxic metal or DNA fragment including cis element, was directly mixed with cow’s milk or yoghurt within a neutral pH range. The fluorescence of GFP, which is reflected by the association/dissociation ratio between cis element and trans factor, significantly changed with increasing externally added As (III) or Cd (II) whereas smaller responses to externally added Pb (II) and Zn (II) were found. Preparation and dilution of whey fraction at low pH were essential to intrinsic zinc quantification using CadC-GFP. Using the extraction procedure and bioassay, intrinsic Zn (II) concentrations ranging from 1.4 to 4.8 mg/l for milk brands and from 1.2 to 2.9 mg/kg for yoghurt brands were determined, which correlated to those determined using inductively coupled plasma atomic emission spectroscopy. Conclusions GFP-tagged bacterial trans factors and cis elements can work in the neutralized whole composition and diluted whey fraction of milk and yoghurt. The feature of regulatory elements is advantageous for establishment of simple and rapid assays of toxic metals in dairy products. PMID:23098077

  7. Interpretation of bioassay data from nuclear fuel fabrication workers

    International Nuclear Information System (INIS)

    Melo, D.; Xavier, M.

    2005-01-01

    Full text: In nuclear fuel fabrication facilities, workers are exposed to different compounds of enriched uranium. Although in this kind of facility the main route of intake is inhalation, ingestion may occur in some situations. The interpretation of the bioassay data is very complex, since it is necessary taking into account all the different parameters, which is a big challenge. Due to the high cost of the individual monitoring programme for internal dose assessment in the routine monitoring programmes, usually only one type of measurement is assigned. In complex situations like the one described in this paper, where several parameters can compromise the accuracy of the bioassay interpretation it is need to have a combination of techniques to evaluate the internal dose. According to ICRP 78 (1997), the general order of preference in terms of accuracy of interpretation is: body activity measurement, excreta analysis and personal air sampling. Results of monitoring of working environment may provide information that assists in interpretation on particle size, chemical form and solubility, time of intake. A group of seventeen workers from controlled area of the fuel fabrication facility was selected to evaluate the internal dose using all different available techniques during a certain period. The workers were monitored for determination of uranium content in the daily urinary and faecal excretion (collected over a period of 3 consecutive days), chest counting and personal air sampling. The results have shown that at least two types of sensitivity techniques must be used, since there are some sources of uncertainties on the bioassay interpretation, like mixture of uranium compounds intake and different routes of intake. The combination of urine and faeces analysis has shown to be the more appropriate methodology for assessing internal dose in this situation. (author)

  8. Efficient algal bioassay based on short-term photosynthetic response

    International Nuclear Information System (INIS)

    Giddings, J.M.; Stewart, A.J.; O'Neill, R.V.; Gardner, R.H.

    1983-01-01

    A procedure is described for measuring the effects of toxicants on algal photosynthesis (carbon-14 bicarbonate (H 14 CO 3 )uptake) in 4-h experiments. The results for individual aromatic compounds and the water-soluble fraction (WSF) of a synthetic oil are presented as examples of applications of the bioassay. The toxicity of the WSF varied among the seven algal species tested, and the responses of some species were pH-dependent. With Selenastrum capricornutum as the test organism, the bioassay results were unaffected by variations in pH from 7.0 to 9.0, light intensity from 40 to 200 μeinsteins m -2 s -1 , culture density up to 0.5 mg chlorophyll a per litre, and agitation up to 100 rpm. The photosynthesis bioassay is simpler and faster (4 h versus 4 to 14 days), uses smaller culture volumes, and requires less space than static culture-growth tests. One person can conveniently test four materials per day, and the entire procedure, including preparation, exposure, and analysis, takes less than two days. The short incubation time reduces bottle effects such as pH changes, accumulation of metabolic products, nutrient depletion, and bacterial growth. Processes that remove or alter the test materials are also minimized. The data presented here indicate that algal photosynthesis is inhibited at toxicant concentrations similar to those that cause acute effects in aquatic animals. A model of a pelagic ecosystem is used to demonstrate that even temporary (seven-day) inhibition of algal photosynthesis can have a measurable impact on other trophic levels, particularly if the other trophic levels are also experiencing toxic effects. 25 references, 6 figures, 1 table

  9. Fluorescent bioassays for toxic metals in milk and yoghurt

    Directory of Open Access Journals (Sweden)

    Siddiki Mohammad Shohel

    2012-10-01

    Full Text Available Abstract Background From a human health viewpoint, contaminated milk and its products could be a source of long-term exposure to toxic metals. Simple, inexpensive, and on-site assays would enable constant monitoring of their contents. Bioassays that can measure toxic metals in milk or yoghurt might reduce the risk. For this purpose, the green fluorescent protein (GFP-tagged trans factors, ArsR-GFP and CadC-GFP, together with their cis elements were used to develop such bioassays. Results ArsR-GFP or CadC-GFP, which binds either toxic metal or DNA fragment including cis element, was directly mixed with cow’s milk or yoghurt within a neutral pH range. The fluorescence of GFP, which is reflected by the association/dissociation ratio between cis element and trans factor, significantly changed with increasing externally added As (III or Cd (II whereas smaller responses to externally added Pb (II and Zn (II were found. Preparation and dilution of whey fraction at low pH were essential to intrinsic zinc quantification using CadC-GFP. Using the extraction procedure and bioassay, intrinsic Zn (II concentrations ranging from 1.4 to 4.8 mg/l for milk brands and from 1.2 to 2.9 mg/kg for yoghurt brands were determined, which correlated to those determined using inductively coupled plasma atomic emission spectroscopy. Conclusions GFP-tagged bacterial trans factors and cis elements can work in the neutralized whole composition and diluted whey fraction of milk and yoghurt. The feature of regulatory elements is advantageous for establishment of simple and rapid assays of toxic metals in dairy products.

  10. Lanthanide-doped upconverting phosphors for bioassay and therapy

    Science.gov (United States)

    Guo, Huichen; Sun, Shiqi

    2012-10-01

    Lanthanide-doped fluorescent materials have gained increasing attention in recent years due to their unique luminescence properties which have led to their use in wide-ranging fields including those of biological applications. Aside from being used as agents for in vivo imaging, lanthanide-doped fluorescent materials also present many advantages for use in bioassays and therapy. In this review, we summarize the applications of lanthanide-doped up-converting phosphors (UCPs) in protein and gene detection, as well as in photodynamic and gene therapy in recent years, and outline their future potential in biological applications. The current report could serve as a reference for researchers in relevant fields.

  11. BIOSAY: a computer program to store and report bioassay data

    International Nuclear Information System (INIS)

    Williams, G.E.; Parlagreco, J.R.

    1978-12-01

    BIOSAY is a computer program designed to manipulate bioassay data. Using BIOSAY, the Dosimetry Group can generate a report suitable for an individual's dosimetry record. A second copy of this report may be mailed to the individual who provided the sample or the area health physicist for review. BIOSAY also contains a data sorting option which allows all the results for particular individuals, or groups of individuals with common attributes, to be separated from the data base. The computer code is written in a conversational tone with aids which make it usable by even casual users of the computer system

  12. Field and Bioassay Indicators for Internal Dose Intervention Therapy

    International Nuclear Information System (INIS)

    Carbaugh, Eugene H.

    2007-01-01

    Guidance is presented that is used at the U.S. Department of Energy Hanford Site to identify the potential need for medical intervention in response to intakes of radioactivity. The guidance, based on ICRP Publication 30 models and committed effective dose equivalents of 20 mSv and 200 mSv, is expressed as numerical workplace measurements and derived first-day bioassay results for large intakes. It is used by facility radiation protection staff and on-call dosimetry support staff during the first few days following an intake

  13. Herbicide impact on Hormosira banksii gametes measured by fluorescence and germination bioassays

    Energy Technology Data Exchange (ETDEWEB)

    Seery, Cliff R. [Institute for Water and Environmental Resource Management, Department of Environmental Sciences, University of Technology, Sydney, Westbourne Street, Gore Hill, 2065 NSW (Australia); Gunthorpe, Leanne [Primary Industries Research Victoria (PIRVic), VIC (Australia); Ralph, Peter J. [Institute for Water and Environmental Resource Management, Department of Environmental Sciences, University of Technology, Sydney, Westbourne Street, Gore Hill, 2065 NSW (Australia)]. E-mail: peter.ralph@uts.edu.au

    2006-03-15

    The innovative bioassay described here involves chlorophyll a fluorescence measurements of gametes from the macroalgae, Hormosira banksii, where gametes (eggs) were exposed to Diuron, Irgarol and Bromacil. Response was assessed as percent inhibition from control of effective quantum yield ({delta}F/Fm') of photosystem II, herein referred to as % PSII Inhibition. This was measured with the dual-channelled pulse amplitude modulated (PAM) fluorometer, ToxY-PAM. The fluorescence bioassay was run simultaneously with an established H. banksii germination bioassay to compare sensitivity, precision, and time-to-result. The fluorescence bioassay gave highly sensitive results evidenced by EC{sub 5}s (% PSII Inhibition) for Diuron, Irgarol and Bromacil being three, four and three orders of magnitude (respectively) lower than EC{sub 5}s generated from the germination bioassays. Precision of the fluorescence bioassay was demonstrated with low coefficient of variations (<30%) for all three toxicants. With regard to time, the fluorescence bioassay gave results within 6 h, as opposed to more than 50 h for the germination bioassay. - Chlorophyll a fluorescence measurements form the basis of a macroalgal bioassay with many advantages over germination-based methods.

  14. Herbicide impact on Hormosira banksii gametes measured by fluorescence and germination bioassays

    International Nuclear Information System (INIS)

    Seery, Cliff R.; Gunthorpe, Leanne; Ralph, Peter J.

    2006-01-01

    The innovative bioassay described here involves chlorophyll a fluorescence measurements of gametes from the macroalgae, Hormosira banksii, where gametes (eggs) were exposed to Diuron, Irgarol and Bromacil. Response was assessed as percent inhibition from control of effective quantum yield (ΔF/Fm') of photosystem II, herein referred to as % PSII Inhibition. This was measured with the dual-channelled pulse amplitude modulated (PAM) fluorometer, ToxY-PAM. The fluorescence bioassay was run simultaneously with an established H. banksii germination bioassay to compare sensitivity, precision, and time-to-result. The fluorescence bioassay gave highly sensitive results evidenced by EC 5 s (% PSII Inhibition) for Diuron, Irgarol and Bromacil being three, four and three orders of magnitude (respectively) lower than EC 5 s generated from the germination bioassays. Precision of the fluorescence bioassay was demonstrated with low coefficient of variations (<30%) for all three toxicants. With regard to time, the fluorescence bioassay gave results within 6 h, as opposed to more than 50 h for the germination bioassay. - Chlorophyll a fluorescence measurements form the basis of a macroalgal bioassay with many advantages over germination-based methods

  15. Alterations in mtDNA, gastric carcinogenesis and early diagnosis.

    Science.gov (United States)

    Rodrigues-Antunes, S; Borges, B N

    2018-05-26

    Gastric cancer remains one of the most prevalent cancers in the world. Due to this, efforts are being made to improve the diagnosis of this neoplasm and the search for molecular markers that may be involved in its genesis. Within this perspective, the mitochondrial DNA is considered as a potential candidate, since it has several well documented changes and is readily accessible. However, numerous alterations have been reported in mtDNA, not facilitating the visualization of which alterations and molecular markers are truly involved with gastric carcinogenesis. This review presents a compilation of the main known changes relating mtDNA to gastric cancer and their clinical significance.

  16. Perspectives in the paradigm of radiation-induced carcinogenesis

    International Nuclear Information System (INIS)

    Sugakhara, T.; Vatanabe, M.; Niva, O.; Nikajdo, O.

    1995-01-01

    Carcinogenesis is analysed as a multistage process consisting of initiation, promotion and progression. This model includes the mutation of oncogenes and the loss of hetrezygosity by tumor-suppressor genes. The threshold concept of radiation cancerogenesis is proposed, under which ionizing radiation can induce in somatic cell genetic effects a s result of DNA damage and epigenetic changes as well. The epigenetic changes (through DNA or cytoplasma) can be stabilized as mutations observed in many cancer cells and play a dominant role in radiation cancerogenesis induction. The ration of epigenetic and genetic effects largely depends on radiation doses

  17. Bacterial infection increases risk of carcinogenesis by targeting mitochondria

    DEFF Research Database (Denmark)

    Strickertsson, Jesper A.B.; Desler, Claus; Rasmussen, Lene Juel

    2017-01-01

    pathways, and compares the impact of the bacterial alteration of mitochondrial function to that of cancer. Bacterial virulence factors have been demonstrated to induce mutations of mitochondrial DNA (mtDNA) and to modulate DNA repair pathways of the mitochondria. Furthermore, virulence factors can induce...... or impair the intrinsic apoptotic pathway. The effect of bacterial targeting of mitochondria is analogous to behavior of mitochondria in a wide array of tumours, and this strongly suggests that mitochondrial targeting of bacteria is a risk factor for carcinogenesis....

  18. The PTEN/NRF2 Axis Promotes Human Carcinogenesis

    DEFF Research Database (Denmark)

    Rojo, Ana I; Rada, Patricia; Mendiola, Marta

    2014-01-01

    and tumorigenic advantage. Tissue microarrays from endometrioid carcinomas showed that 80% of PTEN-negative tumors expressed high levels of NRF2 or its target heme oxygenase-1 (HO-1). INNOVATION: These results uncover a new mechanism of oncogenic activation of NRF2 by loss of its negative regulation by PTEN/GSK-3....../β-TrCP that may be relevant to a large number of tumors, including endometrioid carcinomas. CONCLUSION: Increased activity of NRF2 due to loss of PTEN is instrumental in human carcinogenesis and represents a novel therapeutic target. Antioxid. Redox Signal. 21, 2498-2514....

  19. Etiologic related studies of ultraviolet light-mediated carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Black, H S; Chan, J T

    1976-01-01

    Comparisons were made of cholesterol-5..cap alpha.. 6..cap alpha..-epoxide (CAE) levels in skin of hairless mice maintained on a regular or antioxidant supplemented diet and receiving chronic ultraviolet light (UVL) radiation over an 18-week period. Cholesterol-5..cap alpha.., 6..cap alpha..-epoxide levels in skin of animals on antioxidant supplemented diet, while reaching a peak four weeks after that of animals on regular diet, thereafter were consistently higher. Dietary antioxidants nevertheless had an inhibitory effect on UVL-induced tumors. These data are inconsistent with the theory of CAE involvement as an ultimate carcinogen in UVL-mediated carcinogenesis.

  20. Abdominal multi-organ segmentation from CT images using conditional shape-location and unsupervised intensity priors.

    Science.gov (United States)

    Okada, Toshiyuki; Linguraru, Marius George; Hori, Masatoshi; Summers, Ronald M; Tomiyama, Noriyuki; Sato, Yoshinobu

    2015-12-01

    This paper addresses the automated segmentation of multiple organs in upper abdominal computed tomography (CT) data. The aim of our study is to develop methods to effectively construct the conditional priors and use their prediction power for more accurate segmentation as well as easy adaptation to various imaging conditions in CT images, as observed in clinical practice. We propose a general framework of multi-organ segmentation which effectively incorporates interrelations among multiple organs and easily adapts to various imaging conditions without the need for supervised intensity information. The features of the framework are as follows: (1) A method for modeling conditional shape and location (shape-location) priors, which we call prediction-based priors, is developed to derive accurate priors specific to each subject, which enables the estimation of intensity priors without the need for supervised intensity information. (2) Organ correlation graph is introduced, which defines how the conditional priors are constructed and segmentation processes of multiple organs are executed. In our framework, predictor organs, whose segmentation is sufficiently accurate by using conventional single-organ segmentation methods, are pre-segmented, and the remaining organs are hierarchically segmented using conditional shape-location priors. The proposed framework was evaluated through the segmentation of eight abdominal organs (liver, spleen, left and right kidneys, pancreas, gallbladder, aorta, and inferior vena cava) from 134 CT data from 86 patients obtained under six imaging conditions at two hospitals. The experimental results show the effectiveness of the proposed prediction-based priors and the applicability to various imaging conditions without the need for supervised intensity information. Average Dice coefficients for the liver, spleen, and kidneys were more than 92%, and were around 73% and 67% for the pancreas and gallbladder, respectively. Copyright © 2015

  1. Phase 3 trial of defibrotide for the treatment of severe veno-occlusive disease and multi-organ failure.

    Science.gov (United States)

    Richardson, Paul G; Riches, Marcie L; Kernan, Nancy A; Brochstein, Joel A; Mineishi, Shin; Termuhlen, Amanda M; Arai, Sally; Grupp, Stephan A; Guinan, Eva C; Martin, Paul L; Steinbach, Gideon; Krishnan, Amrita; Nemecek, Eneida R; Giralt, Sergio; Rodriguez, Tulio; Duerst, Reggie; Doyle, John; Antin, Joseph H; Smith, Angela; Lehmann, Leslie; Champlin, Richard; Gillio, Alfred; Bajwa, Rajinder; D'Agostino, Ralph B; Massaro, Joseph; Warren, Diane; Miloslavsky, Maja; Hume, Robin L; Iacobelli, Massimo; Nejadnik, Bijan; Hannah, Alison L; Soiffer, Robert J

    2016-03-31

    Hepatic veno-occlusive disease (VOD), also called sinusoidal obstruction syndrome (SOS), is a potentially life-threatening complication of hematopoietic stem cell transplantation (HSCT). Untreated hepatic VOD/SOS with multi-organ failure (MOF) is associated with >80% mortality. Defibrotide has shown promising efficacy treating hepatic VOD/SOS with MOF in phase 2 studies. This phase 3 study investigated safety and efficacy of defibrotide in patients with established hepatic VOD/SOS and advanced MOF. Patients (n = 102) given defibrotide 25 mg/kg per day were compared with 32 historical controls identified out of 6867 medical charts of HSCT patients by blinded independent reviewers. Baseline characteristics between groups were well balanced. The primary endpoint was survival at day +100 post-HSCT; observed rates equaled 38.2% in the defibrotide group and 25% in the controls (23% estimated difference; 95.1% confidence interval [CI], 5.2-40.8;P= .0109, using a propensity-adjusted analysis). Observed day +100 complete response (CR) rates equaled 25.5% for defibrotide and 12.5% for controls (19% difference using similar methodology; 95.1% CI, 3.5-34.6;P= .0160). Defibrotide was generally well tolerated with manageable toxicity. Related adverse events (AEs) included hemorrhage or hypotension; incidence of common hemorrhagic AEs (including pulmonary alveolar [11.8% and 15.6%] and gastrointestinal bleeding [7.8% and 9.4%]) was similar between the defibrotide and control groups, respectively. Defibrotide was associated with significant improvement in day +100 survival and CR rate. The historical-control methodology offers a novel, meaningful approach for phase 3 evaluation of orphan diseases associated with high mortality. This trial was registered at www.clinicaltrials.gov as #. © 2016 by The American Society of Hematology.

  2. Compatibility of hydroxypropyl-β-cyclodextrin with algal toxicity bioassays

    International Nuclear Information System (INIS)

    Fai, Patricia Bi; Grant, Alastair; Reid, Brian J.

    2009-01-01

    Numerous reports have indicated that hydrophobic organic compound bioaccessibility in sediment and soil can be determined by extraction using aqueous hydroxypropyl-β-cyclodextrin (HPCD) solutions. This study establishes the compatibility of HPCD with Selenastrum capricornutum and assesses whether its presence influences the toxicity of reference toxicants. Algal growth inhibition (72 h) showed no significant (P > 0.05) difference at HPCD concentrations up to and including 20 mM. HPCD presence did not influence the toxicity of the inorganic reference toxicant (ZnSO 4 ), with IC50 values of 0.82 μM and 0.85 μM, in the presence and absence of HPCD (20 mM), respectively. However, HPCD presence (20 mM) reduced the toxicity of 2,4-dichlorophenol and the herbicides diuron and isoproturon. These reductions were attributed to inclusion complex formation between the toxicants and the HPCD cavity. Liberation of complexed toxicants, by sample manipulation prior to toxicity assessment, is proposed to provide a sensitive, high throughput, bioassay that reflects compound bioaccessibility. - Compatibility of the biomimetic HPCD extraction method with algal cell growth inhibition bioassays to assess toxicity of reference toxicants and environmental relevant herbicides

  3. Progress in herbicide determination with the thylakoid bioassay.

    Science.gov (United States)

    Trapmann, S; Etxebarria, N; Schnabl, H; Grobecker, K H

    1998-01-01

    Chloroplast thylakoids are used as biological units to determine herbicides in different kinds of water samples as well as in aqueous extracts of compost, soil or food samples. The thylakoid bioassay shows clearly inhibition of fluorescence yield in the presence of photosystem II specific herbicides. Due to this method the ecotoxicological effect of samples with unknown pollutants can be tested fast and cost effective. It has been proven that all photosynthetic active compounds are recorded at the same time because only additive interactions occur. Therefore, the contamination level can be expressed as cumulative parameter for photosystem II active substances. Application was improved clearly by the addition of the radical scavenger sodium ascorbate to the isolation media and by a higher concentration of the measuring medium. A new data evaluation method is described yielding in a lower detection limit of 0.4 microg diuron/1. The guidelines for the quality of water for human consumption with an allowable concentration of pesticides in groups is 0,5 microg/1 and can be controlled with the thylakoid bioassay without performing any preconcentration steps.

  4. Compatibility of hydroxypropyl-{beta}-cyclodextrin with algal toxicity bioassays

    Energy Technology Data Exchange (ETDEWEB)

    Fai, Patricia Bi; Grant, Alastair [School of Environmental Sciences, University of East Anglia, Norwich NR4 7TJ (United Kingdom); Reid, Brian J. [School of Environmental Sciences, University of East Anglia, Norwich NR4 7TJ (United Kingdom)], E-mail: b.reid@uea.ac.uk

    2009-01-15

    Numerous reports have indicated that hydrophobic organic compound bioaccessibility in sediment and soil can be determined by extraction using aqueous hydroxypropyl-{beta}-cyclodextrin (HPCD) solutions. This study establishes the compatibility of HPCD with Selenastrum capricornutum and assesses whether its presence influences the toxicity of reference toxicants. Algal growth inhibition (72 h) showed no significant (P > 0.05) difference at HPCD concentrations up to and including 20 mM. HPCD presence did not influence the toxicity of the inorganic reference toxicant (ZnSO{sub 4}), with IC50 values of 0.82 {mu}M and 0.85 {mu}M, in the presence and absence of HPCD (20 mM), respectively. However, HPCD presence (20 mM) reduced the toxicity of 2,4-dichlorophenol and the herbicides diuron and isoproturon. These reductions were attributed to inclusion complex formation between the toxicants and the HPCD cavity. Liberation of complexed toxicants, by sample manipulation prior to toxicity assessment, is proposed to provide a sensitive, high throughput, bioassay that reflects compound bioaccessibility. - Compatibility of the biomimetic HPCD extraction method with algal cell growth inhibition bioassays to assess toxicity of reference toxicants and environmental relevant herbicides.

  5. Multi-organ dysfunction in bodybuilding possibly caused by prolonged hypercalcemia due to multi-substance abuse: case report and review of literature.

    Science.gov (United States)

    Schäfer, C N; Guldager, H; Jørgensen, H L

    2011-01-01

    A 26-year-old male bodybuilder was admitted to the surgical department of a Danish community hospital for hematemesis. During the clinical interview, he revealed that he had recently finished a course of anabolic steroids and erythropoietin. The patient also had a previous history of infections and chronic ulcers due to paraffin-oil injections in both upper arms one year before. Over the course of the next few hours, the patient developed signs of multi-organ dysfunction, including pancreatitis, hemorrhagic gastritis, nephropathy with temporary anuria, and respiratory insufficiency, and was transferred to the ICU. After manometric monitoring on the patient's upper arms proved difficult, invasive blood pressure monitoring was used and revealed that the patient was in a state of hypertensive crisis. This case of multi-organ dysfunction was possibly caused by multi-substance-induced hypercalcemia. © Georg Thieme Verlag KG Stuttgart · New York.

  6. [THE ROLE OF ESTROGENS IN THE CARCINOGENESIS OF LUNG CANCER].

    Science.gov (United States)

    Uchikova, E; Uchikov, A; Dimitrakova, E; Uchikov, P

    2016-01-01

    Morbidity and mortality from lung cancer has dramatically increased in women as compared to men over the past few years. Historically, smoking has been considered the major risk factor for lung cancer regardless of gender. Several recent lines of evidence implicate gender differences in the observed differences in prevalence and histologic type which cannot be explained based on the carcinogenic action of nicotine. Several recent studies underscore the importance of reproductive and hormonal factors in the carcinogenesis of lung cancer Lung cancer morbidity and mortality in Bulgaria was 16.2/100000 women and 14.6/ 100000 women, resp. Lung cancer morbidity in Europe was 39/100000 women. Lung cancer is extremely sensitive to estrogens. The latter act directly or as effect modifiers for the relationship between smoking and lung cancer. Further research examining the relationship between serum estrogen levels and the estrogen receptor expression in normal and tumor lung tissue samples can help elucidate the importance of reproductive and hormonal (exogenous and endogenous) factors in the carcinogenesis of lung cancer.

  7. Is radiation an appropriate model for chemical mutagenesis and carcinogenesis

    International Nuclear Information System (INIS)

    Bond, V.P.

    1982-01-01

    This chapter attempts to show why the quadratic, or ''linear quadratic,'' relationship holds for organ dose-single cell radiation effects, and to explore the extension of this relationship to chemical exposures in general. Demonstrates that although the ''αD + βD 2 relationship'' may be unexpected for normal pharmacologicalmedical dose-response relationships, a linear, no-threshold curve of this kind is expected for all stochastic-type (accidental or risk) situations with health consequences (e.g. all common accidents) including exposure to ''low-level radiation'' (LLR). Discusses the stochastic or risk approach, relevant radiobiology, and the stochastic for chemicals. Assumes that even though actual mutational rates cannot be expected to apply to the relevance of Tradescantia or any other single cell system as a predictor for mutagenesis and carcinogenesis in animals and man, the cardinal principles of genetics largely transcend species and the particular environment in which the cell is located. Concludes that with regard to LLR, the curve shapes and other relationships developed for Tradescantia would be expected to apply in principle to animal and human mutagenesis and carcinogenesis

  8. Etoricoxib in the Prevention of Rat Mammary Carcinogenesis

    Directory of Open Access Journals (Sweden)

    P. Orendáš

    2007-01-01

    Full Text Available Several experimental studies suggest that non-steroidal antiinflammatory drugs have chemopreventive effects in mammary carcinogenesis. In this study, tumour suppressive effects of a selective inhibitor of cyclooxygenase-2 (COX-2 etoricoxib in the prevention of N-methyl-Nnitrosourea (NMU-induced mammary carcinogenesis in Sprague-Dawley rats were evaluated. Etoricoxib was administered in the diet, at two concentrations: 1 0.01 mg/g (ETO 0.001% and 2 0.025 mg/g (ETO 0.0025%. Although the chemopreventive effects were not statistically significant, remarkable tumour suppressive effects with the concentration of ETO 0.0025% were recorded. The incidence decreased by 4.31% and tumour frequency per group decreased by 6.67% when compared to the control group. Latency (the period from carcinogen administration to the first tumour appearance increased by 7.28% in dose-dependent manner. The results of our experiments point to dose-dependent tumour suppressive effects of a higher concentration of etoricoxib (ETO 0.0025% when compared to the control group. They suggest that higher etoricoxib concentrations may enhance its tumour suppressive effects.

  9. Experimental photoimmunology: immunologic ramifications of UV-induced carcinogenesis

    International Nuclear Information System (INIS)

    Daynes, R.A.; Bernhard, E.J.; Gurish, M.F.; Lynch, D.H.

    1981-01-01

    The use of animal model systems to investigate the sequence of events which lead to the induction and progression of skin tumors following chronic ultraviolet light (UVL) exposure has clearly shown that the direct mutagenic effects of UVL is only one of the components involved in this process. In spite of the fact that overt carcinogenesis is only one of the many effects produced by UV light, most hypotheses as to the mechanism by which UVL can cause the mutations necessary to achieve the transformed phenotype have focused on the direct effects of UVL on DNA and the generation of carcinogenic compounds. Investigations during the last 5 yr, however, have clearly demonstrated that immunologic factors are also critically important in the pathogenesis of UV-induced skin cancers. A complete understanding of UV-carcinogenesis must therefore consider the mechanisms which allow the transformed cell to evade immunologic rejection by the host in addition to those aspects which deal with conversion of a normal cell to a cancer cell. It is the object of this review to provide both a historical account of the work which established the immunologic consequences of chronic UVL exposure and the results of recent experiments designed to investigate the kinetics and mechanisms by which UVL affects the immunologic apparatus. In addition, a hypothetical model is presented to explain the sequence of events which ultimately lead to the emergence of the suppressor T-cells which regulate antitumor immune responses

  10. Inherent aerobic capacity-dependent differences in breast carcinogenesis.

    Science.gov (United States)

    Thompson, Henry J; Jones, Lee W; Koch, Lauren G; Britton, Steven L; Neil, Elizabeth S; McGinley, John N

    2017-09-01

    Although regular physical activity is associated with improvement in aerobic capacity and lower breast cancer risk, there are heritable sets of traits that affect improvement in aerobic capacity in response to physical activity. Although aerobic capacity segregates risk for a number of chronic diseases, the effect of the heritable component on cancer risk has not been evaluated. Therefore, we investigated breast carcinogenesis in rodent models of heritable fitness in the absence of induced physical activity. Female offspring of N:NIH rats selectively bred for low (LIAC) or high (HIAC) inherent aerobic capacity were injected intraperitoneally with 1-methyl-1-nitrosurea (70 mg/kg body wt). At study termination 33 weeks post-carcinogen, cancer incidence (14.0 versus 47.3%; P < 0.001) and multiplicity (0.18 versus 0.85 cancers per rat; P < 0.0001) were significantly decreased in HIAC versus LIAC rats, respectively. HIAC had smaller visceral and subcutaneous body fat depots than LIAC and activity of two proteins that regulated the mammalian target of rapamycin, protein kinase B (Akt), and adenosine monophosphate-activated protein kinase were suppressed and activated, respectively, in HIAC. Although many factors distinguish between HIAC and LIAC, it appears that the protective effect of HIAC against breast carcinogenesis is mediated, at least in part, via alterations in core metabolic signaling pathways deregulated in the majority of human breast cancers. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  11. Glutaminolysis and carcinogenesis of oral squamous cell carcinoma.

    Science.gov (United States)

    Cetindis, Marcel; Biegner, Thorsten; Munz, Adelheid; Teriete, Peter; Reinert, Siegmar; Grimm, Martin

    2016-02-01

    Glutaminolysis is a crucial factor for tumor metabolism in the carcinogenesis of several tumors but has not been clarified for oral squamous cell carcinoma (OSCC) yet. Expression of glutaminolysis-related solute carrier family 1, member 5 (SLC1A5)/neutral amino acid transporter (ASCT2), glutaminase (GLS), and glutamate dehydrogenase (GLDH) was analyzed in normal oral mucosa (n = 5), oral precursor lesions (simple hyperplasia, n = 11; squamous intraepithelial neoplasia, SIN I-III, n = 35), and OSCC specimen (n = 42) by immunohistochemistry. SLC1A5/ASCT2 and GLS were significantly overexpressed in the carcinogenesis of OSCC compared with normal tissue, while GLDH was weakly detected. Compared with SIN I-III SLC1A5/ASCT2 and GLS expression were significantly increased in OSCC. GLDH expression did not significantly differ from SIN I-III compared with OSCC. This study shows the first evidence of glutaminolysis-related SLC1A5/ASCT2, GLS, and GLDH expression in OSCC. The very weak GLDH expression indicates that glutamine metabolism is rather related to nucleotide or protein/hexosamine biosynthesis or to the function as an antioxidant (glutathione) than to energy production or generation of lactate through entering the tricarboxylic acid cycle. Overcoming glutaminolysis by targeting c-Myc oncogene (e.g. by natural compounds) and thereby cross-activation of mammalian target of rapamycin complex 1 or SLC1A5/ASCT2, GLS inhibitors may be a useful strategy to sensitize cancer cells to common OSCC cancer therapies.

  12. Sewage sludge does not induce genotoxicity and carcinogenesis

    Science.gov (United States)

    Silva, Paula Regina Pereira; Barbisan, Luis Fernando; Dagli, Maria Lúcia Zaidan; Saldiva, Paulo Hilário Nascimento

    2012-01-01

    Through a series of experiments, the genotoxic/mutagenic and carcinogenic potential of sewage sludge was assessed. Male Wistar rats were randomly assigned to four groups: Group 1 - negative control; Group 2 - liver carcinogenesis initiated by diethylnitrosamine (DEN; 200 mg/kg i.p.); Group 3 and G4-liver carcinogenesis initiated by DEN and fed 10,000 ppm or 50,000 ppm of sewage sludge. The animals were submitted to a 70% partial hepatectomy at the 3rd week. Livers were processed for routine histological analysis and immunohistochemistry, in order to detect glutathione S-transferase positive altered hepatocyte foci (GST-P+ AHF). Peripheral blood samples for the comet assay were obtained from the periorbital plexus immediately prior to sacrificing. Polychromatic erythrocytes (PCEs) were analyzed in femoral bone-marrow smears, and the frequencies of those micronucleated (MNPCEs) registered. There was no sewage-sludge-induced increase in frequency of either DNA damage in peripheral blood leucocytes, or MNPCEs in the femoral bone marrow. Also, there was no increase in the levels of DNA damage, in the frequency of MNPCEs, and in the development of GST-P AHF when compared with the respective control group. PMID:23055806

  13. Role of the chronic bacterial infection in urinary bladder carcinogenesis

    International Nuclear Information System (INIS)

    Higgy, N.A.

    1985-01-01

    The purpose of this thesis was to determine whether or not bacterial infection of the urinary bladder had a role in urinary bladder carcinogenesis. To investigate this proposition, four separate studies were conducted. The first study developed an experimental animal model where bacterial infection of the urinary bladder could be introduced and maintained for a period in excess of one year. The method of infection, inoculation of bacteria (Escherichia coli type 04) subserosally into the vesical wall, successfully caused persistent infection in the majority of animals. In the second study the temporal effects of bacterial infection on the induction of urothelial ornithine decarboxylase (ODC) and 3 H-thymidine uptake and DNA synthesis were examined. Bacterial infection of the urinary bladder induced urothelial ODC with a peak in enzyme activity 6 hr after infection. 3 H-Thymidine uptake and DNA synthesis peaked 48 hr after infection and coincided with the urothelial hyperplasia that occurred in response to the infection. In the third study the specific bladder carcinogen N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) was given to rats concurrent with the urinary bacterial infection. In the fourth study rats were administered sodium nitrate and either dibutylamine or piperazine in the drinking water. The infected group developed bladder tumors while none were detected in the non-infected rats. From these studies it may be concluded that bacterial infection may have a significant role in the process of urinary bladder carcinogenesis

  14. Thrombospondin-1 in a Murine Model of Colorectal Carcinogenesis.

    Directory of Open Access Journals (Sweden)

    Zenaida P Lopez-Dee

    Full Text Available Colorectal Cancer (CRC is one of the late complications observed in patients suffering from inflammatory bowel diseases (IBD. Carcinogenesis is promoted by persistent chronic inflammation occurring in IBD. Understanding the mechanisms involved is essential in order to ameliorate inflammation and prevent CRC. Thrombospondin 1 (TSP-1 is a multidomain glycoprotein with important roles in angiogenesis. The effects of TSP-1 in colonic tumor formation and growth were analyzed in a model of inflammation-induced carcinogenesis. WT and TSP-1 deficient mice (TSP-1-/- of the C57BL/6 strain received a single injection of azoxymethane (AOM and multiple cycles of dextran sodium sulfate (DSS to induce chronic inflammation-related cancers. Proliferation and angiogenesis were histologically analyzed in tumors. The intestinal transcriptome was also analyzed using a gene microarray approach. When the area containing tumors was compared with the entire colonic area of each mouse, the tumor burden was decreased in AOM/DSS-treated TSP-1-/- versus wild type (WT mice. However, these lesions displayed more angiogenesis and proliferation rates when compared with the WT tumors. AOM-DSS treatment of TSP-1-/- mice resulted in significant deregulation of genes involved in transcription, canonical Wnt signaling, transport, defense response, regulation of epithelial cell proliferation and metabolism. Microarray analyses of these tumors showed down-regulation of 18 microRNAs in TSP-1-/- tumors. These results contribute new insights on the controversial role of TSP-1 in cancer and offer a better understanding of the genetics and pathogenesis of CRC.

  15. International Activities in Radiation-Induced Carcinogenesis. Survey Paper

    Energy Technology Data Exchange (ETDEWEB)

    Komarov, E. [World Health Organization, Geneva (Switzerland)

    1969-11-15

    During the past 10 years special attention has been paid to the problem of late effects of radiation and in particular to radiation-induced carcinogenesis and leukaemogenesis. In the UNSCEAR report of 1958-1962 this.problem was mentioned as being of considerable importance from the point of view of estimation of risk to the population from environmental radiation. In 1964 a special report was prepared by UNSCEAR on radiation- induced carcinogenesis. In the ICRP publication No. 8, a chapter dealing with assessment of somatic risks discussed the problem of leukaemia and other neoplasms and particularly stressed the problem of thyroid carcinoma-and bone sarcoma. WHO panels of experts discussed the problem in 1960-1966 and made some recommendations for international activity in this field. In spite of the amount of scientific attention that has been given in recent years to experimental radiobiology in animals and lower forms, it has become abundantly clear that information directly applicable to humans is woefully inadequate and that there is a desperate need for carefully collected data from man on which to base public health planning and day to day work in radiation protection. This has long been recognized in the technical program of WHO in the emphasis given to the practical importance of epidemiology in human radiobiology and the degree to which it depends upon international collaboration.

  16. The use of bioassays to assess the toxicity of sediment in an acid ...

    African Journals Online (AJOL)

    Exposure of river sediment from 7 sampling sites to these bioassays provided an eco-toxicological estimation of the acute toxicity and chronic toxicity emanating from the contaminated sediments. Physico-chemical analyses revealed higher levels of sediment contamination closer to the mine. The bioassays displayed a ...

  17. Validation of a Novel Bioassay for Low-level Perchlorate Determination

    Science.gov (United States)

    2014-04-01

    was not attractive, since these reduce PMS2 , and it was thought they would interfere with the stoichiometry of NADH and perchlorate in the bioassay...these reduce PMS2 directly, and would interfere with the stoichiometry of NADH and perchlorate in the bioassay. Thus the only approach that could be

  18. Sample preparation for combined chemical analysis and bioassay application in water quality assessment

    NARCIS (Netherlands)

    Kolkman, A.; Schriks, M.; Brand, W; Bäuerlein, P.S.; van der Kooi, M.M.E.; van Doorn, R.H.; Emke, E.; Reus, A.; van der Linden, S.; de Voogt, P.; Heringa, M.B.

    2013-01-01

    The combination of in vitro bioassays and chemical screening can provide a powerful toolbox to determine biologically relevant compounds in water extracts. In this study, a sample preparation method is evaluated for the suitability for both chemical analysis and in vitro bioassays. A set of 39

  19. The CALUX bioassay: current status of its application to screening food and feed

    NARCIS (Netherlands)

    Hoogenboom, L.A.P.; Goeyens, L.; Carbonnelle, S.; Loco, van J.; Beernaert, H.; Baeyens, W.; Traag, W.A.; Bovee, T.F.H.; Jacobs, G.; Schoeters, G.

    2006-01-01

    The CALUX bioassay is at present the best screening method for dioxins and dioxin-like (dl) polychlorinated biphenyls (PCBs) in food and feed, and the only assay used in routine monitoring and during larger incidents. Furthermore, the use of bioassays in addition to chemical reference methods allows

  20. Selection of gonadotrophin surge attenuating factor phage antibodies by bioassay.

    Science.gov (United States)

    Sorsa-Leslie, Tarja; Mason, Helen D; Harris, William J; Fowler, Paul A

    2005-09-26

    We aimed to combine the generation of "artificial" antibodies with a rat pituitary bioassay as a new strategy to overcome 20 years of difficulties in the purification of gonadotrophin surge-attenuating factor (GnSAF). A synthetic single-chain antibody (Tomlinson J) phage display library was bio-panned with partially purified GnSAF produced by cultured human granulosa/luteal cells. The initial screening with a simple binding immunoassay resulted in 8 clones that were further screened using our in-vitro rat monolayer bioassay for GnSAF. Initially the antibodies were screened as pooled phage forms and subsequently as individual, soluble, single-chain antibody (scAbs) forms. Then, in order to improve the stability of the scAbs for immunopurification purposes, and to widen the range of labelled secondary antibodies available, these were engineered into full-length human immunoglobulins. The immunoglobulin with the highest affinity for GnSAF and a previously described rat anti-GnSAF polyclonal antiserum was then used to immunopurify bioactive GnSAF protein. The two purified preparations were electrophoresed on 1-D gels and on 7 cm 2-D gels (pH 4-7). The candidate GnSAF protein bands and spots were then excised for peptide mass mapping. Three of the scAbs recognised GnSAF bioactivity and subsequently one clone of the purified scAb-derived immunoglobulin demonstrated high affinity for GnSAF bioactivity, also binding the molecule in such as way as to block its bioactivity. When used for repeated immunopurification cycles and then Western blot, this antibody enabled the isolation of a GnSAF-bioactive protein band at around 66 kDa. Similar results were achieved using the rat anti-GnSAF polyclonal antiserum. The main candidate molecules identified from the immunopurified material by excision of 2-D gel protein spots was human serum albumin precursor and variants. This study demonstrates that the combination of bioassay and phage display technologies is a powerful tool in the

  1. Dietary tomato and lycopene impact androgen signaling- and carcinogenesis-related gene expression during early TRAMP prostate carcinogenesis

    Science.gov (United States)

    Wan, Lei; Tan, Hsueh-Li; Thomas-Ahner, Jennifer M.; Pearl, Dennis K.; Erdman, John W.; Moran, Nancy E.; Clinton, Steven K.

    2014-01-01

    Consumption of tomato products containing the carotenoid lycopene is associated with a reduced risk of prostate cancer. To identify gene expression patterns associated with early testosterone-driven prostate carcinogenesis, which are impacted by dietary tomato and lycopene, wild type (WT) and transgenic adenocarcinoma of the mouse prostate (TRAMP) mice were fed control or tomato- or lycopene-containing diets from 4-10 wk-of-age. Eight-week-old mice underwent sham surgery, castration, or castration followed by testosterone-repletion (2.5 mg/kg/d initiated 1 wk after castration). Ten-wk-old intact TRAMP mice exhibit early multifocal prostatic intraepithelial neoplasia (PIN). Of the 200 prostate cancer-related genes measured by quantitative NanoString®, 189 are detectable, 164 significantly differ by genotype, 179 by testosterone status, and 30 by diet type (Plycopene feeding (Srd5a1) and by tomato-feeding (Srd5a2, Pxn, and Srebf1). Additionally, tomato-feeding significantly reduced expression of genes associated with stem cell features, Aldh1a and Ly6a, while lycopene-feeding significantly reduced expression of neuroendocrine differentiation-related genes, Ngfr and Syp. Collectively, these studies demonstrate a profile of testosterone-regulated genes associated with early stages of prostate carcinogenesis that are potential mechanistic targets of dietary tomato components. Future studies on androgen signaling/metabolism, stem cell features, and neuroendocrine differentiation pathways may elucidate the mechanisms by which dietary tomato and lycopene impact prostate cancer risk. PMID:25315431

  2. The BIDAS: bioassay data analysis software for evaluating radionuclide intake and dose

    International Nuclear Information System (INIS)

    Lee, Tae Young; Lee, Jong Il; Chang, Si Young

    2003-01-01

    The BIDAS (BIoassay Data Analysis Software) computer code was developed for the interpretation of bioassay measurements in terms of the intake and dose using the International Commission on Radiological Protection's(ICRP's) currently recommended respiratory tract, GI-tract and biokinetic models to describe the behavior of the radioactive materials within the body. The code consists of a data base module to the manage bioassay data, a data base module containing the predicted bioassay quantities of each radionuclide, and a computational module to the estimate radionuclide intake and dose from either an acute or a chronic exposure based on the measured bioassay quantities. This paper describes the features of the code as well as the results of the BIDAS validation

  3. Plant genotoxicity: a molecular cytogenetic approach in plant bioassays.

    Science.gov (United States)

    Maluszynska, Jolanta; Juchimiuk, Jolanta

    2005-06-01

    It is important for the prevention of DNA changes caused by environment to understand the biological consequences of DNA damages and their molecular modes of action that lead to repair or alterations of the genetic material. Numerous genotoxicity assay systems have been developed to identify DNA reactive compounds. The available data show that plant bioassays are important tests in the detection of genotoxic contamination in the environment and the establishment of controlling systems. Plant system can detect a wide range of genetic damage, including gene mutations and chromosome aberrations. Recently introduced molecular cytogenetic methods allow analysis of genotoxicity, both at the chromosomal and DNA level. FISH gives a new possibility of the detection and analysis of chromosomal rearrangements in a great detail. DNA fragmentation can be estimated using the TUNEL test and the single cell gel electrophoresis (Comet assay).

  4. Neotropical electric fishes (Gymnotiformes as model organisms for bioassays

    Directory of Open Access Journals (Sweden)

    Milena Ferreira

    2015-04-01

    Full Text Available Electric fishes (Gymnotiformes inhabit Central and South America and form a relatively large group with more than 200 species. Besides a taxonomic challenge due to their still unresolved systematic, wide distribution and the variety of habitats they occupy, these fishes have been intensively studied due to their peculiar use of bioelectricity for electrolocation and communication. Conventional analysis of cells, tissues and organs have been complemented with the studies on the electric organ discharges of these fishes. This review compiles the results of 13 bioassays developed during the last 50 years, which used the quickness, low costs and functionality of the bioelectric data collection of Gymnotiformes to evaluate the effects of environmental contaminants and neuroactive drugs.

  5. Bioassay techniques for {sup 55}Fe in urine samples

    Energy Technology Data Exchange (ETDEWEB)

    Cregan, S P; Leon, J W; Linauskas, S H

    1993-11-01

    Solvent extraction, ion chromatography and several rapid screening methods were developed and evaluated for {sup 55}Fe bioassay applications. Isopropyl ether and TNOA column extractions had radiochemical recoveries exceeding 90%. These were very reproducible with a coefficient of variation less than 5%. Screening techniques investigated included direct counting of ashed urine solids, and Fe(OH){sub 3}. precipitated from urine. The sensitivities (2-50 Bq/d urine) of the screening methods were usually limited by the effective urine volume that could be counted in a liquid scintillation counter. The reference isopropyl ether and chromatography methods could easily achieve sensitivities well below the 1 Bq/d urine output target. (author). 49 refs., 3 tabs., 5 figs.

  6. Bioassay techniques for 55Fe in urine samples

    International Nuclear Information System (INIS)

    Cregan, S.P.; Leon, J.W.; Linauskas, S.H.

    1993-11-01

    Solvent extraction, ion chromatography and several rapid screening methods were developed and evaluated for 55 Fe bioassay applications. Isopropyl ether and TNOA column extractions had radiochemical recoveries exceeding 90%. These were very reproducible with a coefficient of variation less than 5%. Screening techniques investigated included direct counting of ashed urine solids, and Fe(OH) 3 . precipitated from urine. The sensitivities (2-50 Bq/d urine) of the screening methods were usually limited by the effective urine volume that could be counted in a liquid scintillation counter. The reference isopropyl ether and chromatography methods could easily achieve sensitivities well below the 1 Bq/d urine output target. (author). 49 refs., 3 tabs., 5 figs

  7. Toxicity assessment using different bioassays and microbial biosensors.

    Science.gov (United States)

    Hassan, Sedky H A; Van Ginkel, Steven W; Hussein, Mohamed A M; Abskharon, Romany; Oh, Sang-Eun

    2016-01-01

    Toxicity assessment of water streams, wastewater, and contaminated sediments, is a very important part of environmental pollution monitoring. Evaluation of biological effects using a rapid, sensitive and cost effective method can indicate specific information on ecotoxicity assessment. Recently, different biological assays for toxicity assessment based on higher and lower organisms such as fish, invertebrates, plants and algal cells, and microbial bioassays have been used. This review focuses on microbial biosensors as an analytical device for environmental, food, and biomedical applications. Different techniques which are commonly used in microbial biosensing include amperometry, potentiometry, conductometry, voltammetry, microbial fuel cells, fluorescence, bioluminescence, and colorimetry. Examples of the use of different microbial biosensors in assessing a variety of environments are summarized. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Seroprevalensi Toxoplasma gondii pada Kambing dan Bioassay Patogenitasnya pada Kucing

    Directory of Open Access Journals (Sweden)

    Ni Made Yunik Novita Dewi Dewi

    2013-11-01

    Full Text Available Normal 0 false false false EN-US X-NONE X-NONE The study aimed to determine seroprevalence of Toxoplasmosis in goats sloughtered at Kampung Jawa, Denpasar, Bali and to evaluate their pathogenicities through bioassay in cats.One hundred serums and meats of goats were collected. Anti-Toxoplasma gondii antibody was determined using Indirect Haemaglutination (IHA test. The pathogenicity bioassay of Toxoplasma gondii was carried out through inoculating the meats of goats which had seropositive of Toxoplasma gondii to the cats. The pathogenicity was evaluated using the intensity of oocyte sheding from the cats. The result showed that the seroprevalence of Toxoplasmosis was 46%. There was not significant difference between pathogenicity of Toxoplasma gondii in cat inoculated with meat of goat which had a high and low titer of antibody against Toxoplasma gondii. /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; text-align:justify; line-height:150%; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin;}

  9. Evolving BioAssay Ontology (BAO): modularization, integration and applications.

    Science.gov (United States)

    Abeyruwan, Saminda; Vempati, Uma D; Küçük-McGinty, Hande; Visser, Ubbo; Koleti, Amar; Mir, Ahsan; Sakurai, Kunie; Chung, Caty; Bittker, Joshua A; Clemons, Paul A; Brudz, Steve; Siripala, Anosha; Morales, Arturo J; Romacker, Martin; Twomey, David; Bureeva, Svetlana; Lemmon, Vance; Schürer, Stephan C

    2014-01-01

    The lack of established standards to describe and annotate biological assays and screening outcomes in the domain of drug and chemical probe discovery is a severe limitation to utilize public and proprietary drug screening data to their maximum potential. We have created the BioAssay Ontology (BAO) project (http://bioassayontology.org) to develop common reference metadata terms and definitions required for describing relevant information of low-and high-throughput drug and probe screening assays and results. The main objectives of BAO are to enable effective integration, aggregation, retrieval, and analyses of drug screening data. Since we first released BAO on the BioPortal in 2010 we have considerably expanded and enhanced BAO and we have applied the ontology in several internal and external collaborative projects, for example the BioAssay Research Database (BARD). We describe the evolution of BAO with a design that enables modeling complex assays including profile and panel assays such as those in the Library of Integrated Network-based Cellular Signatures (LINCS). One of the critical questions in evolving BAO is the following: how can we provide a way to efficiently reuse and share among various research projects specific parts of our ontologies without violating the integrity of the ontology and without creating redundancies. This paper provides a comprehensive answer to this question with a description of a methodology for ontology modularization using a layered architecture. Our modularization approach defines several distinct BAO components and separates internal from external modules and domain-level from structural components. This approach facilitates the generation/extraction of derived ontologies (or perspectives) that can suit particular use cases or software applications. We describe the evolution of BAO related to its formal structures, engineering approaches, and content to enable modeling of complex assays and integration with other ontologies and

  10. Potential effects of the herbicide Diuron on mammary and urinary bladder two-stage carcinogenesis in a female Swiss mouse model.

    Science.gov (United States)

    de Moura, Nelci Antunes; Grassi, Tony Fernando; Rodrigues, Maria Aparecida Marchesan; Barbisan, Luís Fernando

    2010-02-01

    The potential promoting effect of Diuron was investigated in a mouse model of mammary and urinary bladder carcinogenesis induced by 7,12-dimethylbenz(a)anthracene (DMBA) and N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). Four-week old female Swiss mice were allocated to five groups: Groups G1-G3 received DMBA (5 x 1.5 mg/mouse) and BBN (8 x 7.5 mg/mouse) and G4 and G5 groups received only vehicles during the first 6 weeks. At week 7, G1 and G5 groups received basal diet and G2, G3 and G4 groups were fed a diet containing Diuron at 1,250, 2,500 and 2,500 ppm, respectively, during 13 weeks. At week 20, the animals were euthanized and the gross tumors were registered. Mammary glands and urinary bladder were processed for histopathological analysis. Samples from non-tumor areas were evaluated for cell proliferation by 5-bromodeoxyuridine labeling index (BrdU-LI%) and apoptosis. Dietary treatment with Diuron at 1,250 and 2,500 ppm significantly increased BrdU-LI% (P Diuron 2,500 ppm (G3). In contrast, in the mammary gland, Diuron feeding for 13 weeks did not significantly alter cell proliferation and apoptosis indexes or the incidence of hyperplastic lesions or neoplasms in the DMBA/BBN-initiated groups. These findings suggest that Diuron is a promoting agent to the urinary bladder but not to the mammary gland in female Swiss mice submitted to a medium-term two-stage carcinogenesis bioassay.

  11. 9 CFR 147.16 - Procedure for the evaluation of mycoplasma reactors by in vivo bio-assay (enrichment).

    Science.gov (United States)

    2010-01-01

    ... mycoplasma reactors by in vivo bio-assay (enrichment). 147.16 Section 147.16 Animals and Animal Products... the evaluation of mycoplasma reactors by in vivo bio-assay (enrichment). This procedure has been shown... publications: (a) Bigland, C. H. and A. J. DaMassa, “A Bio-Assay for Mycoplasma Gallisepticum.” In: United...

  12. Biological parameters for lung cancer in mathematical models of carcinogenesis

    International Nuclear Information System (INIS)

    Jacob, P.; Jacob, V.

    2003-01-01

    Applications of the two-step model of carcinogenesis with clonal expansion (TSCE) to lung cancer data are reviewed, including those on atomic bomb survivors from Hiroshima and Nagasaki, British doctors, Colorado Plateau miners, and Chinese tin miners. Different sets of identifiable model parameters are used in the literature. The parameter set which could be determined with the lowest uncertainty consists of the net proliferation rate gamma of intermediate cells, the hazard h 55 at an intermediate age, and the hazard H? at an asymptotically large age. Also, the values of these three parameters obtained in the various studies are more consistent than other identifiable combinations of the biological parameters. Based on representative results for these three parameters, implications for the biological parameters in the TSCE model are derived. (author)

  13. Altered DNA methylation: a secondary mechanism involved in carcinogenesis.

    Science.gov (United States)

    Goodman, Jay I; Watson, Rebecca E

    2002-01-01

    This review focuses on the role that DNA methylation plays in the regulation of normal and aberrant gene expression and on how, in a hypothesis-driven fashion, altered DNA methylation may be viewed as a secondary mechanism involved in carcinogenesis. Research aimed at discerning the mechanisms by which chemicals can transform normal cells into frank carcinomas has both theoretical and practical implications. Through an increased understanding of the mechanisms by which chemicals affect the carcinogenic process, we learn more about basic biology while, at the same time, providing the type of information required to make more rational safety assessment decisions concerning their actual potential to cause cancer under particular conditions of exposure. One key question is: does the mechanism of action of the chemical in question involve a secondary mechanism and, if so, what dose may be below its threshold?

  14. Collagen mRNA levels changes during colorectal cancer carcinogenesis

    DEFF Research Database (Denmark)

    Skovbjerg, Hanne; Anthonsen, Dorit; Lothe, Inger M B

    2009-01-01

    BACKGROUND: Invasive growth of epithelial cancers is a complex multi-step process which involves dissolution of the basement membrane. Type IV collagen is a major component in most basement membranes. Type VII collagen is related to anchoring fibrils and is found primarily in the basement membrane...... zone of stratified epithelia. Immunohistochemical studies have previously reported changes in steady-state levels of different alpha(IV) chains in several epithelial cancer types. In the present study we aimed to quantitatively determine the mRNA levels of type IV collagen (alpha1/alpha 4/alpha 6......) and type VII collagen (alpha1) during colorectal cancer carcinogenesis. METHODS: Using quantitative RT-PCR, we have determined the mRNA levels for alpha1(IV), alpha 4(IV), alpha 6(IV), and alpha1(VII) in colorectal cancer tissue (n = 33), adenomas (n = 29) and in normal tissue from the same individuals...

  15. Studies on the multistage nature of radiation carcinogenesis

    International Nuclear Information System (INIS)

    Fry, R.J.M.; Ley, R.D.; Grube, D.; Staffeldt, E.

    1980-01-01

    With low dose levels of ionizing or ultraviolet radiation, the number of initiation events exceeds the number of tumors that grow to a detectable size. Ionizing radiation, which is a complete carcinogen, appears to be a more effective initiator than an enhancer or promoter. However, the initiation and promotion aspects of ionizing radiation have been studied in very few organ systems. In the case of UVR, with or without photosensitizers such as psoralens, the requirement of a relatively large number of exposures for carcinogenesis suggests that the expression of the initiated cells as frank tumors requires a number of events spread out over the time of the development of the tumor. Both ionizing and ultraviolet radiation are, perhaps, underutilized as tools for probing the mechanism of both initiation and promotion

  16. Mechanistic modelling of genetic and epigenetic events in radiation carcinogenesis

    International Nuclear Information System (INIS)

    Andreev, S. G.; Eidelman, Y. A.; Salnikov, I. V.; Khvostunov, I. K.

    2006-01-01

    Methodological problems arise on the way of radiation carcinogenesis modelling with the incorporation of radiobiological and cancer biology mechanistic data. The results of biophysical modelling of different endpoints [DNA DSB induction, repair, chromosome aberrations (CA) and cell proliferation] are presented and applied to the analysis of RBE-LET relationships for radiation-induced neoplastic transformation (RINT) of C3H/10T1/2 cells in culture. Predicted values for some endpoints correlate well with the data. It is concluded that slowly repaired DSB clusters, as well as some kind of CA, may be initiating events for RINT. As an alternative interpretation, it is possible that DNA damage can induce RINT indirectly via epigenetic process. A hypothetical epigenetic pathway for RINT is discussed. (authors)

  17. Oxidative DNA base modifications as factors in carcinogenesis

    International Nuclear Information System (INIS)

    Olinski, R.; Jaruga, P.; Zastawny, T.H.

    1998-01-01

    Reactive oxygen species can cause extensive DNA modifications including modified bases. Some of the DNA base damage has been found to possess premutagenic properties. Therefore, if not repaired, it can contribute to carcinogenesis. We have found elevated amounts of modified bases in cancerous and precancerous tissues as compared with normal tissues. Most of the agents used in anticancer therapy are paradoxically responsible for induction of secondary malignancies and some of them may generate free radicals. The results of our experiments provide evidence that exposure of cancer patients to therapeutic doses of ionizing radiation and anticancer drugs cause base modifications in genomic DNA of lymphocytes. Some of these base damages could lead to mutagenesis in critical genes and ultimately to secondary cancers such as leukemias. This may point to an important role of oxidative base damage in cancer initiation. Alternatively, the increased level of the modified base products may contribute to genetic instability and metastatic potential of tumor cells. (author)

  18. Carcinogenesis related to intense pulsed light and UV exposure

    DEFF Research Database (Denmark)

    Hedelund, L; Lerche, C; Wulf, H C

    2006-01-01

    This study examines whether intense pulsed light (IPL) treatment has a carcinogenic potential itself or may influence ultraviolet (UV)-induced carcinogenesis. Secondly, it evaluates whether UV exposure may influence IPL-induced side effects. Hairless, lightly pigmented mice (n=144) received three...... observation period. Side effects were evaluated clinically. No tumors appeared in untreated control mice or in just IPL-treated mice. Skin tumors developed in UV-exposed mice independently of IPL treatments. The time it took for 50% of the mice to first develop skin tumor ranged from 47 to 49 weeks...... in preoperative UV-exposed mice (p=0.94) and from 22 to 23 weeks in pre- and postoperative UV-exposed mice (p=0.11). IPL rejuvenation of lightly pigmented skin did not induce pigmentary changes (p=1.00). IPL rejuvenation of UV-pigmented skin resulted in an immediate increased skin pigmentation and a subsequent...

  19. Paradoxes in carcinogenesis: New opportunities for research directions

    Directory of Open Access Journals (Sweden)

    Kramer Barnett S

    2007-08-01

    Full Text Available Abstract Background The prevailing paradigm in cancer research is the somatic mutation theory that posits that cancer begins with a single mutation in a somatic cell followed by successive mutations. Much cancer research involves refining the somatic mutation theory with an ever increasing catalog of genetic changes. The problem is that such research may miss paradoxical aspects of carcinogenesis for which there is no likely explanation under the somatic mutation theory. These paradoxical aspects offer opportunities for new research directions that should not be ignored. Discussion Various paradoxes related to the somatic mutation theory of carcinogenesis are discussed: (1 the presence of large numbers of spatially distinct precancerous lesions at the onset of promotion, (2 the large number of genetic instabilities found in hyperplastic polyps not considered cancer, (3 spontaneous regression, (4 higher incidence of cancer in patients with xeroderma pigmentosa but not in patients with other comparable defects in DNA repair, (5 lower incidence of many cancers except leukemia and testicular cancer in patients with Down's syndrome, (6 cancer developing after normal tissue is transplanted to other parts of the body or next to stroma previously exposed to carcinogens, (7 the lack of tumors when epithelial cells exposed to a carcinogen were transplanted next to normal stroma, (8 the development of cancers when Millipore filters of various pore sizes were was inserted under the skin of rats, but only if the holes were sufficiently small. For the latter paradox, a microarray experiment is proposed to try to better understand the phenomena. Summary The famous physicist Niels Bohr said "How wonderful that we have met with a paradox. Now we have some hope of making progress." The same viewpoint should apply to cancer research. It is easy to ignore this piece of wisdom about the means to advance knowledge, but we do so at our peril.

  20. Relevance of CCL3/CCR5 axis in oral carcinogenesis.

    Science.gov (United States)

    da Silva, Janine Mayra; Moreira Dos Santos, Tálita Pollyanna; Sobral, Lays Martin; Queiroz-Junior, Celso Martins; Rachid, Milene Alvarenga; Proudfoot, Amanda E I; Garlet, Gustavo Pompermaier; Batista, Aline Carvalho; Teixeira, Mauro Martins; Leopoldino, Andréia Machado; Russo, Remo Castro; Silva, Tarcília Aparecida

    2017-08-01

    The chemokine CCL3 is a chemotactic cytokine crucial for inflammatory cell recruitment in homeostatic and pathological conditions. CCL3 might stimulate cancer progression by promoting leukocyte accumulation, angiogenesis and tumour growth. The expression of CCL3 and its receptors CCR1 and CCR5 was demonstrated in oral squamous cell carcinoma (OSCC), but their role was not defined. Here, the functions of CCL3 were assessed using a model of chemically induced tongue carcinogenesis with 4-nitroquinoline-1-oxide (4NQO). Lineages of OSCC were used to analyse the effects of CCL3 in vitro . The 4NQO-induced lesions exhibited increased expression of CCL3, CCR1 and CCR5. CCL3 -/- and CCR5 -/- mice presented reduced incidence of tongue tumours compared to wild-type (WT) and CCR1 -/- mice. Consistently, attenuated cytomorphological atypia and reduced cell proliferation were observed in lesions of CCL3 -/- and CCR5 -/- mice. OSCC from CCL3 -/- mice exhibited lower infiltration of eosinophils and reduced expression of Egf, Fgf1, Tgf-β1, Vegfa, Vegfb, Itga-4, Vtn, Mmp-1a, Mmp-2 and Mmp-9 than WT mice. In vitro , CCL3 induced invasion and production of CCL5, IL-6, MMP -2, -8, -9. Blockage of CCL3 in vitro using α-CCL3 or Evasin-1 (a CCL3-binding protein) impaired tumour cell invasion. In conclusion, CCL3/CCR5 axis has pro-tumourigenic effects in oral carcinogenesis. The induction of inflammatory and angiogenic pathways and eosinophils recruitment appear to be the underlying mechanism explaining these effects. These data reveal potential protective effects of CCL3 blockade in oral cancer.

  1. Protein expression analysis of inflammation-related colon carcinogenesis

    Directory of Open Access Journals (Sweden)

    Yasui Yumiko

    2009-01-01

    Full Text Available Background: Chronic inflammation is a risk factor for colorectal cancer (CRC development. The aim of this study was to determine the differences in protein expression between CRC and the surrounding nontumorous colonic tissues in the mice that received azoxymethane (AOM and dextran sodium sulfate (DSS using a proteomic analysis. Materials and Methods: Male ICR mice were given a single intraperitoneal injection of AOM (10 mg/kg body weight, followed by 2% (w/v DSS in their drinking water for seven days, starting one week after the AOM injection. Colonic adenocarcinoma developed after 20 weeks and a proteomics analysis based on two-dimensional gel electrophoresis and ultraflex TOF/TOF mass spectrometry was conducted in the cancerous and nontumorous tissue specimens. Results: The proteomic analysis revealed 21 differentially expressed proteins in the cancerous tissues in comparison to the nontumorous tissues. There were five markedly increased proteins (beta-tropomyosin, tropomyosin 1 alpha isoform b, S100 calcium binding protein A9, and an unknown protein and 16 markedly decreased proteins (Car1 proteins, selenium-binding protein 1, HMG-CoA synthase, thioredoxin 1, 1 Cys peroxiredoxin protein 2, Fcgbp protein, Cytochrome c oxidase, subunit Va, ETHE1 protein, and 7 unknown proteins. Conclusions: There were 21 differentially expressed proteins in the cancerous tissues of the mice that received AOM and DSS. Their functions include metabolism, the antioxidant system, oxidative stress, mucin production, and inflammation. These findings may provide new insights into the mechanisms of inflammation-related colon carcinogenesis and the establishment of novel therapies and preventative strategies to treat carcinogenesis in the inflamed colon.

  2. Mechanisms of caffeine-induced inhibition of UVB carcinogenesis

    Directory of Open Access Journals (Sweden)

    Allan H Conney

    2013-06-01

    Full Text Available Sunlight-induced nonmelanoma skin cancer is the most prevalent cancer in the United States with more than 2 million cases per year. Several studies have shown an inhibitory effect of caffeine administration on UVB-induced skin cancer in mice, and these studies are paralleled by epidemiology studies that indicate an inhibitory effect of coffee drinking on nonmelanoma skin cancer in humans. Strikingly, decaffeinated coffee consumption had no such inhibitory effect.Mechanism studies indicate that caffeine has a sunscreen effect that inhibits UVB-induced formation of thymine dimers and sunburn lesions in the epidermis of mice. In addition, caffeine administration has a biological effect that enhances UVB-induced apoptosis thereby enhancing the elimination of damaged precancerous cells, and caffeine administration also enhances apoptosis in tumors. Caffeine administration enhances UVB-induced apoptosis by p53-dependent and p53-independent mechanisms. Exploration of the p53-independent effect indicated that caffeine administration enhanced UVB-induced apoptosis by inhibiting the UVB-induced increase in ATR-mediated formation of phospho-Chk1 (Ser345 and abolishing the UVB-induced decrease in cyclin B1 which resulted in caffeine-induced premature and lethal mitosis in mouse skin. In studies with cultured primary human keratinocytes, inhibition of ATR with siRNA against ATR inhibited Chk1 phosphorylation and enhanced UVB-induced apoptosis. Transgenic mice with decreased epidermal ATR function that were irradiated chronically with UVB had 69% fewer tumors at the end of the study compared with irradiated littermate controls with normal ATR function. These results, which indicate that genetic inhibition of ATR (like pharmacologic inhibition of ATR via caffeine inhibits UVB-induced carcinogenesis and supports the concept that ATR-mediated phosphorylation of Chk1 is an important target for caffeine’s inhibitory effect on UVB-induced carcinogenesis.

  3. Role of oxidative stress in cadmium toxicity and carcinogenesis

    International Nuclear Information System (INIS)

    Liu Jie; Qu Wei; Kadiiska, Maria B.

    2009-01-01

    Cadmium (Cd) is a toxic metal, targeting the lung, liver, kidney, and testes following acute intoxication, and causing nephrotoxicity, immunotoxicity, osteotoxicity and tumors after prolonged exposures. Reactive oxygen species (ROS) are often implicated in Cd toxicology. This minireview focused on direct evidence for the generation of free radicals in intact animals following acute Cd overload and discussed the association of ROS in chronic Cd toxicity and carcinogenesis. Cd-generated superoxide anion, hydrogen peroxide, and hydroxyl radicals in vivo have been detected by the electron spin resonance spectra, which are often accompanied by activation of redox sensitive transcription factors (e.g., NF-κB, AP-1 and Nrf2) and alteration of ROS-related gene expression. It is generally agreed upon that oxidative stress plays important roles in acute Cd poisoning. However, following long-term Cd exposure at environmentally-relevant low levels, direct evidence for oxidative stress is often obscure. Alterations in ROS-related gene expression during chronic exposures are also less significant compared to acute Cd poisoning. This is probably due to induced adaptation mechanisms (e.g., metallothionein and glutathione) following chronic Cd exposures, which in turn diminish Cd-induced oxidative stress. In chronic Cd-transformed cells, less ROS signals are detected with fluorescence probes. Acquired apoptotic tolerance renders damaged cells to proliferate with inherent oxidative DNA lesions, potentially leading to tumorigenesis. Thus, ROS are generated following acute Cd overload and play important roles in tissue damage. Adaptation to chronic Cd exposure reduces ROS production, but acquired Cd tolerance with aberrant gene expression plays important roles in chronic Cd toxicity and carcinogenesis.

  4. Mushroom Ganoderma lucidum Prevents Colitis-Associated Carcinogenesis in Mice

    Science.gov (United States)

    Sliva, Daniel; Loganathan, Jagadish; Jiang, Jiahua; Jedinak, Andrej; Lamb, John G.; Terry, Colin; Baldridge, Lee Ann; Adamec, Jiri; Sandusky, George E.; Dudhgaonkar, Shailesh

    2012-01-01

    Background Epidemiological studies suggest that mushroom intake is inversely correlated with gastric, gastrointestinal and breast cancers. We have recently demonstrated anticancer and anti-inflammatory activity of triterpene extract isolated from mushroom Ganoderma lucidum (GLT). The aim of the present study was to evaluate whether GLT prevents colitis-associated carcinogenesis in mice. Methods/Principal Findings Colon carcinogenesis was induced by the food-borne carcinogen (2-Amino-1-methyl-6-phenylimidazol[4,5-b]pyridine [PhIP]) and inflammation (dextran sodium sulfate [DSS]) in mice. Mice were treated with 0, 100, 300 and 500 mg GLT/kg of body weight 3 times per week for 4 months. Cell proliferation, expression of cyclin D1 and COX-2 and macrophage infiltration was assessed by immunohistochemistry. The effect of GLT on XRE/AhR, PXR and rPXR was evaluated by the reporter gene assays. Expression of metabolizing enzymes CYP1A2, CYP3A1 and CYP3A4 in colon tissue was determined by immunohistochemistry. GLT treatment significantly suppressed focal hyperplasia, aberrant crypt foci (ACF) formation and tumor formation in mice exposed to PhIP/DSS. The anti-proliferative effects of GLT were further confirmed by the decreased staining with Ki-67 in colon tissues. PhIP/DSS-induced colon inflammation was demonstrated by the significant shortening of the large intestine and macrophage infiltrations, whereas GLT treatment prevented the shortening of colon lengths, and reduced infiltration of macrophages in colon tissue. GLT treatment also significantly down-regulated PhIP/DSS-dependent expression of cyclin D1, COX-2, CYP1A2 and CYP3A4 in colon tissue. Conclusions Our data suggest that GLT could be considered as an alternative dietary approach for the prevention of colitis-associated cancer. PMID:23118901

  5. Challenging the Myth: Transvaginal Mesh is Not Associated with Carcinogenesis.

    Science.gov (United States)

    Chughtai, Bilal; Sedrakyan, Art; Mao, Jialin; Thomas, Dominique; Eilber, Karyn S; Clemens, J Quentin; Anger, Jennifer T

    2017-10-01

    We sought to determine if there was a potential link between synthetic polypropylene mesh implantation for transvaginal pelvic organ prolapse and stress urinary incontinence, and carcinogenesis using statewide administrative data. Women who underwent transvaginal surgery for pelvic organ prolapse or stress urinary incontinence with mesh between January 2008 and December 2009 in New York State were identified using ICD-9-CM procedure codes and CPT-4 codes. Patients in the mesh cohort were individually matched to 2 control cohorts based on comorbidities and procedure date. Carcinogenesis was determined before and after matching at 1, 2 and 3 years, and during the entire followup time. A total of 2,229 patients who underwent mesh based pelvic organ prolapse surgery and 10,401 who underwent sling surgery for stress urinary incontinence between January 2008 and December 2009 were included in the study. Mean followup was 6 years (range 5 to 7). Exact matching between the mesh and control cohorts resulted in 1,870 pairs for pelvic organ prolapse mesh and cholecystectomy (1:2), 1,278 pairs for pelvic organ prolapse mesh and hysterectomy (1:1), 7,986 pairs for sling and cholecystectomy (1:1) and 3,810 pairs for sling and hysterectomy (1:1). Transvaginal mesh implantation was not associated with an increased risk of a cancer diagnosis (pelvic/local cancers or any cancer) at 1 year and during the entire followup of up to 7 years. Transvaginal surgery with implantation of mesh was not associated with the development of malignancy at a mean followup of 6 years. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  6. Celecoxib prevents colitis associated colon carcinogenesis: an upregulation of apoptosis.

    Science.gov (United States)

    Setia, Shruti; Nehru, Bimla; Sanyal, Sankar N

    2014-12-01

    Uncontrolled cell proliferation and suppressed apoptosis are the critical events transforming a normal cell to a cancerous one wherein the inflammatory microenvironment supports this oncogenic transformation. The process of colon carcinogenesis may be aggravated in chronic inflammatory conditions such as ulcerative colitis where non-steroidal anti-inflammatory drugs (NSAIDs) may effectively prevent the cellular and molecular events. Western blots and immunofluorescent analysis of DNA mismatch repair enzymes, cell cycle regulators and pro- and anti-apoptotic proteins were performed in dextran sulfate sodium (DSS)-induced ulcerative colitis and 1,2-dimethyl benz(a)anthracene (DMH)-induced colon cancer. Also, apoptotic studies were done in isolated colonocytes using fluorescent staining and in paraffin sections using TUNEL assay. An upregulation of cell cycle regulators: cyclin D1/cdk4 and cyclin E/cdk2 and anti-apoptotic Bcl-2, along with the suppression of DNA repair enzymes: MLH1 and MSH2; tumour suppressors: p53, p21and Rb and pro-apoptotic proteins: Bax and Bad were observed in the DSS, DMH and DSS+DMH groups. Proliferating cell nuclear antigen (PCNA) was also overexpressed in these groups. The ultimate executioner of the apoptotic pathway; caspase-3, was suppressed in these groups. Apoptotic studies in colonocytes and paraffin sections revealed suppressed apoptosis in these groups. These effects were corrected with the administration of a second generation NSAID, celecoxib along with the treatment of DSS and DMH. The chemopreventive action of celecoxib in colitis mediated colon carcinogenesis may include the regulation of DNA mismatch repair enzymes, cell cycle check points, cell proliferation and apoptosis. Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  7. Present status of theories and data analyses of mathematical models for carcinogenesis

    International Nuclear Information System (INIS)

    Kai, Michiaki; Kawaguchi, Isao

    2007-01-01

    Reviewed are the basic mathematical models (hazard functions), present trend of the model studies and that for radiation carcinogenesis. Hazard functions of carcinogenesis are described for multi-stage model and 2-event model related with cell dynamics. At present, the age distribution of cancer mortality is analyzed, relationship between mutation and carcinogenesis is discussed, and models for colorectal carcinogenesis are presented. As for radiation carcinogenesis, models of Armitage-Doll and of generalized MVK (Moolgavkar, Venson, Knudson, 1971-1990) by 2-stage clonal expansion have been applied to analysis of carcinogenesis in A-bomb survivors, workers in uranium mine (Rn exposure) and smoking doctors in UK and other cases, of which characteristics are discussed. In analyses of A-bomb survivors, models above are applied to solid tumors and leukemia to see the effect, if any, of stage, age of exposure, time progression etc. In miners and smokers, stages of the initiation, promotion and progression in carcinogenesis are discussed on the analyses. Others contain the analyses of workers in Canadian atomic power plant, and of patients who underwent the radiation therapy. Model analysis can help to understand the carcinogenic process in a quantitative aspect rather than to describe the process. (R.T.)

  8. Comparison of solid and liquid-phase bioassays using ecoscores to assess contaminated soils

    Energy Technology Data Exchange (ETDEWEB)

    Lors, Christine [Universite Lille Nord de France, 1bis rue Georges Lefevre, 59044 Lille Cedex (France); Ecole des Mines de Douai, LGCgE-MPE-GCE, 941 rue Charles-Bourseul, 59500 Douai (France); Centre National de Recherche sur les Sites et Sols Pollues, 930 Boulevard Lahure, BP 537, 59505 Douai Cedex (France); Ponge, Jean-Francois, E-mail: ponge@mnhn.fr [Museum National d' Histoire Naturelle, Departement Ecologie et Gestion de la Biodiversite, CNRS UMR 7179, 4 Avenue du Petit-Chateau, 91800 Brunoy (France); Martinez Aldaya, Maite [Museum National d' Histoire Naturelle, Departement Ecologie et Gestion de la Biodiversite, CNRS UMR 7179, 4 Avenue du Petit-Chateau, 91800 Brunoy (France); Damidot, Denis [Universite Lille Nord de France, 1bis rue Georges Lefevre, 59044 Lille Cedex (France); Ecole des Mines de Douai, LGCgE-MPE-GCE, 941 rue Charles-Bourseul, 59500 Douai (France)

    2011-10-15

    Bioassays on aqueous and solid phases of contaminated soils were compared, belonging to a wide array of trophic and response levels and using ecoscores for evaluating ecotoxicological and genotoxicological endpoints. The method was applied to four coke factory soils contaminated mainly with PAHs, but also to a lesser extent by heavy metals and cyanides. Aquatic bioassays do not differ from terrestrial bioassays when scaling soils according to toxicity but they are complementary from the viewpoint of ecological relevance. Both aquatic and terrestrial endpoints are strongly correlated with concentrations of 3-ring PAHs. This evaluation procedure allows us to propose a cost-effective battery which embraces a wide array of test organisms and response levels: it includes two rapid bioassays (Microtox) and springtail avoidance), a micronucleus test and three bioassays of a longer duration (algal growth, lettuce germination and springtail reproduction). This battery can be recommended for a cost-effective assessment of polluted/remediated soils. - Highlights: > Comparison of liquid- and solid-phase bioassays on contaminated soils, using ecoscores. > Complementarity of liquid- and solid-phase bioassays for the evaluation of environmental hazards. > Proposal for a restricted battery of 5 most sensitive tests. > Use of this restricted battery for a cost-effective assessment of polluted/remediated soils. - Aqueous and solid phases of contaminated soils give similar results in terms of toxicity but are complementary for the evaluation of environmental hazards by ecoscores.

  9. Comparison of solid and liquid-phase bioassays using ecoscores to assess contaminated soils

    International Nuclear Information System (INIS)

    Lors, Christine; Ponge, Jean-Francois; Martinez Aldaya, Maite; Damidot, Denis

    2011-01-01

    Bioassays on aqueous and solid phases of contaminated soils were compared, belonging to a wide array of trophic and response levels and using ecoscores for evaluating ecotoxicological and genotoxicological endpoints. The method was applied to four coke factory soils contaminated mainly with PAHs, but also to a lesser extent by heavy metals and cyanides. Aquatic bioassays do not differ from terrestrial bioassays when scaling soils according to toxicity but they are complementary from the viewpoint of ecological relevance. Both aquatic and terrestrial endpoints are strongly correlated with concentrations of 3-ring PAHs. This evaluation procedure allows us to propose a cost-effective battery which embraces a wide array of test organisms and response levels: it includes two rapid bioassays (Microtox) and springtail avoidance), a micronucleus test and three bioassays of a longer duration (algal growth, lettuce germination and springtail reproduction). This battery can be recommended for a cost-effective assessment of polluted/remediated soils. - Highlights: → Comparison of liquid- and solid-phase bioassays on contaminated soils, using ecoscores. → Complementarity of liquid- and solid-phase bioassays for the evaluation of environmental hazards. → Proposal for a restricted battery of 5 most sensitive tests. → Use of this restricted battery for a cost-effective assessment of polluted/remediated soils. - Aqueous and solid phases of contaminated soils give similar results in terms of toxicity but are complementary for the evaluation of environmental hazards by ecoscores.

  10. Establishment of a bioassay for the toxicity evaluation and quality control of Aconitum herbs

    International Nuclear Information System (INIS)

    Qin, Yi; Wang, Jia-bo; Zhao, Yan-ling; Shan, Li-mei; Li, Bao-cai; Fang, Fang; Jin, Cheng; Xiao, Xiao-he

    2012-01-01

    Highlights: ► A new bioassay was optimized to evaluate the toxicity of Aconitum herbs. ► Characterizing total toxicity is its unique advantage over chemical analysis methods. ► The application of this bioassay promotes the safe use of Aconitum herbs in clinic. - Abstract: Currently, no bioassay is available for evaluating the toxicity of Aconitum herbs, which are well known for their lethal cardiotoxicity and neurotoxicity. In this study, we established a bioassay to evaluate the toxicity of Aconitum herbs. Test sample and standard solutions were administered to rats by intravenous infusion to determine their minimum lethal doses (MLD). Toxic potency was calculated by comparing the MLD. The experimental conditions of the method were optimized and standardized to ensure the precision and reliability of the bioassay. The application of the standardized bioassay was then tested by analyzing 18 samples of Aconitum herbs. Additionally, three major toxic alkaloids (aconitine, mesaconitine, and hypaconitine) in Aconitum herbs were analyzed using a liquid chromatographic method, which is the current method of choice for evaluating the toxicity of Aconitum herbs. We found that for all Aconitum herbs, the total toxicity of the extract was greater than the toxicity of the three alkaloids. Therefore, these three alkaloids failed to account for the total toxicity of Aconitum herbs. Compared with individual chemical analysis methods, the chief advantage of the bioassay is that it characterizes the total toxicity of Aconitum herbs. An incorrect toxicity evaluation caused by quantitative analysis of the three alkaloids might be effectively avoided by performing this bioassay. This study revealed that the bioassay is a powerful method for the safety assessment of Aconitum herbs.

  11. Ulva lactuca polysaccharides prevent Wistar rat breast carcinogenesis through the augmentation of apoptosis, enhancement of antioxidant defense system, and suppression of inflammation

    Directory of Open Access Journals (Sweden)

    Abd-Ellatef GF

    2017-02-01

    Full Text Available Gamal-Eldein F Abd-Ellatef,1 Osama M Ahmed,2 Eman S Abdel-Reheim,2 Abdel-Hamid Z Abdel-Hamid,1 1Pharmaceutical and Drug Industries Research Division, Therapeutic Chemistry Department, National Research Centre, Cairo, Egypt; 2Division of Physiology, Department of Zoology, Faculty of Science, Beni-Suef University, Beni-Suef, Egypt Background: Recently, several research studies have been focused on the isolation and function of the polysaccharides derived from different algal species, which revealed multiple biological activities such as antioxidant and antitumor activities. This study assesses the possible breast cancer chemopreventive properties of common seaweeds, sea lettuce, Ulva lactuca (ulvan polysaccharides using in vitro bioassays on human breast cancer cell line (MCF-7 and an in vivo animal model of breast carcinogenesis. Methods: Cytotoxic effect of ulvan polysaccharides on MCF-7 was tested in vitro. For an in vivo investigation, a single dose of 25 mg/kg body weight 7,12-dimethylbenz[a]anthracene (DMBA and ulvan polysaccharides (50 mg/kg body weight every other day for 10 weeks were administered orally to the Wistar rats. Results: Deleterious histopathological alterations in breast tissues including papillary cyst adenoma and hyperplasia of ductal epithelial lining with intraluminal necrotic materials and calcifications were observed in the DMBA-administered group. These lesions were prevented in the DMBA-administered group treated with ulvan polysaccharides. The immunohistochemical sections depicted that the treatment of DMBA-administered rats with ulvan polysaccharides markedly increased the lowered pro-apoptotic protein, p53, and decreased the elevated anti-apoptotic marker, bcl2, expression in the breast tissue. The elevated lipid peroxidation and the suppressed antioxidant enzyme activities in DMBA-administered control were significantly prevented by the treatment with ulvan polysaccharides. The elevated levels of inflammatory

  12. [Application of bioassay in quality control of Chinese materia medica-taking Radix Isatidis as an example].

    Science.gov (United States)

    Yan, Dan; Ren, Yongshen; Luo, Jiaoyang; Li, Hanbing; Feng, Xue; Xiao, Xiaohe

    2010-10-01

    Bioassay, which construct the characteristics consistents with Chinese medical science, is the core mode and methods for the quality control of Chinese materia medica. Taking the bioassay of Radix Isatidis as an example, the contribution, status and application of bioassay in the quality control of Chinese materia medica were introduced in this article, and two key issue (the selection of reference and measurement methods) in the process of establishing bioassay were also explained. This article expects to provide a reference for the development and improvement of the bioassay of Chinese materia medica in a practical manipulation level.

  13. Review of literature on bioassay methods for estimating radionuclides in urine

    International Nuclear Information System (INIS)

    Prasad, M.V.R.; Surya Narayana, D.S.; Jeevanram, R.K.; Sundarajan, A.R.

    1991-01-01

    Bioassay methods of certain important radionuclides encountered in the nuclear fuel cycle operations, viz., thorium, uranium, sup(239)Pu, sup(241)Am, sup(90)Sr, sup(99)Tc, sup(106)Ru, sup(137)Cs are reviewed, with special emphasis on urinalysis. Since the preconcentration is an important prerequisite for bioassay, various preconcentration methods are also discussed. Brief account of various instruments both nuclear and analytical used in the bioassay programme is included. The sensitivities of the methods cited in the literature vis-a-vis the derived recording levels indicated in ICRP recommendations are compared. Literature surveyed up to 1990 is tabulated. (author). 96 refs., 1 fig ., 3 tabs

  14. Bioassay of Phenol and its Intermediate Products Using Daphnia magna

    Directory of Open Access Journals (Sweden)

    Afshin Maleki

    2008-06-01

    Full Text Available Phenol is one of the most common compounds found in many industrial effluents such as petroleum refining and petrochemicals, pharmaceuticals, pesticides, paint and dye industries, organic chemicals manufacturing, etc. The contamination of bodies of water with phenol is a serious problem in terms of environmental considerations due to its high toxicity. In this study, toxicity of phenol and its degradation mixtures by sonochemical, photochemical, and photosonochemical processes were investigated. Toxicity assay tests were carried out using Daphnia magna as a bio-indicator. The sonochemical and photochemical experiments were carried out using a bath sonicator (500 W working at 35 and 130 kHz frequencies and with a 400 W medium pressure mercury lamp, respectively. Experiments were performed at initial concentrations of 100 mg L-1. Bioassay tests showed that phenol was toxic to D.magna and so resulted in quite low LC50 values. Comparison of toxicity units (TU between phenol and effluent toxicity showed that TU value for photosonochemical effluent was lower than that obtained for phenol, photochemical effluent, and sonochemical effluent. It was found that the toxicity unit of photochemical effluent was lower than that obtained for sonochemical effluent. According to the D.magna acute toxicity test, it is concluded that photosonolysis and photolysis are capable of decreasing the toxicity of by-products formed during the degradation of phenol aqueous solutions. Photosonic and photolytic processes can, therefore, be recommended as a potential approach to the treatment of phenolic wastewater.

  15. Bioassay-based risk assessment of complex mixtures

    Energy Technology Data Exchange (ETDEWEB)

    Donnelly, K.C.; Safe, S.H. [Texas A& M Univ., Houston, TX (United States); Randerath, K.; Randerath, E. [College Station and Baylor College of Medicine, Houston, TX (United States)

    1994-12-31

    To compare the standard chemical-based risk assessment with in vitro genotoxicity assays, two complex environmental mixtures from a wood preserving site were analyzed in the Salmonella/microsome and E. coli prophage induction assays. Using GC/MS, sample 003 was found to contain relatively low levels of polycyclic aromatic hydrocarbons (PNAs) and elevated levels of polychlorinated dibenzo-p-dioxins (PCDDs), while sample 005 had higher levels of PNAs and relatively low levels of PCDDs. The complex mixtures were sequentially extracted with methylene chloride and methanol for analysis in Salmonella, or extracted with 1:1 hexane: acetone mixture for analysis in the prophage induction assay. At a dose of 1.0 mg/plate in Salmonella strain TA98 with metabolic activation, the methanol extract of sample 003 induced 197 net revertants, while sample 005 induced 436 net revertants. In the prophage induction assay, with activation, the hexane:acetone extract of sample 003 induced a fold increase that was slightly lower than that observed with sample 005. The estimated incremental carcinogenic risk for dermal adsorption and ingestion was 1.5E-3 for sample 003, while for sample 005 the estimated risk was 1.5E-2. Thus, the sample which induced the maximum response in both bioassays also had the highest estimated cancer risk. However, the frequency of PNA-DNA adducts in both skin and liver tissues was appreciably higher with sample 005 than with sample 003.

  16. Bioassay-based risk assessment of complex mixtures

    International Nuclear Information System (INIS)

    Donnelly, K.C.; Huebner, H.J.

    1996-01-01

    The baseline risk assessment often plays an integral role in various decision-making processes at Superfund sites. The present study reports on risk characterizations prepared for seven complex mixtures using biological and chemical analysis. Three of the samples (A, B, and C) were complex mixtures of polycyclic aromatic hydrocarbons (PAHs) extracted from coal tar; while four samples extracted from munitions-contaminated soil contained primarily nitroaromatic hydrocarbons. The chemical-based risk assessment ranked sample C as least toxic, while the risk associated with samples A and B was approximately equal. The microbial bioassay was in general agreement for the coal tar samples. The weighted activity of the coal tar extracts in Salmonella was 4,960 for sample C, and 162,000 and 206,000 for samples A and B, respectively. The bacterial mutagenicity of 2,4,6-trinitrotoluene contaminated soils exhibited an indirect correlation with chemical-based risk assessment. The aqueous extract of sample 004 induced 1,292 net revertants in Salmonella, while the estimated risk to ingestion and dermal adsorption was 2E-9. The data indicate that the chemical-based risk assessment accurately predicted the genotoxicity of the PAHs, while the accuracy of the risk assessment for munitions contaminated soils was limited due to the presence of metabolites of TNT degradation. The biological tests used in this research provide a valuable compliment to chemical analysis for characterizing the genotoxic risk of complex mixtures

  17. Detection of organic compounds with whole-cell bioluminescent bioassays.

    Science.gov (United States)

    Xu, Tingting; Close, Dan; Smartt, Abby; Ripp, Steven; Sayler, Gary

    2014-01-01

    Natural and manmade organic chemicals are widely deposited across a diverse range of ecosystems including air, surface water, groundwater, wastewater, soil, sediment, and marine environments. Some organic compounds, despite their industrial values, are toxic to living organisms and pose significant health risks to humans and wildlife. Detection and monitoring of these organic pollutants in environmental matrices therefore is of great interest and need for remediation and health risk assessment. Although these detections have traditionally been performed using analytical chemical approaches that offer highly sensitive and specific identification of target compounds, these methods require specialized equipment and trained operators, and fail to describe potential bioavailable effects on living organisms. Alternatively, the integration of bioluminescent systems into whole-cell bioreporters presents a new capacity for organic compound detection. These bioreporters are constructed by incorporating reporter genes into catabolic or signaling pathways that are present within living cells and emit a bioluminescent signal that can be detected upon exposure to target chemicals. Although relatively less specific compared to analytical methods, bioluminescent bioassays are more cost-effective, more rapid, can be scaled to higher throughput, and can be designed to report not only the presence but also the bioavailability of target substances. This chapter reviews available bacterial and eukaryotic whole-cell bioreporters for sensing organic pollutants and their applications in a variety of sample matrices.

  18. Luminescent Lanthanide Reporters for High-Sensitivity Novel Bioassays

    Energy Technology Data Exchange (ETDEWEB)

    Anstey, Mitchell R. [Sandia National Lab. (SNL-CA), Livermore, CA (United States); Fruetel, Julia A. [Sandia National Lab. (SNL-CA), Livermore, CA (United States); Foster, Michael E. [Sandia National Lab. (SNL-CA), Livermore, CA (United States); Hayden, Carl C. [Sandia National Lab. (SNL-CA), Livermore, CA (United States); Buckley, Heather L. [Sandia National Lab. (SNL-CA), Livermore, CA (United States); Arnold, John [Sandia National Lab. (SNL-CA), Livermore, CA (United States)

    2013-09-01

    Biological imaging and assay technologies rely on fluorescent organic dyes as reporters for a number of interesting targets and processes. However, limitations of organic dyes such as small Stokes shifts, spectral overlap of emission signals with native biological fluorescence background, and photobleaching have all inhibited the development of highly sensitive assays. To overcome the limitations of organic dyes for bioassays, we propose to develop lanthanide-based luminescent dyes and demonstrate them for molecular reporting applications. This relatively new family of dyes was selected for their attractive spectral and chemical properties. Luminescence is imparted by the lanthanide atom and allows for relatively simple chemical structures that can be tailored to the application. The photophysical properties offer unique features such as narrow and non-overlapping emission bands, long luminescent lifetimes, and long wavelength emission, which enable significant sensitivity improvements over organic dyes through spectral and temporal gating of the luminescent signal.Growth in this field has been hindered due to the necessary advanced synthetic chemistry techniques and access to experts in biological assay development. Our strategy for the development of a new lanthanide-based fluorescent reporter system is based on chelation of the lanthanide metal center using absorbing chromophores. Our first strategy involves "Click" chemistry to develop 3-fold symmetric chelators and the other involves use of a new class of tetrapyrrole ligands called corroles. This two-pronged approach is geared towards the optimization of chromophores to enhance light output.

  19. Analyzing bioassay data using Bayesian methods-A primer

    International Nuclear Information System (INIS)

    Miller, G.; Inkret, W.C.; Schillaci, M.E.

    1997-01-01

    The classical statistics approach used in health physics for the interpretation of measurements is deficient in that it does not allow for the consideration of needle in a haystack effects, where events that are rare in a population are being detected. In fact, this is often the case in health physics measurements, and the false positive fraction is often very large using the prescriptions of classical statistics. Bayesian statistics provides an objective methodology to ensure acceptably small false positive fractions. The authors present the basic methodology and a heuristic discussion. Examples are given using numerically generated and real bioassay data (Tritium). Various analytical models are used to fit the prior probability distribution, in order to test the sensitivity to choice of model. Parametric studies show that the normalized Bayesian decision level k α -L c /σ 0 , where σ 0 is the measurement uncertainty for zero true amount, is usually in the range from 3 to 5 depending on the true positive rate. Four times σ 0 rather than approximately two times σ 0 , as in classical statistics, would often seem a better choice for the decision level

  20. Analyzing bioassay data using Bayesian methods -- A primer

    Energy Technology Data Exchange (ETDEWEB)

    Miller, G.; Inkret, W.C.; Schillaci, M.E.; Martz, H.F.; Little, T.T.

    2000-06-01

    The classical statistics approach used in health physics for the interpretation of measurements is deficient in that it does not take into account needle in a haystack effects, that is, correct identification of events that are rare in a population. This is often the case in health physics measurements, and the false positive fraction (the fraction of results measuring positive that are actually zero) is often very large using the prescriptions of classical statistics. Bayesian statistics provides a methodology to minimize the number of incorrect decisions (wrong calls): false positives and false negatives. The authors present the basic method and a heuristic discussion. Examples are given using numerically generated and real bioassay data for tritium. Various analytical models are used to fit the prior probability distribution in order to test the sensitivity to choice of model. Parametric studies show that for typical situations involving rare events the normalized Bayesian decision level k{sub {alpha}} = L{sub c}/{sigma}{sub 0}, where {sigma}{sub 0} is the measurement uncertainty for zero true amount, is in the range of 3 to 5 depending on the true positive rate. Four times {sigma}{sub 0} rather than approximately two times {sigma}{sub 0}, as in classical statistics, would seem a better choice for the decision level in these situations.

  1. Modulation of Estrogen Chemical Carcinogenesis by Botanical Supplements used for Postmenopausal Women’s Health

    Science.gov (United States)

    Snelten, Courtney S.; Dietz, Birgit; Bolton, Judy L.

    2012-01-01

    Breast cancer risk has been associated with long-term estrogen exposure including traditional hormone therapy (HT, formally hormone replacement therapy). To avoid traditional HT and associated risks, women have been turning to botanical supplements such as black cohosh, red clover, licorice, hops, dong gui, and ginger to relieve menopausal symptoms despite a lack of efficacy evidence. The mechanisms of estrogen carcinogenesis involve both hormonal and chemical pathways. Botanical supplements could protect women from estrogen carcinogenesis by modulating key enzymatic steps [aromatase, P4501B1, P4501A1, catechol-O-methyltransferase (COMT), NAD(P)H quinone oxidoreductase 1 (NQO1), and reactive oxygen species (ROS) scavenging] in estradiol metabolism leading to estrogen carcinogenesis as outlined in Figure 1. This review summarizes the influence of popular botanical supplements used for women’s health on these key steps in the estrogen chemical carcinogenesis pathway, and suggests that botanical supplements may have added chemopreventive benefits by modulating estrogen metabolism. PMID:24223609

  2. Preclinical Cancer Chemoprevention Studies Using Animal Model of Inflammation-Associated Colorectal Carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Tanaka, Takuji [Cytopatholgy Division, Tohkai Cytopathology Institute, Cancer Research and Prevention (TCI-CaRP), 5-1-2 Minami-uzura, Gifu 500-8285 (Japan); Department of Tumor Pathology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194 (Japan)

    2012-07-16

    Inflammation is involved in all stages of carcinogenesis. Inflammatory bowel disease, such as ulcerative colitis and Crohn’s disease is a longstanding inflammatory disease of intestine with increased risk for colorectal cancer (CRC). Several molecular events involved in chronic inflammatory process are reported to contribute to multi-step carcinogenesis of CRC in the inflamed colon. They include over-production of free radicals, reactive oxygen and nitrogen species, up-regulation of inflammatory enzymes in arachidonic acid biosynthesis pathway, up-regulation of certain cytokines, and intestinal immune system dysfunction. In this article, firstly I briefly introduce our experimental animal models where colorectal neoplasms rapidly develop in the inflamed colorectum. Secondary, data on preclinical cancer chemoprevention studies of inflammation-associated colon carcinogenesis by morin, bezafibrate, and valproic acid, using this novel inflammation-related colorectal carcinogenesis model is described.

  3. Investigating the Role of FIP200 in Mammary Carcinogenesis Using a Transgenic Mouse Model

    National Research Council Canada - National Science Library

    Nagy, Tamas

    2007-01-01

    ...) deletion in mammary-specific polyoma middle-T transgenic mice. We monitored mammary carcinogenesis in positive control (FAKFlox/Flox; MMTV-PyVT) and target (FAKFlox/Flox; MMTV-Cre; MMTV-PyVT) females...

  4. Age and Space Irradiation Modulate Tumor Progression: Implications for Carcinogenesis Risk

    Data.gov (United States)

    National Aeronautics and Space Administration — Age plays a major role in tumor incidence and is an important consideration when modeling the carcinogenesis process or estimating cancer risks. Epidemiological data...

  5. Effects of environmental stressors on histone modifications and their relevance to carcinogenesis: a systematic review.

    NARCIS (Netherlands)

    Dik, S.; Scheepers, P.T.J.; Godderis, L.

    2012-01-01

    Carcinogenesis is a complex process involving both genetic and epigenetic mechanisms. The cellular molecular epigenetic machinery, including histone modifications, is associated with changes in gene expression induced by exposure to environmental agents. In this paper, we systematically reviewed

  6. Comparison of solid-phase bioassays and ecoscores to evaluate the toxicity of contaminated soils.

    Science.gov (United States)

    Lors, Christine; Ponge, Jean-François; Martínez Aldaya, Maite; Damidot, Denis

    2010-08-01

    Five bioassays (inhibition of lettuce germination and growth, earthworm mortality, inhibition of springtail population growth, avoidance by springtails) were compared, using four coke factory soils contaminated by PAHs and trace elements, before and after biotreatment. For each bioassay, several endpoints were combined in an 'ecoscore', a measure of test sensitivity. Ecoscores pooled over all tested bioassays revealed that most organisms were highly sensitive to the concentration of 3-ring PAHs. When four soils were combined, behavioural tests using the springtail Folsomia candida showed higher ecoscores, i.e. they were most sensitive to soil contamination. However, despite overall higher sensitivity of behavioural tests, which could be used for cheap and rapid assessment of soil toxicity, especially at low levels of contamination, some test endpoints were more sensitive than others, and this may differ from a soil to another, pointing to the need for a battery of bioassays when more itemized results are expected. Copyright 2010 Elsevier Ltd. All rights reserved.

  7. Biomonitoring of cyanotoxins in two tropical reservoirs by cladoceran toxicity bioassays.

    Science.gov (United States)

    da S Ferrão-Filho, Aloysio; Soares, Maria Carolina S; de Freitas Magalhães, Valeria; Azevedo, Sandra M F O

    2009-02-01

    This study evaluates the potential for the use of cladocerans in biomonitoring of cyanobacterial toxins. Two zooplankton species (Daphnia gessneri and Moina micrura) were cultivated in the laboratory for use in acute (48 h) and chronic (10 days) bioassays. Water samples were collected from two reservoirs and diluted in mineral water at four concentrations. Survivorship in the acute bioassays was used to calculate LC50, and survivorship and fecundity in chronic bioassays were used to calculate the intrinsic population growth rate (r) and the EC50. Analysis of phytoplankton in the water samples from one reservoir revealed that cyanobacteria were the dominant group, represented by the genera Anabaena, Cylindrospermopsis, and Microcystis. Results of bioassays showed adverse effects including death, paralysis, and reduced population growth rate, generally proportional to the reservoir water concentration. These effects may be related to the presence of cyanobacteria toxins (microcystins or saxitoxins) in the water.

  8. Comparative susceptibility of bemisia tabaci to imidacloprid in field- and laboratory-based bioassays

    Science.gov (United States)

    Bemisia tabaci biotype B is a resistance-prone pest of protected and open agriculture. Systemic uptake bioassays used in resistance monitoring programs have provided important information on susceptibility to neonicotinoid insecticides, but have remained decoupled from field performance. Simultaneou...

  9. Phototoxicity activity of Psoralea drupacea L. using Atremia salina bioassay system

    Directory of Open Access Journals (Sweden)

    Mohammad Ramezani

    2011-07-01

    Conclusion: The result showed that P. drupacea methanolic extract and chloroform fraction have phototoxicity in A. salina bioassay system and their toxic effect is related to phototoxic constituents such as psoralen.

  10. Integration of laboratory bioassays into the risk-based corrective action process

    International Nuclear Information System (INIS)

    Edwards, D.; Messina, F.; Clark, J.

    1995-01-01

    Recent data generated by the Gas Research Institute (GRI) and others indicate that residual hydrocarbon may be bound/sequestered in soil such that it is unavailable for microbial degradation, and thus possibly not bioavailable to human/ecological receptors. A reduction in bioavailability would directly equate to reduced exposure and, therefore, potentially less-conservative risk-based cleanup soil goals. Laboratory bioassays which measure bioavailability/toxicity can be cost-effectively integrated into the risk-based corrective action process. However, in order to maximize the cost-effective application of bioassays several site-specific parameters should be addressed up front. This paper discusses (1) the evaluation of parameters impacting the application of bioassays to soils contaminated with metals and/or petroleum hydrocarbons and (2) the cost-effective integration of bioassays into a tiered ASTM type framework for risk-based corrective action

  11. The level of claudin-7 is reduced as an early event in colorectal carcinogenesis

    DEFF Research Database (Denmark)

    Lange, Jette Bornholdt; Friis, Stine; Godiksen, Sine

    2011-01-01

    -regulation of the oncogenic serine protease, matriptase, induces leakiness in epithelial barriers both in vivo and in vitro. We found in an in-silico search tight co-regulation between matriptase and claudin-7 expression. We have previously shown that the matriptase expression level decreases during colorectal carcinogenesis....... In the present study we investigated whether claudin-7 expression is likewise decreased during colorectal carcinogenesis, thereby causing or contributing to the compromised epithelial leakiness of dysplastic tissue....

  12. Hierarchical responses to organic contaminants in aquatic ecotoxicological bioassays: from microcystins to biodegradation

    OpenAIRE

    Montenegro, Katia

    2008-01-01

    In this thesis I explore the ecotoxicological responses of aquatic organisms at different hierarchical levels to organic contaminants by means of bioassays. The bioassays use novel endpoints or approaches to elucidate the effects of exposure to contaminants and attempt to give mechanistic explanations that could be used to interpret effects at higher hierarchical scales. The sensitivity of population growth rate in the cyanobacteria species Microcystis aeruginosa to the herbicide glyp...

  13. Issues in weighting bioassay data for use in regressions for internal dose assessments

    International Nuclear Information System (INIS)

    Strom, D.J.

    1992-11-01

    For use of bioassay data in internal dose assessment, research should be done to clarify the goal desired, the choice of method to achieve the goal, the selection of adjustable parameters, and on the ensemble of information that is available. Understanding of these issues should determine choices of weighting factors for bioassay data used in regression models. This paper provides an assessment of the relative importance of the various factors

  14. [Successful continuous renal replacement therapy in a neonate with early-onset group B streptococcal sepsis and multi-organ dysfunction syndrome].

    Science.gov (United States)

    von Schnakenburg, C; Hufnagel, M; Superti-Furga, A; Rieger-Fackeldey, E; Berner, R

    2009-01-01

    Group B streptococcal early-onset sepsis (GBS EOS) in neonates has a mortality rate of approximately 5%, particularly in the presence of multi-organ dysfunction. Fluid management is crucial in these patients, and continuous venovenous haemofiltration (CVVH) should be considered a therapeutic option even in newborn babies. After an uneventful pregnancy within hours after birth, a female term infant presented with dyspnoea, irritability and cyanosis. The systemic inflammatory response syndrome (SIRS) progressed to multi-organ dysfunction with acute respiratory distress syndrome (ARDS), impaired myocardial contractility, pulmonary hypertension and fluid overload. The maximum PRISM score was 51. The child required maximal respiratory and inotropic support with high volume intravenous fluid administration. However, only by using of CVVH from day 5 to 14, we successfully resolved progressive pulmonary and cardiovascular dysfunction. The child improved directly after initiation of fluid removal, was extubated on day 17 and discharged without obvious sequelae on day 57. All microbiology studies revealed GBS. Perinatal GBS-infections remain a major life-threatening event for newborn babies. CVVH should be considered an option for reversing fluid overload even in neonates with overwhelming SIRS. Alternatively, extracorporeal membrane oxygenation (ECMO) is discussed.

  15. Role of mediastinal and multi-organ CT scans in staging presumable surgical candidates with non-small-cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Osada, Hiroaki; Nakajima, Yasuo; Taira, Yasuhiko; Yokote, Kumio; Noguchi, Teruhiko

    1987-09-01

    In order to evaluate the role of CT scan and bone scan in staging patients with non-small-cell lung cancer presumably indicated for surgery, 70 consecutive patients who underwent thoracotomy were reviewed. Most of them received mediastinal and multi-organ (brain, liver and adrenal) CT scans and a bone scan. In the most recent 40 of the 70 patients, CT findings of the mediastinal lymph nodes were compared to the pathology following complete sampling. The overall accuracy of the mediastinal CT was 60.0 per cent (12 true positive and 12 true negative), but the negative predictable value was 12/(12 + 3) or 80.0 per cent, whereas 3 were false negatives though they showed an acceptable postoperative course. Sixteen out of 21 patients with one, or at the most, three enlarged nodes detected on CT also did well postoperatively and retrospectively, were considered not to have required mediastinoscopy. A group of patients showing no, or at the most, three enlarged mediastinal lymph nodes on CT may be considered as candidates for surgery even without mediastinoscopy. Multi-organ survey by means of CT was believed cost-ineffective and omittable. Bone scan however, retrospectively detected three true positives among 20 patients with a positive uptake, so that it cannot be omitted out of hand, though further examination of this point is required.

  16. Recent Concepts of Ovarian Carcinogenesis: Type I and Type II

    Directory of Open Access Journals (Sweden)

    Masafumi Koshiyama

    2014-01-01

    Full Text Available Type I ovarian tumors, where precursor lesions in the ovary have clearly been described, include endometrioid, clear cell, mucinous, low grade serous, and transitional cell carcinomas, while type II tumors, where such lesions have not been described clearly and tumors may develop de novo from the tubal and/or ovarian surface epithelium, comprise high grade serous carcinomas, undifferentiated carcinomas, and carcinosarcomas. The carcinogenesis of endometrioid and clear cell carcinoma (CCC arising from endometriotic cysts is significantly influenced by the free iron concentration, which is associated with cancer development through the induction of persistent oxidative stress. A subset of mucinous carcinomas develop in association with ovarian teratomas; however, the majority of these tumors do not harbor any teratomatous component. Other theories of their origin include mucinous metaplasia of surface epithelial inclusions, endometriosis, and Brenner tumors. Low grade serous carcinomas are thought to evolve in a stepwise fashion from benign serous cystadenoma to a serous borderline tumor (SBT. With regard to high grade serous carcinoma, the serous tubal intraepithelial carcinomas (STICs of the junction of the fallopian tube epithelium with the mesothelium of the tubal serosa, termed the “tubal peritoneal junction” (TPJ, undergo malignant transformation due to their location, and metastasize to the nearby ovary and surrounding pelvic peritoneum. Other theories of their origin include the ovarian hilum cells.

  17. A generalized theory of carcinogenesis due to chronodisruption.

    Science.gov (United States)

    Erren, Thomas C; Reiter, Russel J

    2008-12-01

    For two decades, research has been suggested and conducted into the causation and development of cancers in seemingly diverse and unrelated populations such as blind individuals, shift-workers, flight personnel, Arctic residents and subsets of sleepers. One common denominator of these investigations is "melatonin". Another common denominator is that all these studies implicitly pursued the validity of the so-called "melatonin hypothesis", of a corollary and of associated predictions which can be united in our proposed theory of "carcinogenesis due to chronodisruption". The new theory suggests that the various predictions investigated between 1987 and 2008 represent different aspects of the same problem. Indeed, abundant experimental evidence supports the notion that the final common cause of many cases of cancer may be what has been termed chronodisruption (CD), a relevant disturbance of the temporal organization or order of physiology, endocrinology, metabolism and behaviour. While melatonin as a key time messenger and time keeper can be a marker of CD, it is probably only partially related to the differential cancer occurrence apparent in individuals who chronically or frequently experience an excess or deficit of chronodisruption.

  18. BRAFV600E: implications for carcinogenesis and molecular therapy.

    LENUS (Irish Health Repository)

    Cantwell-Dorris, Emma R

    2012-02-01

    The mitogen-activated protein kinase (MAPK)\\/extracellular signal-regulated kinase (ERK) pathway is frequently mutated in human cancer. This pathway consists of a small GTP protein of the RAS family that is activated in response to extracellular signaling to recruit a member of the RAF kinase family to the cell membrane. Active RAF signals through MAP\\/ERK kinase to activate ERK and its downstream effectors to regulate a wide range of biological activities including cell differentiation, proliferation, senescence, and survival. Mutations in the v-raf murine sarcoma viral oncogenes homolog B1 (BRAF) isoform of the RAF kinase or KRAS isoform of the RAS protein are found as activating mutations in approximately 30% of all human cancers. The BRAF pathway has become a target of interest for molecular therapy, with promising results emerging from clinical trials. Here, the role of the most common BRAF mutation BRAF(V600E) in human carcinogenesis is investigated through a review of the literature, with specific focus on its role in melanoma, colorectal, and thyroid cancers and its potential as a therapeutic target.

  19. Lineage fate of ductular reactions in liver injury and carcinogenesis.

    Science.gov (United States)

    Jörs, Simone; Jeliazkova, Petia; Ringelhan, Marc; Thalhammer, Julian; Dürl, Stephanie; Ferrer, Jorge; Sander, Maike; Heikenwalder, Mathias; Schmid, Roland M; Siveke, Jens T; Geisler, Fabian

    2015-06-01

    Ductular reactions (DRs) are observed in virtually all forms of human liver disease; however, the histogenesis and function of DRs in liver injury are not entirely understood. It is widely believed that DRs contain bipotential liver progenitor cells (LPCs) that serve as an emergency cell pool to regenerate both cholangiocytes and hepatocytes and may eventually give rise to hepatocellular carcinoma (HCC). Here, we used a murine model that allows highly efficient and specific lineage labeling of the biliary compartment to analyze the histogenesis of DRs and their potential contribution to liver regeneration and carcinogenesis. In multiple experimental and genetic liver injury models, biliary cells were the predominant precursors of DRs but lacked substantial capacity to produce new hepatocytes, even when liver injuries were prolonged up to 12 months. Genetic modulation of NOTCH and/or WNT/β-catenin signaling within lineage-tagged DRs impaired DR expansion but failed to redirect DRs from biliary differentiation toward the hepatocyte lineage. Further, lineage-labeled DRs did not produce tumors in genetic and chemical HCC mouse models. In summary, we found no evidence in our system to support mouse biliary-derived DRs as an LPC pool to replenish hepatocytes in a quantitatively relevant way in injury or evidence that DRs give rise to HCCs.

  20. Experimental pulmonary carcinogenesis by radon and its daughters

    International Nuclear Information System (INIS)

    Sato, Fumiaki

    1989-01-01

    Information on experimental pulmonary carcinogenesis by radon and its daughters has come mostly from experiments carried out in France and United States of America. In rats a dose response relation was estimated to be linear with dose at low dose region. Studies of rats exposed daily to radon and radon daughters indicated that the frequency of pulmonary cancer at total exposure greater than 3000 WLM was greater when the exposure rates were low. At low total exposures the dose-rate effect was less apparent. Cigarette smoke increased the pulmonary cancer in rats but decreased in dogs. The decrease may be due to a decrease of absorbed doses with increased secretion of mucus and to an enhancement of mucociliary clearance. After inhalation of 222 Ru at equilibrium with radon daughters, rats were inoculated intrapleurally with asbestos fibres or glass fibres. The additive co-carcinogenic effects of this type of insult were demonstrated by the increased incidence of malignant thoracic tumours. As for species differences, dogs and hamsters are relatively resistant to cancer induction and rats are sensitive. While bronchogenic carcinomas are the most frequently observed radiation-induced pulmonary cancer in humans, bronchioloalveolar carcinomas are the most frequent type in most animal species. (author)

  1. Skin carcinogenesis in man and in experimental models

    International Nuclear Information System (INIS)

    Hecker, E.; Jung, E.G.; Marks, F.; Tilgen, W.

    1993-01-01

    This book presents an updated overview of the current state of the art in scientific, experimental and clinical investigations on the generation and the prevention of cancer of the skin. From the achievements presented, marked refinements in the assessment of the risk of cancer, by environmental and endogenous factors, including tumor virus, will be stimulated. They include the problem of the stratospheric 'ozone holes' above both poles of the earth causing much public concern as expressed by current headlines in the media and by the United Nations Environmental Program. Moreover, new ideas will merge for developing specific approaches to explore the mechanistic, i.e. ultimately the molecular-biological, causes of skin cancer and others. In addition, the experimental utilization of oncogens and of other techniques of molecular biology at all levels of the biology of tissues and cells, may open up entirely new facets in the research on skin cancer. Detailed knowledge of the mechanistic aspects of skin carcinogenesis may give important hints with respect to 'tailor-make' and utilize new anti-tumor agents in the therapy of skin cancer for the benefit of the cancer patient. (orig.). 67 figs., 44 tabs

  2. Carcinogenesis in mice after low doses and dose rates

    International Nuclear Information System (INIS)

    Ullrich, R.L.

    1979-01-01

    The results from the experimental systems reported here indicate that the dose-response curves for tumor induction in various tissues cannot be described by a single model. Furthermore, although the understanding of the mechanisms involved in different systems is incomplete, it is clear that very different mechanisms for induction are involved. For some tumors the mechanism of carcinogenesis may be mainly a result of direct effects on the target cell, perhaps involving one or more mutations. While induction may occur, in many instances, through such direct effects, the eventual expression of the tumor can be influenced by a variety of host factors including endocrine status, competence of the immune system, and kinetics of target and interacting cell populations. In other tumors, indirect effects may play a major role in the initiation or expression of tumors. Some of the hormone-modulated tumors would fall into this class. Despite the complexities of the experimental systems and the lack of understanding of the types of mechanisms involved, in nearly every example the tumorigenic effectiveness per rad of low-LET radiation tends to decrease with decreasing dose rate. For some tumor types the differences may be small or may appear only with very low dose rates, while for others the dose-rate effects may be large

  3. Effects of retinoids on ultraviolet-induced carcinogenesis

    International Nuclear Information System (INIS)

    Epstein, J.H.

    1981-01-01

    The evidence for effects of the retinoids on UV-induced carcinogenesis is sparse. Clinical observations indicate that topical RA can cause significant regression of premalignant actinic keratoses. Also there is some evidence that this agent can cause dissolution of some basal cell epitheliomas. However this latter effect does not appear to be of therapeutic value. Systemic retinoids are of little value in the treatment of premalignant and malignant cutaneous lesions though 13-cis-retinoic acid might be of use in the basal cell nevus syndrome. Examination of the influence of the retinoids on photocarcinogenesis essentially has been confined to RA and animal experimentation. RA in nontoxic concentrations can both stimulate and inhibit photocarcinogenesis depending upon the circumstances of the study. The mechanisms of these responses are not clear. Influences on DNA synthesis directly and/or indirectly or on immune responses may be involved in both effects. Preliminary studies with oral 13-cis-retinoic acid have not demonstrated any effects to date on UV-induced skin cancer formation

  4. Influence of animal age upon antioxidant-modified UV carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Black, H S [Photobiology Laboratory, Veterans Administration Medical Center, Houston, TX (USA); McCann, V [Baylor Univ., Houston, TX (USA). Coll. of Medicine; Thornby, J I [Biostatistics Section, Research Service, Veterans Administration Medical Center, Houston, TX (USA)

    1982-08-01

    Studies were undertaken to examine the effects of animal age on the anticarcinogenic properties of antioxidants. Female hairless mice, 2.5, 4.5 and 9.5 months of age, were subjected to daily irradiation from Westinghouse BZS-WLG lamps for 19 weeks. Experimental groups of animals were maintained on a commercial rodent meal supplemented with a 2% (w/w) antioxidant mixture. Control groups received only the meal. Tumour latency, expressed as median time to tumor development, was significantly greater for all age groups receiving antioxidants than for their similarly aged controls. However, the response to antioxidants appeared to decrease with age and the antioxidant effect was significantly less in the 9.5 month-old group than in the 2.5 month-old group. Likewise, the two youngest groups receiving antioxidants demonstrated a significantly fewer number of tumors per animal. It is concluded that animal age influences the degree of photoprotection provided by antioxidants. Whether this effect is related to dietary intake, and thus dependent upon resident antioxidant levels, is unknown. Nevertheless, dietary antioxidants provide significant protection in young animals against carcinogenesis induced by radiation of predominantly UVB wavelengths.

  5. Review of hepatocellular carcinoma: Epidemiology, etiology, and carcinogenesis

    Directory of Open Access Journals (Sweden)

    Yezaz Ahmed Ghouri

    2017-01-01

    Full Text Available Since the 1970s, the epidemic of hepatocellular carcinoma (HCC has spread beyond the Eastern Asian predominance and has been increasing in Northern hemisphere, especially in the United States (US and Western Europe. It occurs more commonly in males in the fourth and fifth decades of life. Among all cancers, HCC is one of the fastest growing causes of death in the US and poses a significant economic burden on healthcare. Chronic liver disease due to hepatitis B virus or hepatitis C virus and alcohol accounts for the majority of HCC cases. Incidence of nonalcoholic fatty liver disease has been on the risem and it has also been associated with the development of HCC. Its pathogenesis varies based on the underlying etiological factor although majority of cases develop in the setting of background cirrhosis. Carcinogenesis of HCC includes angiogenesis, chronic inflammation, and tumor macroenvironment and microenvironment. There is a significant role of both intrinsic genetic risk factors and extrinsic influences such as alcohol or viral infections that lead to the development of HCC. Understanding its etiopathogenesis helps select appropriate diagnostic tests and treatments.

  6. Review of hepatocellular carcinoma: Epidemiology, etiology, and carcinogenesis.

    Science.gov (United States)

    Ghouri, Yezaz Ahmed; Mian, Idrees; Rowe, Julie H

    2017-01-01

    Since the 1970s, the epidemic of hepatocellular carcinoma (HCC) has spread beyond the Eastern Asian predominance and has been increasing in Northern hemisphere, especially in the United States (US) and Western Europe. It occurs more commonly in males in the fourth and fifth decades of life. Among all cancers, HCC is one of the fastest growing causes of death in the US and poses a significant economic burden on healthcare. Chronic liver disease due to hepatitis B virus or hepatitis C virus and alcohol accounts for the majority of HCC cases. Incidence of nonalcoholic fatty liver disease has been on the risem and it has also been associated with the development of HCC. Its pathogenesis varies based on the underlying etiological factor although majority of cases develop in the setting of background cirrhosis. Carcinogenesis of HCC includes angiogenesis, chronic inflammation, and tumor macroenvironment and microenvironment. There is a significant role of both intrinsic genetic risk factors and extrinsic influences such as alcohol or viral infections that lead to the development of HCC. Understanding its etiopathogenesis helps select appropriate diagnostic tests and treatments.

  7. Short-term carcinogenesis evaluation of Casearia sylvestris

    Directory of Open Access Journals (Sweden)

    Cleide A.S. Tirloni

    Full Text Available Abstract Casearia sylvestris Sw., Salicaceae, is an important medicinal plant widely used in Brazil for the treatment of various cardiovascular disorders. This species was included as of interest by Brazilian Unified Health System. Although preclinical studies described cardiovascular protective effects and apparent absence of toxicity, no studies have evaluated its carcinogenic potential. In this study, we proposed a short-term carcinogenesis evaluation of C. sylvestris in Wistar rats, aiming to check the safety of this species to use it as proposed by Brazilian Unified Health System. C. sylvestris leaves were obtained and the crude extract was prepared by maceration from methanol/water. Wistar rats were orally treated for 12 weeks with 50, 250 or 500 mg kg−1 of crude extract or vehicle. Body weight, daily morbidity and mortality were monitored. Blood and bone marrow samples were collect for micronucleus test, comet assay and tumor markers evaluation. Vital organs were removed to macro and histopathological analyses. The crude extract did not induce mutagenic and genotoxic effects and no alterations were observed in important tumor markers. Finally, no detectable signs of injury through gross pathology or histopathological examinations were observed. Our results certify the absence of the crude extract toxicity, indicating its safety, even at prolonged exposure as proposed by Brazilian Unified Health System.

  8. Development and validation of microbial bioassay for quantification of Levofloxacin in pharmaceutical preparations

    Directory of Open Access Journals (Sweden)

    Nishant A. Dafale

    2015-02-01

    Full Text Available The aim of this study was to develop and validate a simple, sensitive, precise and cost-effective one-level agar diffusion (5+1 bioassay for estimation of potency and bioactivity of Levofloxacin in pharmaceutical preparation which has not yet been reported in any pharmacopoeia. Among 16 microbial strains, Bacillus pumilus ATCC-14884 was selected as the most significant strain against Levofloxacin. Bioassay was optimized by investigating several factors such as buffer pH, inoculums concentration and reference standard concentration. Identification of Levofloxacin in commercial sample Levoflox tablet was done by FTIR spectroscopy. Mean potency recovery value for Levofloxacin in Levoflox tablet was estimated as 100.90%. A validated bioassay method showed linearity (r2=0.988, precision (Interday RSD=1.05%, between analyst RSD=1.02% and accuracy (101.23%, RSD=0.72%. Bioassay was correlated with HPLC using same sample and estimated potencies were 100.90% and 99.37%, respectively. Results show that bioassay is a suitable method for estimation of potency and bioactivity of Levofloxacin pharmaceutical preparations. Keywords: Levofloxacin, Antibiotic resistance, Microbiological bioassay, HPLC, Pharmacopoeia

  9. A rapid bioassay for detecting saxitoxins using a Daphnia acute toxicity test

    Energy Technology Data Exchange (ETDEWEB)

    Ferrao-Filho, Aloysio da S., E-mail: aloysio@ioc.fiocruz.b [Laboratorio de Avaliacao e Promocao da Saude Ambiental, Departamento de Biologia, Instituto Oswaldo Cruz, FIOCRUZ, Av. Brasil 4365, Manguinhos, Rio de Janeiro, RJ 21045-900 (Brazil); Soares, Maria Carolina S., E-mail: mcarolsoares@gmail.co [Departamento de Engenharia Sanitaria e Ambiental Faculdade de Engenharia, Universidade Federal de Juiz de Fora, Juiz de Fora, MG 36036-900 (Brazil); Freitas de Magalhaes, Valeria, E-mail: valeria@biof.ufrj.b [Laboratorio de Ecofisiologia e Toxicologia de Cianobacterias, Instituto de Biofisica Carlos Chagas Filho, CCS, Universidade Federal do Rio de Janeiro, Ilha do Fundao, Rio de Janeiro, RJ 21949-900 (Brazil); Azevedo, Sandra M.F.O., E-mail: sazevedo@biof.ufrj.b [Laboratorio de Ecofisiologia e Toxicologia de Cianobacterias, Instituto de Biofisica Carlos Chagas Filho, CCS, Universidade Federal do Rio de Janeiro, Ilha do Fundao, Rio de Janeiro, RJ 21949-900 (Brazil)

    2010-06-15

    Bioassays using Daphnia pulex and Moina micrura were designed to detect cyanobacterial neurotoxins in raw water samples. Phytoplankton and cyanotoxins from seston were analyzed during 15 months in a eutrophic reservoir. Effective time to immobilize 50% of the exposed individuals (ET{sub 50}) was adopted as the endpoint. Paralysis of swimming movements was observed between approx0.5-3 h of exposure to lake water containing toxic cyanobacteria, followed by an almost complete recovery of the swimming activity within 24 h after being placed in control water. The same effects were observed in bioassays with a saxitoxin-producer strain of Cylindrospermopsis raciborskii isolated from the reservoir. Regression analysis showed significant relationships between ET{sub 50}vs. cell density, biomass and saxitoxins content, suggesting that the paralysis of Daphnia in lake water samples was caused by saxitoxins found in C. raciborskii. Daphnia bioassay was found to be a sensitive method for detecting fast-acting neurotoxins in natural samples, with important advantages over mouse bioassays. - A new Daphnia bioassay, as an alternative to the mouse bioassay, is able to detect effects of fast-acting, potent neurotoxins in raw water.

  10. A rapid bioassay for detecting saxitoxins using a Daphnia acute toxicity test

    International Nuclear Information System (INIS)

    Ferrao-Filho, Aloysio da S.; Soares, Maria Carolina S.; Freitas de Magalhaes, Valeria; Azevedo, Sandra M.F.O.

    2010-01-01

    Bioassays using Daphnia pulex and Moina micrura were designed to detect cyanobacterial neurotoxins in raw water samples. Phytoplankton and cyanotoxins from seston were analyzed during 15 months in a eutrophic reservoir. Effective time to immobilize 50% of the exposed individuals (ET 50 ) was adopted as the endpoint. Paralysis of swimming movements was observed between ∼0.5-3 h of exposure to lake water containing toxic cyanobacteria, followed by an almost complete recovery of the swimming activity within 24 h after being placed in control water. The same effects were observed in bioassays with a saxitoxin-producer strain of Cylindrospermopsis raciborskii isolated from the reservoir. Regression analysis showed significant relationships between ET 50 vs. cell density, biomass and saxitoxins content, suggesting that the paralysis of Daphnia in lake water samples was caused by saxitoxins found in C. raciborskii. Daphnia bioassay was found to be a sensitive method for detecting fast-acting neurotoxins in natural samples, with important advantages over mouse bioassays. - A new Daphnia bioassay, as an alternative to the mouse bioassay, is able to detect effects of fast-acting, potent neurotoxins in raw water.

  11. An ion quencher operated lamp for multiplexed fluorescent bioassays.

    Science.gov (United States)

    Qing, Taiping; Sun, Huanhuan; He, Xiaoxiao; Huang, Xiaoqin; He, Dinggeng; Bu, Hongchang; Qiao, Zhenzhen; Wang, Kemin

    2018-02-01

    A novel and adjustable lamp based on competitive interaction among dsDNA-SYBR Green I (SGI), ion quencher, and analyte was designed for bioanalysis. The "filament" and switch of the lamp could be customized by employing different dsDNA and ion quencher. The poly(AT/TA) dsDNA was successfully screened as the most effective filament of the lamp. Two common ions, Hg 2+ and Fe 3+ , were selected as the model switch, and the corresponding ligand molecules cysteine (Cys) and pyrophosphate ions (PPi) were selected as the targets. When the fluorescence-quenched dsDNA/SGI-ion complex was introduced into a target-containing system, ions could be bound by competitive molecules and separate from the complex, thereby lighting the lamp. However, no light was observed if the biomolecule could not snatch the metal ions from the complex. Under the optimal conditions, sensitive and selective detection of Cys and PPi was achieved by the lamp, with practical applications in fetal bovine serum and human urine. This ion quencher regulated lamp for fluorescent bioassays is simple in design, fast in operation, and is more convenient than other methods. Significantly, as many molecules could form stable complexes with metal ions selectively, this ion quencher operated lamp has potential for the detection of a wide spectrum of analytes. Graphical abstract A novel and adjustable lamp on the basis of competitive interaction among dsDNA-SYBR Green I, ions quencher and analyte was designed for bioanalysis. The filament and switch of lamp could be customized by employing different dsDNA and ions quencher.

  12. Development of Androgen- and Estrogen-Responsive bio-assays, members of a panel of human cell line-based highly selective steroid-responsive bioassays

    NARCIS (Netherlands)

    Sonneveld, E.; Jansen, H.J.

    2004-01-01

    We have established highly sensitive and specific androgen and estrogen reporter cell lines which we have named AR (androgen receptor) and ERα (estrogen receptor alpha) CALUX® (Chemically Activated LUciferase eXpression), respectively. Both bioassays are member of a panel of CALUX reporter cell

  13. Development of androgen-and estrogen-responsive bioassays, members of a panel of human cell line-based highly selective steroid-responsive bioassays

    NARCIS (Netherlands)

    Sonneveld, E.; Jansen, H.J..; Riteco, J.A.C.; Brouwer, A.

    2005-01-01

    We have established highly sensitive and specific androgen and estrogen reporter cell lines which we have named AR (androgen receptor) and ERα (estrogen receptor alpha) CALUX® (Chemically Activated LUciferase eXpression), respectively. Both bioassays are member of a panel of CALUX reporter cell

  14. Immunophenotypic Analysis in Early Müllerian Serous Carcinogenesis.

    Science.gov (United States)

    Nafisi, Houman; Ghorab, Zeina; Ismill, Nadia; Dubé, Valerie; Plotkin, Anna; Han, Guangming; Cesari, Matthew; Lu, Fang-I; Saad, Reda; Khalifa, Mahmoud; Nofech-Mozes, Sharon

    2015-09-01

    Studies on the immunophenotypes of early forms of serous carcinoma arising from female genital tract are limited. We aimed to examine p53, p16(Ink4a), estrogen receptor (ER), progesterone receptor (PR), ERBB2, WT1, and Ki-67 protein expression in endometrial intraepithelial carcinoma (n=29), serous tubal intraepithelial lesion (n=4) and carcinoma (STIC, n=10), and the putative precursor p53 signature (n=11). Among endometrial intraepithelial carcinoma, 80% demonstrated p53 overexpression and 10% were consistent with a null phenotype. p16(Ink4a) immunostaining were observed in all endometrial intraepithelial carcinoma cases. ER, PR, ERBB2, and WT1 were positive in 54%, 25%, 11%, and 18% of cases, respectively. STIC cases demonstrated p53 overexpression and null phenotype in 90% and 10%, respectively. All STIC cases were p16(Ink4a) and WT1 positive, whereas ER and PR were positive in 70% and 20%, respectively. All STICs were negative for ERBB2. Among serous tubal intraepithelial lesion cases, 75% demonstrated p53 overexpression and 25% a null phenotype. p53 was positive in all 11 p53 signature cases, whereas p16(Ink4a) was universally negative. Finally, ER and PR were positive in 100% and 73% of p53 signature cases, respectively. These results suggest that p16(Ink4a) has a role in early Müllerian serous carcinogenesis but is absent in the earliest noncommitted lesion. p16(Ink4a) immunohistochemistry can be used as an adjunct confirmatory tool in p53-null cases with limited surface area.

  15. Relationship to carcinogenesis of repetitive low-dose radiation exposure

    International Nuclear Information System (INIS)

    Ootsuyama, Akira

    2016-01-01

    We studied the carcinogenic effects caused by repetitive irradiation at a low dose, which has received attention in recent years, and examined the experimental methods used to evaluate radiation-induced carcinogenesis. For this experiment, we selected a mouse with as few autochthonous cancers as possible. Skin cancer was selected as the target for analysis, because it is a rare cancer in mice. Beta-rays were selected as the radiation source. The advantage of using beta-rays is weaker penetration power into tissues, thus protecting organs, such as the digestive and hematogenous organs. The benefit of our experimental method is that only skin cancer requires monitoring, and it is possible to perform long-term experiments. The back skin of mice was exposed repetitively to beta-rays three times a week until the occurrence of cancer or death, and the dose per exposure ranged from 0.5 to 11.8 Gy. With the high-dose range (2.5-11.8 Gy), the latency period and carcinogenic rate were almost the same in each experimental group. When the dose was reduced to 1-1.5 Gy, the latency period increased, but the carcinogenic rate remained. When the dose was further reduced to 0.5 Gy, skin cancer never happened, even though we continued irradiation until death of the last mouse in this group. The lifespan of 0.5 Gy group mice was the same as that of the controls. We showed that the 0.5 Gy dose did not cause cancer, even in mice exposed repetitively throughout their life span, and thus refer to 0.5 Gy as the threshold-like dose. (author)

  16. Three molecular pathways model colorectal carcinogenesis in Lynch syndrome.

    Science.gov (United States)

    Ahadova, Aysel; Gallon, Richard; Gebert, Johannes; Ballhausen, Alexej; Endris, Volker; Kirchner, Martina; Stenzinger, Albrecht; Burn, John; von Knebel Doeberitz, Magnus; Bläker, Hendrik; Kloor, Matthias

    2018-07-01

    Lynch syndrome is caused by germline mutations of DNA mismatch repair (MMR) genes. MMR deficiency has long been regarded as a secondary event in the pathogenesis of Lynch syndrome colorectal cancers. Recently, this concept has been challenged by the discovery of MMR-deficient crypt foci in the normal mucosa. We aimed to reconstruct colorectal carcinogenesis in Lynch syndrome by collecting molecular and histology evidence from Lynch syndrome adenomas and carcinomas. We determined the frequency of MMR deficiency in adenomas from Lynch syndrome mutation carriers by immunohistochemistry and by systematic literature analysis. To trace back the pathways of pathogenesis, histological growth patterns and mutational signatures were analyzed in Lynch syndrome colorectal cancers. Literature and immunohistochemistry analysis demonstrated MMR deficiency in 491 (76.7%) out of 640 adenomas (95% CI: 73.3% to 79.8%) from Lynch syndrome mutation carriers. Histologically normal MMR-deficient crypts were found directly adjacent to dysplastic adenoma tissue, proving their role as tumor precursors in Lynch syndrome. Accordingly, mutation signature analysis in Lynch colorectal cancers revealed that KRAS and APC mutations commonly occur after the onset of MMR deficiency. Tumors lacking evidence of polypous growth frequently presented with CTNNB1 and TP53 mutations. Our findings demonstrate that Lynch syndrome colorectal cancers can develop through three pathways, with MMR deficiency commonly representing an early and possibly initiating event. This underlines that targeting MMR-deficient cells by chemoprevention or vaccines against MMR deficiency-induced frameshift peptide neoantigens holds promise for tumor prevention in Lynch syndrome. © 2018 UICC.

  17. Colorectal carcinogenesis: Review of human and experimental animal studies

    Directory of Open Access Journals (Sweden)

    Tanaka Takuji

    2009-01-01

    Full Text Available This review gives a comprehensive overview of cancer development and links it to the current understanding of tumorigenesis and malignant progression in colorectal cancer. The focus is on human and murine colorectal carcinogenesis and the histogenesis of this malignant disorder. A summary of a model of colitis-associated colon tumorigenesis (an AOM/DSS model will also be presented. The earliest phases of colorectal oncogenesis occur in the normal mucosa, with a disorder of cell replication. The large majority of colorectal malignancies develop from an adenomatous polyp (adenoma. These can be defined as well-demarcated masses of epithelial dysplasia, with uncontrolled crypt cell proliferation. When neoplastic cells pass through the muscularis mucosa and infiltrate the submucosa, they are malignant. Carcinomas usually originate from pre-existing adenomas, but this does not imply that all polyps undergo malignant changes and does not exclude de novo oncogenesis. Besides adenomas, there are other types of pre-neoplasia, which include hyperplastic polyps, serrated adenomas, flat adenomas and dysplasia that occurs in the inflamed colon in associated with inflammatory bowel disease. Colorectal neoplasms cover a wide range of pre-malignant and malignant lesions, many of which can easily be removed during endoscopy if they are small. Colorectal neoplasms and/or pre-neoplasms can be prevented by interfering with the various steps of oncogenesis, which begins with uncontrolled epithelial cell replication, continues with the formation of adenomas and eventually evolves into malignancy. The knowledge described herein will help to reduce and prevent this malignancy, which is one of the most frequent neoplasms in some Western and developed countries.

  18. Interaction between APC and Fen1 during breast carcinogenesis.

    Science.gov (United States)

    Narayan, Satya; Jaiswal, Aruna S; Law, Brian K; Kamal, Mohammad A; Sharma, Arun K; Hromas, Robert A

    2016-05-01

    Aberrant DNA base excision repair (BER) contributes to malignant transformation. However, inter-individual variations in DNA repair capacity plays a key role in modifying breast cancer risk. We review here emerging evidence that two proteins involved in BER - adenomatous polyposis coli (APC) and flap endonuclease 1 (Fen1) - promote the development of breast cancer through novel mechanisms. APC and Fen1 expression and interaction is increased in breast tumors versus normal cells, APC interacts with and blocks Fen1 activity in Pol-β-directed LP-BER, and abrogation of LP-BER is linked with cigarette smoke condensate-induced transformation of normal breast epithelial cells. Carcinogens increase expression of APC and Fen1 in spontaneously immortalized human breast epithelial cells, human colon cancer cells, and mouse embryonic fibroblasts. Since APC and Fen1 are tumor suppressors, an increase in their levels could protect against carcinogenesis; however, this does not seem to be the case. Elevated Fen1 levels in breast and lung cancer cells may reflect the enhanced proliferation of cancer cells or increased DNA damage in cancer cells compared to normal cells. Inactivation of the tumor suppressor functions of APC and Fen1 is due to their interaction, which may act as a susceptibility factor for breast cancer. The increased interaction of APC and Fen1 may occur due to polypmorphic and/or mutational variation in these genes. Screening of APC and Fen1 polymorphic and/or mutational variations and APC/Fen1 interaction may permit assessment of individual DNA repair capability and the risk for breast cancer development. Such individuals might lower their breast cancer risk by reducing exposure to carcinogens. Stratifying individuals according to susceptibility would greatly assist epidemiologic studies of the impact of suspected environmental carcinogens. Additionally, a mechanistic understanding of the interaction of APC and Fen1 may provide the basis for developing new and

  19. Biogenic silica fibre promotes carcinogenesis in mouse skin.

    Science.gov (United States)

    Bhatt, T; Coombs, M; O'Neill, C

    1984-10-15

    Silica fibres derived from plants are common contaminants of human diet in certain regions of the world where oesophageal cancer reaches extremely high incidences. We show here that one of these types of fibre (derived from Phalaris canariensis L) promotes the occurrence of tumours in the skin of mice initiated with a polycyclic carcinogen. Three experiments are described. In the first, the grain which bears these fibres was added to the diet. This did not result in any abnormality in any part of the gastrointestinal tract, but there was a significant induction of tumours in the skin around the mouth and nose; these were the areas of the body surface which most frequently came into contact with the grain. In the second experiment, the mice were separated from the grain by an intervening wire gauze barrier; a similar number of tumours appeared on initiated mice treated in this way. In this case, contact now occurred most frequently on the dorsal surface, which was rubbed against the gauze barrier, and it was on this surface that the tumours appeared. No tumours appeared if the grain was removed. In the third experiment, pure fibres were isolated from the surface of the grain and boiled in strong nitric acid so as to remove any organic material. When these acid-cleaned fibres were applied to the initiated skin with light pressure, they promoted carcinogenesis in the same way as croton oil. In each experiment the majority of tumours produced were benign neoplasms, together with at least one squamous carcinoma. It seems possible that the size and shape of these fibres are the critical properties determining their promoting activity. Their mean diameter is 15 microns, their modal length close to 200 microns, and they are sharply pointed with a tip diameter of 0.5 micron.

  20. Evaluation of the toxicity of two soils from Jales Mine (Portugal) using aquatic bioassays.

    Science.gov (United States)

    Loureiro, Susana; Ferreira, Abel L G; Soares, Amadeu M V M; Nogueira, António J A

    2005-10-01

    Soil contamination can be one path for streams and groundwater contamination. As a complement of chemical analysis and total contaminants determination, bioassays can provide information on the bioavailable fraction of chemical compounds, focusing on the retention and habitat function of soils. In this study the evaluation of the toxicity of two soils from the abandoned Jales Mine (Portugal) regarded both functions. The buffer capacity of soils was tested with bioassays carried out using the cladoceran Daphnia magna and the marine bacteria Vibrio fischeri. The habitat function of soils was evaluated with the reproduction bioassay with the collembolan Folsomia candida. The Microtox solid-phase test was performed with V. fischeri using soil as test medium, and soil elutriates were extracted to perform the Microtox basic test, and an immobilization and reproduction bioassay with D. magna. The marine bacteria showed high sensitivity to the soil with low heavy metal content (JNC soil) and to JNC soil elutriates, while the soil with highest heavy metal content (JC soil) or soil elutriates exposure did not cause any toxic effect. In the bioassays with D. magna, organisms showed sensitivity to JNC and also to JC soil elutriates. Both mobilization and reproduction features were inhibited. The bioassay with F. candida did not reflect any influence of the contaminants on their reproduction. Although JNC soil presented lower heavy metal contents, elutriates showed different patterns of contamination when compared to JC soil and elutriates, which indicates different retention and buffer capacities between soils. Results obtained in this study underlined the sensitivity and importance of soil elutriate bioassays with aquatic organisms in the evaluation strategy in soil ERA processes.

  1. Benchmarking organic micropollutants in wastewater, recycled water and drinking water with in vitro bioassays.

    Science.gov (United States)

    Escher, Beate I; Allinson, Mayumi; Altenburger, Rolf; Bain, Peter A; Balaguer, Patrick; Busch, Wibke; Crago, Jordan; Denslow, Nancy D; Dopp, Elke; Hilscherova, Klara; Humpage, Andrew R; Kumar, Anu; Grimaldi, Marina; Jayasinghe, B Sumith; Jarosova, Barbora; Jia, Ai; Makarov, Sergei; Maruya, Keith A; Medvedev, Alex; Mehinto, Alvine C; Mendez, Jamie E; Poulsen, Anita; Prochazka, Erik; Richard, Jessica; Schifferli, Andrea; Schlenk, Daniel; Scholz, Stefan; Shiraishi, Fujio; Snyder, Shane; Su, Guanyong; Tang, Janet Y M; van der Burg, Bart; van der Linden, Sander C; Werner, Inge; Westerheide, Sandy D; Wong, Chris K C; Yang, Min; Yeung, Bonnie H Y; Zhang, Xiaowei; Leusch, Frederic D L

    2014-01-01

    Thousands of organic micropollutants and their transformation products occur in water. Although often present at low concentrations, individual compounds contribute to mixture effects. Cell-based bioassays that target health-relevant biological endpoints may therefore complement chemical analysis for water quality assessment. The objective of this study was to evaluate cell-based bioassays for their suitability to benchmark water quality and to assess efficacy of water treatment processes. The selected bioassays cover relevant steps in the toxicity pathways including induction of xenobiotic metabolism, specific and reactive modes of toxic action, activation of adaptive stress response pathways and system responses. Twenty laboratories applied 103 unique in vitro bioassays to a common set of 10 water samples collected in Australia, including wastewater treatment plant effluent, two types of recycled water (reverse osmosis and ozonation/activated carbon filtration), stormwater, surface water, and drinking water. Sixty-five bioassays (63%) showed positive results in at least one sample, typically in wastewater treatment plant effluent, and only five (5%) were positive in the control (ultrapure water). Each water type had a characteristic bioanalytical profile with particular groups of toxicity pathways either consistently responsive or not responsive across test systems. The most responsive health-relevant endpoints were related to xenobiotic metabolism (pregnane X and aryl hydrocarbon receptors), hormone-mediated modes of action (mainly related to the estrogen, glucocorticoid, and antiandrogen activities), reactive modes of action (genotoxicity) and adaptive stress response pathway (oxidative stress response). This study has demonstrated that selected cell-based bioassays are suitable to benchmark water quality and it is recommended to use a purpose-tailored panel of bioassays for routine monitoring.

  2. Assessing arsenic bioavailability through the use of bioassays

    Science.gov (United States)

    Diesel, E.; Nadimpalli, M.; Hull, M.; Schreiber, M. E.; Vikesland, P.

    2009-12-01

    Various methods have been used to characterize the bioavailability of a contaminant, including chemical extractions from soils, toxicity tests, bioaccumulation measurements, estimation from soil properties, in vitro/in vivo tests, and microbial biossays. Unfortunately, these tests are all unique (i.e. they measure bioavailability through different mechanisms) and it is difficult to compare measurements collected using one method to those collected from another. Additionally, there are fundamental aspects of bioavailability research that require further study. In particular, changes in bioavailability over time are not well understood, as well as what the geochemical controls are on changes in bioavailability. In addition, there are no studies aimed at the integration of bioavailability measurements and potential geochemical controls. This research project seeks to find a standard set of assays and sensors that can be used to assess arsenic bioavailability at any field site, as well as to use these tools and techniques to better understand changes in, and controls on, arsenic bioavailability. The bioassays to be utilized in this research are a bioluminescent E. coli assay and a Corbicula fluminea (Asian clam) assay. Preliminary experiments to determine the suitability of the E. coli and C. fluminea assays have been completed. The E. coli assay can be utilized to analyze As(III) and As(V) with a linear standard curve between 5 and 200 ppb for As(III) and 100 ppb and 5 ppm for As(V); no bioluminescent response above background was elicited in the presence of Roxarsone, an organoarsenical. The C. fluminea assay is capable of bioaccumulating As(III), As(V), Roxarsone, and MSMA, with As(III) being the most readily accumulated, followed by As(V), Roxarsone and MSMA, respectively. Additional research will include assessing bioavailability of various arsenic species adsorbed to natural colloidal materials (i.e. clays, iron oxides, NOM) to the E. coli and C. fluminea assays

  3. Structuring a risk-based bioassay program for uranium usage in university laboratories

    Science.gov (United States)

    Dawson, Johnne Talia

    Bioassay programs are integral in a radiation safety program. They are used as a method of determining whether individuals working with radioactive material have been exposed and have received a resulting dose. For radionuclides that are not found in nature, determining an exposure is straightforward. However, for a naturally occurring radionuclide like uranium, it is not as straightforward to determine whether a dose is the result of an occupational exposure. The purpose of this project is to address this issue within the University of Nevada, Las Vegas's (UNLV) bioassay program. This project consisted of two components that studied the effectiveness of a bioassay program in determining the dose for an acute inhalation of uranium. The first component of the plan addresses the creation of excretion curves, utilizing MATLAB that would allow UNLV to be able to determine at what time an inhalation dose can be attributed to. The excretion curves were based on the ICRP 30 lung model, as well as the Annual Limit Intake (ALI) values located in the Nuclear Regulatory Commission's 10CFR20 which is based on ICRP 30 (International Commission on Radiological Protection). The excretion curves would allow UNLV to be able to conduct in-house investigations of inhalation doses without solely depending on outside investigations and sources. The second component of the project focused on the creation of a risk based bioassay program to be utilized by UNLV that would take into account bioassay frequency that depended on the individual. Determining the risk based bioassay program required the use of baseline variance in order to minimize the investigation of false positives among those individuals who undergo bioassays for uranium work. The proposed program was compared against an evaluation limit of 10 mrem per quarter, an investigational limit of 125 mrem per quarter, and the federal/state requirement of 1.25 rem per quarter. It was determined that a bioassay program whose bioassay

  4. Comparison of solid-phase bioassays and ecoscores to evaluate the toxicity of contaminated soils

    International Nuclear Information System (INIS)

    Lors, Christine; Ponge, Jean-Francois; Martinez Aldaya, Maite; Damidot, Denis

    2010-01-01

    Five bioassays (inhibition of lettuce germination and growth, earthworm mortality, inhibition of springtail population growth, avoidance by springtails) were compared, using four coke factory soils contaminated by PAHs and trace elements, before and after biotreatment. For each bioassay, several endpoints were combined in an 'ecoscore', a measure of test sensitivity. Ecoscores pooled over all tested bioassays revealed that most organisms were highly sensitive to the concentration of 3-ring PAHs. When four soils were combined, behavioural tests using the springtail Folsomia candida showed higher ecoscores, i.e. they were most sensitive to soil contamination. However, despite overall higher sensitivity of behavioural tests, which could be used for cheap and rapid assessment of soil toxicity, especially at low levels of contamination, some test endpoints were more sensitive than others, and this may differ from a soil to another, pointing to the need for a battery of bioassays when more itemized results are expected. - The avoidance test using the soil springtail Folsomia candida is globally more sensitive to PAH contamination than acute and chronic toxicity bioassays using plants and animals but a battery of tests could reveal better in detail.

  5. Comparison of solid-phase bioassays and ecoscores to evaluate the toxicity of contaminated soils

    Energy Technology Data Exchange (ETDEWEB)

    Lors, Christine [Universite Lille Nord de France, 1bis rue Georges Lefevre, 59044 Lille Cedex (France); Ecole des Mines de Douai, MPE-GCE, 941 rue Charles-Bourseul, 59500 Douai (France); Centre National de Recherche sur les Sites et Sols Pollues, 930 Boulevard Lahure, BP 537, 59505 Douai Cedex (France); Ponge, Jean-Francois, E-mail: ponge@mnhn.f [Museum National d' Histoire Naturelle, CNRS UMR 7179, 4 Avenue du Petit-Chateau, 91800 Brunoy (France); Martinez Aldaya, Maite [Museum National d' Histoire Naturelle, CNRS UMR 7179, 4 Avenue du Petit-Chateau, 91800 Brunoy (France); Damidot, Denis [Universite Lille Nord de France, 1bis rue Georges Lefevre, 59044 Lille Cedex (France); Ecole des Mines de Douai, MPE-GCE, 941 rue Charles-Bourseul, 59500 Douai (France)

    2010-08-15

    Five bioassays (inhibition of lettuce germination and growth, earthworm mortality, inhibition of springtail population growth, avoidance by springtails) were compared, using four coke factory soils contaminated by PAHs and trace elements, before and after biotreatment. For each bioassay, several endpoints were combined in an 'ecoscore', a measure of test sensitivity. Ecoscores pooled over all tested bioassays revealed that most organisms were highly sensitive to the concentration of 3-ring PAHs. When four soils were combined, behavioural tests using the springtail Folsomia candida showed higher ecoscores, i.e. they were most sensitive to soil contamination. However, despite overall higher sensitivity of behavioural tests, which could be used for cheap and rapid assessment of soil toxicity, especially at low levels of contamination, some test endpoints were more sensitive than others, and this may differ from a soil to another, pointing to the need for a battery of bioassays when more itemized results are expected. - The avoidance test using the soil springtail Folsomia candida is globally more sensitive to PAH contamination than acute and chronic toxicity bioassays using plants and animals but a battery of tests could reveal better in detail.

  6. Natural products phytotoxicity A bioassay suitable for small quantities of slightly water-soluble compounds.

    Science.gov (United States)

    Dornbos, D L; Spencer, G F

    1990-02-01

    A large variety of secondary metabolites that can inhibit germination and/or seedling growth are produced by plants in low quantities. The objective of this study was to develop a bioassay capable of reliably assessing reductions in germination percentage and seedling length of small-seeded plant species caused by exposure to minute quantities of these compounds. The germination and growth of alfalfa (Medicago saliva), annual ryegrass (Lolium multiflorum), and velvetleaf (Abutilon theophrasti) were evaluated against six known phytotoxins from five chemical classes; cinmethylin (a herbicidal cineole derivative) was selected as a comparison standard. Each phytotoxin, dissolved in a suitable organic solvent, was placed on water-agar in small tissue culture wells. After the solvent evaporated, imbibed seeds were placed on the agar; after three days, germination percentages and seedling lengths were measured. Compared to a commonly used filter paper procedure, this modified agar bioassay required smaller quantities of compound per seed for comparable bioassay results. This bioassay also readily permitted the measurement of seedling length, a more sensitive indicator of phytotoxicity than germination. Seedling length decreased sigmoidally as the toxin concentration increased logarithmically. Phytotoxicity was a function of both compound and plant species. Cinmethylin, a grass herbicide, reduced the length of annual ryegrass seedlings by 90-100%, whereas that of alfalfa and velvetleaf was inhibited slightly. The agar bioassay facilitated the rapid and reliable testing of slightly water-soluble compounds, requiring only minute quantities of each compound to give reproducible results.

  7. O-GlcNAcylation of RACK1 promotes hepatocellular carcinogenesis.

    Science.gov (United States)

    Duan, Fangfang; Wu, Hao; Jia, Dongwei; Wu, Weicheng; Ren, Shifang; Wang, Lan; Song, Shushu; Guo, Xinying; Liu, Fenglin; Ruan, Yuanyuan; Gu, Jianxin

    2018-06-01

    Aberrant oncogenic mRNA translation and protein O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) are general features during tumorigenesis. Nevertheless, whether and how these two pathways are interlinked remain unknown. Our previous study indicated that ribosomal receptor for activated C-kinase 1 (RACK1) promoted chemoresistance and growth in hepatocellular carcinoma (HCC). The aim of this study is to examine the role of RACK1 O-GlcNAcylation in oncogene translation and HCC carcinogenesis. The site(s) of RACK1 for O-GlcNAcylation was mapped by mass spectrometry analysis. HCC cell lines were employed to examine the effects of RACK1 O-GlcNAcylation on the translation of oncogenic factors and behaviors of tumor cells in vitro. Transgenic knock-in mice were used to detect the role of RACK1 O-GlcNAcylation in modulating HCC tumorigenesis in vivo. The correlation of RACK1 O-GlcNAcylation with tumor progression and relapse were analyzed in clinical HCC samples. We found that ribosomal RACK1 was highly modified by O-GlcNAc at Ser122. O-GlcNAcylation of RACK1 enhanced its protein stability, ribosome binding and interaction with PKCβII (PRKCB), leading to increased eukaryotic translation initiation factor 4E phosphorylation and translation of potent oncogenes in HCC cells. Genetic ablation of RACK1 O-GlcNAcylation at Ser122 dramatically suppressed tumorigenesis, angiogenesis, and metastasis in vitro and in diethylnitrosamine (DEN)-induced HCC mouse model. Increased RACK1 O-GlcNAcylation was also observed in HCC patient samples and correlated with tumor development and recurrence after chemotherapy. These findings demonstrate that RACK1 acts as key mediator linking O-GlcNAc metabolism to cap-dependent translation during HCC tumorigenesis. Targeting RACK1 O-GlcNAcylation provides promising options for HCC treatment. O-GlcNAcylation of ribosomal receptor for activated C-kinase 1 at the amino acid serine122 promotes its stability, ribosome localization and interaction

  8. Development by flow cytometry of bioassays based on chlorella for environmental monitoring

    Directory of Open Access Journals (Sweden)

    Petrescu C-M,

    2016-05-01

    Full Text Available In ecotoxicological assessments, bioassays (ecotoxicity tests or biotests are one of the main tools, defined as methods which use living cells, tissues, organism or communities to assess exposure-related effects of chemicals. The increasing complexity of environmental degradation requires an increase in the capacity of scientific approach in monitoring and notification as early as possible risks. Our own objective concerns the detection of aquatic environment pollution in Romania and particularly in the Danube basin. For assessing aquatic environment pollution degree or for assessing cytotoxicity or ecotoxicity of pollutants (heavy metals, nanoparticles, pesticides, etc. we developed news experimental bioassays based on the use of viability and apoptosis biomarkers of Chlorella cells by flow cytometry. Our proposed bioassays could be rapid and very sensitive tests for in laboratory aquatic risk assessment and biomonitoring.

  9. Methodology for estimation of 32P in bioassay samples by Cerenkov counting

    International Nuclear Information System (INIS)

    Wankhede, Sonal; Sawant, Pramilla D.; Yadav, R.K.B.; Rao, D.D.

    2016-01-01

    Radioactive phosphorus ( 32 P) as phosphate is used to effectively reduce bone pain in terminal cancer patients. Several hospitals in India carry out this palliative care procedure on a regular basis. Thus, production as well as synthesis of 32 P compounds has increased over the years to meet this requirement. Monitoring of radiation workers handling 32 P compounds is important for further strengthening of radiological protection program at processing facility. 32 P being a pure beta emitter (β max = 1.71 MeV, t 1/2 = 14.3 d), bioassay is the preferred individual monitoring technique. Method standardized at Bioassay Lab, Trombay, includes estimation of 32 P in urine by co-precipitation with ammonium phosphomolybdate (AMP) followed by gross beta counting. In the present study, feasibility of Cerenkov counting for detection of 32 P in bioassay samples was explored and the results obtained were compared with the gross beta counting technique

  10. Comparison of liquid chromatographic and bioassay procedures for determining depletion of intramuscularly injected tylosin.

    Science.gov (United States)

    Moats, W A; Harris, E W; Steele, N C

    1985-01-01

    Crossbred pigs weighing 80-110 kg were injected intramuscularly in the ham with 8.8 mg/kg tylosin. Animals were slaughtered in groups of 3 at intervals of 4 h, and 1, 2, 4, and 8 days after injection, and samples of blood, injected muscle, uninjected muscle, liver, and kidney were analyzed by liquid chromatography (LC) and by bioassay using Sarcina lutea as the test organism. The LC method was far more sensitive with a detection limit of less than 0.1 ppm, while the detection limit by bioassay was about 0.5 ppm in tissue. Results by bioassay and LC sometimes differed considerably for tissue samples. Residues in all tissues were below the tolerance limit of 0.2 ppm at 24 h, except in the injected muscle in one animal. Residues were not detected in any tissue of any animal at 48 h after treatment.

  11. Requirements for radiation emergency urine bioassay techniques for the public and first responders.

    Science.gov (United States)

    Li, Chunsheng; Vlahovich, Slavica; Dai, Xiongxin; Richardson, Richard B; Daka, Joseph N; Kramer, Gary H

    2010-11-01

    Following a radiation emergency, the affected public and the first responders may need to be quickly assessed for internal contamination by the radionuclides involved. Urine bioassay is one of the most commonly used methods for assessing radionuclide intake and radiation dose. This paper attempts to derive the sensitivity requirements (from inhalation exposure) for the urine bioassay techniques for the top 10 high-risk radionuclides that might be used in a terrorist attack. The requirements are based on a proposed reference dose to adults of 0.1 Sv (CED, committed effective dose). In addition, requirements related to sample turnaround time and field deployability of the assay techniques are also discussed. A review of currently available assay techniques summarized in this paper reveals that method development for ²⁴¹Am, ²²⁶Ra, ²³⁸Pu, and ⁹⁰Sr urine bioassay is needed.

  12. A rapid and inexpensive bioassay to evaluate the decontamination of organophosphates.

    Science.gov (United States)

    Claborn, David M; Martin-Brown, Skylar A; Sagar, Sanjay Gupta; Durham, Paul

    2012-01-01

    An inexpensive and rapid bioassay using adult red flour beetles was developed for use in assessing the decontamination of environments containing organophosphates and related chemicals. A decontamination protocol was developed which demonstrated that 2 to 3 applications of 5% bleach solution were required to obtain nearly complete decontamination of malathion. The bioassay was also used to screen common household cleaners as potential decontaminating agents, but only 5% bleach was effective at improving survival of insects on steel plates treated with 25% malathion. A toxic degradation product (malaoxon) was detected using gas chromatography/mass spectrophotometry; this toxin affected the decontamination efficacy and resulted in continued toxicity to the beetles until subsequent decontaminations. The bioassay provides evidence to support the use of red flour beetles as a sensitive, less expensive method for determining safety levels of environments contaminated with malathion and other toxins, and may have application in the study of chemical warfare agents.

  13. Sampling method, storage and pretreatment of sediment affect AVS concentrations with consequences for bioassay responses.

    Science.gov (United States)

    De Lange, H J; Van Griethuysen, C; Koelmans, A A

    2008-01-01

    Sediment treatment and sediment storage may alter sediment toxicity, and consequently biotic response. Purpose of our study was to combine these three aspects (treatment-toxicity-biotic response) in one integrated approach. We used Acid Volatile Sulfide (AVS) concentrations as a proxy of the disturbance of the sediment. AVS and Simultaneously Extracted Metal (SEM) concentrations were compared to bioassay responses with the freshwater benthic macroinvertebrate Asellus aquaticus. Storage conditions and sediment treatment affected AVS but not SEM levels. AVS can be used as a proxy for sediment disturbance. The best way to pretreat the sediment for use in a bioassay in order to maintain initial AVS conditions was to sample the sediment with an Ekman grab, immediately store it in a jar without headspace, and freeze it as soon as possible. In a survey using seven different sediments, bioassay responses of A. aquaticus were correlated with SEM and AVS characteristics.

  14. Mouse Models of the Skin: Models to Define Mechanisms of Skin Carcinogenesis

    International Nuclear Information System (INIS)

    Wheeler, D. L.; Verma, A. K.; Denning, M. F.

    2013-01-01

    The multistep model of mouse skin carcinogenesis has facilitated identification of irreversible genetic events of initiation and progression, and epigenetic events of tumor promotion. Mouse skin tumor initiation can be accomplished by a single exposure to a sufficiently small dose of a carcinogen, and this step is rapid and irreversible. However, promotion of skin tumor formation requires a repeated and prolonged exposure to a promoter, and that tumor promotion is reversible. Investigations focused on the mechanisms of mouse carcinogenesis have resulted in the identifications of potential molecular targets of cancer induction and progression useful in planning strategies for human cancer prevention trials. This special issue contains eight papers that focus on mouse models used to study individual proteins expressed in the mouse skin and the role they play in differentiation, tissue homeostasis, skin carcinogenesis, and chemo prevention of skin cancer.

  15. In vitro bioassays to evaluate complex chemical mixtures in recycled water

    Science.gov (United States)

    Jia, Ai; Escher, Beate I.; Leusch, Frederic D.L.; Tang, Janet Y.M.; Prochazka, Erik; Dong, Bingfeng; Snyder, Erin M.; Snyder, Shane A.

    2016-01-01

    With burgeoning population and diminishing availability of freshwater resources, the world continues to expand the use of alternative water resources for drinking, and the quality of these sources has been a great concern for the public as well as public health professionals. In vitro bioassays are increasingly being used to enable rapid, relatively inexpensive toxicity screening that can be used in conjunction with analytical chemistry data to evaluate water quality and the effectiveness of water treatment. In this study, a comprehensive bioassay battery consisting of 36 bioassays covering 18 biological endpoints was applied to screen the bioactivity of waters of varying qualities with parallel treatments. Samples include wastewater effluent, ultraviolet light (UV) and/or ozone advanced oxidation processed (AOP) recycled water, and infiltrated recycled groundwater. Based on assay sensitivity and detection frequency in the samples, several endpoints were highlighted in the battery, including assays for genotoxicity, mutagenicity, estrogenic activity, glucocorticoid activity, aryl hydrocarbon receptor activity, oxidative stress response, and cytotoxicity. Attenuation of bioactivity was found to be dependent on the treatment process and bioassay endpoint. For instance, ozone technology significantly removed oxidative stress activity, while UV based technologies were most efficient for the attenuation of glucocorticoid activity. Chlorination partially attenuated genotoxicity and greatly decreased herbicidal activity, while groundwater infiltration efficiently attenuated most of the evaluated bioactivity with the exception of genotoxicity. In some cases, bioactivity (e.g., mutagenicity, genotoxicity, and arylhydrocarbon receptor) increased following water treatment, indicating that transformation products of water treatment may be a concern. Furthermore, several types of bioassays with the same endpoint were compared in this study, which could help guide the selection

  16. In vitro bioassays to evaluate complex chemical mixtures in recycled water.

    Science.gov (United States)

    Jia, Ai; Escher, Beate I; Leusch, Frederic D L; Tang, Janet Y M; Prochazka, Erik; Dong, Bingfeng; Snyder, Erin M; Snyder, Shane A

    2015-09-01

    With burgeoning population and diminishing availability of freshwater resources, the world continues to expand the use of alternative water resources for drinking, and the quality of these sources has been a great concern for the public as well as public health professionals. In vitro bioassays are increasingly being used to enable rapid, relatively inexpensive toxicity screening that can be used in conjunction with analytical chemistry data to evaluate water quality and the effectiveness of water treatment. In this study, a comprehensive bioassay battery consisting of 36 bioassays covering 18 biological endpoints was applied to screen the bioactivity of waters of varying qualities with parallel treatments. Samples include wastewater effluent, ultraviolet light (UV) and/or ozone advanced oxidation processed (AOP) recycled water, and infiltrated recycled groundwater. Based on assay sensitivity and detection frequency in the samples, several endpoints were highlighted in the battery, including assays for genotoxicity, mutagenicity, estrogenic activity, glucocorticoid activity, arylhydrocarbon receptor activity, oxidative stress response, and cytotoxicity. Attenuation of bioactivity was found to be dependent on the treatment process and bioassay endpoint. For instance, ozone technology significantly removed oxidative stress activity, while UV based technologies were most efficient for the attenuation of glucocorticoid activity. Chlorination partially attenuated genotoxicity and greatly decreased herbicidal activity, while groundwater infiltration efficiently attenuated most of the evaluated bioactivity with the exception of genotoxicity. In some cases, bioactivity (e.g., mutagenicity, genotoxicity, and arylhydrocarbon receptor) increased following water treatment, indicating that transformation products of water treatment may be a concern. Furthermore, several types of bioassays with the same endpoint were compared in this study, which could help guide the selection

  17. Biological Complexities in Radiation Carcinogenesis and Cancer Radiotherapy: Impact of New Biological Paradigms

    Directory of Open Access Journals (Sweden)

    Hossein Mozdarani

    2012-01-01

    Full Text Available Although radiation carcinogenesis has been shown both experimentally and epidemiologically, the use of ionizing radiation is also one of the major modalities in cancer treatment. Various known cellular and molecular events are involved in carcinogenesis. Apart from the known phenomena, there could be implications for carcinogenesis and cancer prevention due to other biological processes such as the bystander effect, the abscopal effect, intrinsic radiosensitivity and radioadaptation. Bystander effects have consequences for mutation initiated cancer paradigms of radiation carcinogenesis, which provide the mechanistic justification for low-dose risk estimates. The abscopal effect is potentially important for tumor control and is mediated through cytokines and/or the immune system (mainly cell-mediated immunity. It results from loss of growth and stimulatory and/or immunosuppressive factors from the tumor. Intrinsic radiosensitivity is a feature of some cancer prone chromosomal breakage syndromes such as ataxia telangectiasia. Radiosensitivity is manifested as higher chromosomal aberrations and DNA repair impairment is now known as a good biomarker for breast cancer screening and prediction of prognosis. However, it is not yet known whether this effect is good or bad for those receiving radiation or radiomimetic agents for treatment. Radiation hormesis is another major concern for carcinogenesis. This process which protects cells from higher doses of radiation or radio mimic chemicals, may lead to the escape of cells from mitotic death or apoptosis and put cells with a lower amount of damage into the process of cancer induction. Therefore, any of these biological phenomena could have impact on another process giving rise to genome instability of cells which are not in the field of radiation but still receiving a lower amount of radiation. For prevention of radiation induced carcinogenesis or risk assessment as well as for successful radiation

  18. Implementation of bioassay methods to improve assessment of incorporated radionuclides

    International Nuclear Information System (INIS)

    Oeh, U.; Hoellriegl, V.; Li, W.B.; Roth, P.; Wahl, W.; Andrasi, A.; Zombori, P.; Bouvier, C.; Carlan de, L.; Franck, D.; Ritt, J.; Fischer, H.; Schmitzer, C.

    2005-01-01

    Full text: Internal exposure to uranium and thorium can principally be assessed from external radiation measurements, exhalation measurements, or the assay of these elements excreted in urine or feces. Since both 232 Th and 238 U emit only photon radiations of low energy and with low emission probabilities, their detection limits by in vivo counting are of the order of kBq even when sophisticated devices are used. Consequently, usually bioassay methods are used for the incorporation monitoring of workers. Alpha spectrometry is the commonly applied technique, usually employed to measure 232 Th and 238 U in urine or fecel samples. For accurate analysis of body contents, 24 hours collections of urine or feces are usually used. The fecal activity, however, resembles predominantly the intake by ingestion of these nuclides during the last few days whereas the urinary excretion is more closely related to the body content of the nuclides. However, urinary excretion is also varying with the actual intake of 232 Th and/or 238 U. The measurement of these nuclides in urine by alpha-spectrometry requires tedious and time-consuming chemical work-up to prepare the samples for spectrometric analysis. Therefore, the number of analyses, which can be carried out is quite low and the results are available only after a time lag of several days. Additionally, under certain conditions the alpha-spectrometry is not sensitive enough. Other methods that have been developed may be confined to the availability of certain devices being difficult to access (e.g. nuclear reactors for radiochemical neutron activation analysis). Much better suitable as routine method is the application of inductively coupled plasma mass spectrometry (ICP-MS) for measurements of 232 Th and 238 U concentrations in urine. For elemental analyses, ICP-MS can already be considered as commonly used method. The present work which was carried out in the framework of an EU project (IDEA: Internal Dosimetry - Enhancements in

  19. Review of Bioassays for Monitoring Fate and Transport ofEstrogenic Endocrine Disrupting Compounds in Water

    Energy Technology Data Exchange (ETDEWEB)

    CGCampbell@lbl.gov

    2004-01-30

    Endocrine disrupting compounds (EDCs) are recognizedcontaminants threatening water quality. Despite efforts in sourceidentification, few strategies exist for characterization or treatment ofthis environmental pollution. Given that there are numerous EDCs that cannegatively affect humans and wildlife, general screening techniques likebioassays and biosensors provide an essential rapid and intensiveanalysis capacity. Commonly applied bioassays include the ELISA and YESassays, but promising technologies include ER-CALUXa, ELRA, Endotecta,RIANA, and IR-bioamplification. Two biosensors, Endotecta and RIANA, arefield portable using non-cellular biological detection strategies.Environmental management of EDCs in water requires integration ofbiosensors and bioassays for monitoring and assessment.

  20. Resolutions of ICRP models with BIOKMOD: Application for the bioassays evaluation

    International Nuclear Information System (INIS)

    Sanchez, G.

    2005-01-01

    Biokmod is a tool box developed using Mathematic for solving compartmental modes. It gives analytic and numeric solutions. Biokmod solves the current ICRP models including Acute, constant, continuous variable, multi-inputs and random intakes. All parameters (deposition factors, rate transfer coefficients, fractional rate of absorption, etc.) can be modified by users. It can be also applied for evaluating unknown intakes fitting bioassay experimental data and for evacuating uncertainties in the ICRP models. There is a web version (BiokmodWeb) at http://www3.enusa.es//webMathematica/public/biokmode.html. In this article we describe the application of Biokmod for evaluating Bioassays. (Author) 8 refs

  1. A versatile electrowetting-based digital microfluidic platform for quantitative homogeneous and heterogeneous bio-assays

    Science.gov (United States)

    Vergauwe, Nicolas; Witters, Daan; Ceyssens, Frederik; Vermeir, Steven; Verbruggen, Bert; Puers, Robert; Lammertyn, Jeroen

    2011-05-01

    Electrowetting-on-dielectric (EWOD) lab-on-a-chip systems have already proven their potential within a broad range of bio-assays. Nevertheless, research on the analytical performance of those systems is limited, yet crucial for a further breakthrough in the diagnostic field. Therefore, this paper presents the intrinsic possibilities of an EWOD lab-on-a-chip as a versatile platform for homogeneous and heterogeneous bio-assays with high analytical performance. Both droplet dispensing and splitting cause variations in droplet size, thereby directly influencing the assay's performance. The extent to which they influence the performance is assessed by a theoretical sensitivity analysis, which allows the definition of a basic framework for the reduction of droplet size variability. Taking advantage of the optimized droplet manipulations, both homogeneous and heterogeneous bio-assays are implemented in the EWOD lab-on-a-chip to demonstrate the analytical capabilities and versatility of the device. A fully on-chip enzymatic assay is realized with high analytical performance. It demonstrates the promising capabilities of an EWOD lab-on-a-chip in food-related and medical applications, such as nutritional and blood analyses. Further, a magnetic bio-assay for IgE detection using superparamagnetic nanoparticles is presented whereby the nanoparticles are used as solid carriers during the bio-assay. Crucial elements are the precise manipulation of the superparamagnetic nanoparticles with respect to dispensing and separation. Although the principle of using nano-carriers is demonstrated for protein detection, it can be easily extended to a broader range of bio-related applications like DNA sensing. In heterogeneous bio-assays the chip surface is actively involved during the execution of the bio-assay. Through immobilization of specific biological compounds like DNA, proteins and cells a reactive chip surface is realized, which enhances the bio-assay performance. To demonstrate

  2. Overview of osseous tissue findings from the lifespan carcinogenesis studies: From whole animals to molecules

    International Nuclear Information System (INIS)

    Miller, S.C.; Jee, W.S.S.; Bruenger, F.B.; Lloyd, R.D.; Taylor, G.N.

    1991-01-01

    This summary presents some of the findings from the 226 Ra and 239 Pu lifespan carcinogenesis studies in Beagle dogs and discusses these findings relative to the tissue, cellular and molecular biology of osseous tissues. This report attempts to integrate some of the dosimetric and pathological findings with current understanding of the factors that may influence carcinogenesis (and non-carcinogenic pathologies) at the various levels of biological organization. Emphasis is placed on the findings from the 226 Ra study, as this study has recently been completely reviewed and verified

  3. Estrogen receptor beta, a possible tumor suppressor involved in ovarian carcinogenesis

    Science.gov (United States)

    Lazennec, Gwendal

    2006-01-01

    Ovarian cancer is one of the leading cause of death from gynecological tumors in women. Several lines of evidence suggest that estrogens may play an important role in ovarian carcinogenesis, through their receptors, ERα and ERβ. Interestingly, malignant ovarian tumors originating from epithelial surface constitute about 90% of ovarian cancers and expressed low levels of ERβ, compared to normal tissues. In addition, restoration of ERβ in ovarian cancer cells, leads to strong inhibition of their proliferation and invasion, while apoptosis is enhanced. In this manuscript, recent data suggesting a possible tumor-suppressor role for ERβ in ovarian carcinogenesis are discussed. PMID:16399219

  4. Estimating radiation-induced cancer risk using MVK two-stage model for carcinogenesis

    International Nuclear Information System (INIS)

    Kai, M.; Kusama, T.; Aoki, Y.

    1993-01-01

    Based on the carcinogenesis model as proposed by Moolgavkar et al., time-dependent relative risk models were derived for projecting the time variation in excess relative risk. If it is assumed that each process is described by time-independent linear dose-response relationship, the time variation in excess relative risk is influenced by the parameter related with the promotion process. The risk model based carcinogenesis theory would play a marked role in estimating radiation-induced cancer risk in constructing a projection model or transfer model

  5. Standardization of a fluconazole bioassay and correlation of results with those obtained by high-pressure liquid chromatography.

    Science.gov (United States)

    Rex, J H; Hanson, L H; Amantea, M A; Stevens, D A; Bennett, J E

    1991-01-01

    An improved bioassay for fluconazole was developed. This assay is sensitive in the clinically relevant range (2 to 40 micrograms/ml) and analyzes plasma, serum, and cerebrospinal fluid specimens; bioassay results correlate with results obtained by high-pressure liquid chromatography (HPLC). Bioassay and HPLC analyses of spiked plasma, serum, and cerebrospinal fluid samples (run as unknowns) gave good agreement with expected values. Analysis of specimens from patients gave equivalent results by both HPLC and bioassay. HPLC had a lower within-run coefficient of variation (less than 2.5% for HPLC versus less than 11% for bioassay) and a lower between-run coefficient of variation (less than 5% versus less than 12% for bioassay) and was more sensitive (lower limit of detection, 0.1 micrograms/ml [versus 2 micrograms/ml for bioassay]). The bioassay is, however, sufficiently accurate and sensitive for clinical specimens, and its relative simplicity, low sample volume requirement, and low equipment cost should make it the technique of choice for analysis of routine clinical specimens. PMID:1854166

  6. High-throughput mosquito and fly bioassay system for natural and artificial substrates treated with residual insecticides.

    Science.gov (United States)

    Aldridge, Robert L; Wynn, W Wayne; Britch, Seth C; Allan, Sandra A; Walker, Todd W; Geden, Christopher J; Hogsette, Jerome A; Linthicum, Kenneth J

    2013-03-01

    A high-throughput bioassay system to evaluate the efficacy of residual pesticides against mosquitoes and muscid flies with minimal insect handling was developed. The system consisted of 4 components made of readily available materials: 1) a CO2 anaesthetizing chamber, 2) a specialized aspirator, 3) a cylindrical flat-bottomed glass bioassay chamber assembly, and 4) a customized rack.

  7. UTILITY OF A FULL LIFE-CYCLE COPEPOD BIOASSAY APPROACH FOR ASSESSMENT OF SEDIMENT-ASSOCIATED CONTAMINANT MIXTURES. (R825279)

    Science.gov (United States)

    AbstractWe compared a 21 day full life-cycle bioassay with an existing 14 day partial life-cycle bioassay for two species of meiobenthic copepods, Microarthridion littorale and Amphiascus tenuiremis. We hypothesized that full life-cycle tests would bette...

  8. Preoperative optimization of multi-organ failure following acute myocardial infarction and ischemic mitral regurgitation by placement of a transthoracic intra-aortic balloon pump.

    Science.gov (United States)

    Umakanthan, Ramanan; Dubose, Robert; Byrne, John G; Ahmad, Rashid M

    2010-10-01

    The management of acute myocardial infarction with resultant acute ischemic mitral regurgitation and acute multi-organ failure can prove to be a very challenging scenario. The presence of concomitant vascular disease can only serve to further compromise the complexity of the situation. We demonstrate a new indication for the transthoracic intra-aortic balloon pump as a preoperative means of unloading the heart and improving clinical outcome in such high-risk patients with severe vascular disease. We present the case of a 75-year-old man with a history of severe vascular disease who was transferred emergently to Vanderbilt University Medical Center with an acute inferolateral wall myocardial infarction resulting in severe acute ischemic mitral regurgitation and acute multi-organ failure. He presented with shock liver (serum glutamic-oxaloacetic transaminase [SGOT] of 958), renal failure (creatinine of 3.0), and respiratory failure with a pH of 7.18. Emergent cardiac catheterization revealed 100% occlusion of the left circumflex artery as well as severe ileofemoral disease. The advanced nature of his ileofemoral disease was such that the arterial access catheter occluded the right femoral artery. The duration of time that the catheter was in the artery led to transient limb ischemia with an elevation of his creatine phosphokinase (CPK) to 10,809. Balloon angioplasty followed by stent placement was successfully performed, which restored flow to the coronary vessel. Given the grave nature of the patient's condition, we were very concerned that immediate operative intervention for his condition would entail prohibitively high risk. In fact, the Society of Thoracic Surgeons predicted risk adjusted mortality was calculated to be 56%. In order to minimize patient mortality and morbidity, it was critical to help restore perfusion and organ recovery. Therefore, we decided that the chances for this patient's survival would improve if his condition could be optimized by

  9. [Histologic study on impeding leukoplakia carcinogenesis of golden hamster cheek pouch about Erigeron breviscapus (Vant) Hand-Mazz].

    Science.gov (United States)

    Zhou, C T; Zhong, W J; Hua, L; Hu, H F; Jin, Z G

    2000-06-01

    To observe the effect of Erigeron breviscapus (Vant) Hand Mazz (HEr) in impeding oral leukoplakia carcinogenesis, and to seek effective Chinese herb medicine that can impede precarcinoma of oral mucosas. 132 golden hamsters were randomly divided into model group (60 animals), HEr group (60 animals), and control group 12 animals. Salley's leukoplakia carcinogenesis model of golden hamster cheek pouch was used in this study. HEr was injected into the stomach to impede evolution of carcinogenesis. Pathological specimens were observed via naked eye and light microscope between model group and HEr group. Results were compared. Observation via naked-eye showed that leukoplakia rate of HEr group (18.2%) was lower than that of model group (27.3%). Observation via light microscope showed that carcinogenesis rate descended one fold and displasia rate descended 0.4 fold in HEr group. HEr has exact effect in impeding leukoplakia carcinogenesis.

  10. Comparison of mouse and swine bioassays for determination of soil arsenic relative bioavailability

    Science.gov (United States)

    Evaluation of soil arsenic (As) relative bioavailability (RBA) is essential to accurately assess human exposure to As contaminated soils via the incidental ingestion pathway. A variety of animal bioassays have been developed to estimate As RBA in contaminated soils and dusts, wit...

  11. Development of K-bioassay for the efficient potassium fertilization of citrus tree

    Energy Technology Data Exchange (ETDEWEB)

    U, Jang Kual [Cheju National University, Cheju (Korea, Republic of); Han, Hae Ryong [Cheju National University, Cheju (Korea, Republic of); Moon, Duk Young; Kim, Chang Myung; Lim, Han Cheol; Moon, Do Kyung [Cheju Citrus Research Institute, Cheju (Korea, Republic of); Song, Sung Jun [Cheju National Univerisity, Cheju (Korea, Republic of)

    1994-12-31

    a Similar to the {sup 42} K uptake, {sup 86} Rb uptake by the roots of Hordeum distichum grown in the hydroponic culture was negatively correlated with the concentration of K supplied previously, showing that {sup 86} Rb can be used for the K-bioassay. {sup 86} Rb having longer half life(18.86 day) than {sup 42} K(12.36 hr) allowed the use of larger number of root samples. {sup 86} Rb uptake of 3 years old Citrus unshiu Marc. grown in water culture decreased drastically with the increase of K concentration of the culture solution, thus demonstrating that the nutrition status of K for citrus trees can be diagnosed by K-bioassay using {sup 86} Rb tracer. {sup 86} Rb uptake by the excised roots of Hordeum distichum correlated with the exchangeable K in soil. The amount of exchangeable K in soil for the optimal plant growth can be determined by its relationship. {sup 42} K- and {sup 86} Rb-uptake by the Hordeum distichum roots were markedly inhibited by 5 x 10{sup -3} M KCN in the bioassay solution, indicating that uptake is metabolically controlled. There was no significant relationship between K content in citrus leaves and K concentration in the water-culture medium. It is concluded that K-bioassay is a potentially useful tool for determining of K requirement in citrus trees. (author)

  12. Sensitivity and Specificity of Bioassay of Estrogenicity on Mammary Gland and Uterus of Female Mice

    Czech Academy of Sciences Publication Activity Database

    Škarda, Josef

    2002-01-01

    Roč. 51, - (2002), s. 407-412 ISSN 0862-8408 R&D Projects: GA ČR GA523/99/0843; GA AV ČR KSK5020115 Institutional research plan: CEZ:AV0Z5045916 Keywords : Bioassay * Estrogenicity * Mammary gland Subject RIV: ED - Physiology Impact factor: 0.984, year: 2002

  13. Bioassays for Evaluating Water Quality: Screening for total bioactivity to assess water safety

    Science.gov (United States)

    Bioassays are a potential solution for assessing complex samples since they screen for total bioactivity for a given pathway or mode of action (MOA), such as estrogen receptor activation, in the samples. Overall, they can account for the three challenges listed above, and can sim...

  14. Ecotoxicological assessment of metal-polluted urban soils using bioassays with three soil invertebrates.

    NARCIS (Netherlands)

    Santarufo, L.; van Gestel, C.A.M.; Maisto, G.

    2012-01-01

    This study aimed at assessing the quality of urban soils by integrating chemical and ecotoxicological approaches. Soils from five sites in downtown Naples, Italy, were sampled and characterized for physical-chemical properties and total and water-extractable metal concentrations. Bioassays with

  15. Evaluation of soil bioassays for use at Washington state hazardous waste sites: A pilot study

    International Nuclear Information System (INIS)

    Blakley, N.; Norton, D.; Stinson, M.; Boyer, R.

    1994-01-01

    The Washington State Department of Ecology (Ecology) is developing guidelines to assess soil toxicity at hazardous waste sites being investigated under the Washington Model Toxics Control Act Cleanup Regulation. To evaluate soil toxicity, Ecology selected five bioassay protocols -- Daphnia, Earthworm, Seedling, Fathead Minnow, and Frog Embryo Teratogenesis Assay Xenopus (FETAX) -- for use as screening level assessment tools at six State hazardous waste sites. Sites contained a variety of contaminants including metals, creosote, pesticides, and petroleum products (leaking underground storage tanks). Three locations, representing high, medium, and low levels of contamination, were samples at each site. In general, the high contaminant samples resulted in the highest toxic response in all bioassays. The order of site toxicity, as assessed by overall toxic response, is creosote, petroleum products, metals, and pesticides. Results indicate that human health standards, especially for metals, may not adequately protect some of the species tested. The FETAX bioassay had the greatest overall number of toxic responses and lowest variance. The seedling and Daphnia bioassays had lower and similar overall toxic response results, followed by the earthworm and fathead minnow. Variability was markedly highest for the seedling. The Daphnia and fathead minnow variability were similar to the FETAX level, while the earthworm variability was slightly higher

  16. APPLICATION OF PLANT AND EARTHWORM BIOASSAYS TO EVALUATE REMEDIATION OF A LEAD-CONTAMINATED SOIL

    Science.gov (United States)

    Earthworm acute toxicity, plant seed germination/root elongation (SG/RE) and plant genotoxicity bioassays were employed to evaluate the remediation of a lead-contaminated soil. The remediation involved removal of heavy metals by a soil washing/soil leaching treatment process. A p...

  17. Strategies for Transferring Mixtures of Organic Contaminants from Aquatic Environments into Bioassays

    DEFF Research Database (Denmark)

    Jahnke, Annika; Mayer, Philipp; Schäfer, Sabine

    2016-01-01

    and monitoring of such mixtures, a variety of cell-based in vitro and low-complexity in vivo bioassays based on algae, daphnids or fish embryos are available. A very important and sometimes unrecognized challenge is how to combine sampling, extraction and dosing to transfer the mixtures from the environment...

  18. BIOASSAY STUDIES OF METAL(II) COMPLEXES OF 2,2'-(ETHANE ...

    African Journals Online (AJOL)

    Preferred Customer

    diyldiimino)diacetic acid (EDDA) were prepared and characterized. Coordination complexes of the EDDA ... corresponding amines with alkyl halide to bear diammines of the same class with different substituents. ... Bioassay studies of metal(II) complexes of 2,2'-(ethane-1,2-diyldiimino)diacetic acid. Bull. Chem. Soc. Ethiop.

  19. Bioassay-guided studies on the cytotoxic and in vitro trypanocidal ...

    African Journals Online (AJOL)

    This paper reports a bioassay-guided study to search for possible biological activity (cytotoxic and trypanocidal) in two Ugandan medicinal plants. The methodology adopted was the so-called ping-pong approach, involving phytochemical purification (column chromatography and preparative thin layer chromatography), ...

  20. Bioassay directed identification of natural aryl hydrocarbon-receptor agonists in marmalade

    NARCIS (Netherlands)

    Ede, van K.I.; Li, A.; Antunes Fernandes, E.C.; Mulder, P.P.J.; Peijnenburg, A.A.C.M.; Hoogenboom, L.A.P.

    2008-01-01

    Citrus fruit and citrus fruit products, like grapefruit, lemon and marmalade were shown to contain aryl hydrocarbon receptor (AhR) agonists, as detected with the DR CALUX® bioassay. This is of interest regarding the role of the Ah-receptor pathway in the adverse effects of dioxins, PCBs and other

  1. Experience with NQA-1 quality assurance standards applied to in vitro bioassay

    International Nuclear Information System (INIS)

    Bihl, D.E.; MacLellan, J.A.

    1991-10-01

    On June 1, 1990, the large (about 4000 samples per year) excreta bioassay program at the Hanford Site ceased abruptly when the contract with the bioassay laboratory was terminated. An intense, high-priority effort was begun to replace the services on an interim basis until a new contract could be procured. Despite the urgency to get the excreta bioassay program going again, the Hanford Internal Dosimetry Program was constrained to use only labs that could meet stringent quality assurance (QA) requirements, even during the interim period. The QA requirements were based on NQA-1 with selected additions from the Environmental Protection Agency's QAMS 005/80 (EPA 1983) and the American Society for Testing and Materials' C 1009-83 (ASTM 1984). This constraint was driven both by legal reasons and by the Hanford Site contractors and workers not wanting the quality of the data to be sacrificed. Finding labs that could (1) handle the large throughput, (2) meet the technical requirements, and (3) pass the QA audit proved more difficult than first anticipated. This presentation focuses on the QA requirements that the labs had to meet and how those very broad requirements were applied specifically to excreta bioassay. 5 refs

  2. The Intersection of CMOS Microsystems and Upconversion Nanoparticles for Luminescence Bioimaging and Bioassays

    Directory of Open Access Journals (Sweden)

    Liping Wei

    2014-09-01

    Full Text Available Organic fluorophores and quantum dots are ubiquitous as contrast agents for bio-imaging and as labels in bioassays to enable the detection of biological targets and processes. Upconversion nanoparticles (UCNPs offer a different set of opportunities as labels in bioassays and for bioimaging. UCNPs are excited at near-infrared (NIR wavelengths where biological molecules are optically transparent, and their luminesce in the visible and ultraviolet (UV wavelength range is suitable for detection using complementary metal-oxide-semiconductor (CMOS technology. These nanoparticles provide multiple sharp emission bands, long lifetimes, tunable emission, high photostability, and low cytotoxicity, which render them particularly useful for bio-imaging applications and multiplexed bioassays. This paper surveys several key concepts surrounding upconversion nanoparticles and the systems that detect and process the corresponding luminescence signals. The principle of photon upconversion, tuning of emission wavelengths, UCNP bioassays, and UCNP time-resolved techniques are described. Electronic readout systems for signal detection and processing suitable for UCNP luminescence using CMOS technology are discussed. This includes recent progress in miniaturized detectors, integrated spectral sensing, and high-precision time-domain circuits. Emphasis is placed on the physical attributes of UCNPs that map strongly to the technical features that CMOS devices excel in delivering, exploring the interoperability between the two technologies.

  3. Effect of the Changes of Respiratory Tract Model on the Uranium Bioassay Data

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Taeeun; Noh, Siwan; Kim, Meeryeong; Lee, Jaiki [Hanyang Univ., Seoul (Korea, Republic of); Lee, Jongil; Kim, Jang Lyul [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2014-05-15

    The HRTM, however, was revised based on the recent experimental data in OIR (Occupational Intakes of Radionuclides) draft report of ICRP. The changes of respiratory tract model are predicted to directly affect bioassay data like retention and excretion functions. Lung retention function is especially important to internal exposure assessment for workers related to fuel manufacturing because the place could be contaminated by uranium. In addition, faecel samples are recommended to be used for in-vitro bioassay of uranium because of very slow excretion via urine. More reliable assessments for the workers in fuel manufacturing could be achieved by recalculation of bioassay data for uranium and the comparing study using original and revised HRTM. In this study, therefore, the lung retention and faecal excretion functions for inhalation of UO{sub 2} and U{sub 3}O{sub 8} were recalculated using revised HRTM and the results were compared with those of original HRTM. In this study the lung retention and faecal excretion functions for inhalation of UO{sub 2} and U{sub 3}O{sub 8} were calculated based on original and revised HRTM. The results show that the revised HRTM increases lung retention and uptakes to alimentary tract which cause the more faecal excretion. The results in this study confirm the effect of the changes of respiratory tract model on the uranium bioassay data although the more study is needed to apply to practical fields.

  4. Kinetic microplate bioassays for relative potency of antibiotics improved by partial Least Square (PLS) regression.

    Science.gov (United States)

    Francisco, Fabiane Lacerda; Saviano, Alessandro Morais; Almeida, Túlia de Souza Botelho; Lourenço, Felipe Rebello

    2016-05-01

    Microbiological assays are widely used to estimate the relative potencies of antibiotics in order to guarantee the efficacy, safety, and quality of drug products. Despite of the advantages of turbidimetric bioassays when compared to other methods, it has limitations concerning the linearity and range of the dose-response curve determination. Here, we proposed to use partial least squares (PLS) regression to solve these limitations and to improve the prediction of relative potencies of antibiotics. Kinetic-reading microplate turbidimetric bioassays for apramacyin and vancomycin were performed using Escherichia coli (ATCC 8739) and Bacillus subtilis (ATCC 6633), respectively. Microbial growths were measured as absorbance up to 180 and 300min for apramycin and vancomycin turbidimetric bioassays, respectively. Conventional dose-response curves (absorbances or area under the microbial growth curve vs. log of antibiotic concentration) showed significant regression, however there were significant deviation of linearity. Thus, they could not be used for relative potency estimations. PLS regression allowed us to construct a predictive model for estimating the relative potencies of apramycin and vancomycin without over-fitting and it improved the linear range of turbidimetric bioassay. In addition, PLS regression provided predictions of relative potencies equivalent to those obtained from agar diffusion official methods. Therefore, we conclude that PLS regression may be used to estimate the relative potencies of antibiotics with significant advantages when compared to conventional dose-response curve determination. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. 'Dose per unit content' functions: A robust tool for the interpretation of bioassay data

    International Nuclear Information System (INIS)

    Berkovski, V.; Bonchuk, Y.; Ratia, G.

    2003-01-01

    The purposes of this study were to investigate the influence of the consequences of the lack of primary bioassay information and to elaborate approaches which could improve the reliability of dose assessments. The aggregated time-dependent functions 'dose per unit organ (excretion) content' z(t) have been proposed in this study as a convenient and reliable tool for bioassay. The analysis of the variation of z with changes of AMAD has demonstrated the existence of areas of the relative invariance of z, which permits the selection of one (reference) function z for the whole area of stability. Within the framework of such an approach an arbitrary set of bioassay data can be approximated by the linear combination F(t) S i E/ i z(t-t i ), whereI> F(t) function of time t, which approximates the observed bioassay time trend; t i = time shift of the acute intake i; E i effective dose, associated with the acute intake i (the two last parameters are results of the approximation procedure). (author)

  6. Experience with NQA-1 quality assurance standards applied to in vitro bioassay

    International Nuclear Information System (INIS)

    Bihl, D.E.; MacLellan, J.A.

    1991-01-01

    On June 1, 1990, the large (about 4,000 samples per year) excreta bioassay program at the Hanford Site ceased abruptly when the contract with the bioassay laboratory was terminated. An intense, high-priority effort was begun to replace the services on an interim basis until a new contract could be procured. Despite the urgency to get the excreta bioassay program going again, the Hanford Internal Dosimetry Program was constrained to use only labs that could meet stringent quality assurance (QA) requirements, even during the interim period. The QA requirements were based on NQA-1 with selected additions from the Environmental Protection Agency's QAMS 005/80 (EPA 1983) and the American Society for Testing and Materials' C 1009-83 (ASTM 1984). This constraint was driven both by legal reasons and by the Hanford Site contractors and workers not wanting the quality of the data to be sacrificed. Finding labs that could (1) handle the large throughput, (2) meet the technical requirements, and (3) pass the QA audit proved more difficult than first anticipated. This presentation focuses on the QA requirements that the labs had to meet and how those very broad requirements were applied specifically to excreta bioassay

  7. Androgen Bioassay for the Detection of Nonlabeled Androgenic Compounds in Nutritional Supplements.

    Science.gov (United States)

    Cooper, Elliot R; McGrath, Kristine C Y; Li, XiaoHong; Heather, Alison K

    2018-01-01

    Both athletes and the general population use nutritional supplements. Athletes often turn to supplements hoping that consuming the supplement will help them be more competitive and healthy, while the general population hopes to improve body image or vitality. While many supplements contain ingredients that may have useful properties, there are supplements that are contaminated with compounds that are banned for use in sport or have been deliberately adulterated to fortify a supplement with an ingredient that will produce the advertised effect. In the present study, we have used yeast cell and mammalian cell androgen bioassays to characterize the androgenic bioactivity of 112 sports supplements available from the Australian market, either over the counter or via the Internet. All 112 products did not declare an androgen on the label as an included ingredient. Our findings show that six out of 112 supplements had strong androgenic bioactivity in the yeast cell bioassay, indicating products spiked or contaminated with androgens. The mammalian cell bioassay confirmed the strong androgenic bioactivity of five out of six positive supplements. Supplement 6 was metabolized to weaker androgenic bioactivity in the mammalian cells. Further to this, Supplement 6 was positive in a yeast cell progestin bioassay. Together, these findings highlight that nutritional supplements, taken without medical supervision, could expose or predispose users to the adverse consequences of androgen abuse. The findings reinforce the need to increase awareness of the dangers of nutritional supplements and highlight the challenges that clinicians face in the fast-growing market of nutritional supplements.

  8. New in vitro reporter gene bioassays for screening of hormonal active compounds in the environment

    Czech Academy of Sciences Publication Activity Database

    Svobodová, Kateřina; Cajthaml, Tomáš

    2010-01-01

    Roč. 88, č. 4 (2010), s. 839-847 ISSN 0175-7598 R&D Projects: GA ČR GAP503/10/0408 Institutional research plan: CEZ:AV0Z50200510 Keywords : endocrine disruptors * in vitro bioassays * reporter gene assays Subject RIV: EE - Microbiology, Virology Impact factor: 3.280, year: 2010

  9. Development and application of bioassays for a site-specific risk assessment of contaminated soil

    NARCIS (Netherlands)

    Rila, J.-P.

    2008-01-01

    Soil risk assessment based on generic approaches is accompanied by a large number of uncertainties. In site-specific risk assessment aimed at identifying the actual effects on the ecosystem by using e.g. bioassays in soil elutriates and taking into account land-use these uncertainties can be largely

  10. A rapid bioassay for detecting saxitoxins using a Daphnia acute toxicity test.

    Science.gov (United States)

    Ferrão-Filho, Aloysio da S; Soares, Maria Carolina S; de Magalhães, Valéria Freitas; Azevedo, Sandra M F O

    2010-06-01

    Bioassays using Daphnia pulex and Moina micrura were designed to detect cyanobacterial neurotoxins in raw water samples. Phytoplankton and cyanotoxins from seston were analyzed during 15 months in a eutrophic reservoir. Effective time to immobilize 50% of the exposed individuals (ET50) was adopted as the endpoint. Paralysis of swimming movements was observed between approximately 0.5-3 h of exposure to lake water containing toxic cyanobacteria, followed by an almost complete recovery of the swimming activity within 24 h after being placed in control water. The same effects were observed in bioassays with a saxitoxin-producer strain of Cylindrospermopsis raciborskii isolated from the reservoir. Regression analysis showed significant relationships between ET50 vs. cell density, biomass and saxitoxins content, suggesting that the paralysis of Daphnia in lake water samples was caused by saxitoxins found in C. raciborskii. Daphnia bioassay was found to be a sensitive method for detecting fast-acting neurotoxins in natural samples, with important advantages over mouse bioassays. Copyright 2010 Elsevier Ltd. All rights reserved.

  11. Determination of Biochemical Oxygen Demand of Area Waters: A Bioassay Procedure for Environmental Monitoring

    Science.gov (United States)

    Riehl, Matthew

    2012-01-01

    A graphical method for determining the 5-day biochemical oxygen demand (BOD5) for a body of water is described. In this bioassay, students collect a sample of water from a designated site, transport it to the laboratory, and evaluate the amount of oxygen consumed by naturally occurring bacteria during a 5-day incubation period. An accuracy check,…

  12. Olfactoryresponse of the predatory mite Typhlodromus pyri (Acari: Phytoseiidae) to methyl salicylate in laboratory bioassays

    Science.gov (United States)

    The response of Typhlodromus pyri, a key predator of grapevine rust mite (Calepitrimerus vitis), to MeSA was tested using a Y-tube olfactometer in laboratory bioassays. Six doses ranging from 200 to 0.002 µg of diluted MeSA were tested. Significantly higher proportions of T. pyri preferred MeSA at ...

  13. Lactobacillus salivarius Ren prevent the early colorectal carcinogenesis in 1, 2-dimethylhydrazine-induced rat model.

    Science.gov (United States)

    Zhu, J; Zhu, C; Ge, S; Zhang, M; Jiang, L; Cui, J; Ren, F

    2014-07-01

    The objective of this study was to investigate the impact of Lactobacillus salivarius Ren (LS) on modulating colonic micro flora structure and influencing host colonic health in a rat model with colorectal precancerous lesions. Male F344 rats were injected with 1, 2-dimethylhydrazine (DMH) and treated with LS of two doses (5 × 10(8) and 1 × 10(10) CFU kg(-1) body weight) for 15 weeks. The colonic microflora profiles, luminal metabolites, epithelial proliferation and precancerous lesions [aberrant crypt foci (ACF)] were determined. A distinct segregation of colonic microflora structures was observed in LS-treated group. The abundance of one Prevotella-related strain was increased, and the abundance of one Bacillus-related strain was decreased by LS treatment. These changes were accompanied by increased short-chain fatty acid levels and decreased azoreductase activity. LS treatment also reduced the number of ACF by c. 40% and suppressed epithelial proliferation. Lactobacillus salivarius Ren improved the colonic microflora structures and the luminal metabolisms in addition preventing the early colorectal carcinogenesis in DMH-induced rat model. Colonic microflora is an important factor in colorectal carcinogenesis. Modulating the structural shifts of microflora may provide a novel option for preventing colorectal carcinogenesis. This study suggested a potential probiotic-based approach to modulate the intestinal microflora in the prevention of colorectal carcinogenesis. © 2014 The Society for Applied Microbiology.

  14. E-cadherin Mediates the Preventive Effect of Vitamin D3 in Colitis-associated Carcinogenesis.

    Science.gov (United States)

    Xin, Yu; He, Longmei; Luan, Zijian; Lv, Hong; Yang, Hong; Zhou, Ying; Zhao, Xinhua; Zhou, Weixun; Yu, Songlin; Tan, Bei; Wang, Hongying; Qian, Jiaming

    2017-09-01

    Vitamin D3 is beneficial in ameliorating or preventing inflammation and carcinogenesis. Here, we evaluated if vitamin D3 has a preventive effect on colitis-associated carcinogenesis. Administration of azoxymethane (AOM), followed with dextran sulfate sodium (DSS), was used to simulate colitis-associated colon cancer in mice. The supplement of vitamin D3 at different dosages (15, 30, 60 IU·g·w), started before AOM or immediately after DSS treatment (post 60), was sustained to the end of the experiment. Dietary vitamin D3 significantly reduced the number of tumors and tumor burden in a dose-dependent manner. Of note, vitamin D3 in high doses showed significant preventive effects on carcinogenesis regardless of administration before or after AOM-DSS treatment. Cell proliferation decreased in vitamin D3 groups compared with the control group after inhibition of expression of β-catenin and its downstream target gene cyclin D1 in the colon. In vitro, vitamin D3 reduced the transcriptional activity and nuclear level of β-catenin, and it also increased E-cadherin expression and its binding affinity for β-catenin. Moreover, repression of E-cadherin was rescued by supplemental vitamin D3 in mouse colons. Taken together, our results indicate that vitamin D3 effectively suppressed colonic carcinogenesis in the AOM-DSS mouse model. Our findings further suggest that upregulation of E-cadherin contributes to the preventive effect of vitamin D3 on β-catenin activity.

  15. Role of Stat in Skin Carcinogenesis: Insights Gained from Relevant Mouse Models

    International Nuclear Information System (INIS)

    Macias, E.; Rao, D.; DiGiovanni, J.; DiGiovanni, J.; DiGiovanni, J.

    2013-01-01

    Signal transducer and activator of transcription 3 (Stat) is a cytoplasmic protein that is activated in response to cytokines and growth factors and acts as a transcription factor. Stat plays critical roles in various biological activities including cell proliferation, migration, and survival. Studies using keratinocyte-specific Stat-deficient mice have revealed that Stat plays an important role in skin homeostasis including keratinocyte migration, wound healing, and hair follicle growth. Use of both constitutive and inducible keratinocyte-specific Stat-deficient mouse models has demonstrated that Stat is required for both the initiation and promotion stages of multistage skin carcinogenesis. Further studies using a transgenic mouse model with a gain of function mutant of Stat (Stat3C) expressed in the basal layer of the epidermis revealed a novel role for Stat in skin tumor progression. Studies using similar Stat-deficient and gain-of-function mouse models have indicated its similar roles in ultraviolet B (UVB) radiation-mediated skin carcinogenesis. This paper summarizes the use of these various mouse models for studying the role and underlying mechanisms for the function of Stat in skin carcinogenesis. Given its significant role throughout the skin carcinogenesis process, Stat is an attractive target for skin cancer prevention and treatment.

  16. Epidemiological studies on radiation carcinogenesis in human populations following acute exposure: nuclear explosions and medical radiation

    International Nuclear Information System (INIS)

    Fabrikant, J.I.

    1981-05-01

    The current knowledge of the carcinogenic effect of radiation in man is considered. The discussion is restricted to dose-incidence data in humans, particularly to certain of those epidemiological studies of human populations that are used most frequently for risk estimation for low-dose radiation carcinogenesis in man. Emphasis is placed solely on those surveys concerned with nuclear explosions and medical exposures

  17. Prevention of mammary carcinogenesis by short-term estrogen and progestin treatments

    International Nuclear Information System (INIS)

    Rajkumar, Lakshmanaswamy; Guzman, Raphael C; Yang, Jason; Thordarson, Gudmundur; Talamantes, Frank; Nandi, Satyabrata

    2004-01-01

    Women who have undergone a full-term pregnancy before the age of 20 have one-half the risk of developing breast cancer compared with women who have never gone through a full-term pregnancy. This protective effect is observed universally among women of all ethnic groups. Parity in rats and mice also protects them against chemically induced mammary carcinogenesis. Seven-week-old virgin Lewis rats were given N-methyl-N-nitrosourea. Two weeks later the rats were treated with natural or synthetic estrogens and progestins for 7–21 days by subcutaneous implantation of silastic capsules. In our current experiment, we demonstrate that short-term sustained exposure to natural or synthetic estrogens along with progestins is effective in preventing mammary carcinogenesis in rats. Treatment with 30 mg estriol plus 30 mg progesterone for 3 weeks significantly reduced the incidence of mammary cancer. Short-term exposure to ethynyl estradiol plus megesterol acetate or norethindrone was effective in decreasing the incidence of mammary cancers. Tamoxifen plus progesterone treatment for 3 weeks was able to confer only a transient protection from mammary carcinogenesis, while 2-methoxy estradiol plus progesterone was effective in conferring protection against mammary cancers. The data obtained in the present study demonstrate that, in nulliparous rats, long-term protection against mammary carcinogenesis can be achieved by short-term treatments with natural or synthetic estrogen and progesterone combinations

  18. Molecular and cellular pathways associated with chromosome 1p deletions during colon carcinogenesis

    Directory of Open Access Journals (Sweden)

    Payne CM

    2011-05-01

    Full Text Available Claire M Payne, Cheray Crowley-Skillicorn, Carol Bernstein, Hana Holubec, Harris BernsteinDepartment of Cell Biology and Anatomy, College of Medicine, University of Arizona Tucson, AZ, USAAbstract: Chromosomal instability is a major pathway of sporadic colon carcinogenesis. Chromosome arm 1p appears to be one of the “hot spots” in the non-neoplastic mucosa that, when deleted, is associated with the initiation of carcinogenesis. Chromosome arm 1p contains genes associated with DNA repair, spindle checkpoint function, apoptosis, multiple microRNAs, the Wnt signaling pathway, tumor suppression, antioxidant activities, and defense against environmental toxins. Loss of 1p is dangerous since it would likely contribute to genomic instability leading to tumorigenesis. The 1p deletion-associated colon carcinogenesis pathways are reviewed at the molecular and cellular levels. Sporadic colon cancer is strongly linked to a high-fat/low-vegetable/low-micronutrient, Western-style diet. We also consider how selected dietary-related compounds (eg, excess hydrophobic bile acids, and low levels of folic acid, niacin, plant-derived antioxidants, and other modulatory compounds might affect processes leading to chromosomal deletions, and to the molecular and cellular pathways specifically altered by chromosome 1p loss.Keywords: chromosome 1p, colon carcinogenesis, molecular pathways, cellular pathways

  19. Gastric microbiota and carcinogenesis: the role of non-Helicobacter pylori bacteria - A systematic review.

    Science.gov (United States)

    Dias-Jácome, Emanuel; Libânio, Diogo; Borges-Canha, Marta; Galaghar, Ana; Pimentel-Nunes, Pedro

    2016-09-01

    Helicobacter pylori is the strongest risk factor for gastric cancer. However, recent advances in DNA sequencing technology have revealed a complex microbial community in the stomach that could also contribute to the development of gastric cancer. The aim of this study was to present recent scientific evidence regarding the role of non-Helicobacter pylori bacteria in gastric carcinogenesis. A systematic review of original articles published in PubMed in the last ten years related to gastric microbiota and gastric cancer in humans was performed. Thirteen original articles were included. The constitution of gastric microbiota appears to be significantly affected by gastric cancer and premalignant lesions. In fact, differences in gastric microbiota have been documented, depending on Helicobacter pylori status and gastric conditions, such as non-atrophic gastritis, intestinal metaplasia and cancer. Gastric carcinogenesis can be associated with an increase in many bacteria (such as Lactobacillus coleohominis, Klebsiella pneumoniae or Acinetobacter baumannii) as well as decrease in others (such as Porphyromonas spp, Neisseria spp, Prevotella pallens or Streptococcus sinensis). However, there is no conclusive data that confirms if these changes in microbiota are a cause or consequence of the process of carcinogenesis. Even though there is limited evidence in humans, microbiota differences between normal individuals, pre-malignant lesions and gastric cancer could suggest a progressive shift in the constitution of gastric microbiota in carcinogenesis, possibly resulting from a complex cross-talk between gastric microbiota and Helicobacter pylori. However, further studies are needed to elucidate the specific role (if any) of different microorganisms.

  20. Mammary carcinogenesis in rats: basic facts and recent results in Brookhaven

    International Nuclear Information System (INIS)

    Shellabarger, C.J.; Stone, J.P.; Holtzman, s.

    1982-01-01

    Some research results from experiments investigating neutron-induced mammary carcinogenesis in rats are presented. The additive effects of neutrons and 3-methylcholanthrene on mammary adenocarcinoma were determined. Synergism between diethylstilbestrol and neutrons was likewise studied. Differences in mammary neoplastic response between strains of laboratory rats was also investigated

  1. Radiation carcinogenesis. Comprehensive three-year progress report, 1 May 1972--15 March 1976

    International Nuclear Information System (INIS)

    Warren, S.; Gates, O.

    1976-03-01

    Progress is reported on studies on the pathological effects of various doses of x radiation on rats and mice, with emphasis on radioinduced carcinogenesis in parabiont rats with one of the pair exposed to 1000 R of whole body x radiation and the other shielded. Results are included from studies on alterations in metabolic parameters and life span induced by irradiation

  2. Dietary fish oil (MaxEPA) enhances pancreatic carcinogenesis in azaserine-treated rats

    NARCIS (Netherlands)

    Appel, M.J.; Woutersen, R.A.

    1996-01-01

    In the present study the putative chemopreventive effect of dietary fish oil (MaxEPA) on azaserine-induced pancreatic carcinogenesis in rats was investigated. Groups of rats were maintained on a semipurified low-fat (LF; 5 wt%) diet or on semipurified high-fat (HF; 25 wt%) diets containing 5 wt%

  3. Nucleophosmin in the pathogenesis of arsenic-related bladder carcinogenesis revealed by quantitative proteomics

    International Nuclear Information System (INIS)

    Chen Shuhui; Wang Yiwen; Hsu Jueliang; Chang Hongyi; Wang Chiyun; Shen Potsun; Chiang Chiwu; Chuang Jingjing; Tsai Hungwen; Gu Powen; Chang Fangchih; Liu Hsiaosheng; Chow Nanhaw

    2010-01-01

    To investigate the molecular mechanisms of arsenic (As)-associated carcinogenesis, we performed proteomic analysis on E7 immortalized human uroepithelial cells after treatment with As in vitro. Quantitative proteomics was performed using stable isotope dimethyl labeling coupled with two-dimensional liquid chromatography peptide separation and mass spectrometry (MS)/MS analysis. Among 285 proteins, a total of 26 proteins were upregulated (ratio > 2.0) and 18 proteins were downregulated (ratio < 0.65) by As treatment, which are related to nucleotide binding, lipid metabolism, protein folding, protein biosynthesis, transcription, DNA repair, cell cycle control, and signal transduction. This study reports the potential significance of nucleophosmin (NPM) in the As-related bladder carcinogenesis. NPM was universally expressed in all of uroepithelial cell lines examined, implying that NPM may play a role in human bladder carcinogenesis. Upregulation of NPM tends to be dose- and time-dependent after As treatment. Expression of NPM was associated with cell proliferation, migration and anti-apoptosis. On the contrary, soy isoflavones inhibited the expression of NPM in vitro. The results suggest that NPM may play a role in the As-related bladder carcinogenesis, and soybean-based foods may have potential in the suppression of As/NPM-related tumorigenesis.

  4. Palytoxin: exploiting a novel skin tumor promoter to explore signal transduction and carcinogenesis.

    Science.gov (United States)

    Wattenberg, Elizabeth V

    2007-01-01

    Palytoxin is a novel skin tumor promoter, which has been used to help probe the role of different types of signaling mechanisms in carcinogenesis. The multistage mouse skin model indicates that tumor promotion is an early, prolonged, and reversible phase of carcinogenesis. Understanding the molecular mechanisms underlying tumor promotion is therefore important for developing strategies to prevent and treat cancer. Naturally occurring tumor promoters that bind to specific cellular receptors have proven to be useful tools for investigating important biochemical events in multistage carcinogenesis. For example, the identification of protein kinase C as the receptor for the prototypical skin tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) (also called phorbol 12-myristate 13-acetate, PMA) provided key evidence that tumor promotion involves the aberrant modulation of signaling cascades that govern cell fate and function. The subsequent discovery that palytoxin, a marine toxin isolated from zoanthids (genus Palythoa), is a potent skin tumor promoter yet does not activate protein kinase C indicated that investigating palytoxin action could help reveal new aspects of tumor promotion. Interestingly, the putative receptor for palytoxin is the Na(+),K(+)-ATPase. This review focuses on palytoxin-stimulated signaling and how palytoxin has been used to investigate alternate biochemical mechanisms by which important targets in carcinogenesis can be modulated.

  5. 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.

  6. Worldwide bioassay data resources for plutonium/americium internal dosimetry studies

    International Nuclear Information System (INIS)

    Miller, G.; Bertelli, L.; Little, T.; Guilmette, R.; Riddell, T.; Filipy, R.

    2005-01-01

    Full text: Biokinetic models are the scientific underpinning of internal dosimetry. These models describe how materials of interest taken into the body by various routes (for example inhalation) are transported through the body, allowing the modelling of bioassay measurements and the estimation of radiation dose. The International Commission on Radiation Protection (ICRP) publishes biokinetic models for use in internal dosimetry. These models represent the consensus judgement of a committee of experts, based on human and animal data. Nonetheless, it is important to validate biokinetic models using directly applicable data, in a scientifically transparent manner, especially for internal dosimetry research purposes (as opposed to radiation protection), as in epidemiology studies. Two major goals would be to determine individual variations of model parameters for the purpose of assessing this source of uncertainty in internal dose calculations, and to determine values of workplace specific parameters (such as particle solubility in lung fluids) for different representative workplaces. Furthermore, data on the observed frequency of intakes under various conditions can be used in the interpretation of bioassay data. All of the above may be couched in the terminology of Bayesian statistical analysis and amount to the determination of the Bayesian prior probability distributions needed in a Bayesian interpretation of bioassay data. The authors have direct knowledge of several significant databases of plutonium/americium bioassay data (including autopsy data). The purpose of this paper is to acquaint the worldwide community with these resources and to invite others who may know of other such databases to participate with us in a publication that would document the content, form, and the procedures for seeking access to these databases. These databases represent a tremendous scientific resource in this field. Examples of databases known to the authors include: the

  7. Paper-based chromatic toxicity bioassay by analysis of bacterial ferricyanide reduction.

    Science.gov (United States)

    Pujol-Vila, F; Vigués, N; Guerrero-Navarro, A; Jiménez, S; Gómez, D; Fernández, M; Bori, J; Vallès, B; Riva, M C; Muñoz-Berbel, X; Mas, J

    2016-03-03

    Water quality assessment requires a continuous and strict analysis of samples to guarantee compliance with established standards. Nowadays, the increasing number of pollutants and their synergistic effects lead to the development general toxicity bioassays capable to analyse water pollution as a whole. Current general toxicity methods, e.g. Microtox(®), rely on long operation protocols, the use of complex and expensive instrumentation and sample pre-treatment, which should be transported to the laboratory for analysis. These requirements delay sample analysis and hence, the response to avoid an environmental catastrophe. In an attempt to solve it, a fast (15 min) and low-cost toxicity bioassay based on the chromatic changes associated to bacterial ferricyanide reduction is here presented. E. coli cells (used as model bacteria) were stably trapped on low-cost paper matrices (cellulose-based paper discs, PDs) and remained viable for long times (1 month at -20 °C). Apart from bacterial carrier, paper matrices also acted as a fluidic element, allowing fluid management without the need of external pumps. Bioassay evaluation was performed using copper as model toxic agent. Chromatic changes associated to bacterial ferricyanide reduction were determined by three different transduction methods, i.e. (i) optical reflectometry (as reference method), (ii) image analysis and (iii) visual inspection. In all cases, bioassay results (in terms of half maximal effective concentrations, EC50) were in agreement with already reported data, confirming the good performance of the bioassay. The validation of the bioassay was performed by analysis of real samples from natural sources, which were analysed and compared with a reference method (i.e. Microtox). Obtained results showed agreement for about 70% of toxic samples and 80% of non-toxic samples, which may validate the use of this simple and quick protocol in the determination of general toxicity. The minimum instrumentation

  8. Multi-organ abnormalities and mTORC1 activation in zebrafish model of multiple acyl-CoA dehydrogenase deficiency.

    Directory of Open Access Journals (Sweden)

    Seok-Hyung Kim

    2013-06-01

    Full Text Available Multiple Acyl-CoA Dehydrogenase Deficiency (MADD is a severe mitochondrial disorder featuring multi-organ dysfunction. Mutations in either the ETFA, ETFB, and ETFDH genes can cause MADD but very little is known about disease specific mechanisms due to a paucity of animal models. We report a novel zebrafish mutant dark xavier (dxa(vu463 that has an inactivating mutation in the etfa gene. dxa(vu463 recapitulates numerous pathological and biochemical features seen in patients with MADD including brain, liver, and kidney disease. Similar to children with MADD, homozygote mutant dxa(vu463 zebrafish have a spectrum of phenotypes ranging from moderate to severe. Interestingly, excessive maternal feeding significantly exacerbated the phenotype. Homozygous mutant dxa(vu463 zebrafish have swollen and hyperplastic neural progenitor cells, hepatocytes and kidney tubule cells as well as elevations in triacylglycerol, cerebroside sulfate and cholesterol levels. Their mitochondria were also greatly enlarged, lacked normal cristae, and were dysfunctional. We also found increased signaling of the mechanistic target of rapamycin complex 1 (mTORC1 with enlarged cell size and proliferation. Treatment with rapamycin partially reversed these abnormalities. Our results indicate that etfa gene function is remarkably conserved in zebrafish as compared to humans with highly similar pathological, biochemical abnormalities to those reported in children with MADD. Altered mTORC1 signaling and maternal nutritional status may play critical roles in MADD disease progression and suggest novel treatment approaches that may ameliorate disease severity.

  9. Responses of lone star tick (acari: ixodidae) nymphs to the repellent deet applied in acetone and ethanol solutions in vitro bioassays

    Science.gov (United States)

    Behavioral bioassays remain a standard tool in the discovery, development, and registration of repellents. Although tick repellent bioassays tend to be rather uncomplicated, several factors can influence their outcomes. Typically repellent bioassays use a solvent, such as acetone or ethanol, to disp...

  10. Analysing traces of autoinducer-2 requires standardization of the Vibrio harveyi bioassay.

    Science.gov (United States)

    Vilchez, Ramiro; Lemme, André; Thiel, Verena; Schulz, Stefan; Sztajer, Helena; Wagner-Döbler, Irene

    2007-01-01

    Autoinducer-2 (furanosyl borate diester) is a biologically active compound whose role as a universal bacterial signalling molecule is currently under intense investigation. Because of its instability and the low concentrations of it found in biological samples, its detection relies at present on a bioassay that measures the difference in the timing of the luminescence of the Vibrio harveyi BB170 sensor strain with and without externally added AI-2. Here we systematically investigated which parameters affected the fold induction values of luminescence obtained in the bioassay and developed a modified protocol. Our experiments showed that growth and luminescence of V. harveyi BB170 are strongly influenced by trace elements. In particular, addition of Fe(3+) within a certain concentration range to the growth medium of the preinoculum culture improved the reproducibility and reduced the variance of the bioassay. In contrast, trace elements and vitamins introduced directly into the bioassay caused inhibitory effects. The initial density and luminescence of the sensor strain are very important and the values required for these parameters were defined. Borate interferes with the detection of AI-2 by giving false positive results. The response of V. harveyi BB170 to chemically synthesized AI-2 in the bioassay is nonlinear except over a very small concentration range; it is maximum over three orders of magnitude and shows inhibition above 35 microM. Based on the modified protocol, we were able to detect AI-2 in the absence of inhibitors with maximum fold induction values for the positive control (chemically synthesized AI-2) of >120 with a standard deviation of approximately 30% in a reliable and reproducible way.

  11. Induction of human breast cell carcinogenesis by triclocarban and intervention by curcumin

    Energy Technology Data Exchange (ETDEWEB)

    Sood, Shilpa; Choudhary, Shambhunath; Wang, Hwa-Chain Robert, E-mail: hcrwang@utk.edu

    2013-09-06

    Highlights: •Triclocarban exposure induces breast epithelial cell carcinogenesis. •Triclocarban induces the Erk–Nox pathway, ROS elevation, and DNA damage. •Physiological doses of triclocarban induce cellular carcinogenesis. •Non-cytotoxic curcumin blocks triclocarban-induced carcinogenesis and pathways. -- Abstract: More than 85% of breast cancers are sporadic and attributable to long-term exposure to environmental carcinogens and co-carcinogens. To identify co-carcinogens with abilities to induce cellular pre-malignancy, we studied the activity of triclocarban (TCC), an antimicrobial agent commonly used in household and personal care products. Here, we demonstrated, for the first time, that chronic exposure to TCC at physiologically-achievable nanomolar concentrations resulted in progressive carcinogenesis of human breast cells from non-cancerous to pre-malignant. Pre-malignant carcinogenesis was measured by increasingly-acquired cancer-associated properties of reduced dependence on growth factors, anchorage-independent growth and increased cell proliferation, without acquisition of cellular tumorigenicity. Long-term TCC exposure also induced constitutive activation of the Erk–Nox pathway and increases of reactive oxygen species (ROS) in cells. A single TCC exposure induced transient induction of the Erk–Nox pathway, ROS elevation, increased cell proliferation, and DNA damage in not only non-cancerous breast cells but also breast cancer cells. Using these constitutively- and transiently-induced changes as endpoints, we revealed that non-cytotoxic curcumin was effective in intervention of TCC-induced cellular pre-malignancy. Our results lead us to suggest that the co-carcinogenic potential of TCC should be seriously considered in epidemiological studies to reveal the significance of TCC in the development of sporadic breast cancer. Using TCC-induced transient and constitutive endpoints as targets will likely help identify non-cytotoxic preventive

  12. Impact of Spodoptera frugiperda neonate pretreatment conditions on Vip3Aa19 insecticidal protein activity and laboratory bioassay variation.

    Science.gov (United States)

    Da Silva, Karen F; Spencer, Terence A; Camargo Gil, Carolina; Siegfried, Blair D; Walters, Frederick S

    2016-04-01

    Variation in response to insecticidal proteins is common upon repetition of insect bioassays. Understanding this variation is a prerequisite to detecting biologically important differences. We tracked neonate Spodoptera frugiperda (J.E. Smith) susceptibility to Vip3Aa19 over 17 generations using standardized bioassay methods. Five larval pretreatment conditions and one bioassay condition were tested to determine whether susceptibility was affected. These included: storage time; prefeeding; storage at reduced temperature; storage at reduced humidity; colony introgression of field-collected individuals. Extremes of photoperiod during the bioassay itself were also examined. LC50 values for two strains of S. frugiperda varied 6.6-fold or 8.8-fold over 17 generations. Storage time and humidity had no impact on Vip3Aa19 susceptibility, whereas prefeeding significantly reduced subsequent mortality (by 27%). Storage at reduced temperature increased mortality for one colony (from 45.6 to 73.0%) but not for the other. Introgression of field-collected individuals affected susceptibility at the first generation but not for subsequent generations. A 24 h bioassay photophase significantly reduced susceptibility (by 26%) for both colonies. Certain pretreatment and bioassay conditions were identified that can affect S. frugiperda Vip3Aa19 susceptibility, but innate larval heterogeneity was also present. Our observations should help to increase the consistency of insecticidal protein bioassay results. © 2015 Syngenta Crop Protection, LLC. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

  13. [Investigation on pattern of quality control for Chinese materia medica based on famous-region drug and bioassay--the work reference].

    Science.gov (United States)

    Yan, Dan; Xiao, Xiaohe

    2011-05-01

    Selection and standardization of the work reference are the technical issues to be faced with in the bioassay of Chinese materia medica. Taking the bioassay of Coptis chinensis. as an example, the manufacture process of the famous-region drugs extraction was explained from the aspects of original identification, routine examination, component analysis and bioassay. The common technologies were extracted, and the selection and standardization procedures of the work reference for the bioassay of Chinese materia medica were drawn up, so as to provide technical support for constructing a new mode and method of the quality control of Chinese materia medica based on the famous-region drugs and bioassay.

  14. Fathead minnows (Pimephales promelas) and goldfish (Carassius auratus) as standard fish in bioassays and their reaction to potential reference toxicants

    Energy Technology Data Exchange (ETDEWEB)

    Adelman, I.R.; Smith, L.L. Jr.

    1976-02-01

    Fathead minnows (Pimephales promelas) and goldfish (Carassius auratus) were compared for their suitability as standard bioassay fish. Both species showed the same variability of bioassay results when tested with four toxicants. Fathead minnows are recommended on the basis of their small size and on their capability for use in complete life cycle tests. On the basis of minimum variability of bioassay results, sodium chloride was superior for use as a reference toxicant. Both sodium chloride and pentachlorophenol seemed capable of detecting abnormal fish. On the basis of seven listed criteria either sodium chloride or pentachlorophenol would be acceptable as a reference toxicant.

  15. Evaluating the efficacy of biological and conventional insecticides with the new 'MCD bottle' bioassay.

    Science.gov (United States)

    Sternberg, Eleanore D; Waite, Jessica L; Thomas, Matthew B

    2014-12-16

    Control of mosquitoes requires the ability to evaluate new insecticides and to monitor resistance to existing insecticides. Monitoring tools should be flexible and low cost so that they can be deployed in remote, resource poor areas. Ideally, a bioassay should be able to simulate transient contact between mosquitoes and insecticides, and it should allow for excito-repellency and avoidance behaviour in mosquitoes. Presented here is a new bioassay, which has been designed to meet these criteria. This bioassay was developed as part of the Mosquito Contamination Device (MCD) project and, therefore, is referred to as the MCD bottle bioassay. Presented here are two experiments that serve as a proof-of-concept for the MCD bottle bioassay. The experiments used four insecticide products, ranging from fast-acting, permethrin-treated, long-lasting insecticide nets (LLINs) that are already widely used for malaria vector control, to the slower acting entomopathogenic fungus, Beauveria bassiana, that is currently being evaluated as a prospective biological insecticide. The first experiment used the MCD bottle to test the effect of four different insecticides on Anopheles stephensi with a range of exposure times (1 minute, 3 minutes, 1 hour). The second experiment is a direct comparison of the MCD bottle and World Health Organization (WHO) cone bioassay that tests a subset of the insecticides (a piece of LLIN and a piece of netting coated with B. bassiana spores) and a further reduced exposure time (5 seconds) against both An. stephensi and Anopheles gambiae. Immediate knockdown and mortality after 24 hours were assessed using logistic regression and daily survival was assessed using Cox proportional hazards models. Across both experiments, fungus performed much more consistently than the chemical insecticides but measuring the effect of fungus required monitoring of mosquito mortality over several days to a week. Qualitatively, the MCD bottle and WHO cone performed comparably

  16. Dietary interventions designed to protect the perinatal brain from hypoxic-ischemic encephalopathy--Creatine prophylaxis and the need for multi-organ protection.

    Science.gov (United States)

    Ellery, Stacey J; Dickinson, Hayley; McKenzie, Matthew; Walker, David W

    2016-05-01

    Birth asphyxia or hypoxia arises from impaired placental gas exchange during labor and remains one of the leading causes of neonatal morbidity and mortality worldwide. It is a condition that can strike in pregnancies that have been uneventful until these final moments, and leads to fundamental loss of cellular energy reserves in the newborn. The cascade of metabolic changes that occurs in the brain at birth as a result of hypoxia can lead to significant damage that evolves over several hours and days, the severity of which can be ameliorated with therapeutic cerebral hypothermia. However, this treatment is only applied to a subset of newborns that meet strict inclusion criteria and is usually administered only in facilities with a high level of medical surveillance. Hence, a number of neuropharmacological interventions have been suggested as adjunct therapies to improve the efficacy of hypothermia, which alone improves survival of the post-hypoxic infant but does not altogether prevent adverse neurological outcomes. In this review we discuss the prospect of using creatine as a dietary supplement during pregnancy and nutritional intervention that can significantly decrease the risk of brain damage in the event of severe oxygen deprivation at birth. Because brain damage can also arise secondarily to compromise of other fetal organs (e.g., heart, diaphragm, kidney), and that compromise of mitochondrial function under hypoxic conditions may be a common mechanism leading to damage of these tissues, we present data suggesting that dietary creatine supplementation during pregnancy may be an effective prophylaxis that can protect the fetus from the multi-organ consequences of severe hypoxia at birth. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Brine shrimp bioassay: importance of correct taxonomic identification of Artemia (Anostraca) species.

    Science.gov (United States)

    Ruebhart, David R; Cock, Ian E; Shaw, Glen R

    2008-08-01

    Despite the common use of the brine shrimp bioassay in toxicology, there is confusion in the literature regarding citation of the correct taxonomic identity of the Artemia species used. The genus Artemia, once thought to be represented by a single species Artemia salina, is now known to be composed of several bisexual species as well as parthenogenetic populations. Artemia franciscana is the best studied of the Artemia species and is considered to represent the vast majority of studies in which Artemia is used as an experimental test organism. We found that in studies referring to the use of A. salina, the zoogeography of the cyst harvest site indicated that the species used was actually A. franciscana. Those performing bioassays with Artemia need to exercise diligence in assigning correct species identification, as the identity of the test organism is an important parameter in assuring the validity of the results of the assay.

  18. Genotoxic evaluation of an industrial effluent from an oil refinery using plant and animal bioassays

    Directory of Open Access Journals (Sweden)

    Fernando Postalli Rodrigues

    2010-01-01

    Full Text Available Polycyclic aromatic hydrocarbons (PAHs are genotoxic chemicals commonly found in effluents from oil refineries. Bioassays using plants and cells cultures can be employed for assessing environmental safety and potential genotoxicity. In this study, the genotoxic potential of an oil refinery effluent was analyzed by means of micronucleus (MN testing of Alium cepa, which revealed no effect after 24 h of treatment. On the other hand, primary lesions in the DNA of rat (Rattus norvegicus hepatoma cells (HTC were observed through comet assaying after only 2 h of exposure. On considering the capacity to detect DNA damage of a different nature and of these cells to metabolize xenobiotics, we suggest the association of the two bioassays with these cell types, plant (Allium cepa and mammal (HTC cells, for more accurately assessing genotoxicity in environmental samples.

  19. Genotoxic evaluation of an industrial effluent from an oil refinery using plant and animal bioassays.

    Science.gov (United States)

    Rodrigues, Fernando Postalli; Angeli, José Pedro Friedmann; Mantovani, Mário Sérgio; Guedes, Carmen Luisa Barbosa; Jordão, Berenice Quinzani

    2010-01-01

    Polycyclic aromatic hydrocarbons (PAHs) are genotoxic chemicals commonly found in effluents from oil refineries. Bioassays using plants and cells cultures can be employed for assessing environmental safety and potential genotoxicity. In this study, the genotoxic potential of an oil refinery effluent was analyzed by means of micronucleus (MN) testing of Alium cepa, which revealed no effect after 24 h of treatment. On the other hand, primary lesions in the DNA of rat (Rattus norvegicus) hepatoma cells (HTC) were observed through comet assaying after only 2 h of exposure. On considering the capacity to detect DNA damage of a different nature and of these cells to metabolize xenobiotics, we suggest the association of the two bioassays with these cell types, plant (Allium cepa) and mammal (HTC) cells, for more accurately assessing genotoxicity in environmental samples.

  20. Methods for conducting bioassays using embryos and larvae of Pacific herring, Clupea pallasi.

    Science.gov (United States)

    Dinnel, Paul A; Middaugh, Douglas P; Schwarck, Nathan T; Farren, Heather M; Haley, Richard K; Hoover, Richard A; Elphick, James; Tobiason, Karen; Marshall, Randall R

    2011-02-01

    The rapid decrease of several stocks of Pacific herring, Clupea pallasi, in Puget Sound, Washington, has led to concerns about the effects of industrial and nonpoint source contamination on the embryo and larval stages of this and related forage fish species. To address these concerns, the state of Washington and several industries have funded efforts to develop embryo and larval bioassay protocols that can be used by commercial laboratories for routine effluent testing. This article presents the results of research to develop herring embryo and larval bioassay protocols. Factors evaluated during protocol development included temperature, salinity, dissolved oxygen (DO), light intensity, photoperiod, larval feeding regimes, use of brine and artificial sea salts, gonad sources, collection methods, and egg quality.

  1. Biomagnification of bioassay derived 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents

    Science.gov (United States)

    Jones, P.D.; Ankley, G.T.; Best, D. A.; Crawford, R.; DeGalan, N.; Giesy, J.P.; Kubiak, T.J.; Ludwig, J. P.; Newsted, J.L.; Tillitt, D. E.; Verbrugge, D.A.

    1993-01-01

    In recent years contamination of the Great Lakes ecosystem with planar chlorinated hydrocarbons (PCHs) has attracted considerable concern due to their known reproductive and teratogenic effects. The H4IIE bioassay has been standardized as a means of measuring the biological potency of a PCH mixture as 2,3,7,8-tetrachloro-p-dibenzodioxin equivalents (TCDD-EQ). Using this bioassay we have investigated the biomagnification of TCDD-EQ in a semi-closed ecosystem. The biomagnification of TCDD-EQ is demonstrated and results indicate that the food chain is the major pathway for TCDD-EQ through this ecosystem. The H4IIE assay system is demonstrated to be a viable integrative measure of the total concentration of TCDD-EQ in different trophic levels.

  2. Isolation of Fungi from Heterodera glycines and in vitro Bioassays for Their Antagonism to Eggs.

    Science.gov (United States)

    Meyer, S L; Huettel, R N; Sayre, R M

    1990-10-01

    Twenty fungi were assayed in vitro for antagonism to eggs of Heterodera glycines. Eight of the fungi were isolated from cysts or eggs of H. glycines during the current study, one was isolated from Panagrellus redivivus, and eleven were obtained from other researchers or collections. The bioassays were conducted on eggs from nematodes that had been grown monoxenically on excised root tips. Phoma chrysanthemicola, one strain of Verticillium chlamydosporium, and one strain of V. lecanii caused a decrease (P Trichoderma polysporum infected live eggs but enhanced (P Fusarium sp., Neocosmospora vasinfecta, Scytalidium fulvum, Trichoderma harzianum (two strains), V. chlamydosporium (one strain), V. lecanii (three strains), and an unidentified fungus did not measurably affect egg viability, even though hyphae of five of these fungi were seen in live eggs. The bioassay provides a useful step in the selection of a biological control agent for this major nematode pest.

  3. Rapid bioassay method for estimation of 90Sr in urine samples by liquid scintillation counting

    International Nuclear Information System (INIS)

    Wankhede, Sonal; Chaudhary, Seema; Sawant, Pramilla D.

    2018-01-01

    Radiostrontium (Sr) is a by-product of the nuclear fission of uranium and plutonium in nuclear reactors and is an important radionuclide in spent nuclear fuel and radioactive waste. Rapid bioassay methods are required for estimating Sr in urine following internal contamination. Decision regarding medical intervention, if any can be based upon the results of urinalysis. The present method used at Bioassay Laboratory, Trombay is by Solid Extraction Chromatography (SEC) technique. The Sr separated from urine sample is precipitated as SrCO 3 and analyzed gravimetrically. However, gravimetric procedure is time consuming and therefore, in the present study, feasibility of Liquid Scintillation Counting for direct detection of radiostrontium in effluent was explored. The results obtained in the present study were compared with those obtained using gravimetric method

  4. High-throughput tri-colour flow cytometry technique to assess Plasmodium falciparum parasitaemia in bioassays

    DEFF Research Database (Denmark)

    Tiendrebeogo, Regis W; Adu, Bright; Singh, Susheel K

    2014-01-01

    BACKGROUND: Unbiased flow cytometry-based methods have become the technique of choice in many laboratories for high-throughput, accurate assessments of malaria parasites in bioassays. A method to quantify live parasites based on mitotracker red CMXRos was recently described but consistent...... distinction of early ring stages of Plasmodium falciparum from uninfected red blood cells (uRBC) remains a challenge. METHODS: Here, a high-throughput, three-parameter (tri-colour) flow cytometry technique based on mitotracker red dye, the nucleic acid dye coriphosphine O (CPO) and the leucocyte marker CD45...... for enumerating live parasites in bioassays was developed. The technique was applied to estimate the specific growth inhibition index (SGI) in the antibody-dependent cellular inhibition (ADCI) assay and compared to parasite quantification by microscopy and mitotracker red staining. The Bland-Altman analysis...

  5. Intake retention functions and their applications to bioassay and the estimation of internal radiation doses

    International Nuclear Information System (INIS)

    Skrable, K.W.; Chabot, G.E.; French, C.S.; La Bone, T.R.

    1988-01-01

    This paper describes a way of obtaining and gives applications of intake retention functions. These functions give the fraction of an intake of radioactive material expected to be present in a specified bioassay compartment at any time after a single acute exposure or after onset of a continuous exposure. The intake retention functions are derived from a multicompartmental model and a recursive catenary kinetics equation that completely describe the metabolism of radioelements from intake to excretion, accounting for the delay in uptake from compartments in the respiratory and gastrointestinal tracts and the recycling of radioelements between systemic compartments. This approach, which treats excretion as the 'last' compartment of all catenary metabolic pathways, avoids the use of convolution integrals and provides algebraic solutions that can be programmed on hand held calculators or personal computers. The estimation of intakes and internal radiation doses and the use of intake retention functions in the design of bioassay programs are discussed along with several examples

  6. The pleiotropic roles of transforming growth factor beta inhomeostasis and carcinogenesis of endocrine organs.

    Energy Technology Data Exchange (ETDEWEB)

    Fleisch, Markus C.; Maxwell, Christopher A.; Barcellos-Hoff,Mary-Helen

    2006-01-13

    Transforming growth factor beta (TGF-beta) is a ubiquitous cytokine that plays a critical role in numerous pathways regulating cellular and tissue homeostasis. TGF-beta is regulated by hormones and is a primary mediator of hormone response in uterus, prostate and mammary gland. This review will address the role of TGF-beta in regulating hormone dependent proliferation and morphogenesis. The subversion of TGF-beta regulation during the processes of carcinogenesis, with particular emphasis on its effects on genetic stability and epithelial to mesenchymal transition (EMT), will also be examined. An understanding of the multiple and complex mechanisms of TGF-beta regulation of epithelial function, and the ultimate loss of TGF-beta function during carcinogenesis, will be critical in the design of novel therapeutic interventions for endocrine-related cancers.

  7. Defining the role of polyamines in colon carcinogenesis using mouse models

    Directory of Open Access Journals (Sweden)

    Natalia A Ignatenko

    2011-01-01

    Full Text Available Genetics and diet are both considered important risk determinants for colorectal cancer, a leading cause of death in the US and worldwide. Genetically engineered mouse (GEM models have made a significant contribution to the characterization of colorectal cancer risk factors. Reliable, reproducible, and clinically relevant animal models help in the identification of the molecular events associated with disease progression and in the development of effictive treatment strategies. This review is focused on the use of mouse models for studying the role of polyamines in colon carcinogenesis. We describe how the available mouse models of colon cancer such as the multiple intestinal neoplasia (Min mice and knockout genetic models facilitate understanding of the role of polyamines in colon carcinogenesis and help in the development of a rational strategy for colon cancer chemoprevention.

  8. The influence of chromosome density variations on the increase in nuclear disorder strength in carcinogenesis

    International Nuclear Information System (INIS)

    Kim, Jun Soo; Pradhan, Prabhakar; Backman, Vadim; Szleifer, Igal

    2011-01-01

    Microscopic structural changes have long been observed in cancer cells and used as a marker in cancer diagnosis. Recent development of an optical technique, partial-wave spectroscopy (PWS), enabled more sensitive detection of nanoscale structural changes in early carcinogenesis in terms of the disorder strength related to density variations. These nanoscale alterations precede the well-known microscopic morphological changes. We investigate the influence of nuclear density variations due to chromosome condensation on changes of disorder strength by computer simulations of model chromosomes. Nuclear configurations with different degrees of chromosome condensation are realized from simulations of decondensing chromosomes and the disorder strength is calculated for these nuclear configurations. We found that the disorder strength increases significantly for configurations with slightly more condensed chromosomes. Coupled with PWS measurements, the simulation results suggest that the chromosome condensation and the resulting spatial density inhomogeneity may represent one of the earliest events in carcinogenesis

  9. Use of medaka as a tool in studies of radiation effects and chemical carcinogenesis

    International Nuclear Information System (INIS)

    Hyodo-Taguchi, Y.; Aoki, K.; Matsudaira, H.

    1982-01-01

    The medaka, Oryzias latipes, a small freshwater oviparous fish, is common in Japan and found in some parts of Asia. Adult fish are 3.0-3.5 cm long and weigh 0.5-0.7 g. The small fish have been used extensively in this laboratory for analysis of radiation effects and for study of chemical carcinogenesis. These fish are relatively easy to rear and their reproductive biology is well known. Recently, inbred strains of the fish have been established by full sister-brother mating. In this report, we will review experimental results using medaka in studies of : 1) radiation effects on spermatogenesis, and 2) induction of hepatic tumors by MAM acetate, we will also review use of medaka in related studies of radiation effects and chemical carcinogenesis. (author)

  10. The effect of synthetic immunomodulator thymogen on radiation carcinogenesis in rats

    International Nuclear Information System (INIS)

    Anisimov, V.N.; Miretskij, G.I.; Morozov, V.G.; Pavel'eva, I.A.; Khavinson, V.Kh.

    1992-01-01

    Five month-old female rats were given a mixture of Sr-90 and Cs-137 in drinking water in the dose of 0.1 and 0.2 μCi/day per animal over 12 months. Some animals received 12 monthly course of a synthetic immunomodulating dipeptide-thymogen in the dose of 5 μg/animal for 5 consecutive days. Radionuclide-treated rats showed higher occurence of tumors on the whole and of breast adenocarcinoma, in particular. Thymogen was shown to inhibit Sr-90- and Cs-137-induced radiation carcinogenesis, namely, a decrease in the total tumor and cancer occurence was observed. The animals receiving thymogen alone showed longer life span, slower rate of aging and lower overall tumor and cancer occurence. In this study, the ability of asynthetic peptide immunomodulator-thymogen to inhibit spontaneous and radionuclide-induced carcinogenesis in female rats was first established

  11. The application of bioassays as indicators of petroleum-contaminated soil remediation.

    Science.gov (United States)

    Płaza, Grazyna; Nałecz-Jawecki, Grzegorz; Ulfig, Krzysztof; Brigmon, Robin L

    2005-04-01

    Bioremediation has proven successful in numerous applications to petroleum contaminated soils. However, questions remain as to the efficiency of bioremediation in lowering long-term soil toxicity. In the present study, the bioassays Spirotox, Microtox, Ostracodtoxkit F, umu-test with S-9 activation, and plant assays were applied, and compared to evaluate bioremediation processes in heavily petroleum contaminated soils. Six higher plant species (Secale cereale L., Lactuca sativa L., Zea mays L., Lepidium sativum L., Triticum vulgare L., Brassica oleracea L.) were used for bioassay tests based on seed germination and root elongation. The ecotoxicological analyses were made in DMSO/H2O and DCM/DMSO soil extracts. Soils were tested from two biopiles at the Czechowice oil refinery, Poland, that have been subjected to different bioremediation applications. In biopile 1 the active or engineered bioremediation process lasted four years, while biopile 2 was treated passively or non-engineered for eight months. The test species demonstrated varying sensitivity to soils from both biopiles. The effects on test organisms exposed to biopile 2 soils were several times higher compared to those in biopile 1 soils, which correlated with the soil contaminants concentration. Soil hydrocarbon concentrations indeed decreased an average of 81% in biopile 1, whereas in biopile 2 TPH/TPOC concentrations only decreased by 30% after eight months of bioremediation. The bioassays were presented to be sensitive indicators of soil quality and can be used to evaluate the quality of bioremediated soil. The study encourages the need to combine the bioassays with chemical monitoring for evaluation of the bioremediation effectiveness and assessing of the contaminated/remediated soils.

  12. Mouse bioassay to assess oestrogenic and anti-oestrogenic compounds: Hydroxytamoxifen, Diethylstilbestrol and Genistein

    Czech Academy of Sciences Publication Activity Database

    Köhlerová, Eva; Škarda, Josef

    2004-01-01

    Roč. 51, č. 5 (2004), s. 209-217 ISSN 0931-184X R&D Projects: GA ČR GA524/02/0406; GA AV ČR IBS5045302; GA AV ČR KSK5020115 Institutional research plan: CEZ:AV0Z5045916 Keywords : bioassay * anti-oestrogens * oestrogenicity Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 0.471, year: 2004

  13. Seasonally and regionally determined indication potential of bioassays in contaminated river sediments.

    Science.gov (United States)

    Hilscherová, Klára; Dusek, Ladislav; Sídlová, Tereza; Jálová, Veronika; Cupr, Pavel; Giesy, John P; Nehyba, Slavomír; Jarkovský, Jirí; Klánová, Jana; Holoubek, Ivan

    2010-03-01

    River sediments are a dynamic system, especially in areas where floods occur frequently. In the present study, an integrative approach is used to investigate the seasonal and spatial dynamics of contamination of sediments from a regularly flooded industrial area in the Czech Republic, which presents a suitable model ecosystem for pollutant distribution research at a regional level. Surface sediments were sampled repeatedly to represent two different hydrological situations: spring (after the peak of high flow) and autumn (after longer period of low flow). Samples were characterized for abiotic parameters and concentrations of priority organic pollutants. Toxicity was assessed by Microtox test; genotoxicity by SOS-chromotest and green fluorescent protein (GFP)-yeast test; and the presence of compounds with specific mode of action by in vitro bioassays for dioxin-like activity, anti-/androgenicity, and anti-/estrogenicity. Distribution of organic contaminants varied among regions and seasonally. Although the results of Microtox and genotoxicity tests were relatively inconclusive, all other specific bioassays led to statistically significant regional and seasonal differences in profiles and allowed clear separation of upstream and downstream regions. The outcomes of these bioassays indicated an association with concentrations of polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs) as master variables. There were significant interrelations among dioxin-like activity, antiandrogenicity and content of organic carbon, clay, and concentration of PAHs and PCBs, which documents the significance of abiotic factors in accumulation of pollutants. The study demonstrates the strength of the specific bioassays in indicating the changes in contamination and emphasizes the crucial role of a well-designed sampling plan, in which both spatial and temporal dynamics should be taken into account, for the correct interpretations of information in risk assessments.

  14. Polycyclic aromatic hydrocarbons bioavailability in industrial and agricultural soils: Linking SPME and Tenax extraction with bioassays.

    Science.gov (United States)

    Guo, Meixia; Gong, Zongqiang; Li, Xiaojun; Allinson, Graeme; Rookes, James; Cahill, David

    2017-06-01

    The aims of this study were to evaluate the bioavailability of polycyclic aromatic hydrocarbons (PAHs) in industrial and agricultural soils using chemical methods and a bioassay, and to study the relationships between the methods. This was conducted by comparing the quantities of PAHs extracted from two manufactured gas plant (MGP) soils and an agricultural soil with low level contamination by solid-phase micro-extraction (SPME) and Tenax-TA extraction with the quantities taken up by the earthworm (Eisenia fetida). In addition, a biodegradation experiment was conducted on one MGP soil (MGP-A) to clarify the relationship between PAH removal by biodegradation and the variation in PAH concentrations in soil pore water. Results demonstrated that the earthworm bioassay could not be used to examine PAH bioavailability in the tested MGP soils; which was the case even in the diluted MGP-A soils after biodegradation. However, the bioassay was successfully applied to the agricultural soil. These results suggest that earthworms can only be used for bioassays in soils with low toxicity. In general, rapidly desorbing concentrations extracted by Tenax-TA could predict PAH concentrations accumulated in earthworms (R 2 =0.66), while SPME underestimated earthworm concentrations by a factor of 2.5. Both SPME and Tenax extraction can provide a useful tool to predict PAH bioavailability for earthworms, but Tenax-TA extraction was proven to be a more sensitive and precise method than SPME for the prediction of earthworm exposure in the agricultural soil. Copyright © 2017. Published by Elsevier Inc.

  15. Bioassays with terrestrial and aquatic species as monitoring tools of hydrocarbon degradation.

    Science.gov (United States)

    Bori, Jaume; Vallès, Bettina; Ortega, Lina; Riva, Maria Carme

    2016-09-01

    In this study chemical analyses and ecotoxicity tests were applied for the assessment of a heavily hydrocarbon-contaminated soil prior and after the application of a remediation procedure that consisted in the stimulation of soil autochthonous populations of hydrocarbon degraders in static-ventilated biopiles. Terrestrial bioassays were applied in mixtures of test soils and artificial control soil and studied the survival and reproduction of Eisenia fetida and the avoidance response of E. fetida and Folsomia candida. Effects on aquatic organisms were studied by means of acute tests with Vibrio fischeri, Raphidocelis subcapitata, and Daphnia magna performed on aqueous elutriates from test soils. The bioremediation procedure led to a significant reduction in the concentration of hydrocarbons (from 34264 to 3074 mg kg(-1), i.e., 91 % decrease) and toxicity although bioassays were not able to report a percentage decrease of toxicity as high as the percentage reduction. Sublethal tests proved the most sensitive terrestrial bioassays and avoidance tests with earthworms and springtails showed potential as monitoring tools of hydrocarbon remediation due to their high sensitivity and short duration. The concentrations of hydrocarbons in water extracts from test soils were 130 and 100 μg L(-1) before and after remediation, respectively. Similarly to terrestrial tests, most aquatic bioassays detected a significant reduction in toxicity, which was almost negligible at the end of the treatment. D. magna survival was the most affected by soil elutriates although toxicity to the crustacean was associated to the salinity of the samples rather than to the concentration of hydrocarbons. Ecotoxicity tests with aqueous soil elutriates proved less relevant in the assessment of hydrocarbon-contaminated soils due to the low hydrosolubility of hydrocarbons and the influence of the physicochemical parameters of the aquatic medium.

  16. Cryopreserved semen in ecotoxicological bioassays: sensitivity and reliability of cryopreserved Sparus aurata spermatozoa.

    Science.gov (United States)

    Fabbrocini, Adele; D'Adamo, Raffaele; Del Prete, Francesco; Langellotti, Antonio Luca; Rinna, Francesca; Silvestri, Fausto; Sorrenti, Gerarda; Vitiello, Valentina; Sansone, Giovanni

    2012-10-01

    The aim of this study was to evaluate the feasibility of using cryopreserved S. aurata semen in spermiotoxicity tests. Cryopreservation is a biotechnology that can provide viable gametes and embryos on demand, rather than only in the spawning season, thus overcoming a limitation that has hindered the use of some species in ecotoxicological bioassays. Firstly, the sperm motility pattern of cryopreserved semen was evaluated after thawing by means of both visual and computer-assisted analyses. Motility parameters in the cryopreserved semen did not change significantly in the first hour after thawing, meaning that they were maintained for long enough to enable their use in spermiotoxicity tests. In the second phase of the research, bioassays were performed, using cadmium as the reference toxicant, in order to evaluate the sensitivity of cryopreserved S. aurata semen to ecotoxicological contamination. The sensitivity of the sperm motility parameters used as endpoints (motility percentages and velocities) proved to be comparable to what has been recorded for the fresh semen of other aquatic species (LOECs from 0.02 to 0.03 mg L(-1)). The test showed good reliability and was found to be rapid and easy to perform, requiring only a small volume of the sample. Moreover, cryopreserved semen is easy to store and transfer and makes it possible to perform bioassays in different sites or at different times with the same batch of semen. The proposed bioassay is therefore a promising starting point for the development of toxicity tests that are increasingly tailored to the needs of ecotoxicology and environmental quality evaluation strategies. Copyright © 2012 Elsevier Inc. All rights reserved.

  17. Functional diagnostics for thyrotropin hormone receptor autoantibodies: bioassays prevail over binding assays.

    Science.gov (United States)

    Lytton, Simon David; Schluter, Anke; Banga, Paul J

    2018-06-01

    Autoantibodies to the thyrotropin hormone receptor (TSH-R) are directly responsible for the hyperthyroidism in Graves' disease and mediate orbital manifestations in Graves' orbitopathy (otherwise known as thyroid eye disease). These autoantibodies are heterogeneous in their function and collectively referred to as TRAbs. Measurement of TRAbs is clinically important for diagnosis of a variety of conditions and different commercial assays with high sensitivity and specificity are available for diagnostic purposes. This review provides overwhelming evidence that the TRAbs detected in binding assays by mainly the automated electrochemical luminescence immunoassays (ECLIA) do not distinguish TRAbs that stimulate the TSH-R (called TSIs or TSAbs) and TRAbs that just inhibit the binding of TSH without stimulating the TSH-R (called TBAbs). However, TSAbs and TBAbs have divergent pathogenic roles, and depending which fraction predominates cause different clinical symptoms and engender different therapeutic regimen. Therefore, diagnostic distinction of TSAbs and TBAbs is of paramount clinical importance. To date, only bioassays such as the Mc4 TSH-R bioassay (Thyretain TM , Quidel) and the Bridge assay (Immulite 2000, Siemens) can measure TSAbs, with only the former being able to distinguish between TSAbs and TBAbs. On this note, it is strongly recommended to only use the term TSI or TSAb when reporting the results of bioassays, whereas the results of automated TRAb binding assays should be reported as TRAbs (of undetermined functional significance). This review aims to present a technical and analytical account of leading commercial diagnostic methods of anti-TSH-R antibodies, a metaanalysis of their clinical performance and a perspective for the use of cell based TSH-R bioassays in the clinical diagnostics of Graves' disease.

  18. Bioassay method for toxicity studies of insecticide formulations to Tuta absoluta (meyrick, 1917)

    OpenAIRE

    Galdino, Tarcísio Visintin da Silva; Picanço, Marcelo Coutinho; Morais, Elisangela Gomes Fidelis de; Silva, Nilson Rodrigues; Silva, Geverson Aelton Rezende da; Lopes, Mayara Cristina

    2011-01-01

    Chemical control is the main method for controlling the tomato leafminer, Tuta absoluta (Meyrick, 1917) (Lepidoptera: Gelechiidae). Reported techniques for the evaluation of insecticide toxicity to the tomato leafminer are not in agreement with field conditions and do not allow us to verify whether doses used in the field are efficient for control. Thus, the objective of this work was to develop a bioassay methodology to study the toxicity of insecticide formulations to T. absoluta that repre...

  19. Bioassay method for toxicity studies of insecticide formulations to tuta absoluta (meyrick, 1917).

    OpenAIRE

    GALDINO, T. V. da S.; PICANÇO, M. C.; MORAIS, E. G. F. de; SILVA, N. R.; SILVA, G. A. R da; LOPES, M. C.

    2014-01-01

    Chemical control is the main method for controlling the tomato leafminer, Tuta absoluta (Meyrick, 1917) (Lepidoptera: Gelechiidae). Reported techniques for the evaluation of insecticide toxicity to the tomato leafminer are not in agreement with field conditions and do not allow us to verify whether doses used in the field are efficient for control. Thus, the objective of this work was to develop a bioassay methodology to study the toxicity of insecticide formulations to T. absoluta that repre...

  20. Bioassay using the water soluble fraction of a Nigerian Light Crude ...

    African Journals Online (AJOL)

    Summary: A 96-hour bioassay was conducted using the water soluble fraction of a Nigerian light crude oil sample on Clarias gariepinus fingerlings. 0, 2.5, 5.0, 7.5 and 10 mls of water soluble fractions (WSF) of the oil were added to 1000 litres of de-chlorinated tap water to form 0, 25, 50 , 75 and 100 parts per million ...

  1. Genotoxicity monitoring of industrial wastes using plant bioassays and management through vermitechnology: A review

    Directory of Open Access Journals (Sweden)

    Sartaj Ahmad Bhat

    2017-10-01

    Full Text Available The main objective of this review was to summarize and present a comprehensive account of the cytotoxic, genotoxic and mutagenic potential of various industrial wastes/sludges using some well-known plant bioassays followed by their bioremediation using vermitechnology. Industries are the main origin of discharges of various types of chemical wastes and are the main causes of environmental degradation. The direct application of industrial sludges could also harm the local biota. The genotoxicity of industrial sludges is assessed using various plant bioassays (for example Allium cepa, Vicia faba and these bioassays are comparatively more sensitive and cost-effective compared to other in-vitro genotoxicity bioassays. In addition, the materials used for toxicity evaluation are easily available and are being routinely used for the monitoring of environmental pollution. In most studies, the increases in root length and mitotic index, as well as the decrease in chromosomal aberrations in post vermicomposted sludges/wastes indicate that earthworms have the ability to reduce the ecotoxicogenetic effects of sludges/wastes. Post vermicompost is considered an excellent material of a homogenous nature as it has reduced levels of contaminants and holds more nutrients over a longer time without affecting the environment. The biotransformation potential of earthworms and their ability to detoxify most of the heavy metals in industrial sludges is because of their strong metabolic system and the involvement of diverse intestinal microflora and chloragocytic cells that reduce toxic forms to nontoxic forms. This unique ability of earthworms confirms the effectiveness of vermitechnology in reducing the toxicity of industrial wastes. Keywords: Allium cepa, Earthworm, Industrial sludge, Toxicity, Vermicomposting

  2. Development of a chick bioassay for determination of infectivity of viral pathogens in poultry litter.

    Science.gov (United States)

    Islam, A F M F; Walkden-Brown, S W; Groves, P J; Wells, B

    2013-01-01

    To develop a chicken bioassay to detect infective viral pathogens in poultry litter and to determine the effects of type of chicken and age of exposure, as well as the effect of simulated litter transportation, on the level of viral infectivity detected. A 5 × 2 × 2 factorial design, plus negative controls. Five chicken litters, including two with deliberate contamination (one transported and one not), two chicken types (specific-pathogen-free (SPF) Leghorns and Cobb broilers) and two ages at initial exposure (days 1 and 8). Two replicates of each treatment combination. The 10 chickens in each of 22 isolators were either exposed (20 isolators) or not (2 isolators) to 8 L of previously used or deliberately contaminated poultry litter in two deep scratch trays. At day 35 post-exposure, sera were assayed for antibodies against chicken anaemia virus (CAV), infectious bronchitis virus (IBV), infectious bursal disease virus (IBDV), Newcastle disease virus (NDV) and fowl adenovirus (FAV). Spleen samples were tested for Marek's disease virus (MDV) using real-time polymerase chain reaction. The bioassay detected CAV, IBDV and FAV, but not NDV, IBV or MDV, in chickens exposed to infected litters. Infection in SPF chickens was detected with greater sensitivity than in the broiler chickens. Sensitivity increased with age at exposure in broiler but not SPF chickens. Simulated transportation for 24 h had little effect on pathogen detection. A bioassay based on the exposure of day-old SPF chickens to poultry litter and measurement of seroconversion at day 35 post-exposure is a useful semi-quantitative assay for viral infectivity in poultry litter, with overnight transportation of litter having little effect on the level of viral infectivity detected. This bioassay has applications in research on litter treatment protocols. © 2013 The Authors. Australian Veterinary Journal © 2013 Australian Veterinary Association.

  3. Estimation of uranium in bioassay samples of occupational workers by laser fluorimetry

    International Nuclear Information System (INIS)

    Suja, A.; Prabhu, S.P.; Sawant, P.D.; Sarkar, P.K.; Tiwari, A.K.; Sharma, R.

    2010-01-01

    A newly established uranium processing facility has been commissioned at BARC, Trombay. Monitoring of occupational workers at regulars intervals is essential to assess intake of uranium by the workers in this facility. The design and engineering safety features of the plant are such that there is very low probability of uranium getting air borne during normal operations. However, the leakages from the system during routine maintenance of the plant may result in intake of uranium by workers. As per the new biokinetic model for uranium, 63% of uranium entering the blood stream gets directly excreted in urine. Therefore, bioassay monitoring (urinalysis) was recommended for these workers. A group of 21 workers was selected for bioassay monitoring to assess the existing urinary excretion levels of uranium before the commencement of actual work. For this purpose, sample collection kit along with an instruction slip was provided to the workers. Bioassay samples received were wet ashed with conc. nitric acid and hydrogen peroxide to break down the metabolized complexes of uranium and it was co-precipitated with calcium phosphate. Separation of uranium from the matrix was done using ion exchange technique and final activity quantification in these samples was done using laser fluorimeter (Quantalase, Model No. NFL/02). Calibration of the laser fluorimeter is done using 10 ppb uranium standard (WHO, France Ref. No. 180000). Verification of the system performance is done by measuring concentration of uranium in the standards (1 ppb to 100 ppb). Standard addition method was followed for estimation of uranium concentration in the samples. Uranyl ions present in the sample get excited by pulsed nitrogen laser at 337.1 nm, and on de-excitation emit fluorescence light (540 nm) intensity which is measured by the PMT. To estimate the uranium in the bioassay samples, a known aliquot of the sample was mixed with 5% sodium pyrophosphate and fluorescence intensity was measured

  4. Recombinant cell bioassays for the detection of (gluco) corticosteroids and endocrine-disrupting potencies of several enviromental PCB contaminants

    NARCIS (Netherlands)

    Bovee, T.F.H.; Helsdingen, J.R.; Hamers, A.R.M.; Brouwer, B.A.; Nielen, M.W.F.

    2011-01-01

    Sensitive and robust bioassays for glucocorticoids are very useful for the pharmaceutical industry, environmental scientists and veterinary control. Here, a recombinant yeast cell was constructed that expresses the human glucocorticoid receptor alpha and a green fluorescent reporter protein in

  5. Continuous flow bioassay method to evaluate the effects of outboard motor exhausts and selected aromatic toxicants on fish. [Carassius auratus

    Energy Technology Data Exchange (ETDEWEB)

    Brenniman, G. (Univ. of Illinois, Chicago); Hartung, R.; Weber, W.J. Jr.

    1976-01-01

    A continuous flow bioassay system was designed to measure the effects of outboard motor exhaust (OME) emissions and selected volatile and evaporative aromatic toxicants on goldfish (Carassius auratus). Continuous flow bioassays were run for 24, 48, 72, 96, and 720 h to determine lethal concentrations for 50 percent of individuals (LC 50's) for leaded OME, non-leaded OME, toluene, xylene, and 1,3,5 trimethylbenzene, the three individual compounds having been identified as significant aromatic components of OME. The 96 h LC-50's for these substances were found to be 171, 168, 23, 17, and 13 ppm, respectively. The values of 171 and 168 ppm for the two OME's are given in terms of gallons of fuel burned per million gallons of water. The continuous flow bioassay method was demonstrated to be a more reliable indicator of the effects of OME pollutants on aquatic organisms than is the static bioassay method.

  6. Ionizing radiation, inflammation, and their interactions in colon carcinogenesis in Mlh1-deficient mice.

    Science.gov (United States)

    Morioka, Takamitsu; Miyoshi-Imamura, Tomoko; Blyth, Benjamin J; Kaminishi, Mutsumi; Kokubo, Toshiaki; Nishimura, Mayumi; Kito, Seiji; Tokairin, Yutaka; Tani, Shusuke; Murakami-Murofushi, Kimiko; Yoshimi, Naoki; Shimada, Yoshiya; Kakinuma, Shizuko

    2015-03-01

    Genetic, physiological and environmental factors are implicated in colorectal carcinogenesis. Mutations in the mutL homolog 1 (MLH1) gene, one of the DNA mismatch repair genes, are a main cause of hereditary colon cancer syndromes such as Lynch syndrome. Long-term chronic inflammation is also a key risk factor, responsible for colitis-associated colorectal cancer; radiation exposure is also known to increase colorectal cancer risk. Here, we studied the effects of radiation exposure on inflammation-induced colon carcinogenesis in DNA mismatch repair-proficient and repair-deficient mice. Male and female Mlh1(-/-) and Mlh1(+/+) mice were irradiated with 2 Gy X-rays when aged 2 weeks or 7 weeks and/or were treated with 1% dextran sodium sulfate (DSS) in drinking water for 7 days at 10 weeks old to induce mild inflammatory colitis. No colon tumors developed after X-rays and/or DSS treatment in Mlh1(+/+) mice. Colon tumors developed after DSS treatment alone in Mlh1(-/-) mice, and exposure to radiation prior to DSS treatment increased the number of tumors. Histologically, colon tumors in the mice resembled the subtype of well-to-moderately differentiated adenocarcinomas with tumor-infiltrating lymphocytes of human Lynch syndrome. Immunohistochemistry revealed that expression of both p53 and β-catenin and loss of p21 and adenomatosis polyposis coli proteins were observed at the later stages of carcinogenesis, suggesting a course of molecular pathogenesis distinct from typical sporadic or colitis-associated colon cancer in humans. In conclusion, radiation exposure could further increase the risk of colorectal carcinogenesis induced by inflammation under the conditions of Mlh1 deficiency. © 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

  7. Wnt5a Is Associated with Cigarette Smoke-Related Lung Carcinogenesis via Protein Kinase C

    OpenAIRE

    Whang, Young Mi; Jo, Ukhyun; Sung, Jae Sook; Ju, Hyun Jung; Kim, Hyun Kyung; Park, Kyong Hwa; Lee, Jong Won; Koh, In Song; Kim, Yeul Hong

    2013-01-01

    Wnt5a is overexpressed during the progression of human non-small cell lung cancer. However, the roles of Wnt5a during smoking-related lung carcinogenesis have not been clearly elucidated. We investigated the associations between Wnt5a and the early development of cigarette smoke related lung cancer using human bronchial epithelial (HBE) cells (NHBE, BEAS-2B, 1799, 1198 and 1170I) at different malignant stages established by exposure to cigarette smoke condensate (CSC). Abnormal up-regulation ...

  8. Gastric microbiota and carcinogenesis: the role of non-Helicobacter pylori bacteria: a systematic review

    Directory of Open Access Journals (Sweden)

    Emanuel Dias-Jácome

    Full Text Available Background and aim: Helicobacter pylori is the strongest risk factor for gastric cancer. However, recent advances in DNA sequencing technology have revealed a complex microbial community in the stomach that could also contribute to the development of gastric cancer. The aim of this study was to present recent scientific evidence regarding the role of non-Helicobacter pylori bacteria in gastric carcinogenesis. Methods: A systematic review of original articles published in PubMed in the last ten years related to gastric microbiota and gastric cancer in humans was performed. Results: Thirteen original articles were included. The constitution of gastric microbiota appears to be significantly affected by gastric cancer and premalignant lesions. In fact, differences in gastric microbiota have been documented, depending on Helicobacter pylori status and gastric conditions, such as non-atrophic gastritis, intestinal metaplasia and cancer. Gastric carcinogenesis can be associated with an increase in many bacteria (such as Lactobacillus coleohominis, Klebsiella pneumoniae or Acinetobacter baumannii as well as decrease in others (such as Porphyromonas spp, Neisseria spp, Prevotella pallens or Streptococcus sinensis. However, there is no conclusive data that confirms if these changes in microbiota are a cause or consequence of the process of carcinogenesis. Conclusions: Even though there is limited evidence in humans, microbiota differences between normal individuals, pre-malignant lesions and gastric cancer could suggest a progressive shift in the constitution of gastric microbiota in carcinogenesis, possibly resulting from a complex cross-talk between gastric microbiota and Helicobacter pylori. However, further studies are needed to elucidate the specific role (if any of different microorganisms.

  9. Differentiation and carcinogenesis: an integrated multilevel study of mechanisms from molecules to man. Progress report

    International Nuclear Information System (INIS)

    1985-01-01

    This study sought to identify and characterize mesenchymal progenitor cells (MPCs) in vitro, to identify the in vivo equivalent of the in vitro MPCs, and to determine the relationship between the presence or response of these cells both in vitro and eventually in vivo to altered proliferative capacity (in vitro cellular senescence, in vivo organismal aging) and altered susceptibility to carcinogenesis (frequency of in vitro neoplastic transformation and age-related frequency of in vivo cancer incidence). 16 refs

  10. In Vitro Androgen Bioassays as a Detection Method for Designer Androgens

    Directory of Open Access Journals (Sweden)

    Alison K. Heather

    2013-02-01

    Full Text Available Androgens are the class of sex steroids responsible for male sexual characteristics, including increased muscle mass and decreased fat mass. Illicit use of androgen doping can be an attractive option for those looking to enhance sporting performance and/or physical appearance. The use of in vitro bioassays to detect androgens, especially designer or proandrogens, is becoming increasingly important in combating androgen doping associated with nutritional supplements. The nutritional sports supplement market has grown rapidly throughout the past decade. Many of these supplements contain androgens, designer androgens or proandrogens. Many designer or proandrogens cannot be detected by the standard highly-sensitive screening methods such as gas chromatography-mass spectrometry because their chemical structure is unknown. However, in vitro androgen bioassays can detect designer and proandrogens as these assays are not reliant on knowing the chemical structure but instead are based on androgen receptor activation. For these reasons, it may be advantageous to use routine androgen bioassay screening of nutraceutical samples to help curb the increasing problem of androgen doping.

  11. Application of the CALUX bioassay for epidemiological study. Analyses of Belgian human plasma

    Energy Technology Data Exchange (ETDEWEB)

    Wouwe, N. van; Debacker, N.; Sasse, A. [Scientific Institute of Public Health, Brussels (BE)] (and others)

    2004-09-15

    The CALUX bioassay is a promising screening method for the detection of dioxin-like compounds. The observed good sensitivity, low number of false negative results as well as the good correlations with the GC-HRMS TEQ-values in case of feed and food analyses allow this method to climb in the first assessment methods' scale. The low amount of sample needed in addition to those latest advantages suggest that the CALUX bioassay could be a good screening method for epidemiological studies. The Belgian epidemiological study concerning the possible effect of the dioxin incident on the body burden of the Belgian population was an opportunity to test this method in comparison to the gold reference one: the GC-HRMS. The first part of this abstract presents epidemiological parameters (sensibility, specificity,) of the CALUX bioassay using CALUX TEQ-values as estimators of the TEQ-values of the 17 PCDD/Fs. The second part examines epidemiological determinants observed for CALUX and GCHRMS TEQ-values.

  12. Intercomparison programs - a tool for the implementation of a quality assurance program in bioassay

    International Nuclear Information System (INIS)

    Mesquita, Sueli A. de; Sousa, Wanderson O.; Juliao, Ligia M.Q.C.; Santos, Maristela S.; Fernandes, Paulo C.P.

    2009-01-01

    In vitro bioassay laboratories need to have means to demonstrate that they are technically competent, operate an effective quality system, and are able to generate technically valid calibration and test results. The reliability of the results of measurements has a high influence on the reliability of the dose assessment. Inter-laboratory tests are one of the tools for assessing the analytical consistency of in vitro bioassay laboratories. The intercomparison exercises provide an opportunity to compare radiochemistry techniques for in vitro analysis of biological samples. The in vitro Laboratory of the Instituto de Radioprotecao e Dosimetria has therefore participated in the intercomparison exercises sponsored by PROCORAD, ARCAL and IAEA since 1998. The intercomparison exercises comprise measurements of gamma and beta emitters in urine samples and alpha emitters in urine and faecal samples. This paper presents the performance of the IRD in vitro bioassay laboratory in the past intercomparisons. The results demonstrate that in vitro laboratory is able to generate technically valid results, which also guarantee the support for a quality assurance program and accreditation by competent organism in Brazil. (author)

  13. Development of bacteria-based bioassays for arsenic detection in natural waters.

    Science.gov (United States)

    Diesel, Elizabeth; Schreiber, Madeline; van der Meer, Jan Roelof

    2009-06-01

    Arsenic contamination of natural waters is a worldwide concern, as the drinking water supplies for large populations can have high concentrations of arsenic. Traditional techniques to detect arsenic in natural water samples can be costly and time-consuming; therefore, robust and inexpensive methods to detect arsenic in water are highly desirable. Additionally, methods for detecting arsenic in the field have been greatly sought after. This article focuses on the use of bacteria-based assays as an emerging method that is both robust and inexpensive for the detection of arsenic in groundwater both in the field and in the laboratory. The arsenic detection elements in bacteria-based bioassays are biosensor-reporter strains; genetically modified strains of, e.g., Escherichia coli, Bacillus subtilis, Staphylococcus aureus, and Rhodopseudomonas palustris. In response to the presence of arsenic, such bacteria produce a reporter protein, the amount or activity of which is measured in the bioassay. Some of these bacterial biosensor-reporters have been successfully utilized for comparative in-field analyses through the use of simple solution-based assays, but future methods may concentrate on miniaturization using fiberoptics or microfluidics platforms. Additionally, there are other potential emerging bioassays for the detection of arsenic in natural waters including nematodes and clams.

  14. Fluorescence-based bioassays for the detection and evaluation of food materials.

    Science.gov (United States)

    Nishi, Kentaro; Isobe, Shin-Ichiro; Zhu, Yun; Kiyama, Ryoiti

    2015-10-13

    We summarize here the recent progress in fluorescence-based bioassays for the detection and evaluation of food materials by focusing on fluorescent dyes used in bioassays and applications of these assays for food safety, quality and efficacy. Fluorescent dyes have been used in various bioassays, such as biosensing, cell assay, energy transfer-based assay, probing, protein/immunological assay and microarray/biochip assay. Among the arrays used in microarray/biochip assay, fluorescence-based microarrays/biochips, such as antibody/protein microarrays, bead/suspension arrays, capillary/sensor arrays, DNA microarrays/polymerase chain reaction (PCR)-based arrays, glycan/lectin arrays, immunoassay/enzyme-linked immunosorbent assay (ELISA)-based arrays, microfluidic chips and tissue arrays, have been developed and used for the assessment of allergy/poisoning/toxicity, contamination and efficacy/mechanism, and quality control/safety. DNA microarray assays have been used widely for food safety and quality as well as searches for active components. DNA microarray-based gene expression profiling may be useful for such purposes due to its advantages in the evaluation of pathway-based intracellular signaling in response to food materials.

  15. Fluorescence-Based Bioassays for the Detection and Evaluation of Food Materials

    Directory of Open Access Journals (Sweden)

    Kentaro Nishi

    2015-10-01

    Full Text Available We summarize here the recent progress in fluorescence-based bioassays for the detection and evaluation of food materials by focusing on fluorescent dyes used in bioassays and applications of these assays for food safety, quality and efficacy. Fluorescent dyes have been used in various bioassays, such as biosensing, cell assay, energy transfer-based assay, probing, protein/immunological assay and microarray/biochip assay. Among the arrays used in microarray/biochip assay, fluorescence-based microarrays/biochips, such as antibody/protein microarrays, bead/suspension arrays, capillary/sensor arrays, DNA microarrays/polymerase chain reaction (PCR-based arrays, glycan/lectin arrays, immunoassay/enzyme-linked immunosorbent assay (ELISA-based arrays, microfluidic chips and tissue arrays, have been developed and used for the assessment of allergy/poisoning/toxicity, contamination and efficacy/mechanism, and quality control/safety. DNA microarray assays have been used widely for food safety and quality as well as searches for active components. DNA microarray-based gene expression profiling may be useful for such purposes due to its advantages in the evaluation of pathway-based intracellular signaling in response to food materials.

  16. A new approach for bioassays based on frequency- and time-domain measurements of magnetic nanoparticles.

    Science.gov (United States)

    Oisjöen, Fredrik; Schneiderman, Justin F; Astalan, Andrea Prieto; Kalabukhov, Alexey; Johansson, Christer; Winkler, Dag

    2010-01-15

    We demonstrate a one-step wash-free bioassay measurement system capable of tracking biochemical binding events. Our approach combines the high resolution of frequency- and high speed of time-domain measurements in a single device in combination with a fast one-step bioassay. The one-step nature of our magnetic nanoparticle (MNP) based assay reduces the time between sample extraction and quantitative results while mitigating the risks of contamination related to washing steps. Our method also enables tracking of binding events, providing the possibility of, for example, investigation of how chemical/biological environments affect the rate of a binding process or study of the action of certain drugs. We detect specific biological binding events occurring on the surfaces of fluid-suspended MNPs that modify their magnetic relaxation behavior. Herein, we extrapolate a modest sensitivity to analyte of 100 ng/ml with the present setup using our rapid one-step bioassay. More importantly, we determine the size-distributions of the MNP systems with theoretical fits to our data obtained from the two complementary measurement modalities and demonstrate quantitative agreement between them. Copyright 2009 Elsevier B.V. All rights reserved.

  17. Investigation of animal and algal bioassays for reliable saxitoxin ecotoxicity and cytotoxicity risk evaluation.

    Science.gov (United States)

    Perreault, François; Matias, Marcelo Seleme; Melegari, Silvia Pedroso; Pinto, Catia Regina Silva de Carvalho; Creppy, Edmond Ekué; Popovic, Radovan; Matias, William Gerson

    2011-05-01

    Contamination of water bodies by saxitoxin can result in various toxic effects in aquatic organisms. Saxitoxin contamination has also been shown to be a threat to human health in several reported cases, even resulting in death. In this study, we evaluated the sensitivity of animal (Neuro-2A) and algal (Chlamydomonas reinhardtii) bioassays to saxitoxin effect. Neuro-2A cells were found to be sensitive to saxitoxin, as shown by a 24 h EC50 value of 1.5 nM, which was obtained using a cell viability assay. Conversely, no saxitoxin effect was found in any of the algal biomarkers evaluated, for the concentration range tested (2-128 nM). These results indicate that saxitoxin may induce toxic effects in animal and human populations at concentrations where phytoplankton communities are not affected. Therefore, when evaluating STX risk of toxicity, algal bioassays do not appear to be reliable indicators and should always be conducted in combination with animal bioassays. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. Development of acute and chronic sediment bioassays with the harpacticoid copepod Quinquelaophonte sp.

    Science.gov (United States)

    Stringer, Tristan J; Glover, Chris N; Keesing, Vaughan; Northcott, Grant L; Gaw, Sally; Tremblay, Louis A

    2014-01-01

    Reliable environmentally realistic bioassay methodologies are increasingly needed to assess the effects of environmental pollution. This study describes two estuarine sediment bioassays, one acute (96 h) and one chronic (14 d), with the New Zealand harpacticoid copepod Quinquelaophonte sp. utilising behavioural and reproductive endpoints. Spiked sediments were used to expose Quinquelaophonte sp. to three reference compounds representing important categories of estuarine chemical stressors: zinc (a metal), atrazine (a pesticide), and phenanthrene (a polycyclic aromatic hydrocarbon). Acute-to-chronic ratios (ACR) were used to further characterise species responses. Acute sediment (sandy and low total organic content) 96 h EC50 values for the sublethal inhibition of mobility for zinc, atrazine and phenanthrene were 137, 5.4, and 2.6 µg/g, respectively. The chronic EC50 values for inhibition of reproduction (total offspring) were 54.5, 0.0083, and 0.067 µg/g for zinc, atrazine, and phenanthrene, respectively. For phenanthrene, a potentially novel mode of action was identified on reproduction. Quinquelaophonte sp. was found to be more sensitive than several other estuarine species indicating choice of test organism is important to characterising the effects of environmentally relevant levels of contamination. The bioassay sediment results demonstrate the sensitivity and suitability of Quinquelaophonte sp. as a tool for the assessment use of estuarine health. © 2013 Published by Elsevier Inc.

  19. Determination of an Environmental Background Level of Sr-90 in Urine for the Hanford Bioassay Program

    International Nuclear Information System (INIS)

    Antonio, Cheryl L.; Rivard, James W.

    2009-01-01

    During the decommissioning and maintenance of some of the facilities at the U.S. Department of Energy Hanford Site in Washington State, workers have potential for a 90Sr intake. However, because of worldwide radioactive fallout, 90Sr is present in our environment, and can be detectable in routine urine bioassay samples. It is important for the Hanford Site bioassay program to discern an occupational intake from a non-occupational environmental one. A detailed study of the background 90Sr in the urine of unexposed Hanford workers was performed. A survey of the Hanford Site bioassay database found 128 Hanford workers who were hired between 1997 and 2002 and who had a very low potential for an occupational exposure prior to the baseline strontium urinalysis. Each urinalysis sample represented excretion during an approximate 24-hr period. The arithmetic mean value for the 128 pre-exposure baselines was 3.6 ± 5.1 mBq d-1. The 90Sr activities in urine varied from -12 to 20 mBq. The 99th percentile result was 16.4 mBqd-1, which was interpreted to mean that 1% of Hanford workers not occupationally exposed to strontium might exceed 16.4 mBq d-1.

  20. Assessing the genotoxicity of urban air pollutants using two in situ plant bioassays

    Energy Technology Data Exchange (ETDEWEB)

    Villarini, M.; Fatigoni, C.; Dominici, L.; Maestri, S. [Department of Medical-Surgical Specialties and Public Health, University of Perugia, I-06126 (Italy); Ederli, L.; Pasqualini, S. [Department of Applied Biology, University of Perugia, I-06121 (Italy); Monarca, S. [Department of Medical-Surgical Specialties and Public Health, University of Perugia, I-06126 (Italy); Moretti, M., E-mail: massimo.moretti@unipg.i [Department of Medical-Surgical Specialties and Public Health, University of Perugia, I-06126 (Italy)

    2009-12-15

    Genotoxicity of urban air has been analysed almost exclusively in airborne particulates. We monitored the genotoxic effects of airborne pollutants in the urban air of Perugia (Central Italy). Two plant bioindicators with different genetic endpoints were used: micronuclei in meiotic pollen mother cells using Tradescantia-micronucleus bioassay (Trad-MCN) and DNA damage in nuclei of Nicotiana tabacum leaves using comet assay (Nicotiana-comet). Buds of Tradescantia clone no. 4430 and young N. tabacum cv. Xanthi plants were exposed for 24 h at three sites with different pollution levels. One control site (indoor control) was also used. The two bioassays showed different sensitivities toward urban pollutants: Trad-MCN assay was the most sensitive, but DNA damage in N. tabacum showed a better correlation with the pollutant concentrations. In situ biomonitoring of airborne genotoxins using higher plants combined with chemical analysis is thus recommended for characterizing genotoxicity of urban air. - Plant bioassays used to explore in situ the correlation between air pollution and genotoxicity.

  1. Development of bacteria-based bioassays for arsenic detection in natural waters

    Energy Technology Data Exchange (ETDEWEB)

    Diesel, Elizabeth; Schreiber, Madeline [Virginia Tech, Department of Geosciences, Blacksburg, VA (United States); Meer, Jan Roelof van der [University of Lausanne, Department of Fundamental Microbiology, Lausanne (Switzerland)

    2009-06-15

    Arsenic contamination of natural waters is a worldwide concern, as the drinking water supplies for large populations can have high concentrations of arsenic. Traditional techniques to detect arsenic in natural water samples can be costly and time-consuming; therefore, robust and inexpensive methods to detect arsenic in water are highly desirable. Additionally, methods for detecting arsenic in the field have been greatly sought after. This article focuses on the use of bacteria-based assays as an emerging method that is both robust and inexpensive for the detection of arsenic in groundwater both in the field and in the laboratory. The arsenic detection elements in bacteria-based bioassays are biosensor-reporter strains; genetically modified strains of, e.g., Escherichia coli, Bacillus subtilis, Staphylococcus aureus, and Rhodopseudomonas palustris. In response to the presence of arsenic, such bacteria produce a reporter protein, the amount or activity of which is measured in the bioassay. Some of these bacterial biosensor-reporters have been successfully utilized for comparative in-field analyses through the use of simple solution-based assays, but future methods may concentrate on miniaturization using fiberoptics or microfluidics platforms. Additionally, there are other potential emerging bioassays for the detection of arsenic in natural waters including nematodes and clams. (orig.)

  2. Noninvasive quantitation of human liver steatosis using magnetic resonance and bioassay methods

    Energy Technology Data Exchange (ETDEWEB)

    D' Assignies, Gaspard; Ruel, Martin; Khiat, Abdesslem; Lepanto, Luigi; Kauffmann, Claude; Tang, An [Centre Hospitalier de l' Universite de Montreal (CHUM), Departement de Radiologie, Montreal, Quebec (Canada); Chagnon, Miguel [Universite de Montreal (UDEM), Departement de Mathematiques et de Statistique, Montreal, Quebec (Canada); Gaboury, Louis [Centre Hospitalier de l' Universite de Montreal (CHUM), Departement d' Anatomo-Pathologie, Montreal, Quebec (Canada); Boulanger, Yvan [Centre Hospitalier de l' Universite de Montreal (CHUM), Departement de Radiologie, Montreal, Quebec (Canada); Hopital Saint-Luc du CHUM, Departement de Radiologie, Montreal, Quebec (Canada)

    2009-08-15

    The purpose was to evaluate the ability of three magnetic resonance (MR) techniques to detect liver steatosis and to determine which noninvasive technique (MR, bioassays) or combination of techniques is optimal for the quantification of hepatic fat using histopathology as a reference. Twenty patients with histopathologically proven steatosis and 24 control subjects underwent single-voxel proton MR spectroscopy (MRS; 3 voxels), dual-echo in phase/out of phase MR imaging (DEI) and diffusion-weighted MR imaging (DWI) examinations of the liver. Blood or urine bioassays were also performed for steatosis patients. Both MRS and DEI data allowed to detect steatosis with a high sensitivity (0.95 for MRS; 1 for DEI) and specificity (1 for MRS; 0.875 for DEI) but not DWI. Strong correlations were found between fat fraction (FF) measured by MRS, DEI and histopathology segmentation as well as with low density lipoprotein (LDL) and cholesterol concentrations. A Bland-Altman analysis showed a good agreement between the FF measured by MRS and DEI. Partial correlation analyses failed to improve the correlation with segmentation FF when MRS or DEI data were combined with bioassay results. Therefore, FF from MRS or DEI appear to be the best parameters to both detect steatosis and accurately quantify fat liver noninvasively. (orig.)

  3. Experimental and Computational Characterization of Biological Liquid Crystals: A Review of Single-Molecule Bioassays

    Directory of Open Access Journals (Sweden)

    Sungsoo Na

    2009-09-01

    Full Text Available Quantitative understanding of the mechanical behavior of biological liquid crystals such as proteins is essential for gaining insight into their biological functions, since some proteins perform notable mechanical functions. Recently, single-molecule experiments have allowed not only the quantitative characterization of the mechanical behavior of proteins such as protein unfolding mechanics, but also the exploration of the free energy landscape for protein folding. In this work, we have reviewed the current state-of-art in single-molecule bioassays that enable quantitative studies on protein unfolding mechanics and/or various molecular interactions. Specifically, single-molecule pulling experiments based on atomic force microscopy (AFM have been overviewed. In addition, the computational simulations on single-molecule pulling experiments have been reviewed. We have also reviewed the AFM cantilever-based bioassay that provides insight into various molecular interactions. Our review highlights the AFM-based single-molecule bioassay for quantitative characterization of biological liquid crystals such as proteins.

  4. Sampling method, storage and pretreatment of sediment affect AVS concentrations with consequences for bioassay responses

    Energy Technology Data Exchange (ETDEWEB)

    Lange, H.J. de [Aquatic Ecology and Water Quality Management Group, Wageningen University, Wageningen University and Research Centre, P.O. Box 8080, 6700 DD, Wageningen (Netherlands); Centre for Ecosystem Studies, Alterra, Wageningen University and Research Centre, P.O. Box 47, 6700 AA, Wageningen (Netherlands)], E-mail: marieke.delange@wur.nl; Griethuysen, C. van; Koelmans, A.A. [Aquatic Ecology and Water Quality Management Group, Wageningen University, Wageningen University and Research Centre, P.O. Box 8080, 6700 DD, Wageningen (Netherlands)

    2008-01-15

    Sediment treatment and sediment storage may alter sediment toxicity, and consequently biotic response. Purpose of our study was to combine these three aspects (treatment-toxicity-biotic response) in one integrated approach. We used Acid Volatile Sulfide (AVS) concentrations as a proxy of the disturbance of the sediment. AVS and Simultaneously Extracted Metal (SEM) concentrations were compared to bioassay responses with the freshwater benthic macroinvertebrate Asellus aquaticus. Storage conditions and sediment treatment affected AVS but not SEM levels. AVS can be used as a proxy for sediment disturbance. The best way to pretreat the sediment for use in a bioassay in order to maintain initial AVS conditions was to sample the sediment with an Ekman grab, immediately store it in a jar without headspace, and freeze it as soon as possible. In a survey using seven different sediments, bioassay responses of A. aquaticus were correlated with SEM and AVS characteristics. - Change in AVS is a good proxy for sediment disturbance and combined with SEM it can be used as a suitable predictor for biotic effects of sediment contamination.

  5. Assessing the genotoxicity of urban air pollutants using two in situ plant bioassays

    International Nuclear Information System (INIS)

    Villarini, M.; Fatigoni, C.; Dominici, L.; Maestri, S.; Ederli, L.; Pasqualini, S.; Monarca, S.; Moretti, M.

    2009-01-01

    Genotoxicity of urban air has been analysed almost exclusively in airborne particulates. We monitored the genotoxic effects of airborne pollutants in the urban air of Perugia (Central Italy). Two plant bioindicators with different genetic endpoints were used: micronuclei in meiotic pollen mother cells using Tradescantia-micronucleus bioassay (Trad-MCN) and DNA damage in nuclei of Nicotiana tabacum leaves using comet assay (Nicotiana-comet). Buds of Tradescantia clone no. 4430 and young N. tabacum cv. Xanthi plants were exposed for 24 h at three sites with different pollution levels. One control site (indoor control) was also used. The two bioassays showed different sensitivities toward urban pollutants: Trad-MCN assay was the most sensitive, but DNA damage in N. tabacum showed a better correlation with the pollutant concentrations. In situ biomonitoring of airborne genotoxins using higher plants combined with chemical analysis is thus recommended for characterizing genotoxicity of urban air. - Plant bioassays used to explore in situ the correlation between air pollution and genotoxicity.

  6. Building bio-assays with magnetic particles on a digital microfluidic platform.

    Science.gov (United States)

    Kokalj, Tadej; Pérez-Ruiz, Elena; Lammertyn, Jeroen

    2015-09-25

    Digital microfluidics (DMF) has emerged as a promising liquid handling technology for a variety of applications, demonstrating great potential both in terms of miniaturization and automation. DMF is based on the manipulation of discrete, independently controllable liquid droplets, which makes it highly reconfigurable and reprogrammable. One of its most exclusive advantages, compared to microchannel-based microfluidics, is its ability to precisely handle solid nano- and microsized objects, such as magnetic particles. Magnetic particles have become very popular in the last decade, since their high surface-to-volume ratio and the possibility to magnetically separate them from the matrix make them perfect suitable as a solid support for bio-assay development. The potential of magnetic particles in DMF-based bio-assays has been demonstrated for various applications. In this review we discuss the latest developments of magnetic particle-based DMF bio-assays with the aim to present, identify and analyze the trends in the field. We also discuss the state-of-the art of device integration, current status of commercialization and issues that still need to be addressed. With this paper we intend to stimulate researchers to exploit and unveil the potential of these exciting tools, which will shape the future of modern biochemistry, microbiology and biomedical diagnostics. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Use of a modified microplate bioassay method to investigate antibacterial activity in the Peruvian medicinal plant Peperomia galioides.

    Science.gov (United States)

    Langfield, Richard D; Scarano, Frank J; Heitzman, Mary E; Kondo, Miwako; Hammond, Gerald B; Neto, Catherine C

    2004-10-01

    A versatile microplate bioassay for quick and sensitive determination of antibacterial activity was developed for use in screening medicinal plants and identification of their active principles. This assay can be used to determine minimum inhibitory concentrations for small quantities of organic or water-soluble plant extracts. Bioassay-guided fractionation of the stem and leaves of Peperomia galioides using this method found fractions containing grifolin and grifolic acid, which inhibited growth of Staphylococcus aureus and Staphylococcus epidermidis.

  8. 65Zn kinetics as a biomarker of DMH induced colon carcinogenesis

    International Nuclear Information System (INIS)

    Chadha, Vijayta Dani

    2012-01-01

    Dietary factors are considered crucial for the prevention of initiating events in the multistep progression of colon carcinoma. There is substantial evidence that zinc may play a pivotal role in host defense against several malignancies, including colon cancer. The present study was conducted to evaluate the kinetics of zinc utilization following experimental colon carcinogenesis in rat model. The rats were segregated into two groups viz., untreated control and DMH treated. Colon carcinogenesis was established through weekly subcutaneous injections of DMH (30mg/Kg body weight) for 16 weeks. Whole body 65 Zn kinetics followed two compartment kinetics, with Tb1 representing the initial fast component of the biological half-life and Tb2, the slower component. The present study revealed a significant depression in the Tb1 and Tb2 components of 65 Zn in DMH treated rats. Further, DMH treatment caused a significant increase in the percent uptake values of 65 Zn in the colon, small intestine, kidney and blood, whereas a significant decrease was observed in the liver. Subcellular distribution revealed a significant increase in 65 Zn uptake in the mitochondrial and microsomal fractions following 16 weeks of DMH supplementation. The present study demonstrated a slow mobilization of zinc during promotion of experimentally induced colon carcinogenesis and provides a physiological basis for the role of zinc in colon tumorigenesis, a paradigm which may have clinical implications in the management of colon cancer. (author)

  9. Modification of N-Methyl-N-Nitrosourea initiated bladder carcinogenesis in Wistar rats by terephthalic acid

    International Nuclear Information System (INIS)

    Cui Lunbiao; Shi Yuan; Dai Guidong; Pan Hongxin; Chen Jianfeng; Song Ling; Wang Shouling; Chang, Hebron C.; Sheng Hongbing; Wang Xinru

    2006-01-01

    The effect of terephthalic acid (TPA) on urinary bladder carcinogenesis was examined. Male Wistar rats were initiated by injection of N-Methyl-N-Nitrosourea (MNU) (20 mg/kg b.w. ip) twice a week for 4 weeks, then given basal diet containing 5% TPA, 5% TPA plus 4% Sodium bicarbonate (NaHCO 3 ) or 1% TPA for the next 22 weeks, and then euthanized. 5% TPA treatment induced a high incidence of urinary bladder calculi and a large amount of precipitate. Though 5% TPA plus 4% Sodium bicarbonate (NaHCO 3 ) and 1% TPA treatment did not induce urinary bladder calculi formation, they resulted in a moderate increase in urinary precipitate. Histological examination of urinary bladder revealed that MNU-5% TPA treatment resulted in a higher incidence of simple hyperplasia, papillary or nodular hyperplasia (PN hyperplasia), papilloma and cancer than MNU control. MNU-5% TPA plus 4% Sodium bicarbonate (NaHCO 3 ) and 1% TPA treatment increased slightly the incidence of simple hyperplasia and PN hyperplasia (not statistically significant). The major elements of the precipitate are phosphorus, potassium, sulfur, chloride, calcium and TPA. The present study indicated that the calculi induced by TPA had a strong promoting activity on urinary bladder carcinogenesis and the precipitate containing calcium terephthalate (CaTPA) may also have weak promoting activity on urinary bladder carcinogenesis

  10. Mast cells are dispensable for normal and activin-promoted wound healing and skin carcinogenesis.

    Science.gov (United States)

    Antsiferova, Maria; Martin, Caroline; Huber, Marcel; Feyerabend, Thorsten B; Förster, Anja; Hartmann, Karin; Rodewald, Hans-Reimer; Hohl, Daniel; Werner, Sabine

    2013-12-15

    The growth and differentiation factor activin A is a key regulator of tissue repair, inflammation, fibrosis, and tumorigenesis. However, the cellular targets, which mediate the different activin functions, are still largely unknown. In this study, we show that activin increases the number of mature mast cells in mouse skin in vivo. To determine the relevance of this finding for wound healing and skin carcinogenesis, we mated activin transgenic mice with CreMaster mice, which are characterized by Cre recombinase-mediated mast cell eradication. Using single- and double-mutant mice, we show that loss of mast cells neither affected the stimulatory effect of overexpressed activin on granulation tissue formation and reepithelialization of skin wounds nor its protumorigenic activity in a model of chemically induced skin carcinogenesis. Furthermore, mast cell deficiency did not alter wounding-induced inflammation and new tissue formation or chemically induced angiogenesis and tumorigenesis in mice with normal activin levels. These findings reveal that mast cells are not major targets of activin during wound healing and skin cancer development and also argue against nonredundant functions of mast cells in wound healing and skin carcinogenesis in general.

  11. Deficiency of the Erc/mesothelin gene ameliorates renal carcinogenesis in Tsc2 knockout mice.

    Science.gov (United States)

    Zhang, Danqing; Kobayashi, Toshiyuki; Kojima, Tetsuo; Kanenishi, Kenji; Hagiwara, Yoshiaki; Abe, Masaaki; Okura, Hidehiro; Hamano, Yoshitomo; Sun, Guodong; Maeda, Masahiro; Jishage, Kou-ichi; Noda, Tetsuo; Hino, Okio

    2011-04-01

    Genetic crossing experiments were performed between tuberous sclerosis-2 (Tsc2) KO and expressed in renal carcinoma (Erc) KO mice to analyze the function of the Erc/mesothelin gene in renal carcinogenesis. We found the number and size of renal tumors were significantly less in Tsc2+/-;Erc-/- mice than in Tsc2+/-;Erc+/+ and Tsc2+/-;Erc+/- mice. Tumors from Tsc2+/-;Erc-/- mice exhibited reduced cell proliferation and increased apoptosis, as determined by proliferating cell nuclear antigen (Ki67) and TUNEL analysis, respectively. Adhesion to collagen-coated plates in vitro was enhanced in Erc-restored cells and decreased in Erc-suppressed cells with siRNA. Tumor formation by Tsc2-deficient cells in nude mice was remarkably suppressed by stable knockdown of Erc with shRNA. Western blot analysis showed that the phosphorylation of focal adhesion kinase, Akt and signal transducer and activator of transcription protein 3 were weaker in Erc-deficient/suppressed cells compared with Erc-expressed cells. These results indicate that deficiency of the Erc/mesothelin gene ameliorates renal carcinogenesis in Tsc2 KO mice and inhibits the phosphorylation of several kinases of cell adhesion mechanism. This suggests that Erc/mesothelin may have an important role in the promotion and/or maintenance of carcinogenesis by influencing cell-substrate adhesion via the integrin-related signal pathway. © 2011 Japanese Cancer Association.

  12. Antibiotic suppression of intestinal microbiota reduces heme-induced lipoperoxidation associated with colon carcinogenesis in rats.

    Science.gov (United States)

    Martin, O C B; Lin, C; Naud, N; Tache, S; Raymond-Letron, I; Corpet, D E; Pierre, F H

    2015-01-01

    Epidemiological studies show that heme iron from red meat is associated with increased colorectal cancer risk. In carcinogen-induced-rats, a heme iron-rich diet increases the number of precancerous lesions and raises associated fecal biomarkers. Heme-induced lipoperoxidation measured by fecal thiobarbituric acid reagents (TBARs) could explain the promotion of colon carcinogenesis by heme. Using a factorial design we studied if microbiota could be involved in heme-induced carcinogenesis, by modulating peroxidation. Rats treated or not with an antibiotic cocktail were given a control or a hemoglobin-diet. Fecal bacteria were counted on agar and TBARs concentration assayed in fecal water. The suppression of microbiota by antibiotics was associated with a reduction of crypt height and proliferation and with a cecum enlargement, which are characteristics of germ-free rats. Rats given hemoglobin diets had increased fecal TBARs, which were suppressed by the antibiotic treatment. A duplicate experiment in rats given dietary hemin yielded similar results. These data show that the intestinal microbiota is involved in enhancement of lipoperoxidation by heme iron. We thus suggest that microbiota could play a role in the heme-induced promotion of colorectal carcinogenesis.

  13. Carcinogenesis associated with parasites other than Schistosoma, Opisthorchis and Clonorchis: A systematic review.

    Science.gov (United States)

    Machicado, Claudia; Marcos, Luis A

    2016-06-15

    Only three helminths (Schistosoma haematobium, Opisthorchis viverrini and Clonorchis sinensis) are directly associated with carcinogenesis in humans whereas the role of other parasites in cancer remains unclear. This study aimed to perform a systematic review to identify recent insights in the role of other parasite infections in carcinogenesis. We conducted systematic searches of MEDLINE and EMBASE on July 2015. Our primary outcome was the association between parasitic infections and carcinogenesis. Out of 1,266 studies, 19 were selected for detailed evaluation (eight for helminths and 11 for protozoa). The mechanisms of helminth-induced cancer included chronic inflammation, sustained proliferation, modulation of the host immune system, reprogramming of glucose metabolism and redox signaling, induction of genomic instability and destabilization of suppressor tumor proteins, stimulation of angiogenesis, resisting cell death, and activation of invasion and metastasis. In addition to the current knowledge, the following parasites were found in cancers or tumors: Echinococcus, Strongyloides, Fasciola, Heterakis, Platynosomum and Trichuris. Additional parasites were found in this systematic review that could potentially be associated with cancers or tumors but further evidence is needed to elaborate a cause-effect relationship. © 2016 UICC.

  14. Detouring the Undesired Route of Helicobacter pylori-Induced Gastric Carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Eun-Hee; Hong, Kyung-Sook; Hong, Hua [Lab of Translational Medicine, Lee Gil Ya Cancer and Diabetes Institute, Gachon University of Medicine and Science, 7-45 Songdo-dong, Yeonsu-gu, Incheon 406-840 (Korea, Republic of); Hahm, Ki Baik, E-mail: hahmkb@gachon.ac.kr [Lab of Translational Medicine, Lee Gil Ya Cancer and Diabetes Institute, Gachon University of Medicine and Science, 7-45 Songdo-dong, Yeonsu-gu, Incheon 406-840 (Korea, Republic of); Department of Gastroenterology, Gachon Graduate School of Medicine, Gil Hospital, Incheon 406-840 (Korea, Republic of)

    2011-07-25

    Epidemiological and experimental evidence has emerged that a dysregulated inflammation is associated with most of the tumors, and many studies have begun to unravel the molecular pathways linking inflammation and cancer. As a typical example linking these associations, Helicobacter pylori (H. pylori) infection-associated atrophic gastritis has been recognized as precursor lesion of gastric cancer. The identification of transcription factors such as NF-κB and STAT3, and their gene products such as IL-8, COX-2, iNOS, cytokines, chemokines and their receptors, etc have laid the molecular foundation for our understanding of the decisive role of inflammation in carcinogenesis. In addition to the role as the initiator of cancer, inflammation contributes to survival and proliferation of malignant cells, tumor angiogenesis, and even metastasis. In this review, the fundamental mechanisms of H. pylori-induced carcinogenesis as well as the possibility of cancer prevention through suppressing H. pylori-induced inflammation are introduced. We infer that targeting inflammatory pathways have a potential role to detour the unpleasant journey to H. pylori-associated gastric carcinogenesis.

  15. Quantification of nanoscale density fluctuations by electron microscopy: probing cellular alterations in early carcinogenesis

    International Nuclear Information System (INIS)

    Pradhan, Prabhakar; Damania, Dhwanil; Turzhitsky, Vladimir; Subramanian, Hariharan; Backman, Vadim; Joshi, Hrushikesh M; Dravid, Vinayak P; Roy, Hemant K; Taflove, Allen

    2011-01-01

    Most cancers are curable if they are diagnosed and treated at an early stage. Recent studies suggest that nanoarchitectural changes occur within cells during early carcinogenesis and that such changes precede microscopically evident tissue alterations. It follows that the ability to comprehensively interrogate cell nanoarchitecture (e.g., macromolecular complexes, DNA, RNA, proteins and lipid membranes) could be critical to the diagnosis of early carcinogenesis. We present a study of the nanoscale mass-density fluctuations of biological tissues by quantifying their degree of disorder at the nanoscale. Transmission electron microscopy images of human tissues are used to construct corresponding effective disordered optical lattices. The properties of nanoscale disorder are then studied by statistical analysis of the inverse participation ratio (IPR) of the spatially localized eigenfunctions of these optical lattices at the nanoscale. Our results show an increase in the disorder of human colonic epithelial cells in subjects harboring early stages of colon neoplasia. Furthermore, our findings strongly suggest that increased nanoscale disorder correlates with the degree of tumorigenicity. Therefore, the IPR technique provides a practicable tool for the detection of nanoarchitectural alterations in the earliest stages of carcinogenesis. Potential applications of the technique for early cancer screening and detection are also discussed

  16. Detouring the Undesired Route of Helicobacter pylori-Induced Gastric Carcinogenesis

    International Nuclear Information System (INIS)

    Kim, Eun-Hee; Hong, Kyung-Sook; Hong, Hua; Hahm, Ki Baik

    2011-01-01

    Epidemiological and experimental evidence has emerged that a dysregulated inflammation is associated with most of the tumors, and many studies have begun to unravel the molecular pathways linking inflammation and cancer. As a typical example linking these associations, Helicobacter pylori (H. pylori) infection-associated atrophic gastritis has been recognized as precursor lesion of gastric cancer. The identification of transcription factors such as NF-κB and STAT3, and their gene products such as IL-8, COX-2, iNOS, cytokines, chemokines and their receptors, etc have laid the molecular foundation for our understanding of the decisive role of inflammation in carcinogenesis. In addition to the role as the initiator of cancer, inflammation contributes to survival and proliferation of malignant cells, tumor angiogenesis, and even metastasis. In this review, the fundamental mechanisms of H. pylori-induced carcinogenesis as well as the possibility of cancer prevention through suppressing H. pylori-induced inflammation are introduced. We infer that targeting inflammatory pathways have a potential role to detour the unpleasant journey to H. pylori-associated gastric carcinogenesis

  17. Detouring the Undesired Route of Helicobacter pylori-Induced Gastric Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Ki Baik Hahm

    2011-07-01

    Full Text Available Epidemiological and experimental evidence has emerged that a dysregulated inflammation is associated with most of the tumors, and many studies have begun to unravel the molecular pathways linking inflammation and cancer. As a typical example linking these associations, Helicobacter pylori (H. pylori infection-associated atrophic gastritis has been recognized as precursor lesion of gastric cancer. The identification of transcription factors such as NF-κB and STAT3, and their gene products such as IL-8, COX-2, iNOS, cytokines, chemokines and their receptors, etc have laid the molecular foundation for our understanding of the decisive role of inflammation in carcinogenesis. In addition to the role as the initiator of cancer, inflammation contributes to survival and proliferation of malignant cells, tumor angiogenesis, and even metastasis. In this review, the fundamental mechanisms of H. pylori-induced carcinogenesis as well as the possibility of cancer prevention through suppressing H. pylori-induced inflammation are introduced. We infer that targeting inflammatory pathways have a potential role to detour the unpleasant journey to H. pylori-associated gastric carcinogenesis.

  18. A Review of ERCC1 Gene in Bladder Cancer: Implications for Carcinogenesis and Resistance to Chemoradiotherapy

    Directory of Open Access Journals (Sweden)

    Atsunari Kawashima

    2012-01-01

    Full Text Available The excision repair cross-complementing group 1 (ERCC1 gene performs a critical incision step in DNA repair and is reported to be correlated with carcinogenesis and resistance to drug or ionizing radiation therapy. We reviewed the correlation between ERCC1 and bladder cancer. In carcinogenesis, several reports discussed the relation between ERCC1 single nucleotide polymorphisms and carcinogenesis in bladder cancer only in case-control studies. Regarding the relation between ERCC1 and resistance to chemoradiotherapy, in vitro and clinical studies indicate that ERCC1 might be related to resistance to radiation therapy rather than cisplatin therapy. It is controversial whether ERCC1 predicts prognosis of bladder cancer treated with cisplatin-based chemotherapy. Tyrosine kinase receptors or endothelial-mesenchymal transition are reported to regulate the expression of ERCC1, and further study is needed to clarify the mechanism of ERCC1 expression and resistance to chemoradiotherapy in vitro and to discover novel therapies for advanced and metastatic bladder cancer.

  19. A Review of ERCC1 Gene in Bladder Cancer: Implications for Carcinogenesis and Resistance to Chemoradiotherapy.

    Science.gov (United States)

    Kawashima, Atsunari; Takayama, Hitoshi; Tsujimura, Akira

    2012-01-01

    The excision repair cross-complementing group 1 (ERCC1) gene performs a critical incision step in DNA repair and is reported to be correlated with carcinogenesis and resistance to drug or ionizing radiation therapy. We reviewed the correlation between ERCC1 and bladder cancer. In carcinogenesis, several reports discussed the relation between ERCC1 single nucleotide polymorphisms and carcinogenesis in bladder cancer only in case-control studies. Regarding the relation between ERCC1 and resistance to chemoradiotherapy, in vitro and clinical studies indicate that ERCC1 might be related to resistance to radiation therapy rather than cisplatin therapy. It is controversial whether ERCC1 predicts prognosis of bladder cancer treated with cisplatin-based chemotherapy. Tyrosine kinase receptors or endothelial-mesenchymal transition are reported to regulate the expression of ERCC1, and further study is needed to clarify the mechanism of ERCC1 expression and resistance to chemoradiotherapy in vitro and to discover novel therapies for advanced and metastatic bladder cancer.

  20. Review: the Contribution of both Nature and Nurture to Carcinogenesis and Progression in Solid Tumours.

    Science.gov (United States)

    Hyndman, Iain Joseph

    2016-04-01

    Cancer is a leading cause of mortality worldwide. Cancer arises due to a series of somatic mutations that accumulate within the nucleus of a cell which enable the cell to proliferate in an unregulated manner. These mutations arise as a result of both endogenous and exogenous factors. Genes that are commonly mutated in cancer cells are involved in cell cycle regulation, growth and proliferation. It is known that both nature and nurture play important roles in cancer development through complex gene-environment interactions; however, the exact mechanism of these interactions in carcinogenesis is presently unclear. Key environmental factors that play a role in carcinogenesis include smoking, UV light and oncoviruses. Angiogenesis, inflammation and altered cell metabolism are important factors in carcinogenesis and are influenced by both genetic and environmental factors. Although the exact mechanism of nature-nurture interactions in solid tumour formation are not yet fully understood, it is evident that neither nature nor nurture can be considered in isolation. By understanding more about gene-environment interactions, it is possible that cancer mortality could be reduced.

  1. The scientific basis for the establishment of threshold levels and dose response relationships of carcinogenesis

    International Nuclear Information System (INIS)

    1975-01-01

    The International Atomic Energy Agency hosted a two day Symposium from 2-3 December 1974 at its Headquarters, organized by the 'International Academy for Environmental Safety and the Forum fur Wissenschaft, Wirtschaft und Politik' on the subject 'Scientific Basis for the Establishment of Threshold. Levels and Dose Response Relationships of Carcinogenesis'. Following an introductory paper by the Radiation Biology Section of the Agency on 'Radiation Carcinogenesis - Dose Response Relationship, Threshold and Risk Estimates', a series of papers dealt with this problem in chemical carcinogenesis.It was suggested that more experiments should be done using non-human primates for tests of carcinogens, especially chemicals. Preliminary experiments using monkeys with a potent carcinogen - nitrosoamine - indicate that there could possibly be a dose where no effect can be observed during the 5 year period of study. It was also pointed out that the overall cost/benefit and risk/ benefit relationships should be taken into consideration in determining limits for chemicals which are potentially carcinogenic but are used routinely by the public and industries; these considerations have been weighed in setting exposure limits for radiation

  2. Experimental studies on lung carcinogenesis and their relationship to future research on radiation-induced lung cancer in humans

    International Nuclear Information System (INIS)

    Cross, F.T.

    1991-03-01

    The usefulness of experimental systems for studying human lung carcinogenesis lies in the ease of studying components of a total problem. As an example, the main thrust of attack on possible synergistic interactions between radiation, cigarette smoke, and other irritants must be by means of research on animals. Because animals can be serially sacrificed, a systematic search can be made for progressive lung changes, thereby improving our understanding of carcinogenesis. The mechanisms of radiation-induced carcinogenesis have not yet been delineated, but modern concepts of molecular and cellular biology and of radiation dosimetry are being increasingly applied to both in vivo and in vitro exposure to determine the mechanisms of radiation-induced carcinogenesis, to elucidate human data, and to aid in extrapolating experimental animal data to human exposures. In addition, biologically based mathematical models of carcinogenesis are being developed to describe the nature of the events leading to malignancy; they are also an essential part of a rational approach to quantitative cancer risk assessment. This paper summarizes recent experimental and modeling data on radon-induced lung cancer and includes the confounding effects of cigarette-smoke exposures. The applicability of these data to understanding human exposures is emphasized, and areas of future research on human radiation-induced carcinogenesis are discussed. 7 refs., 2 figs., 3 tabs

  3. In vitro bioassays for detecting dioxin-like activity--application potentials and limits of detection, a review.

    Science.gov (United States)

    Eichbaum, Kathrin; Brinkmann, Markus; Buchinger, Sebastian; Reifferscheid, Georg; Hecker, Markus; Giesy, John P; Engwall, Magnus; van Bavel, Bert; Hollert, Henner

    2014-07-15

    Use of in vitro assays as screening tool to characterize contamination of a variety of environmental matrices has become an increasingly popular and powerful toolbox in the field of environmental toxicology. While bioassays cannot entirely substitute analytical methods such as gas chromatography-mass spectrometry (GC-MS), the increasing improvement of cell lines and standardization of bioassay procedures enhance their utility as bioanalytical pre-screening tests prior to more targeted chemical analytical investigations. Dioxin-receptor-based assays provide a holistic characterization of exposure to dioxin-like compounds (DLCs) by integrating their overall toxic potential, including potentials of unknown DLCs not detectable via e.g. GC-MS. Hence, they provide important additional information with respect to environmental risk assessment of DLCs. This review summarizes different in vitro bioassay applications for detection of DLCs and considers the comparability of bioassay and chemical analytically derived toxicity equivalents (TEQs) of different approaches and various matrices. These range from complex samples such as sediments through single reference to compound mixtures. A summary of bioassay derived detection limits (LODs) showed a number of current bioassays to be equally sensitive as chemical methodologies, but moreover revealed that most of the bioanalytical studies conducted to date did not report their LODs, which represents a limitation with regard to low potency samples. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Toxicity of hydrogen sulfide to goldfish (Carassius auratus L. ) as influenced by temperature, oxygen, and bioassay techniques

    Energy Technology Data Exchange (ETDEWEB)

    Adelman, I.R.; Smith, L.L. Jr.

    1972-01-01

    Bioassays were conducted to test the effect of temperature and oxygen on H/sub 2/S toxicity to goldfish (Carassius auratus L.) and to investigate some factors that influence bioassay results. Relation of H/sub 2/S toxicity to temperature is negatively logarithmic over the range of 6.5-25 C. The mean 96-hr TL50 at 6 C was 530 ..mu..g/liter and at 25 C was 4 ..mu..g/liter. At temperatures of 14, 20, and 26 C, most acute mortality from H/sub 2/S ended by 11 days and the 11-day TL50's at these temperatures were significantly different. In bioassays with and without prior oxygen acclimation, decreasing oxygen concentrations increased H/sub 2/S toxicity. In the former, mean TL50's were 62 and 48 ..mu..g/liter H/sub 2/S at oxygen concentrations of 6 and 1.5 mg/liter, respectively, and in the latter, 71 and 53 ..mu..g/liter H/sub 2/S at the same oxygen concentrations. Variability in bioassay results was not affected by test temperatures of 14, 20, and 26 C, and in most cases 1 week of temperature acclimation was adequate. Stocks of fish responded differently after 11 days of bioassay, although differences were not detected after 4 days of bioassay. 27 references, 4 figures, 3 tables.

  5. The 1-Week and 8-Month Effects of a Ketogenic Diet or Ketone Salt Supplementation on Multi-Organ Markers of Oxidative Stress and Mitochondrial Function in Rats

    Science.gov (United States)

    Kephart, Wesley C.; Mumford, Petey W.; Mao, Xuansong; Romero, Matthew A.; Hyatt, Hayden W.; Zhang, Yufeng; Mobley, Christopher B.; Quindry, John C.; Young, Kaelin C.; Beck, Darren T.; McCullough, Danielle J.; D’Agostino, Dominic P.; Lowery, Ryan P.; Wilson, Jacob M.; Kavazis, Andreas N.; Roberts, Michael D.

    2017-01-01

    We determined the short- and long-term effects of a ketogenic diet (KD) or ketone salt (KS) supplementation on multi-organ oxidative stress and mitochondrial markers. For short-term feedings, 4 month-old male rats were provided isocaloric amounts of KD (n = 10), standard chow (SC) (n = 10) or SC + KS (~1.2 g/day, n = 10). For long-term feedings, 4 month-old male rats were provided KD (n = 8), SC (n = 7) or SC + KS (n = 7) for 8 months and rotarod tested every 2 months. Blood, brain (whole cortex), liver and gastrocnemius muscle were harvested from all rats for biochemical analyses. Additionally, mitochondria from the brain, muscle and liver tissue of long-term-fed rats were analyzed for mitochondrial quantity (maximal citrate synthase activity), quality (state 3 and 4 respiration) and reactive oxygen species (ROS) assays. Liver antioxidant capacity trended higher in short-term KD- and SC + KS-fed versus SC-fed rats, and short-term KD-fed rats exhibited significantly greater serum ketones compared to SC + KS-fed rats indicating that the diet (not KS supplementation) induced ketonemia. In long term-fed rats: (a) serum ketones were significantly greater in KD- versus SC- and SC + KS-fed rats; (b) liver antioxidant capacity and glutathione peroxidase protein was significantly greater in KD- versus SC-fed rats, respectively, while liver protein carbonyls were lowest in KD-fed rats; and (c) gastrocnemius mitochondrial ROS production was significantly greater in KD-fed rats versus other groups, and this paralleled lower mitochondrial glutathione levels. Additionally, the gastrocnemius pyruvate-malate mitochondrial respiratory control ratio was significantly impaired in long-term KD-fed rats, and gastrocnemius mitochondrial quantity was lowest in these animals. Rotarod performance was greatest in KD-fed rats versus all other groups at 2, 4 and 8 months, although there was a significant age-related decline in performance existed in KD-fed rats which was not evident in the

  6. Epigenome remodelling in breast cancer: insights from an early in vitro model of carcinogenesis.

    Science.gov (United States)

    Locke, Warwick J; Clark, Susan J

    2012-11-15

    Epigenetic gene regulation has influence over a diverse range of cellular functions, including the maintenance of pluripotency, differentiation, and cellular identity, and is deregulated in many diseases, including cancer. Whereas the involvement of epigenetic dysregulation in cancer is well documented, much of the mechanistic detail involved in triggering these changes remains unclear. In the current age of genomics, the development of new sequencing technologies has seen an influx of genomic and epigenomic data and drastic improvements in both resolution and coverage. Studies in cancer cell lines and clinical samples using next-generation sequencing are rapidly delivering spectacular insights into the nature of the cancer genome and epigenome. Despite these improvements in technology, the timing and relationship between genetic and epigenetic changes that occur during the process of carcinogenesis are still unclear. In particular, what changes to the epigenome are playing a driving role during carcinogenesis and what influence the temporal nature of these changes has on cancer progression are not known. Understanding the early epigenetic changes driving breast cancer has the exciting potential to provide a novel set of therapeutic targets or early-disease biomarkers or both. Therefore, it is important to find novel systems that permit the study of initial epigenetic events that potentially occur during the first stages of breast cancer. Non-malignant human mammary epithelial cells (HMECs) provide an exciting in vitro model of very early breast carcinogenesis. When grown in culture, HMECs are able to temporarily escape senescence and acquire a pre-malignant breast cancer-like phenotype (variant HMECs, or vHMECs). Cultured HMECs are composed mainly of cells from the basal breast epithelial layer. Therefore, vHMECs are considered to represent the basal-like subtype of breast cancer. The transition from HMECs to vHMECs in culture recapitulates the epigenomic

  7. A novel method for standardized application of fungal spore coatings for mosquito exposure bioassays.

    Science.gov (United States)

    Farenhorst, Marit; Knols, Bart G J

    2010-01-20

    Interest in the use of fungal entomopathogens against malaria vectors is growing. Fungal spores infect insects via the cuticle and can be applied directly on the insect to evaluate infectivity. For flying insects such as mosquitoes, however, application of fungal suspensions on resting surfaces is more realistic and representative of field settings. For this type of exposure, it is essential to apply specific amounts of fungal spores homogeneously over a surface for testing the effects of fungal dose and exposure time. Contemporary methods such as spraying or brushing spore suspensions onto substrates do not produce the uniformity and consistency that standardized laboratory assays require. Two novel fungus application methods using equipment developed in the paint industry are presented and compared. Wired, stainless steel K-bars were tested and optimized for coating fungal spore suspensions onto paper substrates. Different solvents and substrates were evaluated. Two types of coating techniques were compared, i.e. manual and automated coating. A standardized bioassay set-up was designed for testing coated spores against malaria mosquitoes. K-bar coating provided consistent applications of spore layers onto paper substrates. Viscous Ondina oil formulations were not suitable and significantly reduced spore infectivity. Evaporative Shellsol T solvent dried quickly and resulted in high spore infectivity to mosquitoes. Smooth proofing papers were the most effective substrate and showed higher infectivity than cardboard substrates. Manually and mechanically applied spore coatings showed similar and reproducible effects on mosquito survival. The standardized mosquito exposure bioassay was effective and consistent in measuring effects of fungal dose and exposure time. K-bar coating is a simple and consistent method for applying fungal spore suspensions onto paper substrates and can produce coating layers with accurate effective spore concentrations. The mosquito bioassay

  8. A novel method for standardized application of fungal spore coatings for mosquito exposure bioassays

    Directory of Open Access Journals (Sweden)

    Knols Bart GJ

    2010-01-01

    Full Text Available Abstract Background Interest in the use of fungal entomopathogens against malaria vectors is growing. Fungal spores infect insects via the cuticle and can be applied directly on the insect to evaluate infectivity. For flying insects such as mosquitoes, however, application of fungal suspensions on resting surfaces is more realistic and representative of field settings. For this type of exposure, it is essential to apply specific amounts of fungal spores homogeneously over a surface for testing the effects of fungal dose and exposure time. Contemporary methods such as spraying or brushing spore suspensions onto substrates do not produce the uniformity and consistency that standardized laboratory assays require. Two novel fungus application methods using equipment developed in the paint industry are presented and compared. Methods Wired, stainless steel K-bars were tested and optimized for coating fungal spore suspensions onto paper substrates. Different solvents and substrates were evaluated. Two types of coating techniques were compared, i.e. manual and automated coating. A standardized bioassay set-up was designed for testing coated spores against malaria mosquitoes. Results K-bar coating provided consistent applications of spore layers onto paper substrates. Viscous Ondina oil formulations were not suitable and significantly reduced spore infectivity. Evaporative Shellsol T solvent dried quickly and resulted in high spore infectivity to mosquitoes. Smooth proofing papers were the most effective substrate and showed higher infectivity than cardboard substrates. Manually and mechanically applied spore coatings showed similar and reproducible effects on mosquito survival. The standardized mosquito exposure bioassay was effective and consistent in measuring effects of fungal dose and exposure time. Conclusions K-bar coating is a simple and consistent method for applying fungal spore suspensions onto paper substrates and can produce coating layers

  9. Using a macroalgal δ15N bioassay to detect cruise ship waste water effluent inputs

    International Nuclear Information System (INIS)

    Kaldy, James

    2011-01-01

    Highlights: → Green macroalgae exposed to nutrient solutions exhibited changes in tissue 15 N signatures. → Macroalgae exhibited no fractionation with NO 3 and slight fractionation with NH 4 . → Algae exposed to cruise ship waste water had increased tissue δ 15 N indicating a heavy N source. → Field bioassays exhibited decreased δ 15 N indicating isotopically light riverine δ 15 N-NO 3 was likely the dominant N source. → Algal bioassays could not detect a δ 15 N cruise ship waste water signal in this system. - Abstract: Green macroalgae bioassays were used to determine if the δ 15 N signature of cruise ship waste water effluent (CSWWE) could be detected in a small harbor. Opportunistic green macroalgae (Ulva spp.) were collected, cultured under nutrient depleted conditions and characterized with regard to N content and δ 15 N. Samples of algae were used in controlled incubations to evaluate the direction of isotope shift from exposure to CSWWE. Algae samples exposed to CSWWE exhibited an increase of 1-2.5 per mille in δ 15 N values indicating that the CSWWE had an enriched isotope signature. In contrast, algae samples exposed to field conditions exhibited a significant decrease in the observed δ 15 N indicating that a light N source was used. Isotopically light, riverine nitrogen derived from N 2 -fixing trees in the watershed may be a N source utilized by algae. These experiments indicate that the δ 15 N CSWWE signature was not detectable under the CSWWE loading conditions of this experiment.

  10. Bioassay requirements for 125I and 131I in medical, teaching and research institutions

    International Nuclear Information System (INIS)

    1983-09-01

    The more widespread use of radioactive isotopes of iodine (collectively referred to as radioiodines) as a research tool, coupled with their diagnostic and therapeutic uses in nuclear medicine, has resulted in an increased number of personnel who are exposed to these radioisotopes and who therefore should be monitored for internal radioiodine contamination. This document describes the minimum acceptable features of a bioassay programme which the Atomic Energy Control Board (AECB) requires to be available in institutions holding a prescribed substance licence authorising the use of significant quantities of 125 I or 131 I or both. A licensee may submit details of his own proposed bioassay programme to the AECB for approval. If such a programme fails to be approved, the programme described below shall be adhered to. This document does not deal with individuals who are likely to maintain a significant chronic thyroid burden of radioiodine. It is assumed that the radioiodine taken into the body is in a soluble, inorganic form (I 2 , iodide or iodate) or in an organic form (e.g. methyl iodide) which is metabolised in the body with a resultant release of iodide. Radioiodinated organic compounds which are not catabolised to iodide in the body to any significant degree are not the subject of this document, since the metabolism of the radioiodine will be dictated by the metabolism of the compound. This means that individuals whose only exposure to radioiodine is in the form of prepared radioiodinated compounds such as antigens and antibodies (e.g. individuals using radio immuno assay kits in which the antigen or antibody is supplied as radioiodinated material) are not required to participate in this bioassay programme for radioiodine

  11. Detection of anabolic androgenic steroid abuse in doping control using mammalian reporter gene bioassays.

    Science.gov (United States)

    Houtman, Corine J; Sterk, Saskia S; van de Heijning, Monique P M; Brouwer, Abraham; Stephany, Rainer W; van der Burg, Bart; Sonneveld, Edwin

    2009-04-01

    Anabolic androgenic steroids (AAS) are a class of steroid hormones related to the male hormone testosterone. They are frequently detected as drugs in sport doping control. Being similar to or derived from natural male hormones, AAS share the activation of the androgen receptor (AR) as common mechanism of action. The mammalian androgen responsive reporter gene assay (AR CALUX bioassay), measuring compounds interacting with the AR can be used for the analysis of AAS without the necessity of knowing their chemical structure beforehand, whereas current chemical-analytical approaches may have difficulty in detecting compounds with unknown structures, such as designer steroids. This study demonstrated that AAS prohibited in sports and potential designer AAS can be detected with this AR reporter gene assay, but that also additional steroid activities of AAS could be found using additional mammalian bioassays for other types of steroid hormones. Mixtures of AAS were found to behave additively in the AR reporter gene assay showing that it is possible to use this method for complex mixtures as are found in doping control samples, including mixtures that are a result of multi drug use. To test if mammalian reporter gene assays could be used for the detection of AAS in urine samples, background steroidal activities were measured. AAS-spiked urine samples, mimicking doping positive samples, showed significantly higher androgenic activities than unspiked samples. GC-MS analysis of endogenous androgens and AR reporter gene assay analysis of urine samples showed how a combined chemical-analytical and bioassay approach can be used to identify samples containing AAS. The results indicate that the AR reporter gene assay, in addition to chemical-analytical methods, can be a valuable tool for the analysis of AAS for doping control purposes.

  12. Evaluation of internal exposure of nuclear medicine staff through in vivo and in vitro bioassay techniques

    Energy Technology Data Exchange (ETDEWEB)

    Lucena, E.A.; Araujo, F.; Sousa, W.O.; Dantas, A.L.A.; Dantas, B.M. [Instituto de Radioprotecao e Dosimetria, CNEN, Av. Salvador Allende s/n, CEP 22780-160 Rio de Janeiro (Brazil); Rebelo, A.M.O.; Corbo, R. [Hospital Universitario Clementino Fraga Filho, HU-UFRJ, Av. Brigadeiro Trompowsky, s/n, ILHA do Fundao, CEP 21945-560, Rio de Janeiro, RJ (Brazil)

    2007-07-01

    The manipulation of a wide variety of unsealed sources in Nuclear Medicine results in a significant risk of internal exposure of the workers. {sup 131}I should be highlighted among the most frequently used radionuclides because of its large application for diagnosis and therapy of thyroid diseases. The increasing use of radionuclides for medical purposes creates a demand for feasible methodologies to perform occupational control of internal contamination. Currently in Brazil, there are {approx}300 nuclear medicine centres in operation but individual monitoring is still restricted to the control of external exposure. This work presents the development of in vivo and in vitro bioassay techniques aimed to quantify incorporation of radionuclides used in Nuclear Medicine. It is also presented the results of a preliminary survey of internal exposure of a group of workers involved in the preparation of therapeutic doses of {sup 131}I. Workers were monitored with a gamma camera available in the Nuclear Medicine Service of the University Hospital of Rio de Janeiro and at the Institute of Radiation Protection and Dosimetry Whole-Body Counter (IRDWBC). The in vivo detection systems were calibrated with a neck-thyroid phantom developed in IRD. Urine samples from radiopharmacy workers were collected after preparation and administration of therapeutic doses (10-250 mCi) of {sup 131}I and measured with a HPGe detection system available in the Bioassay Laboratory of IRD. The results show that the bioassay methods developed in this work present enough sensitivity for routine monitoring of nuclear medicine workers. All workers monitored in this survey presented positive results for {sup 131}I in urine samples and two workers presented detectable activities in thyroid when measured at the IRD-WBC. The highest committed effective dose per preparation was estimated to be 17 {mu}Sv. (authors)

  13. Redox-flexible NADH oxidase biosensor: A platform for various dehydrogenase bioassays and biosensors

    International Nuclear Information System (INIS)

    Serban, Simona; El Murr, Nabil

    2006-01-01

    A generic amperometric bioassay based on the enzymatic oxidation catalysed by the stable NADH oxidase (NAox) from Thermus thermophilus has been developed for NADH measurements. The NAox uses O 2 as its natural electron acceptor and produces H 2 O 2 in a two-electron process. Electrochemical and spectrophotometric experiments showed that the NAox used in this work, presents a very good activity towards its substrate and, in contrary to previously mentioned NADH oxidases, does not require the addition of any exogenous flavin cofactor neither to promote nor to maintain its activity. In addition, the NAox used also works with artificial electron acceptors like ferrocene derivatives. O 2 was successfully replaced by redox mediators such as hydroxymethyl ferrocene (FcCH 2 OH) for the regeneration of the active enzyme. Combining the NAox with the mediator and the horseradish peroxidase we developed an original, high sensitive 'redox-flexible' NADH amperometric bioassay working in a large window of applied potentials in both oxidation and reduction modes. The biosensor has a continuous and complementary linearity range permitting to measure NADH concentrations starting from 5 x 10 -6 M in reduction until 2 x 10 3 M in oxidation. This redox-flexibility allows choosing the applied potential in order to avoid electrochemical interferences. The association of the 'redox-flexible' concept with NADH dependent enzymes opens a novel strategy for dehydrogenases based bioassays and biosensors. The great number of dehydrogenases available makes the concept applicable for numerous substrates to analyse. Moreover it allows the development of a wide range of biosensors on the basis of a generic platform. This gives several advantages over the previous manufacturing techniques and offers a general and flexible scheme for the fabrication of biosensors presenting high sensitivities, wide calibration ranges and less affected by electrochemical interferences

  14. Guidance document for prepermit bioassay testing of low-level radioactive waste

    International Nuclear Information System (INIS)

    Anderson, S.L.; Harrison, F.L.

    1990-11-01

    In response to the mandate of Public Law 92-532, the Marine Protection, Research, and Sanctuaries Act (MPRSA) of 1972, as amended, the Environmental Protection Agency (EPA) has developed a program to promulgate regulations and criteria to control the ocean disposal of radioactive wastes. The EPA seeks to understand the mechanisms for biological response of marine organisms to the low levels of radioactivity that may arise from the release of these wastes as a result of ocean-disposal practices. Such information will play an important role in determining the adequacy of environmental assessments provided to the EPA in support of any disposal permit application. Although the EPA requires packaging of low-level radioactive waste to prevent release during radiodecay of the materials, some release of radioactive material into the deep-sea environment may occur when a package deteriorates. Therefore, methods for evaluating the impact on biota are being evaluated. Mortality and phenotypic responses are not anticipated at the expected low environmental levels that might occur if radioactive materials were released from the low-level waste packages. Therefore, traditional bioassay systems are unsuitable for assessing sublethal effects on biota in the marine environment. The EPA Office of Radiation Programs (ORP) has had an ongoing program to examine sublethal responses to radiation at the cellular level, using cytogenetic end points. This technical guidance report represents prepermit bioassay procedures that potentially may be applicable to the assessment of effects from a mixture of radionuclides that could be released from a point source at the ocean bottom. Methodologies along with rationale and a discussion of uncertainty are presented for the sediment benthic bioassay protocols identified in this report

  15. GHSI emergency radionuclide bioassay laboratory network - summary of the second exercise

    International Nuclear Information System (INIS)

    Li, Chunsheng; Ko, Raymond; Quayle, Debora; Sadi, Baki; Bartizel, Christine; Battisti, Paolo; Boettger, Axel; Bouvier, Celine; Paquet, Francois; CapoteCuellar, Antonio; Carr, Zhanat; Hammond, Derek; Hartmann, Martina; Heikkinen, Tarja; Jones, Robert L.; Kim, Eunjoo; Koga, Roberto; Kukhta, Boris; Mitchell, Lorna; Morhard, Ryan; Rulik, Petr; Sergei, Aleksanin; Sierra, Inmaculada; Oliveira Sousa, Wandersonde; Szabo, Gyula

    2017-01-01

    The Global Health Security Initiative (GHSI) established a laboratory network within the GHSI community to develop collective surge capacity for radionuclide bioassay in response to a radiological or nuclear emergency as a means of enhancing response capability, health outcomes and community resilience. GHSI partners conducted an exercise in collaboration with the WHO Radiation Emergency Medical Preparedness and Assistance Network and the IAEA Response and Assistance Network, to test the participating laboratories (18) for their capabilities in in vitro assay of biological samples, using a urine sample spiked with multiple high-risk radionuclides ( 90 Sr, 106 Ru, 137 Cs, and 239 Pu). Laboratories were required to submit their reports within 72 h following receipt of the sample, using a pre-formatted template, on the procedures, methods and techniques used to identify and quantify the radionuclides in the sample, as well as the bioassay results with a 95% confidence interval. All of the participating laboratories identified and measured all or some of the radionuclides in the sample. However, gaps were identified in both the procedures used to assay multiple radionuclides in one sample, as well as in the methods or techniques used to assay specific radionuclides in urine. Two-third of the participating laboratories had difficulties in determining all the radionuclides in the sample. Results from this exercise indicate that challenges remain with respect to ensuring that results are delivered in a timely, consistent and reliable manner to support medical interventions. Laboratories within the networks are encouraged to work together to develop and maintain collective capabilities and capacity for emergency bioassay, which is an important component of radiation emergency response. (authors)

  16. Guidance document for prepermit bioassay testing of low-level radioactive waste

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, S.L.; Harrison, F.L.

    1990-11-01

    In response to the mandate of Public Law 92-532, the Marine Protection, Research, and Sanctuaries Act (MPRSA) of 1972, as amended, the Environmental Protection Agency (EPA) has developed a program to promulgate regulations and criteria to control the ocean disposal of radioactive wastes. The EPA seeks to understand the mechanisms for biological response of marine organisms to the low levels of radioactivity that may arise from the release of these wastes as a result of ocean-disposal practices. Such information will play an important role in determining the adequacy of environmental assessments provided to the EPA in support of any disposal permit application. Although the EPA requires packaging of low-level radioactive waste to prevent release during radiodecay of the materials, some release of radioactive material into the deep-sea environment may occur when a package deteriorates. Therefore, methods for evaluating the impact on biota are being evaluated. Mortality and phenotypic responses are not anticipated at the expected low environmental levels that might occur if radioactive materials were released from the low-level waste packages. Therefore, traditional bioassay systems are unsuitable for assessing sublethal effects on biota in the marine environment. The EPA Office of Radiation Programs (ORP) has had an ongoing program to examine sublethal responses to radiation at the cellular level, using cytogenetic end points. This technical guidance report represents prepermit bioassay procedures that potentially may be applicable to the assessment of effects from a mixture of radionuclides that could be released from a point source at the ocean bottom. Methodologies along with rationale and a discussion of uncertainty are presented for the sediment benthic bioassay protocols identified in this report.

  17. Fast and accurate semantic annotation of bioassays exploiting a hybrid of machine learning and user confirmation.

    Science.gov (United States)

    Clark, Alex M; Bunin, Barry A; Litterman, Nadia K; Schürer, Stephan C; Visser, Ubbo

    2014-01-01

    Bioinformatics and computer aided drug design rely on the curation of a large number of protocols for biological assays that measure the ability of potential drugs to achieve a therapeutic effect. These assay protocols are generally published by scientists in the form of plain text, which needs to be more precisely annotated in order to be useful to software methods. We have developed a pragmatic approach to describing assays according to the semantic definitions of the BioAssay Ontology (BAO) project, using a hybrid of machine learning based on natural language processing, and a simplified user interface designed to help scientists curate their data with minimum effort. We have carried out this work based on the premise that pure machine learning is insufficiently accurate, and that expecting scientists to find the time to annotate their protocols manually is unrealistic. By combining these approaches, we have created an effective prototype for which annotation of bioassay text within the domain of the training set can be accomplished very quickly. Well-trained annotations require single-click user approval, while annotations from outside the training set domain can be identified using the search feature of a well-designed user interface, and subsequently used to improve the underlying models. By drastically reducing the time required for scientists to annotate their assays, we can realistically advocate for semantic annotation to become a standard part of the publication process. Once even a small proportion of the public body of bioassay data is marked up, bioinformatics researchers can begin to construct sophisticated and useful searching and analysis algorithms that will provide a diverse and powerful set of tools for drug discovery researchers.

  18. Fast and accurate semantic annotation of bioassays exploiting a hybrid of machine learning and user confirmation

    Directory of Open Access Journals (Sweden)

    Alex M. Clark

    2014-08-01

    Full Text Available Bioinformatics and computer aided drug design rely on the curation of a large number of protocols for biological assays that measure the ability of potential drugs to achieve a therapeutic effect. These assay protocols are generally published by scientists in the form of plain text, which needs to be more precisely annotated in order to be useful to software methods. We have developed a pragmatic approach to describing assays according to the semantic definitions of the BioAssay Ontology (BAO project, using a hybrid of machine learning based on natural language processing, and a simplified user interface designed to help scientists curate their data with minimum effort. We have carried out this work based on the premise that pure machine learning is insufficiently accurate, and that expecting scientists to find the time to annotate their protocols manually is unrealistic. By combining these approaches, we have created an effective prototype for which annotation of bioassay text within the domain of the training set can be accomplished very quickly. Well-trained annotations require single-click user approval, while annotations from outside the training set domain can be identified using the search feature of a well-designed user interface, and subsequently used to improve the underlying models. By drastically reducing the time required for scientists to annotate their assays, we can realistically advocate for semantic annotation to become a standard part of the publication process. Once even a small proportion of the public body of bioassay data is marked up, bioinformatics researchers can begin to construct sophisticated and useful searching and analysis algorithms that will provide a diverse and powerful set of tools for drug discovery researchers.

  19. Bioassay of circulating luteinizing hormone in the rhesus monkey: comparison with radioimmunoassay during physiological changes

    International Nuclear Information System (INIS)

    Dufau, M.L.; Hodgen, G.D.; Goodman, A.L.; Catt, K.J.

    1977-01-01

    The concentration of biologically active LH in Rhesus monkey (Macaca mulatta) serum was measured by a highly sensitive bioassay based upon testosterone production by dispersed rat interstitial cells. The sensitivity of the in vitro bioassay was equal to or higher than that of radioimmunoassay, with detection limits of 0.1 mIU of human menopausal gonadotropin (hMG) or 10 ng of a Rhesus pituitary gonadotropin preparation (LER-1909-2). Parallel dose-response curves were obtained for hMG and Rhesus monkey pituitary gonadotropin. The method permits bioassay of LH in 20--100 μl of serum from adult male monkeys, and from female monkeys during the follicular and luteal phases of the menstrual cycle. Bioactive LH concentrations could be assayed in 0.25 to 5 μl of serum from mid-cycle, postmenopausal, and castrated female monkeys. Serum LH was undetectable in two hypophysectomized adult female monkeys and six intact immature animals, and was 13 +- 6 (SD) mIU/ml in adult male monkeys. In adult females, follicular phase LH levels ranged from 17 to 169 mIU/ml, with a mean of 76 +- 52 mIU/ml. The midcycle LH peak was 1738 +- 742 mIU/ml and the luteal phase values ranged from 6-47 mIU/ml, with a mean of 35 +- 5 mIU/ml. Serum LH concentrations ranged from 100 to 900 mIU/ml in two menopausal females, and from 590--1480 mIU/ml in castrated females. Treatment of castrated female monkeys with estrogen plus progesterone produced an initial two-fold rise in sepum LH within 3 days, followed by a gradual decline to one-fourth to one-tenth of the initial levels after 10 days of treatment. Serum LH was suppressed to undetectable levels during the third week, and remained so for the duration of the 60-day treatment period

  20. Modul.LES: a multi-compartment, multi-organism aquatic life support system as experimental platform for research in ∆g

    Science.gov (United States)

    Hilbig, Reinhard; Anken, Ralf; Grimm, Dennis

    In view of space exploration and long-term satellite missions, a new generation of multi-modular, multi-organism bioregenerative life support system with different experimental units (Modul.LES) is planned, and subunits are under construction. Modul.LES will be managed via telemetry and remote control and therefore is a fully automated experimental platform for different kinds of investigations. After several forerunner projects like AquaCells (2005), C.E.B.A.S. (1998, 2003) or Aquahab (OHB-System AG the Oreochromis Mossambicus Eu-glena Gracilis Aquatic Habitat (OmegaHab) was successfully flown in 2007 in course of the FOTON-M3 Mission. It was a 3 chamber controlled life support system (CLSS), compris-ing a bioreactor with the green algae Euglena gracilis, a fish chamber with larval cichlid fish Oreochromis mossambicus and a filter chamber with biodegrading bacteria. The sensory super-vision of housekeeping management was registered and controlled by telemetry. Additionally, all scientific data and videos of the organisms aboard were stored and sequentially transmitted to relay stations. Based on the effective performance of OmegaHab, this system was chosen for a reflight on Bion-M1 in 2012. As Bion-M1 is a long term mission (appr. 4 weeks), this CLSS (OmegaHab-XP) has to be redesigned and refurbished with enhanced performance. The number of chambers has been increased from 3 to 4: an algae bioreactor, a fish tank for adult and larval fish (hatchery inserted), a nutrition chamber with higher plants and crustaceans and a filter chamber. The OmegaHab-XP is a full automated system with an extended satellite downlink for video monitoring and housekeeping data acquisition, but no uplink for remote control. OmegaHab-XP provides numerous physical and chemical parameters which will be monitored regarding the state of the biological processes and thus enables the automated con-trol aboard. Besides the two basic parameters oxygen content and temperature, products of the

  1. Toxicity of Single and Mixed Contaminants in Seawater Measured with Acute Toxicity Bioassays

    Directory of Open Access Journals (Sweden)

    A.R. Fernandez-Alba

    2002-01-01

    Full Text Available Different types of organic pollutants commonly detected in seawater have been evaluated by acute toxicity bioassays. Vibrio fischeri, Daphnia magna, and Selenastrum capricornotum were selected to test toxic effects of individual compounds and mixtures of these compounds, obtaining EC50 values in the range of 0.001 to 28.9 mg/l. In the case of mixtures, synergistic toxic responses were seen for a clear majority of the cases (>60%. Mixtures containing methyl-tertiary-butyl ether (MTBE exhibit accelerated processes that result in a change in concentration required to produce a toxic effect; for example, in the case of mixtures containing MTBE and Diuron and Dichlofluanid.

  2. 'In-vivo' and bioassay results from two contrasting cases of plutonium-239 inhalation

    International Nuclear Information System (INIS)

    Ramsden, D.; Bains, M.E.D.; Fraser, D.C.

    1969-06-01

    'In-vivo' and bioassay measurements following two incidents involving plutonium-239 inhalation are described and contrasted. Incident 1, involving the inhalation of insoluble plutonium oxide, resulted in a lung content of about 20 nCi after the initial clearance. Urine excretion was negligible and the estimation of exposure was based on 'in-vivo' data and faecal excretion. Incident,2, involving the inhalation of soluble plutonium, proved negligible and the estimation of exposure, based on urinary excretion, was 0.6 nCi. (author)

  3. A Bayesian approach to the analysis of quantal bioassay studies using nonparametric mixture models.

    Science.gov (United States)

    Fronczyk, Kassandra; Kottas, Athanasios

    2014-03-01

    We develop a Bayesian nonparametric mixture modeling framework for quantal bioassay settings. The approach is built upon modeling dose-dependent response distributions. We adopt a structured nonparametric prior mixture model, which induces a monotonicity restriction for the dose-response curve. Particular emphasis is placed on the key risk assessment goal of calibration for the dose level that corresponds to a specified response. The proposed methodology yields flexible inference for the dose-response relationship as well as for other inferential objectives, as illustrated with two data sets from the literature. © 2013, The International Biometric Society.

  4. Analysis of polonium-210 in food products and bioassay samples by isotope-dilution alpha spectrometry

    International Nuclear Information System (INIS)

    Lin Zhichao; Wu Zhongyu

    2009-01-01

    A rapid and reliable radiochemical method coupled with a simple and compact plating apparatus was developed, validated, and applied for the analysis of 210 Po in variety of food products and bioassay samples. The method performance characteristics, including accuracy, precision, robustness, and specificity, were evaluated along with a detailed measurement uncertainty analysis. With high Po recovery, improved energy resolution, and effective removal of interfering elements by chromatographic extraction, the overall method accuracy was determined to be better than 5% with measurement precision of 10%, at 95% confidence level.

  5. Analysis of polonium-210 in food products and bioassay samples by isotope-dilution alpha spectrometry.

    Science.gov (United States)

    Lin, Zhichao; Wu, Zhongyu

    2009-05-01

    A rapid and reliable radiochemical method coupled with a simple and compact plating apparatus was developed, validated, and applied for the analysis of (210)Po in variety of food products and bioassay samples. The method performance characteristics, including accuracy, precision, robustness, and specificity, were evaluated along with a detailed measurement uncertainty analysis. With high Po recovery, improved energy resolution, and effective removal of interfering elements by chromatographic extraction, the overall method accuracy was determined to be better than 5% with measurement precision of 10%, at 95% confidence level.

  6. Use of 236Pu and 242Pu as a radiochemical tracer for estimation of Pu in bioassay samples by fission track analysis

    International Nuclear Information System (INIS)

    Sawant, Pramilla D.; Prabhu, Supreetha P.; Kalsi, P.C.

    2008-01-01

    236 Pu and 242 Pu are routinely used as radiochemical yield monitors in India for bioassay monitoring of occupational workers by alpha spectrometry. Fission Track Analysis (FTA) is also being standardized for trace level determination of Pu in bioassay samples. The present study, reports the utility of 236 Pu and 242 Pu as radiochemical tracers in estimation of Pu in bioassay samples by FTA technique. The advantages of using 236 Pu tracer in FTA over 242 Pu as well as the interference caused due to presence of 241 Pu in the bioassay samples of occupational workers handling power reactor grade Pu is discussed. (author)

  7. Chronic ultraviolet exposure-induced p53 gene alterations in sencar mouse skin carcinogenesis model

    International Nuclear Information System (INIS)

    Tong, Ying; Smith, M.A.; Tucker, S.B.

    1997-01-01

    Alterations of the tumor suppressor gene p53 have been found in ultraviolet radiation (UVR) related human skin cancers and in UVR-induced murine skin tumors. However, links between p53 gene alterations and the stages of carcinogenesis induced by UVR have not been clearly defined. We established a chronic UVR exposure-induced Sencar mouse skin carcinogenesis model to determine the frequency of p53 gene alterations in different stages of carcinogenesis, including UV-exposed skin, papillomas, squamous-cell carcinomas (SCCs), and malignant spindle-cell tumors (SCTs). A high incidence of SCCs and SCTs were found in this model. Positive p53 nuclear staining was found in 10137 (27%) of SCCs and 12124 (50%) of SCTs, but was not detected in normal skin or papillomas. DNA was isolated from 40 paraffin-embedded normal skin, UV-exposed skin, and tumor sections. The p53 gene (exons 5 and 6) was amplified from the sections by using nested polymerase chain reaction (PCR). Subsequent single-strand conformation polymorphism (SSCP) assay and sequencing analysis revealed one point mutation in exon 6 (coden 193, C → A transition) from a UV-exposed skin sample, and seven point mutations in exon 5 (codens 146, 158, 150, 165, and 161, three C → T, two C → A, one C → G, and one A → T transition, respectively) from four SCTs, two SCCs and one UV-exposed skin sample. These experimental results demonstrate that alterations in the p53 gene are frequent events in chronic UV exposure-induced SCCs and later stage SCTs in Sencar mouse skin. 40 refs., 5 figs., 1 tab

  8. Role of atypical chemokine receptor ACKR2 in experimental oral squamous cell carcinogenesis.

    Science.gov (United States)

    da Silva, Janine Mayra; Dos Santos, Tálita Pollyanna Moreira; Saraiva, Adriana Machado; Fernandes de Oliveira, Ana Laura; Garlet, Gustavo Pompermaier; Batista, Aline Carvalho; de Mesquita, Ricardo Alves; Russo, Remo Castro; da Silva, Tarcília Aparecida

    2018-03-14

    Chemokines and chemokine receptors are critical in oral tumourigenesis. The atypical chemokine receptor ACKR2 is a scavenger of CC chemokines controlling the availability of these molecules at tumour sites, but the role of ACKR2 in the context of oral carcinogenesis is unexplored. In this study, wild-type (WT) and ACKR2 deficient mice (ACKR2 -/- ) were treated with chemical carcinogen 4-nitroquinoline-1-oxide (4NQO) for induction of oral carcinogenesis. Tongues were collected for macro and microscopic analysis and to evaluate the expression of ACKRs, CC chemokines and its receptors, inflammatory cytokines, angiogenic factors, adhesion molecules and extracellular matrix components. An increased expression of ACKR2 in squamous cell carcinoma (SCC) lesions of 4NQO-treated WT mice was observed. No significant differences were seen in the ACKR1, ACKR3 and ACKR4 mRNA expression comparing SCC lesions from WT and ACKR2 -/- treated mice. Significantly higher expression of CCL2, IL-6 and IL-17 was detected in ACKR2 -/- treated mice. In contrast, the expression of other CC-chemokines, and receptors, angiogenic factors, adhesion molecules and extracellular matrix components were similarly increased in SCC lesions of both groups. Clinical and histopathological analysis revealed no differences in inflammatory cell recruitment and in the SCC incidence comparing WT and ACKR2 -/- treated mice. The results suggest that ACKR2 expression regulates inflammation in tumour-microenvironment but the absence of ACKR2 does not impact chemically-induced oral carcinogenesis. Copyright © 2018 Elsevier Ltd. All rights reserved.

  9. Iron and thiols as two major players in carcinogenesis: friends or foes?

    Science.gov (United States)

    Toyokuni, Shinya

    2014-01-01

    Iron is the most abundant metal in the human body and mainly works as a cofactor for proteins such as hemoglobin and various enzymes. No independent life forms on earth can survive without iron. However, excess iron is intimately associated with carcinogenesis by increasing oxidative stress via its catalytic activity to generate hydroxyl radicals. Biomolecules with redox-active sulfhydryl function(s) (thiol compounds) are necessary for the maintenance of mildly reductive cellular environments to counteract oxidative stress, and for the execution of redox reactions for metabolism and detoxification. Involvement of glutathione S-transferase and thioredoxin has long attracted the attention of cancer researchers. Here, I update recent findings on the involvement of iron and thiol compounds during carcinogenesis and in cancer cells. It is now recognized that the cystine/glutamate transporter (antiporter) is intimately associated with ferroptosis, an iron-dependent, non-apoptotic form of cell death, observed in cancer cells, and also with cancer stem cells; the former with transporter blockage but the latter with its stabilization. Excess iron in the presence of oxygen appears the most common known mutagen. Ironically, the persistent activation of antioxidant systems via genetic alterations in Nrf2 and Keap1 also contributes to carcinogenesis. Therefore, it is difficult to conclude the role of iron and thiol compounds as friends or foes, which depends on the quantity/distribution and induction/flexibility, respectively. Avoiding further mutation would be the most helpful strategy for cancer prevention, and myriad of efforts are being made to sort out the weaknesses of cancer cells.

  10. Wnt5a is associated with cigarette smoke-related lung carcinogenesis via protein kinase C.

    Science.gov (United States)

    Whang, Young Mi; Jo, Ukhyun; Sung, Jae Sook; Ju, Hyun Jung; Kim, Hyun Kyung; Park, Kyong Hwa; Lee, Jong Won; Koh, In Song; Kim, Yeul Hong

    2013-01-01

    Wnt5a is overexpressed during the progression of human non-small cell lung cancer. However, the roles of Wnt5a during smoking-related lung carcinogenesis have not been clearly elucidated. We investigated the associations between Wnt5a and the early development of cigarette smoke related lung cancer using human bronchial epithelial (HBE) cells (NHBE, BEAS-2B, 1799, 1198 and 1170I) at different malignant stages established by exposure to cigarette smoke condensate (CSC). Abnormal up-regulation of Wnt5a mRNA and proteins was detected in CSC-exposed transformed 1198 and tumorigenic 1170I cells as compared with other non-CSC exposed HBE cells. Tumor tissues obtained from smokers showed higher Wnt5a expressions than matched normal tissues. In non-CSC exposed 1799 cells, treatment of recombinant Wnt5a caused the activations of PKC and Akt, and the blockage of Wnt5a and PKC significantly decreased the viabilities of CSC-transformed 1198 cells expressing high levels of Wnt5a. This reduced cell survival rate was associated with increased apoptosis via the down-regulation of Bcl2 and the induction of cleaved poly ADP-ribose polymerase. Moreover, CSC-treated 1799 cells showed induction of Wnt5a expression and enhanced colony-forming capacity. The CSC-induced colony forming efficiency was suppressed by the co-incubation with a PKC inhibitor. In conclusion, these results suggest that cigarette smoke induces Wnt5a-coupled PKC activity during lung carcinogenesis, which causes Akt activity and anti-apoptosis in lung cancer. Therefore, current study provides novel clues for the crucial role of Wnt5a in the smoking-related lung carcinogenesis.

  11. Wnt5a is associated with cigarette smoke-related lung carcinogenesis via protein kinase C.

    Directory of Open Access Journals (Sweden)

    Young Mi Whang

    Full Text Available Wnt5a is overexpressed during the progression of human non-small cell lung cancer. However, the roles of Wnt5a during smoking-related lung carcinogenesis have not been clearly elucidated. We investigated the associations between Wnt5a and the early development of cigarette smoke related lung cancer using human bronchial epithelial (HBE cells (NHBE, BEAS-2B, 1799, 1198 and 1170I at different malignant stages established by exposure to cigarette smoke condensate (CSC. Abnormal up-regulation of Wnt5a mRNA and proteins was detected in CSC-exposed transformed 1198 and tumorigenic 1170I cells as compared with other non-CSC exposed HBE cells. Tumor tissues obtained from smokers showed higher Wnt5a expressions than matched normal tissues. In non-CSC exposed 1799 cells, treatment of recombinant Wnt5a caused the activations of PKC and Akt, and the blockage of Wnt5a and PKC significantly decreased the viabilities of CSC-transformed 1198 cells expressing high levels of Wnt5a. This reduced cell survival rate was associated with increased apoptosis via the down-regulation of Bcl2 and the induction of cleaved poly ADP-ribose polymerase. Moreover, CSC-treated 1799 cells showed induction of Wnt5a expression and enhanced colony-forming capacity. The CSC-induced colony forming efficiency was suppressed by the co-incubation with a PKC inhibitor. In conclusion, these results suggest that cigarette smoke induces Wnt5a-coupled PKC activity during lung carcinogenesis, which causes Akt activity and anti-apoptosis in lung cancer. Therefore, current study provides novel clues for the crucial role of Wnt5a in the smoking-related lung carcinogenesis.

  12. Estrogen receptor signaling in prostate cancer: Implications for carcinogenesis and tumor progression.

    Science.gov (United States)

    Bonkhoff, Helmut

    2018-01-01

    The androgen receptor (AR) is the classical target for prostate cancer prevention and treatment, but more recently estrogens and their receptors have also been implicated in prostate cancer development and tumor progression. Recent experimental and clinical data were reviewed to elucidate pathogenetic mechanisms how estrogens and their receptors may affect prostate carcinogenesis and tumor progression. The estrogen receptor beta (ERβ) is the most prevalent ER in the human prostate, while the estrogen receptor alpha (ERα) is restricted to basal cells of the prostatic epithelium and stromal cells. In high grade prostatic intraepithelial neoplasia (HGPIN), the ERα is up-regulated and most likely mediates carcinogenic effects of estradiol as demonstrated in animal models. The partial loss of the ERβ in HGPIN indicates that the ERβ acts as a tumor suppressor. The tumor promoting function of the TMPRSS2-ERG fusion, a major driver of prostate carcinogenesis, is triggered by the ERα and repressed by the ERβ. The ERβ is generally retained in hormone naïve and metastatic prostate cancer, but is partially lost in castration resistant disease. The progressive emergence of the ERα and ERα-regulated genes (eg, progesterone receptor (PR), PS2, TMPRSS2-ERG fusion, and NEAT1) during prostate cancer progression and hormone refractory disease suggests that these tumors can bypass the AR by using estrogens and progestins for their growth. In addition, nongenomic estrogen signaling pathways mediated by orphan receptors (eg, GPR30 and ERRα) has also been implicated in prostate cancer progression. Increasing evidences demonstrate that local estrogen signaling mechanisms are required for prostate carcinogenesis and tumor progression. Despite the recent progress in this research topic, the translation of the current information into potential therapeutic applications remains highly challenging and clearly warrants further investigation. © 2017 Wiley Periodicals, Inc.

  13. Dysregulation of microRNAs in colonic field carcinogenesis: implications for screening.

    Directory of Open Access Journals (Sweden)

    Dhananjay P Kunte

    Full Text Available Colorectal cancer (CRC screening tests often have a trade-off between efficacy and patient acceptability/cost. Fecal tests (occult blood, methylation engender excellent patient compliance but lack requisite performance underscoring the need for better population screening tests. We assessed the utility of microRNAs (miRNAs as markers of field carcinogenesis and their potential role for CRC screening using the azoxymethane (AOM-treated rat model. We found that 63 miRNAs were upregulated and miR-122, miR-296-5p and miR-503# were downregulated in the uninvolved colonic mucosa of AOM rats. We monitored the expression of selected miRNAs in colonic biopsies of AOM rats at 16 weeks and correlated it with tumor development. We noted that the tumor bearing rats had significantly greater miRNA modulation compared to those without tumors. The miRNAs showed good diagnostic performance with an area under the receiver operator curve (AUROC of >0.7. We also noted that the miRNA induction in the colonic mucosa was mirrorred in the mucus layer fecal colonocytes isolated from AOM rat stool and the degree of miRNA induction was greater in the tumor bearing rats compared to those without tumors. Lastly, we also noted significant miRNA modulation in the Pirc rats- the genetic model of colon carcinogenesis, both in the uninvolved colonic mucosa and the fecal colonocytes. We thus demonstrate that miRNAs are excellent markers of field carcinogenesis and could accurately predict future neoplasia. Based on our results, we propose an accurate, inexpensive, non-invasive miRNA test for CRC risk stratification based on rectal brushings or from abraded fecal colonocytes.

  14. Chemoprevention by Probiotics During 1,2-Dimethylhydrazine-Induced Colon Carcinogenesis in Rats.

    Science.gov (United States)

    Walia, Sohini; Kamal, Rozy; Dhawan, D K; Kanwar, S S

    2018-04-01

    Probiotics are believed to have properties that lower the risk of colon cancer. However, the mechanisms by which they exert their beneficial effects are relatively unknown. To assess the impact of probiotics in preventing induction of colon carcinogenesis in rats. The rats were divided into six groups viz., normal control, Lactobacillus plantarum (AdF10)-treated, Lactobacillus rhamnosus GG (LGG)-treated, 1,2-dimethylhydrazine (DMH)-treated, L. plantarum (AdF10) + DMH-treated and L. rhamnosus GG (LGG) + DMH-treated. Both the probiotics were supplemented daily at a dose of 2 × 10 10 cells per day. DMH at a dose of 30 mg/kg body weight was administered subcutaneously twice a week for the first 4 weeks and then once every week for a duration of 16 weeks. Glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and catalase as protein expression of genes involved in apoptosis were assessed during DMH-induced colon carcinogenesis in rats. DMH treatment decreased the activity of GSH, GPx, GST, SOD and catalase. However, AdF10 and LGG supplementation to DMH-treated rats significantly increased the activity of these enzymes. Further, DMH treatment revealed alterations in the protein expressions of various genes involved in the p53-mediated apoptotic pathway such as p53, p21, Bcl-2, Bax, caspase-9 and caspase-3, which, however, were shifted towards normal control levels upon simultaneous supplementation with probiotics. The present study suggests that probiotics can provide protection against oxidative stress and apoptotic-related protein disregulation during experimentally induced colon carcinogenesis.

  15. Single-core magnetic markers in rotating magnetic field based homogeneous bioassays and the law of mass action

    Energy Technology Data Exchange (ETDEWEB)

    Dieckhoff, Jan, E-mail: j.dieckhoff@tu-bs.de [Institut fuer Elektrische Messtechnik und Grundlagen der Elektrotechnik, TU Braunschweig, Braunschweig (Germany); Schrittwieser, Stefan; Schotter, Joerg [Molecular Diagnostics, AIT Austrian Institute of Technology, Vienna (Austria); Remmer, Hilke; Schilling, Meinhard; Ludwig, Frank [Institut fuer Elektrische Messtechnik und Grundlagen der Elektrotechnik, TU Braunschweig, Braunschweig (Germany)

    2015-04-15

    In this work, we report on the effect of the magnetic nanoparticle (MNP) concentration on the quantitative detection of proteins in solution with a rotating magnetic field (RMF) based homogeneous bioassay. Here, the phase lag between 30 nm iron oxide single-core particles and the RMF is analyzed with a fluxgate-based measurement system. As a test analyte anti-human IgG is applied which binds to the protein G functionalized MNP shell and causes a change of the phase lag. The measured phase lag changes for a fixed MNP and a varying analyte concentration are modeled with logistic functions. A change of the MNP concentration results in a nonlinear shift of the logistic function with the analyte concentration. This effect results from the law of mass action. Furthermore, the bioassay results are used to determine the association constant of the binding reaction. - Highlights: • A rotating magnetic field based homogeneous bioassay concept was presented. • Here, single-core iron oxide nanoparticles are applied as markers. • The impact of the particle concentration on the bioassay results is investigated. • The relation between particle concentration and bioassay sensitivity is nonlinear. • This finding can be reasonably explained by the law of mass action.

  16. Thermodynamic considerations on the role of heat and mass transfer in biochemical causes of carcinogenesis

    Science.gov (United States)

    Lucia, Umberto; Grisolia, Giulia; Ponzetto, Antonio; Deisboeck, Thomas S.

    2018-01-01

    Cellular homoeostasis involves a continuous interaction between the cell and its microenvironment. As such, active and passive transport of ions, nutrients, molecules and water are the basis for biochemical-physical cell life. These transport phenomena change the internal and external ionic concentrations, and, as a consequence, the cell membrane's electric potential and the pH. In this paper we focus on the relationship between these ion transport-induced pH and membrane voltage changes to highlight their impact on carcinogenesis. The preliminary results suggest a critical role for Cl- in driving tumour transformation towards a more malignant phenotype.

  17. Prevention of Lung Carcinogenesis by Suppressing Pathogenic CD4 T Cells

    Science.gov (United States)

    2017-05-01

    intestinal inflammation by reducing TH17 cells and preserving group 3 innate lymphoid cells . Nat Med, 2016. 22(3): p. 319-23.   ...stable population of YFP+  cells  similar  to  innate  IL‐17–producing  cells  (e.g., γδ T  cells ) during acute infection (Fig.2) , which is in sharp contrast...AWARD NUMBER: W81XWH-16-1-0100 TITLE: Prevention of Lung Carcinogenesis by Suppressing Pathogenic CD4 T Cells PRINCIPAL INVESTIGATOR: Seon Hee

  18. Is the role of the environment in carcinogenesis overestimated. [Individual health status, modifying factor

    Energy Technology Data Exchange (ETDEWEB)

    Calabrese, E J

    1979-01-01

    The dominant role of the physical and chemical environment in the development of cancer is challenged. Analyses of the etiology of skin, bladder, respiratory and gastric cancers are presented which demonstrate the considerable extent to which one's health status may modify the initiation and promotion of environmentally asociated cancers. It is concluded that although environmental factors may initiate and/or promote 85 to 90 percent of all cancers this is misleading since it neglects the critical role of the individual's health status as a factor modifying carcinogenesis.

  19. Carcinogenesis of the Oral Cavity: Environmental Causes and Potential Prevention by Black Raspberry.

    Science.gov (United States)

    El-Bayoumy, Karam; Chen, Kun-Ming; Zhang, Shang-Min; Sun, Yuan-Wan; Amin, Shantu; Stoner, Gary; Guttenplan, Joseph B

    2017-01-17

    Worldwide, cancers of the oral cavity and pharynx comprise the sixth most common malignancies. Histologically, more than 90% of oral cancers are squamous cell carcinoma (SCC). Epidemiologic data strongly support the role of exogenous factors such as tobacco, alcohol, and human papilloma virus infection as major causative agents. Avoidance of risk factors has only been partially successful, and survival rates have not improved despite advances in therapeutic approaches. Therefore, new or improved approaches to prevention and/or early detection are critical. Better understanding of the mechanisms of oral carcinogenesis can assist in the development of novel biomarkers for early detection and strategies for disease prevention. Toward this goal, several animal models for carcinogenesis in the oral cavity have been developed. Among these are xenograft, and transgenic animal models, and others employing the synthetic carcinogens such as 7,12-dimethylbenz[a]anthracene in hamster cheek pouch and 4-nitroquinoline-N-oxide in rats and mice. Additional animal models employing environmental carcinogens such as benzo[a]pyrene and N'-nitrosonornicotine have been reported. Each model has certain advantages and disadvantages. Models that (1) utilize environmental carcinogens, (2) reflect tumor heterogeneity, and (3) accurately represent the cellular and molecular changes involved in the initiation and progression of oral cancer in humans could provide a realistic platform. To achieve this goal, we introduced a novel nonsurgical mouse model to study oral carcinogenesis induced by dibenzo[a,l]pyrene (DB[a,l]P), an environmental pollutant and tobacco smoke constituent, and its diol epoxide metabolite (±)-anti-11,12-dihydroxy-13,14-epoxy-11,12,13,14-tetrahydrodibenzo[a,l]pyrene [(±)-anti-DB[a,l]PDE]. On the basis of a detailed comparison of oral cancer induced by DB[a,l]P with that induced by the other above-mentioned oral carcinogens with respect to dose, duration, species and

  20. Thyroid cancer. Reevaluation of an experimental model for radiogenic endocrine carcinogenesis

    International Nuclear Information System (INIS)

    Clifton, K.H.

    1984-11-01

    The status of experimental studies of radiogenic thyroid cancer is appraised, and some older data are reinterpreted in the light of more recent findings. Problems of thyroid dosimetry, particularly the dosimetry of internal radioiodides, are discussed. The steps in radiation carcinogenesis during the acute phase, the latent phase, and the phase of tumor growth are discussed in terms of thyroid epithelial cell population changes. The roles of three cell populations (undamaged or completely repaired epithelial cells, oncogenically initiated cells, and terminally damaged but functionally competent cells) in neoplasia are described. Finally, the implications for man of these experimental results and conclusions are discussed. 89 refs., 4 figs