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Sample records for carcinogens rats hamsters

  1. Chronic inhalation toxicity and carcinogenicity studies on β-chloroprene in rats and hamsters

    NARCIS (Netherlands)

    Trochimowicz, H.J.; Löser, E.; Feron, V.J.; Clary, J.J.; Valentine, R.

    1998-01-01

    Three groups of 100 Wistar rats and Syrian golden hamsters of each sex were exposed by inhalation to 0, 10, or 50 ppm (v/v) β-chloroprene for 6 h/day, 5 days a week for up to 24 and 18 too, respectively. To maintain the chemical integrity of this highly reactive material in the exposure chambers, β-

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1978-02-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2009-10-15

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

  4. MULTIPLE-ENDPOINT MUTAGENESIS WITH CHINESE HAMSTER OVARY (CHO) CELLS: EVALUATION WITH EIGHT CARCINOGENIC AND NON-CARCINOGENIC COMPOUNDS

    Science.gov (United States)

    Using Chinese hamster ovary (CHO) cells in culture, the authors have defined an assay, CHO/HGPRT, to quantify mutagen-induced cytotoxicity and mutations at the hypoxanthine-guanine phosphoribosyltransferase (hgprt) locus. This assay permits elucidation of the structure-activity r...

  5. Amplification of SV40 and cellular genes in SV40 transformed Chinese hamster embryo cells treated with chemical carcinogens

    International Nuclear Information System (INIS)

    To study the effect of chemical carcinogens on the amplification of specific genes, we have constructed a model system, utilizing integrated SV40 as an example for an endogenous gene. Recently, we have shown that exposure of SV40 transformed Chinese hamster cells to a variety of carcinogens induced the amplification of the integrated SV40 genome. Functional T-antigen was necessary for the amplification phenomenon. The work presented in this manuscript shows that the functional origin of replication, which consists of the sequences at the origin of replication and an active T-antigen, is required for the amplification. Utilizing cloned SV40 inserts and the adjacent Chinese hamster sequences we were able to show that SV40 and the flanking cellular sequences were amplified. As the distance from the SV40 origin of replication increased, the extent of amplification was decreased. The amplified sequences are associated with both chromosomal and extrachromosomal sequences. Carcinogen-mediated amplification is not restricted to SV40 sequences and endogenous genes such as dehydrofolate reductase (dhfr), the histocompatibility gene (HLA) and c-ras/sup Ha/ gene are amplified. 26 references, 5 figures

  6. Effect of acetylator genotype on the levels of carcinogen-DNA adducts in inbred hamsters treated with 2-aminofluorene

    International Nuclear Information System (INIS)

    A genetic polymorphism in N-acetyltransferase has been described previously in humans and in animal models that is known to affect an individual's susceptibility to certain drug toxicities and diseases including bladder cancer. In hamsters, the polymorphism is known to regulate the conversion of carcinogenic 2-aminofluorene to its amide and of N-hydroxy-2-aminofluorene to a reactive electrophile that forms a covalently-bound adduct with DNA; an event thought to initiate the tumorigenic process. A single dose of 2-aminofluorene (60 mg/kg body wt., i.p) was administered to homozygous rapid- (rr) and homozygous slow-acetylator (ss) hamsters, and the levels of aminofluorene-DNA adducts in bladder and liver were evaluated by a 32P-postlabeling assay. Only a non-acetylated aminofluorene-DNA adduct was detected in the DNA samples. In this study, no differences were detected between the levels of hepatic 2-aminofluorene-DNA adducts in males or females or between the rr or ss hamsters. In contrast, the levels of 2-amino-fluorene-adducts in bladder DNA were 5-fold higher in the male rr than in the ss hamsters, and were 2-fold higher in the male rr than in the female rr animals

  7. Chronic toxicity and carcinogenicity study of erythritol in rats

    NARCIS (Netherlands)

    Lina, B.A.R.; Bos-Kuijpers, M.H.M.; Til, H.P.; Bär, A.

    1996-01-01

    The potential toxicity and carcinogenicity of erythritol, a low-calorie sugar substitute, were examined in Wistar Crl:(WI) WU BR rats. Groups of 50 rats of each sex consumed diets with 0, 2, 5, or 10% erythritol, or 10% mannitol, for a period of 104-107 weeks. To each of these main groups, two satel

  8. Comparison of rat olfactory mucosal responses to carcinogenic and non-carcinogenic chloracetanilides

    OpenAIRE

    Genter, M.B.; Warner, B.M.; Medvedovic, M.; Sartor, M.A.

    2009-01-01

    Alachlor and butachlor are chloracetanilide herbicides that induce olfactory tumors in rats, whereas propachlor does not. The mechanism by which alachlor induces tumors is distinct from many other nasal carcinogens, in that alachlor induces a gradual de-differentiation of the olfactory mucosa (OM) to a more respiratory-like epithelium, in contrast to other agents that induce cytotoxicity, followed by an aberrant regenerative response. We studied biochemical and genomic effects of these compou...

  9. Current and emerging challenges in toxicopathology: Carcinogenic threshold of phenobarbital and proof of arsenic carcinogenicity using rat medium-term bioassays for carcinogens

    International Nuclear Information System (INIS)

    For the last 25 years, Prof. Nobuyuki Ito and his laboratory have focused on the development of liver medium-term bioassay system for detection of carcinogens in F344 rats utilizing glutathione S-transferase placental form (GST-P)-positive foci as an end point marker. In this presentation, the outline and samples of medium-term bioassay systems were described. Furthermore, our data demonstrated the presence of a threshold for the non-genotoxic carcinogen, phenobarbital (PB), and the lack of linearity in the low-dose area of the dose-response curve, providing evidence for hormesis. In addition, the establishment and applications of multiorgan carcinogenicity bioassay (DMBDD model), used for the examination of the carcinogenicity of genotoxic and non-genotoxic chemicals, are discussed. Dimethylarsinic acid, one of organic arsenics, was found to be carcinogenic in rat bladder using DMBDD model and carcinogenicity test

  10. Urethane influence in the urine formation in swiss rats and syrian hamster

    Energy Technology Data Exchange (ETDEWEB)

    Lima, Marina F.; Silva, Natanael G.; Mesquita, Carlos Henrique de, E-mail: mflima@ipen.br, E-mail: ngsilva@ipen.br, E-mail: chmesqui@ipen.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2011-07-01

    Urethane is an anaesthetic agent with minimal cardiovascular and respiratory system depression with long-lasting (6-10h) effects. Its carcinogenic potential avoids it from veterinary use. Either, the knowledge of its effects over the circulating catecholamines (cortisone and corticosterone), with reflects in the muscles physiology, it is widely used in pharmacological studies in laboratory species. At the first minutes, Urethane induces a hyperglycaemia condition due the insulin concentration decrease, later than, the insulin concentration and the condition becomes in hypoglycaemia, but the Urethane interfering in the urine production mechanisms has not been described. It is accepted that the glycolic level would not interferes in the kidney function, except in chronic states, notably associated with insulin related diseases. The relative high biological half-life of {sup 177}Lu-Dotatate allows its use in biodistribution studies among small animals whose metabolic rates are so fast that would be impossible observe them with the most part of the labeled molecules. During the performance of a cross-species extrapolation study using Urethane as anaesthesia and {sup 177}Lu-Dotatate as metabolic tracer, was observed the Urethane influence over urine formation in Swiss rats and Syrian hamster (Mesocricetus auratus). The objective of this work is only describes the Urethane action over the urine production. Firstly, four male inbread Wistar Swiss rats ({+-}250 g), are anesthetized, with around 1200 mg/kg, i.p., in groups of two. One rat from each group get ahead to the injection of {sup 177}Lu-Dotatate and Gamma camera in vivo study, the second ones, anesthetized, waited under warming lights until more than one hour to initiate the biodistribution study. The scintillographical images shown the radiopeptide stopped at the kidneys and the urinary empty in the animals who attempt more than one hour before enter to radiopharmaceutical injection and Gamma camera imaging

  11. Urethane influence in the urine formation in swiss rats and syrian hamster

    International Nuclear Information System (INIS)

    Urethane is an anaesthetic agent with minimal cardiovascular and respiratory system depression with long-lasting (6-10h) effects. Its carcinogenic potential avoids it from veterinary use. Either, the knowledge of its effects over the circulating catecholamines (cortisone and corticosterone), with reflects in the muscles physiology, it is widely used in pharmacological studies in laboratory species. At the first minutes, Urethane induces a hyperglycaemia condition due the insulin concentration decrease, later than, the insulin concentration and the condition becomes in hypoglycaemia, but the Urethane interfering in the urine production mechanisms has not been described. It is accepted that the glycolic level would not interferes in the kidney function, except in chronic states, notably associated with insulin related diseases. The relative high biological half-life of 177Lu-Dotatate allows its use in biodistribution studies among small animals whose metabolic rates are so fast that would be impossible observe them with the most part of the labeled molecules. During the performance of a cross-species extrapolation study using Urethane as anaesthesia and 177Lu-Dotatate as metabolic tracer, was observed the Urethane influence over urine formation in Swiss rats and Syrian hamster (Mesocricetus auratus). The objective of this work is only describes the Urethane action over the urine production. Firstly, four male inbread Wistar Swiss rats (±250 g), are anesthetized, with around 1200 mg/kg, i.p., in groups of two. One rat from each group get ahead to the injection of 177Lu-Dotatate and Gamma camera in vivo study, the second ones, anesthetized, waited under warming lights until more than one hour to initiate the biodistribution study. The scintillographical images shown the radiopeptide stopped at the kidneys and the urinary empty in the animals who attempt more than one hour before enter to radiopharmaceutical injection and Gamma camera imaging procedures. The rates of

  12. Morphological transformation and effect on gap junction intercellular communication in Syrian hamster embryo cells as screening tests for carcinogens devoid of mutagenic activity.

    Science.gov (United States)

    Rivedal, E; Mikalsen, S O; Sanner, T

    2000-04-01

    A large fraction of chemicals observed to cause cancer in experimental animals is devoid of mutagenic activity. It is therefore of importance to develop methods that can be used to detect and study environmental carcinogenic agents that do not interact directly with DNA. Previous studies have indicated that induction of in vitro cell transformation and inhibition of gap junction intercellular communication are endpoints that could be useful for the detection of non-genotoxic carcinogens. In the present work, 13 compounds [chlordane, Arochlor 1260, di(2-ethylhexyl)phthalate, 1,1,1-trichloro-2, 2-bis(4-chlorophenyl)ethane, limonene, sodium fluoride, ethionine, o-anisidine, benzoyl peroxide, o-vanadate, phenobarbital, 12-O-tetradecanoylphorbol 13-acetate and clofibrate] have been tested for their ability to induce morphological transformation and affect intercellular communication in Syrian hamster embryo cells. The substances were selected on the basis of being proven or suspected non-genotoxic carcinogens, and thus difficult to detect in short-term tests. The data show that nine of the 13 compounds induced morphological transformation, and seven of the 13 inhibited intercellular communication in hamster embryo cells. Taken together, 12 of the 13 substances either induced transformation or caused inhibition of communication. The data suggest that the combined use of morphological transformation and gap junction intercellular communication in Syrian hamster embryo cells may be beneficial when screening for non-genotoxic carcinogens. PMID:10793297

  13. Review of genotoxicity and rat carcinogenicity investigations with astaxanthin.

    Science.gov (United States)

    Edwards, James A; Bellion, Phillip; Beilstein, Paul; Rümbeli, Robert; Schierle, Joseph

    2016-03-01

    Synthetic astaxanthin has been extensively tested for safety. Genotoxicity studies including Ames and in vitro Micronucleus Tests show absence of genotoxic potential. Although a long-term mouse study showed no carcinogenicity potential, the rat carcinogenicity study with dietary dosages of 0 (control), 0 (placebo beadlet), 40, 200 and 1000 mg astaxanthin/kg bw/day showed an increased incidence of benign, hepatocellular adenoma in females only, at 200 mg/kg bw/day and above. There was no clear evidence of toxicity during the in-life phase. Discoloration of feces was observed and a reduction in body weight gain in all groups receiving beadlets, probably reflecting a nutritional influence. Blood sampling confirmed systemic exposure and some minor clinical chemistry differences in females at 200 and 1000 mg/kg bw/day. There was no effect on adjusted liver weight. Histopathological examination showed hepatic changes indicative of slight hepatotoxicity and hepatocyte regeneration in females at 200 and 1000 mg/kg bw/day, in addition to the adenoma. Taking into account this pathological background in the female rat, and a wide variety of other supporting information, it is concluded that the hepatocellular adenoma in female rats was secondary to hepatotoxicity and regeneration, and is most probably a species-specific phenomenon of doubtful human relevance. PMID:26713891

  14. A comparative study of the pulmonary effects of NO2 in the rat and hamster.

    OpenAIRE

    Foster, J R; Cottrell, R C; Herod, I. A.; Atkinson, H. A.; Miller, K

    1985-01-01

    A study of the response of rat and hamster to nitrogen dioxide (NO2) under identical conditions has been undertaken. Exposure to 20 parts/IO6 NO2 for 24 h produced a mild cytotoxic effect on the terminal bronchiole and proximal alveoli in the rat, whereas the hamster developed a moderate to severe bronchiolitis and alveolitis. Electron microscopic examination of tissue sections showed accumulation of surfactant in lamellar bodies of the alveolar type II cell in the rat but not in the hamster,...

  15. Long-term carcinogenicity study in Syrian golden hamster of particulate emissions from coal- and oil-fired power plants.

    OpenAIRE

    Persson, S A; Ahlberg, M; Berghem, L.; Könberg, E; Nordberg, G F; Bergman, F

    1988-01-01

    Male Syrian golden hamsters were given 15 weekly intratracheal instillations with suspensions of coal fly ash or oil fly ash. Controls were instilled with saline containing gelatine (0.5 g/100 mL) or to check particle effects with suspensions of hematite (Fe2O3). The common weekly dose was 4.5 mg/hamster. In addition, one subgroup of hamsters was treated with oil fly ash at a weekly dose of 3.0 mg/hamster and another with coal fly ash at a weekly dose of 6.0 mg/hamster. Other groups of hamste...

  16. Carcinogenicity study with technical-grade dichlorodiphenyltrichloroethane and 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene in hamsters.

    Science.gov (United States)

    Rossi, L; Barbieri, O; Sanguineti, M; Cabral, J R; Bruzzi, P; Santi, L

    1983-02-01

    Studies conducted by others have revealed that 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE), a proximal metabolite of dichlorodiphenyltrichloroethane (DDT), is a strong hepatocellular carcinogen in mice. Since hamsters appear to be resistant to tumor induction by DDT, we wanted to investigate whether DDE has any neoplastic effect in this species. DDE (99% pure) was mixed into the diet at doses of 500 or 1000 ppm and given to groups of male and female Syrian golden hamsters for life. Another group of animals received a diet containing 1000 ppm technical-grade DDT, and a further group served as control. Groups contained a minimum of 40 hamsters per sex. The tested compounds had no effect on the incidence of tumors at all sites, compared to controls. A specific finding in animals exposed to DDE was the appearance of hepatocellular tumors late in life. They were classified as neoplastic nodules, and the incidence was 15% in females and 47% in males of the 500-ppm DDE dose groups and 21% in females and 33% in males of the 1000-ppm DDE dose groups. None of the untreated or DDT-treated animals had these tumors. Eight animals treated with 1000 ppm DDE and four of those treated with DDT had hyperplastic foci of the liver. In addition, adrenocortical adenomas, spontaneous to Syrian golden hamsters, were more frequent in DDE- and DDT-treated animals than in control animals. These results showing that DDE, but not its parental compound, induces liver cell tumors in hamsters emphasize the importance of this metabolite as a proximal carcinogen of DDT. PMID:6848191

  17. Kinetics of Syrian hamster cells during x-irradiation enhancement of transformation in vitro by chemical carcinogen

    International Nuclear Information System (INIS)

    The x-irradiation of cultured Syrian hamster cells followed by exposure to a chemical carcinogen after seeding for colony formation results in an enhancement of transformation ordinarily associated with the chemical. Maximum enhancement occurred when 48 hr separated the two treatments and when 250 R was used. With different concentrations of benzo(a)pyrene (0.1-5 μg/ml medium) a similar factor of enhancement was obtained with 250 R, which averaged 8.35, implying that the irradiation pretreatment caused a constant multiplying factor. These results are consistent with the interpretation that transformation occurs through interactions in keeping with a one-hit hypothesis. The transitory effect of irradiation and the lack of transformation with irradiation alone argues against the selection of a special radiation-sensitive cell. At the time of maximum enhancement (48 hr), the cell cycles of irradiated and nonirradiated cells do not differ. The addition of benzo(a)pyrene to irradiated cells does not alter the number of cells capable of synthesizing DNA or the flow of cells from G1 to S. The number of cells accumulated in mitosis also does not appear to differ between irradiated and nonirradiated cultures treated with 2.5 μg benzo(a)pyrene. Chromosome aberrations or alterations in ploidy cannot account for the significant increase in enhancement observed at 48 hr postirradiation; however, twice as many cells with chromosome or chromatid gaps were found at 48 hr as compared to either 24 or 72 hr postirradiation

  18. Discrimination of Carcinogens by Hepatic Transcript Profiling in Rats Following 28-day Administration

    Directory of Open Access Journals (Sweden)

    Hiroshi Matsumoto

    2009-11-01

    Full Text Available This study aimed at discriminating carcinogens on the basis of hepatic transcript profiling in the rats administrated with a variety of carcinogens and non-carcinogens. We conducted 28-day toxicity tests in male F344 rats with 47 carcinogens and 26 non- carcinogens, and then investigated periodically the hepatic gene expression profiles using custom microarrays. By hierarchical cluster analysis based on significantly altered genes, carcinogens were clustered into three major groups (Group 1 to 3. The formation of these groups was not affected by the gene sets used as well as the administration period, indicating that the grouping of carcinogens was universal independent of the conditions of both statistical analysis and toxicity testing. Seventeen carcinogens belonging to Group 1 were composed of mainly rat hepatocarcinogens, most of them being mutagenic ones. Group 2 was formed by three subgroups, which were composed of 23 carcinogens exhibiting distinct properties in terms of genotoxicity and target tissues, namely nonmutagenic hepatocarcinogens, and mutagenic and nonmutagenic carcinogens both of which are targeted to other tissues. Group 3 contained 6 carcinogens including 4 estrogenic substances, implying the group of estrogenic carcinogens. Gene network analyses revealed that the significantly altered genes in Group 1 included Bax, Tnfrsf6, Btg2, Mgmt and Abcb1b, suggesting that p53-mediated signaling pathway involved in early pathologic alterations associated with preceding mutagenic carcinogenesis. Thus, the common transcriptional signatures for each group might reflect the early molecular events of carcinogenesis and hence would enable us to identify the biomarker genes, and then to develop a new assay for carcinogenesis prediction.

  19. Functional cooperation of xenoproteins after hamster-to-rat liver transplantation: With particular reference to hamster C3 and secretory component for rat IgA

    OpenAIRE

    Celli, S.; Valdivia, L.A.; Kelly, R. H.; Demetris, A.J.; Fung, J.J.; Rao, A S; Pan, F.; Tsugita, M.; Starzl, T.E.

    1995-01-01

    Long-term survival after hamster-to-rat liver xenotransplantation has provided the opportunity to study the posttransplantation source of major serum proteins and the functional consequences of several different receptor-ligand interactions, where one or the other is a xenogeneic protein. We report here that serum albumin, α-1-antitrypsin, complement component 3, and other acute phase reactants switch from recipient to donor origin during the first week after transplantation while serum immun...

  20. Partial lipectomy reduces dimethylhydrazine-induced carcinogenic initiation in the colon of rats

    International Nuclear Information System (INIS)

    This study investigated whether visceral adipose tissue directly modulates the development of preneoplastic lesions in the colon of carcinogen-treated rats. Wistar rats (n = 64) were randomly assigned to 8 experimental groups in two experiments. In one experiment, 32 rats were exposed or not to either carcinogen treatment (dimethylhydrazine, DMH; 125 mg/kg) or high-fat diet (standard chow enriched with 14% lard) or both for 56 days. In a second experiment, 32 rats were exposed to a carcinogen or they underwent partial lipectomy or both for 30 days (partial lipectomy groups underwent ablation of mesenteric and parametrial fat pads, whereas sham groups did not; all rats were fed with standard chow). Colon was collected for histopathological analysis. After 56 experimental days a high-fat diet increased carcinogenic mutations in the colonic epithelia. Partial lipectomy reduced weight gain in carcinogen-exposed rats and decreased the de novo formation of mesenteric and parametrial fat pads. Partial lipectomy significantly inhibited the mutational process after 30 days: there were fewer colonic preneoplastic lesions and less proliferation, apoptosis, and inflammation. These data suggest that visceral adipose tissue promotes colon carcinogenesis and enhances the establishment and expansion of genetically mutated cells in colonic epithelia

  1. INFLUENCE OF OZONE ON PENTOBARBITAL-INDUCED SLEEPING TIME IN MICE, RATS, AND HAMSTERS

    Science.gov (United States)

    Prior studies have shown that ozone (O3) increases pentobarbital (PEN)-induced sleeping time (S.T.) in female mice, rats, and hamsters. To investigate some potential mechanisms producing these effects, the authors measured zoxazolamine-induced paralysis time and thiopental- and h...

  2. Metabolism of tributyltin and triphenyltin by rat, hamster and human hepatic microsomes

    Energy Technology Data Exchange (ETDEWEB)

    Ohhira, Shuji; Watanabe, Masatomo; Matsui, Hisao [Department of Hygiene, Dokkyo University School of Medicine, Mibu-machi, 321-0293, Tochigi (Japan)

    2003-03-01

    Tributyltin and triphenyltin are metabolized by cytochrome P-450 system enzymes, and their metabolic fate may contribute to the toxicity of the chemicals. In the current study, the in vitro metabolism of tributyltin and triphenyltin by rat, hamster and human hepatic microsomes was investigated to elucidate the metabolic competence for these compounds in humans. The metabolic reaction using microsome-NADPH system that is usually conducted was not applicable to in vitro metabolism of organotins, especially triphenyltin. We therefore examined the effects of dithiothreitol (DTT), one of the antioxidants for sulfhydryl groups, to determine the in vitro metabolism of tributyltin and triphenyltin. As a result, the treatment with 0.1 mM DTT in vitro increased the activity of the microsomal monooxygenase system for metabolism of tributyltin as well as triphenyltin; the total yield of tributyltin and triphenyltin metabolites as tin increased, respectively, by approximately 1.8 and 8.9 times for rat, 2.1 and 1.2 times for hamster, and 1.6 and 1.5 times for human. It is suggested that the organotins directly inactivate cytochrome P-450 because of the interaction with critical sulfhydryl groups of the hemoprotein. We confirmed the utility of this in vitro metabolic system using DTT in the hepatic microsomes of phenobarbital (PB)-pretreated and untreated hamsters. Thus, the in vitro metabolic system described here was applied to a comparative study of the metabolism of organotins in rats, hamsters and humans. Tributyltin was metabolized more readily than triphenyltin in all the species. In humans, the in vitro metabolic pattern resembled that of hamsters, which were susceptible to in vivo triphenyltin toxicity because of incompetent metabolism. It is possible that the hamster is a qualitatively and quantitatively suitable animal model for exploring the influence of tributyltin and triphenyltin in humans. (orig.)

  3. Carcinogenic potential of some pesticides in a medium-term multi-organ bioassay in rats.

    Science.gov (United States)

    Hasegawa, R; Cabral, R; Hoshiya, T; Hakoi, K; Ogiso, T; Boonyaphiphat, P; Shirai, T; Ito, N

    1993-05-28

    The carcinogenic potential of 5 pesticides was analyzed using a medium-term multi-organ bioassay for carcinogenicity. Male F344 rats were initially treated with 3 known carcinogens (diethylnitrosamine, N-methyl-N-nitrosourea and N-bis(2-hydroxypropyl)nitrosamine) during a period of 4 weeks to induce neoplastic changes in a variety of organs, and then given one of 5 pesticides in the diet for a further 16 weeks. Neoplastic and pre-neoplastic lesions were found in the thyroid, kidney and urinary bladder with propineb, in the forestomach, kidney and thyroid with captan and folpet. The number of glutathione S-transferase placental-form-positive liver-cell foci was significantly increased in the captan- and phosmet-treated groups. Based on these findings, captan and propineb can be considered as carcinogens and carcinogenicity is suspected for folpet and phosmet. These results are in concordance with reported long-term carcinogenicity for captan, folpet and propineb. Daminozide was considered not to be carcinogenic. Thus, the present assay of 20 weeks' duration is useful for the prediction of potential carcinogens. PMID:8509224

  4. Metabolism of radiohafnium in rats and hamsters: a possible analog of plutonium for metabolic studies

    International Nuclear Information System (INIS)

    The metabolism of radiohafnium (175Hf + 181Hf) was studied in male Sprague-Dawley rats and Chinese hamsters for periods of up to 168 days. The results were compared with similar data for 239Pu in the same rat strain. In rats and hamsters the radiohafnium organ distribution was skeleton > skin > muscle > liver at about 7 days postinjection. Retention of radiohafnium and plutonium was similar in plasma and liver, as were the retention time observed for other organs: Absorption of radiohafnium from the gastrointestinal tract of rats was <0.05%. Biochemical studies showed that the radiohafnium was bound mainly to the iron-transport protein, transferrin, in blood plasma and in the liver cytosol of both the rat and the hamster, as has been observed also for plutonium. The metabolic behavior of radiohafnium mimics, to a large extent, that of plutonium, and it is suggested that radiohafnium can serve as a non-α-particle-emitting analog of plutonium for metabolic, biochemical, and selected human investigations

  5. The metabolism of radiohafnium in rats and hamsters: a possible analog of plutonium for metabolic studies

    International Nuclear Information System (INIS)

    The metabolism of radiohafnium (175Hf + 181Hf) was studied in male Sprague-Dawley rats and Chinese hamsters for periods of up to 168 days. The results were compared with similar data for 239Pu in the same rat strain. In rats and hamsters the radiohafnium organ distribution was skeleton greater than skin greater than muscle greater than liver at about 7 days postinjection. Retention of radiohafnium and plutonium was similar in plasma and liver, as were the retention times observed for other organs: Absorption of radiohafnium from the gastrointestinal tract of rats was less than 0.05%. Biochemical studies showed that the radiohafnium was bound mainly to the iron-transport protein, transferrin, in blood plasma and in the liver cytosol of both the rat and the hamster, as has been observed also for plutonium. The metabolic behavior of radiohafnium mimics, to a large extent, that of plutonium, and it is suggested that radiohafnium can serve as a non-alpha-particle-emitting analog of plutonium for metabolic, biochemical, and selected human investigations

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

    International Nuclear Information System (INIS)

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-11-01

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

  8. Comparative metabolic disposition of [1-Me14C]caffeine in rats, mice, and Chinese hamsters

    International Nuclear Information System (INIS)

    The metabolic disposition of [1-Me14C]caffeine has been studied and compared in three male rodent species: the rat, the mouse, and the Chinese hamster. No interspecies differences appeared in urinary and fecal excretion of radioactivity. However, 1-methyldemethylation was significantly more important in the rat with 20.6 +/- 0.8% of the dose recovered as 14CO2 compared with the Chinese hamster, 16.1 +/- 2%, and the mouse, 13.9 +/- 0.9%. HPLC and TLC analysis of 1-methyl-labeled metabolites showed that the rat exhibits a significantly higher urinary excretion of the four trimethyl derivatives: caffeine, 1,3,7-trimethyluric acid, trimethylallantoin, and 6-amino-5-[N-formylmethylamino]-1,3-dimethyluracil [40.8% of total urine radioactivity) when compared with the Chinese hamster (21.1%) and the mouse (19.7%). Compared with man (6%), these rodents have a greater ability to excrete caffeine without any demethylation. The rat was also characterized by a higher excretion of theophylline while the Chinese hamster excreted more paraxanthine, 1-methylxanthine, and the uracil derivative of paraxanthine. In the mouse, in addition to 1-methylxanthine and 1-methyluric acid, higher amounts of 1,3- and 1,7-dimethyluric acid were found. The mouse was particularly characterized by the presence of an unknown polar metabolite amounting to 22 +/- 3% of urine radioactivity. This metabolite must be produced from paraxanthine because its quantitative formation was inversely related to the excretion of paraxanthine and its metabolites. The observations that this metabolite is neither 5-acetylamino-6-amino-3-methyluracil nor 5-acetylamino-6-formylamino-3-methyluracil reported in humans demonstrate that both quantitative and qualitative interspecies differences occur for caffeine metabolism

  9. The effects of argon in the bioenergetics of the hamster and the rat

    Science.gov (United States)

    Tempel, G. E.; Musacchia, X. J.

    1974-01-01

    Oxygen consumption was examined in hamsters and rats exposed to normoxic mixtures of argon at 1 atm. In fasted and nonfasted animals, no marked change in O2 utilization was detectable at 22 C. However, at 7 C a significant decrease in oxygen consumption was observed where the animals were exposed in argon. The data are interpreted in terms of the greater thermal conductivity of nitrogen. The study was prompted by conflicting reports on the metabolic effects of argon and helium.

  10. Comparison of the expression profiles induced by genotoxic and nongenotoxic carcinogens in rat liver

    International Nuclear Information System (INIS)

    Application of recently developed gene expression techniques using microarrays in toxicological studies (toxicogenomics) facilitate the interpretation of a toxic compound's mode of action and may also allow the prediction of selected toxic effects based on gene expression changes. In order to test this hypothesis, we investigated whether carcinogens at doses known to induce liver tumors in the 2-year rat bioassay deregulate characteristic sets of genes in a short term in vivo study and whether these deregulated genes represent defined biological pathways. Male Wistar rats were dosed with the four nongenotoxic hepatocarcinogens methapyrilene (MPy, 60 mg/kg/day), diethylstilbestrol (DES, 10 mg/kg/day), Wy-14643 (Wy, 60 mg/kg/day), and piperonylbutoxide (PBO, 1200 mg/kg/day). After 1, 3, 7, and 14 days, the livers were taken for histopathological evaluation and for analysis of the gene expression profiles on Affymetrix RGU34A arrays. The expression profile of the four nongenotoxic carcinogens were compared to the profiles of the four genotoxic carcinogens 2-nitrofluorene (2-NF), dimethylnitrosamine (DMN), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and aflatoxin B1 (AB1) from a similar study reported previously. By using statistical and clustering tools characteristically deregulated genes were extracted and functionally classified. Distinct cellular pathways were affected by the nongenotoxic carcinogens compared to the genotoxic carcinogens which at least partly correlated with the two-stage model of carcinogenesis. Characteristic to genotoxic carcinogens were a DNA damage response and the activation of proliferative and survival signaling. Nongenotoxic carcinogens showed responses to oxidative DNA or protein damage, as well as cell cycle progression and signs of regeneration. Many of the gene alterations found with the nongenotoxic carcinogens imply compound-specific mechanisms. Although neither a single gene nor a single pathway will be sufficient to

  11. Comparison of the expression profiles induced by genotoxic and nongenotoxic carcinogens in rat liver

    Energy Technology Data Exchange (ETDEWEB)

    Ellinger-Ziegelbauer, Heidrun [Bayer Healthcare AG, Department of Molecular and Genetic Toxicology, Aprather Weg 18a, 42096 Wuppertal (Germany)]. E-mail: heidrun.ellinger-ziegelbauer@bayerhealthcare.com; Stuart, Barry [Bayer Crop Science, Department of Toxicology, Stilwell, KS (United States); Wahle, Brad [Bayer Crop Science, Department of Toxicology, Stilwell, KS (United States); Bomann, Werner [Bayer Crop Science, Department of Toxicology, Stilwell, KS (United States); Ahr, Hans Juergen [Bayer Healthcare AG, Department of Molecular and Genetic Toxicology, Aprather Weg 18a, 42096 Wuppertal (Germany)

    2005-08-04

    Application of recently developed gene expression techniques using microarrays in toxicological studies (toxicogenomics) facilitate the interpretation of a toxic compound's mode of action and may also allow the prediction of selected toxic effects based on gene expression changes. In order to test this hypothesis, we investigated whether carcinogens at doses known to induce liver tumors in the 2-year rat bioassay deregulate characteristic sets of genes in a short term in vivo study and whether these deregulated genes represent defined biological pathways. Male Wistar rats were dosed with the four nongenotoxic hepatocarcinogens methapyrilene (MPy, 60 mg/kg/day), diethylstilbestrol (DES, 10 mg/kg/day), Wy-14643 (Wy, 60 mg/kg/day), and piperonylbutoxide (PBO, 1200 mg/kg/day). After 1, 3, 7, and 14 days, the livers were taken for histopathological evaluation and for analysis of the gene expression profiles on Affymetrix RG{sub U}34A arrays. The expression profile of the four nongenotoxic carcinogens were compared to the profiles of the four genotoxic carcinogens 2-nitrofluorene (2-NF), dimethylnitrosamine (DMN), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and aflatoxin B1 (AB1) from a similar study reported previously. By using statistical and clustering tools characteristically deregulated genes were extracted and functionally classified. Distinct cellular pathways were affected by the nongenotoxic carcinogens compared to the genotoxic carcinogens which at least partly correlated with the two-stage model of carcinogenesis. Characteristic to genotoxic carcinogens were a DNA damage response and the activation of proliferative and survival signaling. Nongenotoxic carcinogens showed responses to oxidative DNA or protein damage, as well as cell cycle progression and signs of regeneration. Many of the gene alterations found with the nongenotoxic carcinogens imply compound-specific mechanisms. Although neither a single gene nor a single pathway will be

  12. Subcellular distribution of 239Pu in the liver of rat, mouse, Syrian and Chinese hamster

    International Nuclear Information System (INIS)

    An attempt was made to elucidate the biochemical mechanisms responsible for the species differences in the biological half life of plutonium-239 in the liver of rats, mice, Syrian hamsters and Chinese hamsters. Six days after intravenously administered Pu-239, the animals were given Triton i.p. which causes a shift of the density of the lysosomes and thus any lysosomally-associated material can be recognised by a parallel shift. On the tenth day, an MLP fraction was obtained by differential centrifugation of the liver homogenates; the distribution of radioactivity and marker enzymes was then examined after centrifugation of the MLP fraction in a sucrose density gradient. If the parallelism between the shift of Pu-239 and acid phosphatase is taken as a measure for the extent of lysosomal binding, there is clear evidence for association with these organelles for rats and mice, the species with rapid Pu elimination; however these organelles appear to become less important in the species with longer Pu retention, Syrian and especially Chinese hamster. (U.K.)

  13. Subcellular distribution of Pu-239 in the liver of rat, mouse, Syrian and Chinese hamster

    International Nuclear Information System (INIS)

    The aim of our studies was to elucidate the biochemical mechanisms responsible for the differences in the biological half life of actinides in the liver of different mammalian species. Rats and mice were chosen as models for rapid elimination, and Syrian and Chinese hamsters as models for slow elimination. To distinguish between fixation in lysosomes and mitochondria, the lysosomes were isolated following injection of Triton WR1339 6 days after 239Pu administration. The animals were sacrificed 4 days later. In order to study the possible association with ferritin, 59Fe was also injected. Liver homogenates were subjected to differential and isopycnic centrifugation in a sucrose density gradient. The typical shift in the density of the lysosomal marker acid phosphatase from rho approximately 1.2 to rho approximately 1.1 following Triton WR1339 injection was observed in all species. It was possible therefore to separate lysosomes from other cell organelles, especially mitochondria. It was concluded that: 1) Mitochondria can virtually be excluded as binding sites in all four species; 2) Lysosomes are one important storage site in rats, mice and Syrian hamsters; 3) If 239Pu is bound to another cell constituent in addition to lysosomes in the hamster species (which is not yet proven) its density should be approximately 1.17. (H.K.)

  14. Comparison of functional biochemical, and morphometric alterations in the lungs of four rat strains and hamsters following repeated intratracheal instillation of crocidolite asbestos

    Science.gov (United States)

    Four rat strains and hamsters were exposed to 0.7mg crocidolite asbestos/g lung once/wk for 3weeks by intratracheal instillation (IT). Pulmonary function, biochemistry, and morphometry were evaluated at 3 and 6-months after IT. Each rat strain, but not the hamster, exhibited ele...

  15. Small Animal Models for Human Metapneumovirus: Cotton Rat is More Permissive than Hamster and Mouse

    OpenAIRE

    Yu Zhang; Stefan Niewiesk; Jianrong Li

    2014-01-01

    Human metapneumovirus (hMPV) is the second most prevalent causative agent of pediatric respiratory infections worldwide. Currently, there are no vaccines or antiviral drugs against this virus. One of the major hurdles in hMPV research is the difficulty to identify a robust small animal model to accurately evaluate the efficacy and safety of vaccines and therapeutics. In this study, we compared the replication and pathogenesis of hMPV in BALB/c mice, Syrian golden hamsters, and cotton rats. It...

  16. Inhalation carcinogenicity study with nickel metal powder in Wistar rats

    International Nuclear Information System (INIS)

    Epidemiological studies of nickel refinery workers have demonstrated an association between increased respiratory cancer risk and exposure to certain nickel compounds (later confirmed in animal studies). However, the lack of an association found in epidemiological analyses for nickel metal remained unconfirmed for lack of robust animal inhalation studies. In the present study, Wistar rats were exposed by whole-body inhalation to 0, 0.1, 0.4, and 1.0 mg Ni/m3 nickel metal powder (MMAD = 1.8 μm, GSD = 2.4 μm) for 6 h/day, 5 days/week for up to 24 months. A subsequent six-month period without exposures preceded the final euthanasia. High mortality among rats exposed to 1.0 mg Ni/m3 nickel metal resulted in the earlier termination of exposures in this group. The exposure level of 0.4 mg Ni/m3 was established as the MTD for the study. Lung alterations associated with nickel metal exposure included alveolar proteinosis, alveolar histiocytosis, chronic inflammation, and bronchiolar-alveolar hyperplasia. No increased incidence of neoplasm of the respiratory tract was observed. Adrenal gland pheochromocytomas (benign and malignant) in males and combined cortical adenomas/carcinomas in females were induced in a dose-dependent manner by the nickel metal exposure. The incidence of pheochromocytomas was statistically increased in the 0.4 mg Ni/m3 male group. Pheochromocytomas appear to be secondary to the lung toxicity associated with the exposure rather than being related to a direct nickel effect on the adrenal glands. The incidence of cortical tumors among 0.4 mg Ni/m3 females, although statistically higher compared to the concurrent controls, falls within the historical control range; therefore, in the present study, this tumor is of uncertain relationship to nickel metal exposure. The lack of respiratory tumors in the present animal study is consistent with the findings of the epidemiological studies

  17. Predicting carcinogenicity of diverse chemicals using probabilistic neural network modeling approaches

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Kunwar P., E-mail: kpsingh_52@yahoo.com [Academy of Scientific and Innovative Research, Council of Scientific and Industrial Research, New Delhi (India); Environmental Chemistry Division, CSIR-Indian Institute of Toxicology Research, Post Box 80, Mahatma Gandhi Marg, Lucknow 226 001 (India); Gupta, Shikha; Rai, Premanjali [Academy of Scientific and Innovative Research, Council of Scientific and Industrial Research, New Delhi (India); Environmental Chemistry Division, CSIR-Indian Institute of Toxicology Research, Post Box 80, Mahatma Gandhi Marg, Lucknow 226 001 (India)

    2013-10-15

    Robust global models capable of discriminating positive and non-positive carcinogens; and predicting carcinogenic potency of chemicals in rodents were developed. The dataset of 834 structurally diverse chemicals extracted from Carcinogenic Potency Database (CPDB) was used which contained 466 positive and 368 non-positive carcinogens. Twelve non-quantum mechanical molecular descriptors were derived. Structural diversity of the chemicals and nonlinearity in the data were evaluated using Tanimoto similarity index and Brock–Dechert–Scheinkman statistics. Probabilistic neural network (PNN) and generalized regression neural network (GRNN) models were constructed for classification and function optimization problems using the carcinogenicity end point in rat. Validation of the models was performed using the internal and external procedures employing a wide series of statistical checks. PNN constructed using five descriptors rendered classification accuracy of 92.09% in complete rat data. The PNN model rendered classification accuracies of 91.77%, 80.70% and 92.08% in mouse, hamster and pesticide data, respectively. The GRNN constructed with nine descriptors yielded correlation coefficient of 0.896 between the measured and predicted carcinogenic potency with mean squared error (MSE) of 0.44 in complete rat data. The rat carcinogenicity model (GRNN) applied to the mouse and hamster data yielded correlation coefficient and MSE of 0.758, 0.71 and 0.760, 0.46, respectively. The results suggest for wide applicability of the inter-species models in predicting carcinogenic potency of chemicals. Both the PNN and GRNN (inter-species) models constructed here can be useful tools in predicting the carcinogenicity of new chemicals for regulatory purposes. - Graphical abstract: Figure (a) shows classification accuracies (positive and non-positive carcinogens) in rat, mouse, hamster, and pesticide data yielded by optimal PNN model. Figure (b) shows generalization and predictive

  18. Curcuma oil ameliorates insulin resistance & associated thrombotic complications in hamster & rat

    Directory of Open Access Journals (Sweden)

    Vishal Singh

    2015-01-01

    Full Text Available Background & objectives: Curcuma oil (C. oil isolated from turmeric (Curcuma longa L. has been shown to have neuro-protective, anti-cancer, antioxidant and anti-hyperlipidaemic effects in experimental animal models. However, its effect in insulin resistant animals remains unclear. The present study was carried out to investigate the disease modifying potential and underlying mechanisms of the C. oil in animal models of diet induced insulin resistance and associated thrombotic complications. Methods: Male Golden Syrian hamsters on high fructose diet (HFr for 12 wk were treated orally with vehicle, fenofibrate (30 mg/kg or C. oil (300 mg/kg in the last four weeks. Wistar rats fed HFr for 12 wk were treated orally with C. oil (300 mg/kg in the last two weeks. To examine the protective effect of C. oil, blood glucose, serum insulin, platelet aggregation, thrombosis and inflammatory markers were assessed in these animals. Results: Animals fed with HFr diet for 12 wk demonstrated hyperlipidaemia, hyperglycaemia, hyperinsulinaemia, alteration in insulin sensitivity indices, increased lipid peroxidation, inflammation, endothelial dysfunction, platelet free radical generation, tyrosine phosphorylation, aggregation, adhesion and intravascular thrombosis. Curcuma oil treatment for the last four weeks in hamsters ameliorated HFr-induced hyperlipidaemia, hyperglycaemia, insulin resistance, oxidative stress, inflammation, endothelial dysfunction, platelet activation, and thrombosis. In HFr fed hamsters, the effect of C. oil at 300 mg/kg [ ] was comparable with the standard drug fenofibrate. Curcuma oil treatment in the last two weeks in rats ameliorated HFr-induced hyperglycaemia and hyperinsulinaemia by modulating hepatic expression of sterol regulatory element binding protein 1c (SREBP-1c, peroxisome proliferator-activated receptor-gamma co-activator 1 (PGC-1α and PGC-1β genes known to be involved in lipid and glucose metabolism. Interpretation

  19. Prepubertal exposure to cow's milk reduces susceptibility to carcinogen-induced mammary tumorigenesis in rats

    DEFF Research Database (Denmark)

    Nielsen, Tina Skau; Khan, Galam; Davis, Jennifer;

    2011-01-01

    Cow's milk contains high levels of estrogens, progesterone and insulin-like growth factor 1 (IGF-1), all of which are associated with breast cancer. We investigated whether prepubertal milk exposure affects mammary gland development and carcinogenesis in rats. Sprague-Dawley rats were given either...... whole milk or tap water to drink from postnatal day (PND) 14 to PND 35, and thereafter normal tap water. Mammary tumorigenesis was induced by administering 7,12-dimethylbenz[a]anthracene on PND 50. Milk exposure increased circulating E2 levels on PND 25 by 10-fold (p < 0.001) and accelerated vaginal...... opening, which marks puberty onset, by 2.5 days (p < 0.001). However, rats exposed to milk before puberty exhibited reduced carcinogen-induced mammary carcinogenesis; that is, their tumor latency was longer (p < 0.03) and incidence was lower (p < 0.05) than in the controls. On PND 25 and 50, mammary...

  20. Inhibition of DNA synthesis by chemical carcinogens in cultures of initiated and normal proliferating rat hepatocytes

    International Nuclear Information System (INIS)

    Rat hepatocytes in primary culture can be stimulated to replicate under the influence of rat serum and sparse plating conditions. Higher replication rates are induced by serum from two-thirds partially hepatectomized rats. The effects of carcinogens and noncarcinogens on the ability of hepatocytes to synthesize DNA were examined by measuring the incorporation of [3H]thymidine by liquid scintillation counting and autoradiography. Hepatocyte DNA synthesis was not decreased by ethanol or dimethyl sulfoxide at concentrations less than 0.5%. No effect was observed when 0.1 mM ketamine, Nembutal, hypoxanthine, sucrose, ascorbic acid, or benzo(e)pyrene was added to cultures of replicating hepatocytes. Estrogen, testosterone, tryptophan, and vitamin E inhibited DNA synthesis by approximately 50% at 0.1 mM, a concentration at which toxicity was noticeable. Several carcinogens requiring metabolic activation as well as the direct-acting carcinogen N-methyl-N'-nitro-N-nitrosoguanidine interfered with DNA synthesis. Aflatoxin B1 inhibited DNA synthesis by 50% (ID50) at concentrations between 1 X 10(-8) and 1 X 10(-7) M. The ID50 for 2-acetylaminofluorene was between 1 X 10(-7) and 1 X 10(-6) M. Benzo(a)pyrene and 3'-methyl-4-dimethylaminoazobenzene inhibited DNA synthesis 50% between 1 X 10(-5) and 1 X 10(-4) M. Diethylnitrosamine and dimethylnitrosamine (ID50 between 1 X 10(-4) and 5 X 10(-4) M) and 1- and 2-naphthylamine (ID50 between 1 X 10(-5) and 5 X 10(-4) M) caused inhibition of DNA synthesis at concentrations which overlapped with concentrations that caused measurable toxicity

  1. Carcinogenicity study of ammonia-process caramel in F344 rats.

    Science.gov (United States)

    Maekawa, A; Ogiu, T; Matsuoka, C; Onodera, H; Furuta, K; Tanigawa, H; Hayashi, Y; Odashima, S

    1983-06-01

    The carcinogenicity of ammonia-process caramel, a food colouring, was examined in F344 rats. Caramel was dissolved in distilled water at levels of 0, 1 and 4% and groups of 50 male and 50 female rats were given 20-25 ml of one of these solutions/rat/day as their drinking water for 2 yr. There were no significant differences between the total incidences of tumours or mean survival times of control and experimental groups. A variety of tumours developed in all groups including the control group, and no dose-related effects were found either in the incidence or induction time of tumours in the various organs and tissues except in the pituitary gland of males, in which the incidence of tumours in males given 4% caramel solution was significantly higher than that in controls. Pituitary tumours are among the most common spontaneous tumours in ageing rats of this strain and have a variable incidence. In addition, almost all pituitary tumours detected in males given the 4% solution were microscopic tumours, and there was no significant difference between controls and treated groups in the incidence of hyperplasia or pre-neoplastic lesions in the pituitary gland. These results indicate that the significantly higher incidence of pituitary tumours in males given the 4% caramel solution was not related to caramel administration, but could be explained by the variability of the incidence of spontaneous pituitary tumours. Thus it is concluded that under these experimental conditions ammonia-process caramel was not carcinogenic in F344 rats. PMID:6683219

  2. A combined chronic toxicity/carcinogenicity study of sucralose in Sprague-Dawley rats.

    Science.gov (United States)

    Mann, S W; Yuschak, M M; Amyes, S J; Aughton, P; Finn, J P

    2000-01-01

    The chronic toxicity and potential carcinogenicity of sucralose was evaluated by exposing Sprague-Dawley rats to dietary concentrations of this low-calorie sweetener both in utero and for up to 104 weeks following parturition. The rats assigned to the toxicity phase of this investigation were administered diets containing either 0% (control), 0.3% (3000 ppm), 1.0% (10,000 ppm) or 3.0% (30,000 ppm) sucralose. Each treatment group comprised 30 male and 30 female rats, of which 15 males and 15 females were sacrificed after 52 weeks of treatment. The surviving rats were killed following 78 weeks of sucralose administration. In the carcinogenicity phase of this investigation, groups of 50 male and 50 female rats were administered dietary sucralose at concentrations of 0% (control 1), 0% (control 2), 0.3%, 1.0% or 3.0% for 104 weeks. Evaluation of the data obtained from the two phases of this study showed that sucralose was not carcinogenic. Sucralose did not adversely affect the survival or clinical condition of the rats, and there were no toxicologically significant findings. Group mean body weight gain and food consumption were significantly decreased in a dose-dependent manner in sucralose-treated rats throughout the treatment period as compared to the controls. The primary effect of sucralose on food consumption, and secondarily on body weight gain, was established in later studies to be due to the fact that diets containing high concentrations of sucralose are unpalatable to rats. These subsequent studies established that the reduction of body weight gain seen in previous rat studies using sucralose in the diet at concentrations of 1% and below resulted from reduced food intake as a direct consequence of the unpalatable nature of sucralose. Similarly, at concentrations of 3% in the diet, it was shown that approximately 95% of the effect on body weight gain could be attributed to the reduction in food intake due to the reduced palatability of the diet, the remainder

  3. Long-term health effects in hamsters and rats exposed chronically to man-made vitreous fibers

    Energy Technology Data Exchange (ETDEWEB)

    Smith, D.M.; Ortiz, L.W.; Archuleta, R.F.; Johnson, N.F.

    1986-01-01

    Rats and hamsters were exposed to several types of airborne man-made vitreous fibers. Exposure protocols were ''nose-only'' 6 h a day, 5 d a week for 24 m with surviving animals maintained for the rest of their lives. Challenge aerosols consisted of 4 types of fibrous glass, 1 refractory ceramic fiber (RCF), and 1 mineral wool fiber. UICC crocidolite asbestos and clean air served as positive and negative controls for the inhalation groups. Groups of additional controls were unmanipulated caged animals, intraperitoneally (IP) injected animals, and intratracheally (IT) instilled animals. Animals, after their deaths, were examined macroscopically and microscopically. Fiber lung burdens were significant for the inhalation exposures and related to the mean diameters of the fibrous challenge aerosols. The inhalation exposures with MMVF did not result in any adverse effects except for a mesothelioma of the lung in 1 hamster exposed to the RCF, not a statistically significant finding. Consistent with other reported work, abdominal mesotheliomas were induced in the groups of hamsters and rats injected IP with 0.45-micron mean diameter fibrous glass, RCF, and crocidolite asbestos. With IT instillations, primary lung tumors were found only in hamsters and rats receiving UICC crocidolite; no lung tumors occurred in animals instilled IT with 2 types of MMVF. 28 refs., 2 figs., 18 tabs.

  4. The subcellular distribution of 239Pu, 241Am and 59Fe in the liver of rat and Chinese hamster as dependent on time

    International Nuclear Information System (INIS)

    The subcellular distribution of monomeric 239Pu, 241Am and iron in rat and Chinese hamster liver has been investigated by sucrose-, metrizamide- and Percoll-density gradients. In rat liver, the transuranium elements become and remain bound to typical lysosomes primary storage organelle in Chinese hamster liver. However, their apparent density in sucrose decreases with time, which possible indicates transition into telolysomes. The transuranium nuclides show a subcellular distribution which is quite different from that of iron. (orig.)

  5. Effects of combined exposure of F344 rats to inhaled 239PuO2 and a chemical carcinogen (NNK)

    International Nuclear Information System (INIS)

    Workers in nuclear weapons facilitates have a significant potential for exposure to chemical carcinogens and to radiation from external sources or from internally deposited radionuclides such as 239Pu. Although the carcinogenic effects of inhaled 239Pu and many chemicals have been studied individually, very little information is available on their combined effects. One chemical carcinogen that workers could be exposed to, via tobacco smoke, is the tobacco-specific nitrosamine 4-(N-Methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a product of the curing of tobacco and pyrolysis of nicotine in tobacco. NNK causes lung tumors in rats, regardless of the route of administration and to a lesser extent tumors in the liver, nasal passages, and pancreas. The purpose of this study is to characterize the effects of combined exposure of rats to NNK and internally deposited plutonium, as well as to these agents alone

  6. Metabolic dephenylation of the rubber antioxidant N-phenyl-2-naphthylamine to carcinogenic 2-naphthylamine in rats.

    Science.gov (United States)

    Weiss, Tobias; Bolt, Hermann M; Schlüter, Gerhard; Koslitz, Stephan; Taeger, Dirk; Welge, Peter; Brüning, Thomas

    2013-07-01

    N-Phenyl-2-naphthylamine (P2NA) was widely used as oxidation inhibitor, particularly in rubber manufacturing. Technical-grade P2NA was contaminated with carcinogenic 2-naphthylamine (2NA), and bladder cancer risk in exposed workers was attributed to this impurity. Investigations in humans and mammalian species revealed that small amounts of 2NA are excreted into urine after exposure to P2NA. However, since 2NA per se is not carcinogenic and main downstream metabolites of 2NA have not been found in urine so far, it remained uncertain if 2NA derived from P2NA dephenylation is further activated to carcinogenic downstream metabolites. An experimental animal study was therefore designed to indicate if, and if yes to which extent, 2NA from P2NA dephenylation is accessible to the metabolic pathway that is held responsible for the carcinogenicity of 2NA. Groups of 5 male and female CD rats were dosed with P2NA (2-550 mg/kg b.w.) and 2NA (0.075-75 mg/kg b.w.); 2NA-haemoglobin adducts and urinary 2NA excretion were determined applying GC-MS/MS. 2NA haemoglobin adducts originated dose-dependently after 2NA and P2NA dosing. To induce identical adduct concentrations, an approximately 100-200-fold higher dose of P2NA was necessary compared to 2NA. Since haemoglobin adducts are formed by the same pathway (N-hydroxylation) as the ultimate carcinogens from 2NA, the comparison of adduct concentrations after 2NA and P2NA dosage permits a quantitative estimate of the carcinogenicity of P2NA. The results show that 2NA derived from dephenylation of P2NA enters the carcinogenic downstream pathway of 2NA in rats. Hence, the bladder cancer risk after human exposures to P2NA must be re-evaluated. PMID:23423714

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1995-12-01

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

  8. In vitro neuroprotective action of recombinant rat erythropoietin produced by astrocyte cell lines and comparative studies with erythropoietin produced by Chinese hamster ovary cells

    OpenAIRE

    Masuda, Seiji; Kada, Emi; Nagao, Masaya; Sasaki, Ryuzo

    1999-01-01

    In the central nervous system, astrocytes produce erythropoietin (Epo) and neurons express its receptor. To examine whether or not the brain Epo protects the in vitro cultured neurons from glutamate-induced cell death, we established rat astrocyte cell lines containing the plasmid for production of recombinant rat Epo. Epo partially purified from the culture medium showed a neuroprotective effect similar to that of rat Epo produced by Chinese hamster ovary (CHO) cells. Comparison was made in ...

  9. The subcellular distribution of 239Pu, 241Am and 59Fe in the liver of rat and Chinese hamster as dependent on time

    International Nuclear Information System (INIS)

    The subcellular distribution of monomeric 239Pu, 241Am and iron in rat and Chinese hamster liver has been investigated by sucrose-, metrizamide- and Percoll-density gradients. In rat liver, the transuranium elements become and remain bound to typical lysosomes up to several months after incorporation. Lysosomes are also the primary storage organelle in Chinese hamster liver. However, their apparent density in sucrose decreases with time, which possibly indicates transition into telolysomes. The transuranium nuclides show a subcellular distribution which is quite different from that of iron. (orig.)

  10. Toxicology and metabolism of nickel compounds. Progress report, December 1, 1975--November 30, 1976. [Tests made with rats and hamsters

    Energy Technology Data Exchange (ETDEWEB)

    Sunderman, F.W. Jr.

    1976-08-15

    The toxicology and metabolism of nickel compounds (NiCl/sub 2/, Ni/sub 3/S/sub 2/, NiS, Ni powder, and Ni(CO)/sub 4/) were investigated in rats and hamsters. Triethylenetetramine (TETA) and d-penicillamine are more effective than other chelating agents (Na-diethyldithiocarbamate, CaNa/sub 2/-versenate, diglycylhistidine-N-methylamide and ..cap alpha..-lipoic acid) as antidotes for acute Ni(II)-toxicity in rats. The antidotal efficacy of triethylenetetramine (TETA) in acute Ni(II)-toxicity is mediated by rapid reduction of the plasma concentration of Ni(II), consistent with renal clearance of the TETA-Ni complex at a rate more than twenty times greater than the renal clearance of non-chelated Ni(II). Fischer rats are more susceptible than other rat strains (Wistar-Lewis, Long-Evans and NIH-Black) to induction of erythrocytosis after an intrarenal injection of Ni/sub 3/S/sub 2/, and elucidation of the serial pathologic changes that occur in rats after an intrarenal injection of Ni/sub 3/S/sub 2/. When amorphous nickel monosulfide (NiS) and nickel subsulfide (Ni/sub 3/S/sub 2/) were administered by im injection to randomly selected Fischer rats in equivalent amounts under identical conditions, NiS did not induce any tumors whereas Ni/sub 3/S/sub 2/ induced sarcomas in almost all of the rats.

  11. Carcinogen-Specific Gene Expression Profiles in Short-term Treated Eker and Wild-type Rats Indicative of Pathways Involved in Renal Tumorigenesis

    OpenAIRE

    Stemmer, Kerstin; Ellinger-Ziegelbauer, Heidrun; Ahr, Hans-Jürgen; Dietrich, Daniel R

    2007-01-01

    Eker rats heterozygous for a dominant germline mutation in the tuberous sclerosis 2 (Tsc2) tumor suppressor gene were used as a model to study renal carcinogenesis. Eker and corresponding wild-type rats were exposed to genotoxic aristolochic acid (AA) or non-genotoxic ochratoxin A (OTA) to elucidate early carcinogen-specific gene expression changes and to test whether Eker rats are more sensitive to carcinogen-induced changes in gene expression. Male Eker and wild-type rats were gavaged daily...

  12. Toxicity and carcinogenicity studies of Caramel Colour IV in F344 rats and B6C3F1 mice.

    Science.gov (United States)

    MacKenzie, K M; Boysen, B G; Field, W E; Petsel, S R; Chappel, C I; Emerson, J L; Stanley, J

    1992-05-01

    Caramel Colour IV, a type of caramel colour used in the manufacture of cola soft drinks, was evaluated for subchronic and chronic toxicity in rats, and carcinogenicity in Fischer-344 (F344) rats and B6C3F1 mice. In each of the studies, Caramel Colour IV was mixed with demineralized water and the solutions given to the animals ad lib. in the drinking fluid. The concentrations of Caramel Colour IV in the drinking fluid were adjusted periodically to achieve the desired caramel colour intake per kg body weight. In the range-finding studies, groups of 30 rats/sex were given Caramel Colour IV at levels of 0, 15, 20, 25 or 30 g/kg for 13 wk, and groups of 10 male rats were given levels of 0, 2.5, 5, 10 or 15 g/kg for 6 wk followed, for some dose groups, by a 2-wk withdrawal period, and then re-initiation of dosing for another 2 wk. In the rat chronic toxicity study, levels of Caramel Colour IV of 0, 2.5, 5, 7.5 or 10 g/kg were given to groups of 25 rats/sex for 12 months. The test groups in the rat and mouse carcinogenicity studies were composed of 50 animals/sex and each species was given the caramel colour at levels of 0, 0, 2.5, 5 or 10 g/kg for 24 months. In each of the studies, treated animals tended to have dose-related lower water consumption than controls. This was attributed to poor palatability of the drinking fluid, and was generally associated with decreased food consumption and body weights. Rats given caramel colour often had soft or liquid malodorous faeces although there were no treatment-related ante-mortem observations in mice. Blood biochemical changes in the rat (i.e. reduced blood urea nitrogen, alkaline phosphatase and total serum protein) appeared to be related to dietary influences and were not considered toxicologically significant. There were no treatment-related alterations in haematological variables or treatment-related differences in survival or in the incidence of benign or malignant tumours among treated and control groups and no

  13. Do cage effects influence tumor incidence? An examination of laboratory animal carcinogenicity studies utilizing Fischer 344 rats.

    Science.gov (United States)

    Haseman, J K

    1988-08-01

    Approximately 125 carcinogenicity studies in Fischer 344 rats conducted by the National Toxicology Program (NTP) were examined to determine the frequency with which cage effects were associated with observed carcinogenic responses. All studies involving groups of 50 rats housed five per cage and showing evidence of chemically-related carcinogenicity were considered. For each of these experiments, two statistical analyses were carried out for each dosed and control group: (i) a test to determine whether or not the occurrence of tumors clustered within cages; and (ii) an evaluation to determine whether or not tumor incidences differed significantly between differing cage shelf levels. These analyses showed that the numbers of statistically significant (P less than 0.05 or P less than 0.01) effects were consistent with the number expected by chance alone. Thus, cage-related factors appeared to have little or no impact upon tumor incidence in these particular studies. Experimental design protocols now used by the NTP (which include random assignment of animals to cages; random assignment of columns of cages to dosed and control groups; and periodic rotation of cage location) further reduce the likelihood that factors associated with the housing of the animals could influence tumor incidence in current studies. PMID:3183292

  14. Synergism of diethylstilbestrol and other carcinogens in concurrent development of hepatic, mammary, and pituitary tumors in castrated male rats

    International Nuclear Information System (INIS)

    Castrated male WF rats, given implants of pellets containing 5.0 mg diethylstilbestrol (DES), were given N-butyl-N-nitrosourea (NBU) in small amounts, which alone produced no mammary tumors in intact female rats. Treatment resulted in the high yield of hepatic tumors (HT), mammary tumors (MT), and pituitary tumors (PT) concurrently in each rat. If animals were further tested with prolactin, the development of HT and MT was accelerated, whereas that of PT was suppressed. None of the intact or castrated rats receiving NBU and/or prolactin developed tumors in any tissues if DES treatment was omitted. Exposure of male rats, preconditioned similarly to NBU treatment, to 200 rads of 14.1-MeV fast-neutron radiation also elicited HT, MT, and PT with an efficiency comparable to that of NBU-treated rats. These findings indicate that DES played an essential role in the whole carcinogenic process in each tissue and that castrated male rats, if conditioned properly with estrogens, are useful for the study of the carcinogenesis mechanism in these tissues

  15. Acrylamide carcinogenicity.

    Science.gov (United States)

    Klaunig, James E

    2008-08-13

    The induction of cancer by chemicals is a multiple-stage process. Acrylamide is carcinogenic to experimental mice and rats, causing tumors at multiple organ sites in both species when given in drinking water or by other means. In mice, acrylamide increased the incidence and multiplicity of lung tumors and skin tumors. In two bioassays in rats, acrylamide administered in drinking water consistently induced mesotheliomas of the testes, thyroid tumors, and mammary gland tumors. In addition, brain tumors appeared to be increased. In one of the rat bioassays, pituitary tumors, pheochromocytomas, uterine tumors, and pituitary tumors were noted. The conversion of acrylamide metabolically to the reactive, mutagenic, and genotoxic product, glycidamide, can occur in both rodent and humans. Glycidamide and frequently acrylamide have been positive for mutagenicity and DNA reactivity in a number of in vitro and in vivo assays. The effects of chronic exposure of glycidamide to rodents have not been reported. Epidemiologic studies of workers for possible health effects from exposures to acrylamide have not shown a consistent increase in cancer risk. Although an increase in the risk for pancreatic cancer (almost double) was seen in highly exposed workers, no exposure response relationship could be determined. The mode of action remains unclear for acrylamide-induced rodent carcinogenicity, but support for a genotoxic mechanism based on in vitro and in vivo DNA reactivity assays cannot be ruled out. In addition, the pattern of tumor formation in the rat following chronic exposure supports a genotoxic mode of action but also suggests a potential role of endocrine modification. PMID:18624430

  16. Formation and persistence of DNA adducts from the carcinogen N-hydroxy-2-acetylaminofluorene in rat mammary gland in vivo

    International Nuclear Information System (INIS)

    The rat mammary carcinogen, N-hydroxy-2-acetylaminofluorene (N-hydroxy-2-AAF), has been proposed to be metabolically activated by mammary cytosolic N,O-acetyltransferase to a DNA binding species. To test this hypothesis, adult female Sprague-Dawley derived CD rats were treated, i.p., with 4.0 mg/kg [ring-3H]N-hydroxy-2-AAF. After 4 h, 1, 3, 14, and 28 days, the animals were killed, the mammary epithelium DNA was isolated and the carcinogen-deoxyribonucleoside adducts present were analyzed by high pressure liquid chromatography. At each time, only one adduct was detected and it was chromatographically identical to N-(deoxyguanosin-8-yl)-2-aminofluorene. The level of the adduct was maximal at 4 h (1.5 adducts/10(6) nucleotides) and then decreased, following first order kinetics with a t1/2 of 14.2 days. The detection of a single non-acetylated aminofluorene adduct is consistent with N,O-acyltransferase being involved in the metabolic activation of N-hydroxy-2-AAF in the rat mammary gland

  17. Major carcinogenic pathways identified by gene expression analysis of peritoneal mesotheliomas following chemical treatment in F344 rats

    International Nuclear Information System (INIS)

    This study was performed to characterize the gene expression profile and to identify the major carcinogenic pathways involved in rat peritoneal mesothelioma (RPM) formation following treatment of Fischer 344 rats with o-nitrotoluene (o-NT) or bromochloracetic acid (BCA). Oligo arrays, with over 20,000 target genes, were used to evaluate o-NT- and BCA-induced RPMs, when compared to a non-transformed mesothelial cell line (Fred-PE). Analysis using Ingenuity Pathway Analysis software revealed 169 cancer-related genes that were categorized into binding activity, growth and proliferation, cell cycle progression, apoptosis, and invasion and metastasis. The microarray data were validated by positive correlation with quantitative real-time RT-PCR on 16 selected genes including igf1, tgfb3 and nov. Important carcinogenic pathways involved in RPM formation included insulin-like growth factor 1 (IGF-1), p38 MAPkinase, Wnt/β-catenin and integrin signaling pathways. This study demonstrated that mesotheliomas in rats exposed to o-NT- and BCA were similar to mesotheliomas in humans, at least at the cellular and molecular level

  18. The role of pancreatic islets in experimental pancreatic carcinogenicity.

    OpenAIRE

    ISHIKAWA, O; Ohigashi, H.; Imaoka, S.; Nakai, I.; Mitsuo, M.; Weide, L. van der; Pour, P. M.

    1995-01-01

    Our previous studies have suggested that the presence of intact islets is essential for the induction of pancreatic exocrine tumors in the Syrian hamster model. To validate this, we investigated the effect of the carcinogen, N-nitrosobis(2-oxo-propyl)amine (BOP) in hamsters, in which homologous isolated intact islets were transplanted into the submandibular gland (SMG). Freshly isolated pure islets from hamster donors were transplanted into the left SMG of 20 female host hamsters. Ten of thes...

  19. (S)-N′-Nitrosonornicotine, a constituent of smokeless tobacco, is a powerful oral cavity carcinogen in rats

    OpenAIRE

    Balbo, Silvia; James-Yi, Sandra; Johnson, Charles S.; O’Sullivan, Michael G.; Stepanov, Irina; Wang, Mingyao; Bandyopadhyay, Dipankar; Kassie, Fekadu; Carmella, Steven; Upadhyaya, Pramod; Hecht, Stephen S

    2013-01-01

    Currently, smokeless tobacco products are being proposed as an alternative mode of tobacco use associated with less harm. All of these products contain the tobacco-specific carcinogen N′-nitrosonornicotine (NNN). The major form of NNN in tobacco products is (S)-NNN, shown in this study to induce a total of 89 benign and malignant oral cavity tumors in a group of 20 male F-344 rats treated chronically with 14 p.p.m. in the drinking water. The opposite enantiomer (R)-NNN was weakly active, but ...

  20. [Experimental therapy in Chinese hamsters and rats infected with larval Echinococcus multilocularis by using mebendazole, albendazole and ivermectin with brief review of chemotherapy of human multilocular echinococcosis].

    Science.gov (United States)

    Inaoka, T; Nakao, M; Ohnishi, K; Kutsumi, H

    1987-01-01

    The effects of the mebendazole, albendazole and ivermectin on secondary multilocular echinococcosis in Chinese hamsters infected with intraperitoneal inoculation of protoscolices and in rats infected with transportal inoculation of protoscolices were investigated. A reduction in weight of the hydatids greater than 95% was recorded in Chinese hamsters intraperitoneally injected with mebendazole suspension. Oral administration of mebendazole moderately inhibited the development of the hydatids. Albendazole was less effective than mebendazole. Ivermectin was ineffective. The treatment with mebendazole of larval E. multilocularis inhibited the growth of the hydatids but it could not completely kill the parasite tissues. The present status of chemotherapy of the human multilocular echinococcosis was briefly discussed. PMID:3546045

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

    International Nuclear Information System (INIS)

    This is a comparative study of the mechanisms by which three different rodent non-genotoxic carcinogens modulate connexin-mediated gap junction intercellular communication in male rat liver in vivo. In the case of the peroxisome proliferating agent Wy-14,643, a non-hepatotoxic dose of 50 mg/kg led to a marked loss of inter-hepatocyte dye transfer associated with a loss of both Cx32 and Cx26 protein expression. In contrast, p,p'-dichlorodiphenyltrichloroethane (DDT) at a non-hepatotoxic dose (25 mg/kg) was not found to alter Cx32 or Cx26 expression or to produce a measurable Cx32 serine phosphorylation but did give a small, significant reduction of cell communication. Carbon tetrachloride (CCl4) did not affect cell communication (despite a small significant reduction of Cx32 content) at a non-hepatotoxic dose. Both loss of communication and Cx32 expression was observed only at a dose that caused hepatocyte toxicity as evidenced by increased serum alanine aminotransferase activity. Overall, the findings emphasise that loss of gap junctional communication in vivo can contribute to carcinogenesis by non-genotoxic carcinogens through different primary mechanism. In contrast to Wy-14,643 and DDT, the results with CCl4 are consistent with a requirement for hepatotoxicity in its carcinogenic action

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

    Science.gov (United States)

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

    2006-12-15

    Some compounds have structural isomers of which one is apparently carcinogenic, and the other not. Because of the similarity of their chemical structures, comparisons of their effects can allow gene expression elicited in response to the basic skeletons of the isomers to be disregarded. We compared the gene expression profiles of male Fischer 344 rats administered by daily oral gavage up to 28 days using an in-house oligo microarray. 2-Acetylaminofluorene (2-AAF), 2,4-diaminotoluene (2,4-DAT), 2-nitropropane (2-NP), and 2-nitro-p-phenylenediamine (2-NpP) are hepatocarcinogenic. However, their isomers, 4-acetylaminofluorene (4-AAF), 2,6-diaminotoluene (2,6-DAT), 1-nitropropane (1-NP), and 4-nitro-o-phenylenediamine (4-NoP), are non-hepatocarcinogenic. Because of the limited carcinogenicity of 2-NpP, we attempted to perform two-parametric comparison analyses with (1) a set of 4 isomers: 2-AAF, 2,4-DAT, 2-NP, and 2-NpP as "carcinogenic", and 4-AAF, 2,6-DAT, 1-NP, and 4-NoP as "non-carcinogenic"; and (2) a set of 3 isomers: 2-AAF, 2,4-DAT, and 2-NP, as "carcinogenic", and 4-AAF, 2,6-DAT, and 1-NP as "non-carcinogenic". After ratio filtering and Welch's approximate t-test analysis, 54 and 28 genes were selected from comparisons between the sets of 3 and 4 isomers, respectively, for day 28 data. Using hierarchical clustering analysis with the 54 or 28 genes, 2-AAF, 2,4-DAT, and 2-NP clustered into a "carcinogenic" branch. 2-NpP was in the same cluster as 4-NoP and 4-AAF. This clustering corresponded to the previous finding that 2-NpP is not carcinogenic in male Fischer 344 rats, which indicates that comparing the differences in gene expression elicited by different isomers is an effective method of developing a prediction system for carcinogenicity. PMID:17070881

  3. Cardiac blood-pool scintigraphy in rats and hamsters: comparison of five radiopharmaceuticals and three pinhole collimator apertures

    International Nuclear Information System (INIS)

    Preclinical evaluation of cardiac drugs may require evaluation of cardiac function in intact animals. To optimize the quality of radionuclide measurements of ventricular function in small animals, a comparison was made of gated blood-pool scans recorded with five blood-pool radiopharmaceuticals (99mTc-labeled human polyclonal IgG, 99mTc-human serum albumin labeled by two methods, and red blood cells radiolabeled with 99mTc via in vivo and in vitro methods) in rats and three pinhole apertures in hamsters. The quality of the radiopharmaceuticals was evaluated by comparing count density ratios (LV/BACKGROUND and LV/LIVER) and ejection fractions recorded with each agent. The edge definition of the left ventricle and count rate performance of the 1-, 2-, and 3-mm apertures was evaluated in hamsters. In general, the images obtained with the radiolabeled cells were superior to those obtained with the labeled proteins and no significant differences between the protein preparations were detected. Left ventricular ejection fractions calculated with all five radiopharmaceuticals were not significantly different. The best quality images were obtained with the 1-mm pinhole collimator. Ejection fraction and acquisition time were inversely related to aperture size. A good compromise between resolution and sensitivity was obtained with the 2-mm pinhole collimator

  4. Analysis of carcinogenic activity of some pesticides in a medium-term liver bioassay in the rat.

    Science.gov (United States)

    Hakoi, K; Cabral, R; Hoshiya, T; Hasegawa, R; Shirai, T; Ito, N

    1992-01-01

    Eight pesticides were tested in a medium-term bioassay based upon the induction of preneoplastic lesions in the liver. Rats were initially given diethylnitrosamine intraperitoneally at a dose of 200 mg/kg body weight and 2 weeks later were treated with the pesticides for 6 weeks and then killed; all rats had a partial hepatectomy at week 3. Hepatocarcinogenic potential was assessed by comparing the number and area of glutathione S-transferase placental form positive foci in the liver with those of controls given diethylnitrosamine (DEN) alone. Positive results were seen with p,p-DDT and Triadimefon. Permethrin (mixture of 39% cis form and 61% trans form) showed borderline results. Permethrin (25/75), Deltamethrin, Cypermethrin (52/48), while Trimorphamide and Propineb gave negative results. Our findings provide experimental evidence to indicate that compounds active in this assay have a potential for liver carcinogenicity in rodents. PMID:1363965

  5. Pulmonary retention and tissue distribution of 239Pu nitrate in F344 rats and syrian hamsters inhaling carbon tetrachloride

    International Nuclear Information System (INIS)

    Carbon tetrachloride (CCl4) has been used extensively in the nuclear weapons industry, so it is possible that nuclear plant workers have been exposed to CCl4 and plutonium compounds. Potential for future exposure exists during open-quotes cleanupclose quotes operations at weapon production sites such as the Hanford, Washington, and Rocky Flats, Colorado, facilities. The current Threshold Limit Value for CCl4 is 5 ppm; however, concentrations of CCl4 occurring in the nuclear weapons facilities over the past 40-50 y are unknown and may have exceeded this value. The pilot study described in this report is designed to determine whether subchronic inhalation of CCl4 by CDFregister(F-344)/CrlBR rats and Syrian golden hamsters, at concentrations expected to produce some histologic changes in liver, alters the hepatic retention and toxic effects of inhaled 239Pu nitrate 239Pu(NO3)4

  6. Concordance between Results of Medium-term Liver Carcinogenesis Bioassays and Long-term Findings for Carcinogenic 2-Nitropropane and Non-carcinogenic 1-Nitropropane in F344 Rats

    OpenAIRE

    Doi, Yuko; Tamano, Seiko; Kawabe, Mayumi; Sano,Masashi; Imai, Norio; Nakashima, Hironao; Furukawa, Fumio; Hagiwara, Akihiro; OTSUKA,MASANORI; Shirai, Tomoyuki

    2012-01-01

    This study was conducted to determine the concordance of results for a pair of structural isomers, 2-nitropropane (2-NP) and 1-nitropropane (1-NP), using the rat medium-term liver carcinogenesis bioassay (Ito test) and previously published long-term carcinogenicity tests. Male F344 rats were given a single intraperitoneal injection of DEN (200 mg/kg b.w.) to initiate hepatocarcinogenesis. After 2 weeks, they received per os 0, 0.8, 4 or 20 mg/kg/day of 2-NP or 1-NP six times a week and were s...

  7. Carcinogenicity study on butylated hydroxytoluene (BHT) in Wistar rats exposed in utero

    DEFF Research Database (Denmark)

    Olsen, P.; Meyer, Otto A.; Bille, N.;

    1986-01-01

    Groups of 60, 40, 40 and 60 F0 Wistar rats of each sex were fed a semi-synthetic diet containing butylated hydroxytoluene (BHT) in concentrations to provide intakes of 0, 25, 100 or 500 mg/kg body weight/day, respectively. The F0 rats were mated and groups of 100, 80, 80 or 100 F1 rats of each sex...

  8. Identification of Differently Expressed Genes in Chemical Carcinogen-induced Rat Bladder Cancers

    Institute of Scientific and Technical Information of China (English)

    Guangfu CHEN; Franky L. CHAN; Xu ZHANG; Peter S.F. CHAN

    2009-01-01

    Possible altered gene expression patterns in bladder turnout carcinogenesis in rat bladder cancers induced by BBN [N-butyl-N-(4-hydroxybutyl)nitrosamine] was examined by cDNA microarray analysis of gene expression profiles.Thirty Sprague-Dawley rats were given drinking water containing 0.05% BBN ad libitum for 24 to 28-weeks.Equal numbers of control rats were given tap water without BBN.After treatment,the rat bladders were excised for RNA extraction and histopathological examinations.Total RNAs were extracted from rat transitional cell carcinoma (TCC) tissues and micro-dissected normal rat bladder epithelia.The atlas glass rat microarray was used,which included oligonucleotides of 1081 rat genes.Some of the up-regulated genes in rat bladder TCCs were further confirmed by Northern blotting.Our results showed that the transcriptions of 30 genes were significantly elevated in the rat bladder TCCs,and these included fly proto-oncogene,Lipocortin 2,COX Ⅳ,COX Ⅴ a,and cathepsin D.Also,15 genes were significantly down-regulated in the rat bladder TCCs and they included B7.1,TNFrl,APOAI and VHL.The resuits of cDNA microarray analysis demonstrated that normal rat bladder epithelia and bladder TCC exhibited different and specific gene statement profiles.The increased expressions of the identified genes may play an important role in the chemically induced bladder carcinogenesis.

  9. Evaluation of toxicogenomics approaches for assessing the risk of nongenotoxic carcinogenicity in rat liver.

    Directory of Open Access Journals (Sweden)

    Johannes Eichner

    Full Text Available The current gold-standard method for cancer safety assessment of drugs is a rodent two-year bioassay, which is associated with significant costs and requires testing a high number of animals over lifetime. Due to the absence of a comprehensive set of short-term assays predicting carcinogenicity, new approaches are currently being evaluated. One promising approach is toxicogenomics, which by virtue of genome-wide molecular profiling after compound treatment can lead to an increased mechanistic understanding, and potentially allow for the prediction of a carcinogenic potential via mathematical modeling. The latter typically involves the extraction of informative genes from omics datasets, which can be used to construct generalizable models allowing for the early classification of compounds with unknown carcinogenic potential. Here we formally describe and compare two novel methodologies for the reproducible extraction of characteristic mRNA signatures, which were employed to capture specific gene expression changes observed for nongenotoxic carcinogens. While the first method integrates multiple gene rankings, generated by diverse algorithms applied to data from different subsamplings of the training compounds, the second approach employs a statistical ratio for the identification of informative genes. Both methods were evaluated on a dataset obtained from the toxicogenomics database TG-GATEs to predict the outcome of a two-year bioassay based on profiles from 14-day treatments. Additionally, we applied our methods to datasets from previous studies and showed that the derived prediction models are on average more accurate than those built from the original signatures. The selected genes were mostly related to p53 signaling and to specific changes in anabolic processes or energy metabolism, which are typically observed in tumor cells. Among the genes most frequently incorporated into prediction models were Phlda3, Cdkn1a, Akr7a3, Ccng1 and Abcb4.

  10. Carcinogen-specific gene expression profiles in short-term treated Eker and wild-type rats indicative of pathways involved in renal tumorigenesis.

    Science.gov (United States)

    Stemmer, Kerstin; Ellinger-Ziegelbauer, Heidrun; Ahr, Hans-Juergen; Dietrich, Daniel R

    2007-05-01

    Eker rats heterozygous for a dominant germline mutation in the tuberous sclerosis 2 (Tsc2) tumor suppressor gene were used as a model to study renal carcinogenesis. Eker and corresponding wild-type rats were exposed to genotoxic aristolochic acid (AA) or non-genotoxic ochratoxin A (OTA) to elucidate early carcinogen-specific gene expression changes and to test whether Eker rats are more sensitive to carcinogen-induced changes in gene expression. Male Eker and wild-type rats were gavaged daily with AA (10 mg/kg body weight) or OTA (210 microg/kg body weight). After 1, 3, 7, and 14 days of exposure, renal histopathology, tubular cell proliferation, and Affymetrix gene expression profiles from renal cortex/outer medulla were analyzed. AA-treated Eker and wild-type rats were qualitatively comparable in all variables assessed, suggesting a Tsc2-independent mechanism of action. OTA treatment resulted in slightly increased cortical pathology and significantly elevated cell proliferation in both strains, although Eker rats were more sensitive. Deregulated genes involved in the phosphatidylinositol 3-kinase-AKT-Tsc2-mammalian target of rapamycin signaling, among other important genes prominent in tumorigenesis, in conjunction with the enhanced cell proliferation and presence of preneoplastic lesions suggested involvement of Tsc2 in OTA-mediated toxicity and carcinogenicity, especially as deregulation of genes involved in this pathway was more prominent in the Tsc2 mutant Eker rat. PMID:17483316

  11. Association of brominated proteins and changes in protein expression in the rat kidney with subcarcinogenic to carcinogenic doses of bromate

    International Nuclear Information System (INIS)

    The water disinfection byproduct bromate (BrO3−) produces cytotoxic and carcinogenic effects in rat kidneys. Our previous studies demonstrated that BrO3− caused sex-dependent differences in renal gene and protein expression in rats and the elimination of brominated organic carbon in their urine. The present study examined changes in renal cell apoptosis and protein expression in male and female F344 rats treated with BrO3− and associated these changes with accumulation of 3-bromotyrosine (3-BT)-modified proteins. Rats were treated with 0, 11.5, 46 and 308 mg/L BrO3− in drinking water for 28 days and renal sections were prepared and examined for apoptosis (TUNEL-staining), 8-oxo-deoxyguanosine (8-oxoG), 3-BT, osteopontin, Kim-1, clusterin, and p-21 expression. TUNEL-staining in renal proximal tubules increased in a dose-related manner beginning at 11.5 mg BrO3−/L in female rats and 46 mg/L in males. Increased 8-oxoG staining was observed at doses as low as 46 mg/L. Osteopontin expression also increased in a dose-related manner after treatment with 46 mg/L, in males only. In contrast, Kim-1 expression increased in a dose-related manner in both sexes, although to a greater extent in females at the highest dose. Clusterin and p21 expression also increased in a dose-related manner in both sexes. The expression of 3-BT-modified proteins only increased in male rats, following a pattern previously reported for accumulation of α-2u-globulin. Increases in apoptosis in renal proximal tubules of male and female rats at the lowest doses suggest a common mode of action for renal carcinogenesis for the two sexes that is independent of α-2u-globulin nephropathy. - Highlights: • Bromate induced nephrotoxicity in both male and female rats by similar mechanisms. • Apoptosis was seen in both male and female rats at the lowest doses tested. • Bromate-induced apoptosis correlated to 8-oxo-deoxyguanosine formation. • Bromate increased the level of 3-bromotyrosine

  12. Association of brominated proteins and changes in protein expression in the rat kidney with subcarcinogenic to carcinogenic doses of bromate

    Energy Technology Data Exchange (ETDEWEB)

    Kolisetty, Narendrababu [Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, GA 30602 (United States); Bull, Richard J. [MoBull Consulting, Richland, WA 99352 (United States); Muralidhara, Srinivasa; Costyn, Leah J. [Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, GA 30602 (United States); Delker, Don A. [School of Medicine, University of Utah, Salt Lake City, UT 84132 (United States); Guo, Zhongxian [Water Quality Office, Public Utilities Board, 608576 (Singapore); Cotruvo, Joseph A. [Joseph Cotruvo and Associates, LLC, Washington, DC 20016 (United States); Fisher, Jeffrey W. [National Center for Toxicological Research, FDA, Jefferson, AR 72079 (United States); Cummings, Brian S., E-mail: bsc@rx.uga.edu [Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, GA 30602 (United States)

    2013-10-15

    The water disinfection byproduct bromate (BrO{sub 3}{sup −}) produces cytotoxic and carcinogenic effects in rat kidneys. Our previous studies demonstrated that BrO{sub 3}{sup −} caused sex-dependent differences in renal gene and protein expression in rats and the elimination of brominated organic carbon in their urine. The present study examined changes in renal cell apoptosis and protein expression in male and female F344 rats treated with BrO{sub 3}{sup −} and associated these changes with accumulation of 3-bromotyrosine (3-BT)-modified proteins. Rats were treated with 0, 11.5, 46 and 308 mg/L BrO{sub 3}{sup −} in drinking water for 28 days and renal sections were prepared and examined for apoptosis (TUNEL-staining), 8-oxo-deoxyguanosine (8-oxoG), 3-BT, osteopontin, Kim-1, clusterin, and p-21 expression. TUNEL-staining in renal proximal tubules increased in a dose-related manner beginning at 11.5 mg BrO{sub 3}{sup −}/L in female rats and 46 mg/L in males. Increased 8-oxoG staining was observed at doses as low as 46 mg/L. Osteopontin expression also increased in a dose-related manner after treatment with 46 mg/L, in males only. In contrast, Kim-1 expression increased in a dose-related manner in both sexes, although to a greater extent in females at the highest dose. Clusterin and p21 expression also increased in a dose-related manner in both sexes. The expression of 3-BT-modified proteins only increased in male rats, following a pattern previously reported for accumulation of α-2{sub u}-globulin. Increases in apoptosis in renal proximal tubules of male and female rats at the lowest doses suggest a common mode of action for renal carcinogenesis for the two sexes that is independent of α-2{sub u}-globulin nephropathy. - Highlights: • Bromate induced nephrotoxicity in both male and female rats by similar mechanisms. • Apoptosis was seen in both male and female rats at the lowest doses tested. • Bromate-induced apoptosis correlated to 8-oxo

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

    International Nuclear Information System (INIS)

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

  14. Kinship alters the effects of forced cohabitation on body weight, mate choice and fitness in the rat-like hamster Tscheskia triton

    OpenAIRE

    Cong, Lin; Liu, Dingzhen; Zhang, Jianxu; Rao, Xiaoping

    2009-01-01

    It has been documented that social isolation imparts deleterious effects on gregarious rodents species, but caging in group imparts such effects on solitary rodents. This study was attempted at examining how kinship to affect body weight, behavioral interaction, mate choice and fitness when we caged male and female rat-like hamsters Tscheskia triton in pair, a solitary species. We found that females paired with nonsibling males became heavier than the females paired with sibling males, but ...

  15. Acrylamide, an in vivo thyroid carcinogenic agent, induces DNA damage in rat thyroid cell lines and primary cultures.

    Science.gov (United States)

    Chico Galdo, V; Massart, C; Jin, L; Vanvooren, V; Caillet-Fauquet, P; Andry, G; Lothaire, P; Dequanter, D; Friedman, M; Van Sande, J

    2006-09-26

    Chronic treatment of rats with acrylamide induces various tumors among which thyroid tumors are the most frequent. The aim of the present study was to develop an in vitro model of acrylamide action on thyroid cells to allow the investigation of the mechanism of this tumorigenic action. The first part of the study considered as targets, characteristics of thyroid metabolism, which could explain the thyroid specificity of acrylamide action: the cAMP mitogenic effect and the important H2O2 generation by thyroid cells. However, acrylamide did not modulate H2O2 or cAMP generation in the thyroid cell models studied. No effect on thyroid cell proliferation was observed in the rat thyroid cell line FRTL5. On the other hand, as shown by the comet assay, acrylamide induced DNA damage, as the positive control H2O2 in the PC Cl3 and FRTL5 rat thyroid cell lines, as well as in thyroid cell primary cultures. The absence of effect of acrylamide on H2AX histone phosphorylation suggests that this effect does not reflect the induction of DNA double strand breaks. DNA damage leads to the generation of mutations. It is proposed that such mutations could play a role in the carcinogenic effect of acrylamide. The mechanism of this effect can now be studied in this in vitro model. PMID:16859826

  16. Sex-dependent differences in the disposition of 2,4-dichlorophenoxyacetic acid in Sprague-Dawley rats, B6C3F1 mice, and Syrian hamsters.

    Science.gov (United States)

    Griffin, R J; Godfrey, V B; Kim, Y C; Burka, L T

    1997-09-01

    2,4-Dichlorophenoxyacetic acid (2,4-D), a widely used broadleaf herbicide, is under investigation in a study of peroxisome proliferators. To supplement that study, male and female rats, mice, and hamsters were dosed with 14C-2,4-D orally at 5 and 200 mg/kg and tissue distributions were determined. Blood, liver, kidney, muscle, skin, fat, brain, testes, and ovaries were examined. At early time points tissues from female rats consistently contained higher amounts of radioactivity than did corresponding tissues from males (up to 9 times). By 72 hr, tissue levels were equivalent and males and females had excreted equal amounts of radioactivity. This sex difference was absent in mice. In hamsters, males had higher tissue levels than females. Taurine, glycine, and glucuronide conjugates of 2,4-D were excreted along with parent. Metabolite profiles differed between species qualitatively and quantitatively; however, differences between sexes were minimal. Plasma elimination curves were generated in male and female rats after iv and oral administration. Kinetic analysis revealed significant differences in elimination and exposure parameters consistent with a greater ability to clear 2,4-D by male rats relative to females. This suggests that at equivalent doses, female rats are exposed to higher concentrations of 2,4-D for a longer time than males and may be more susceptible to 2,4-D-induced toxicity. These sex-dependent variations in the clearance of 2,4-D in rats and hamsters may indicate a need for sex-specific models to accurately assess human health risks. PMID:9311622

  17. Carcinogenicity study on butylated hydroxytoluene (BHT) in Wistar rats exposed in utero

    DEFF Research Database (Denmark)

    Olsen, P.; Meyer, Otto A.; Bille, N.;

    1986-01-01

    Groups of 60, 40, 40 and 60 F0 Wistar rats of each sex were fed a semi-synthetic diet containing butylated hydroxytoluene (BHT) in concentrations to provide intakes of 0, 25, 100 or 500 mg/kg body weight/day, respectively. The F0 rats were mated and groups of 100, 80, 80 or 100 F1 rats of each sex...... were formed from 40, 29, 30 and 44 litters, respectively. After weaning, the highest dose (500 mg BHT/kg/day) was lowered to 250 mg/kg/day for the F1 rats. The numbers of litters of ten or more pups at birth decreased with increasing BHT dose. At weaning, treated F1 rats had lower body weights than the...... controls, the extent of the reduction being dose related; the effect, which persisted throughout the study, was most pronounced in the males. The survival of BHT-treated F1 rats of both sexes was significantly better than that of the controls. No significant changes attributable to BHT treatment were found...

  18. Re-evaluation of the kidney tumors and renal histopathology occurring in a 2-year rat carcinogenicity bioassay of quercetin.

    Science.gov (United States)

    Hard, Gordon C; Seely, John Curtis; Betz, Laura J; Hayashi, Shim-Mo

    2007-04-01

    Renal histopathology in the most recent 2-year carcinogenicity bioassay of quercetin, in Fischer 344 rats, was re-evaluated in an attempt to determine a mode of action underlying a small increase in renal tubule tumors reported in the males (). The re-evaluation confirmed the reported increase in renal tumors in mid- and high-dose males, including a single carcinoma in a high-dose male, as well as an exacerbation of spontaneous, chronic progressive nephropathy (CPN) in male rats only. The re-evaluation also showed that there were no cellular alterations in the kidney indicative of chemical toxicity at 6 months, 15 months, or 2 years. The evidence linked the occurrence of the predominant basophilic adenomas and foci of atypical tubule hyperplasia (ATH) with the exacerbation of CPN to advanced grades of severity, supporting a mode of action involving quercetin interaction with CPN. This mode of action represents a secondary mechanism for renal tumor development, with no relevance for extrapolation to humans. In addition, the single carcinoma present in the high-dose males, along with 4 other lesions ranging from ATH to adenoma in male and female groups, were considered to have a unique phenotype associated previously with neoplasms of spontaneous and familial origin. PMID:17156907

  19. Role of prolactin in induction of mammary tumors in rats with low dose radiations or of a chemical carcinogen

    International Nuclear Information System (INIS)

    Synergy of prolactin with x-ray, fast neutron, N-nitrosobutylurea (NBU), in an induction of mammary tumors was discussed, and the following results were obtained. Conversion of mammary epithelium to malignant tumors was induced in rats which were exposed to x-ray of a dose estimated to be below carcinogenic dose or which were given chemical substances. Cells converted to malignant tumors by carcinogenetic treatment survived for a fairly long term without proliferation, responded to proper stimulations, and formed macroscopical tumors. The effect of prolactin was showed at maximum under the presence of normal function of the ovary. RBE of 14.1 MeV fast neutron in an induction of mammary tumor in rats was about 1.3 - 1.5 times of 180 kVp x-ray. From the above-mentioned results, the author would like to point out and emphasize that at present, radiation used frequently for diagnosis and therapy although in small dose incurs the danger of inducing tumors under the specific circumstances where the host lives, and especially that easy treatments for atomic bomb survivors would bring double misfortunes to them in future. (Ueda, J.)

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2004-09-15

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

  1. Carcinogenic and cocarcinogenic effects of radon and radon daughters in rats

    International Nuclear Information System (INIS)

    It has been previously established that lung cancer could be induced in rats by exposure to radon and radon daughters. Although the oat-cell carcinomas that are common in humans were not found in rats, other histological types of lung carcinomas, especially squamous cell carcinomas and primitive lung adenocarcinomas, were similar to those observed in humans. A dose-effect relationship was established for cumulative doses varying from 25 to 300 working-level-months (WLM), which was similar for medium and high cumulative doses to that observed in uranium miners. This experimental protocol was also used to study the potential cocarcinogenic effects of other environmental or industrial airborne pollutants such as tobacco smoke, mineral fibers, diesel exhausts, or minerals from metallic mine ores that may act synergistically with radon exposure. In rats exposed to radon and tobacco smoke combined, the incidence of malignant thoracic tumors was observed in rats exposed to radon and fibers combined, but synergistic effects resulted in additivity. With diesel exhausts or minerals from metallic ores, a slight, nonsignificant increase in the incidence of lung carcinomas was observed compared with rats exposed to radon alone. These results demonstrated that it is possible to establish the potential cocarcinogenic action, showing either multiplicative, additive, or no effect of various environmental or industrial airborne pollutants combined with radon exposure. This radon model is valid for investigating possible interactions between two occupational exposures. 62 refs., 6 figs., 9 tabs

  2. High-dose stabilized chlorite matrix WF10 prolongs cardiac xenograft survival in the hamster-to-rat model without inducing ultrastructural or biochemical signs of cardiotoxicity

    DEFF Research Database (Denmark)

    Hansen, A; Kemp, K; Kemp, E;

    2001-01-01

    WF10 is a stabilized chlorite matrix with immunosuppressive effects. In vitro studies have demonstrated its ability to suppress T cells and delay or abolish antigen presentation. Hence, WF10 may prove useful to prolong graft survival after transplantation. In this study, we evaluated the use of...... high dose WF10 as a single drug regimen in the hamster-to-rat xenotransplantation model and searched for possible cardiotoxic side effects. WF10 prolonged cardiac xenograft survival, but did not induce tolerence or inhibit pathological signs of acute rejection. Hamsters from the donor population......, receiving high dose WF10 for 5 days, were compared with a matched control group. Ultrastructural examination of cardiac tissue as well as biochemical analysis of the cardiac enzymes troponin I, myoglobin and MB isoenzyme of creatine kinase showed no signs of damage. Thus, while prolonging graft survival...

  3. Carcinogenicity study of the emulsifier TOSOM and the release agent TOS in Wistar rats

    DEFF Research Database (Denmark)

    Meyer, Otto A.; KRISTIANSEN, E.; GRY, J.; Madsen, Charlotte Bernhard; OLSEN, P.; THORUP, I.

    1993-01-01

    Groups of 60 Wistar rats of each sex were fed diets containing 3, 6 or 12% of the margarine emulsifier TOSOM (thermally oxidized soybean oil interacted with mono- and diglycerides of fatty acids) for 2.5 yr. In addition, three groups of 60 rats of each sex were fed two products of the release agent...... TOS (thermally oxidized soybean oil) in dietary levels of 1.2% TOS(G) (TOS from Grindsted Product A/S, Denmark) and 0.3 and 1.2% TOS(N) (TOS from Nexus Aps, Denmark), respectively for 2.5 yr. 120 rats of each sex fed a diet containing mono- and diglycerides served as controls. The diets given to all...

  4. Inhalation toxicity and carcinogenicity of 1,3-butadiene in Sprague-Dawley rats.

    OpenAIRE

    Owen, P E; Glaister, J R

    1990-01-01

    A 2-year inhalation study was conducted in Sprague-Dawley rats with 1,3-butadiene. Groups of 110 male and 110 female rats inhaled 1,3-butadiene at 0, 1000, or 8000 ppm for 6hr/day, 5 days/week. Interim clinical pathology, neuromuscular, and histopathology investigations were carried out. The study terminated at 20 to 25% survival (105 weeks for females, 111 weeks for males). Following exposure to 1,3-butadiene there were no effects on hematology, blood chemistry, urine analysis, and neuromusc...

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

    International Nuclear Information System (INIS)

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

  6. Explant culture of rat colon: A model system for studying metabolism of chemical carcinogens

    DEFF Research Database (Denmark)

    Autrup, Herman; Stoner, G.D.; Jackson, F.;

    1978-01-01

    An explant culture system has been developed for the long-term maintenance of colonic tissue from the rat. Explants of 1 cm2 in size were placed in tissue-culture dishes to which was added 2 ml of CMRL-1066 medium supplemented with glucose, hydrocortisone, beta-retinyl acetate, and either 2......,12-dimethylbenz[alpha]anthracene, aflatoxin B1, dimethylnitrosamine, 1,2-dimethylhydrazine, and methylazoxymethanol acetate into chemical species that bind to cellular DNA and protein....

  7. Effects of sulpiride and ethylene glycol monomethyl ether on endometrial carcinogenicity in Donryu rats.

    Science.gov (United States)

    Taketa, Yoshikazu; Inoue, Kaoru; Takahashi, Miwa; Sakamoto, Yohei; Watanabe, Gen; Taya, Kazuyoshi; Yoshida, Midori

    2016-06-01

    Sulpiride and ethylene glycol monomethyl ether (EGME) are known ovarian toxicants that stimulate prolactin (PRL) secretion, resulting in hypertrophy of the corpora lutea and increased progesterone (P4) production. The purpose of the present study was to investigate how the PRL stimulatory agents affected uterine carcinogenesis and to clarify the effects of PRL on endometrial adenocarcinoma progression in rats. Ten-week-old female Donryu rats were treated once with N-ethyl-N'-nitro-N-nitrosoguanidine (20 mg kg(-1) ), followed by treatment with sulpiride (200 ppm) or EGME (1250 ppm) from 11 weeks of age to 12 months of age. Sulpiride treatment inhibited the incidence of uterine adenocarcinoma and precancerous lesions of atypical endometrial hyperplasia, whereas EGME had no effect on uterine carcinogenesis. Sulpiride markedly prevented the onset of persistent estrus throughout the study period, and EGME delayed and inhibited the onset of persistent estrus. Moreover, sulpiride-treated animals showed high PRL and P4 serum levels without changes in the levels of estradiol-17β, low uterine weights and histological luteal cell hypertrophy. EGME did not affect serum PRL and P4 levels. These results suggest that the prolonged low estradiol-17β to P4 ratio accompanied by persistent estrous cycle abnormalities secondary to the luteal stimulatory effects of PRL may explain the inhibitory effects of sulpiride on uterine carcinogenesis in rats. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26178146

  8. Kinship alters the effects of forced cohabitation on body weight, mate choice and fitness in the rat-like hamster Tscheskia triton

    Directory of Open Access Journals (Sweden)

    Lin CONG

    2009-02-01

    Full Text Available It has been documented that social isolation imparts deleterious effects on gregarious rodents species, but caging in group imparts such effects on solitary rodents. This study was attempted at examining how kinship to affect body weight, behavioral interaction, mate choice and fitness when we caged male and female rat-like hamsters Tscheskia triton in pair, a solitary species. We found that females paired with nonsibling males became heavier than the females paired with sibling males, but both agonistic and amicable behavior between paired males and females did not differ between sibling and nonsibling groups. This indicated that kinship might reduce females’ obesity in response to forced cohabitation, and dissociation might exist between physiological and behavioral responses. Furthermore, binary choice tests revealed that social familiarity between either siblings or nonsiblings decreased their investigating time spent in opposite sex conspecific of cage mates and/or their scents as compared with those of non-mates, suggesting effects of social association on mate and kin selection of the hamsters. On the other side, both females and males caged in pair with siblings show a preference between unfamiliar siblings or their scents and the counterparts of nonsiblings after two month separation, indicating that the kin recognition of the hamsters might also rely on phenotype matching. In addition, cohabitation (or permanent presence of fathers elicited a lower survival of pups in nonsibling pairs than sibling pairs, but did not affect litter size, suggesting that kinship affects fitness when housing male and female ratlike hamsters together. Therefore, inbreeding might be adapted for rare and endangered animals [Current Zoology 55(1: 41–47, 2009].

  9. Kinship alters the effects of forced cohabitation on body weight,mate choice and fitness in the rat-like hamster Tscheskia triton

    Institute of Scientific and Technical Information of China (English)

    Xiaoping RAO; JianXu ZHANG; Dingzhen LIU; Lin CONG

    2009-01-01

    It has been documented that social isolation imparts deleterious effects on gregarious rodents species,but caging in group imparts such effects on solitary rodents. This study was attempted at examining how kinship to affect body weight,behavioral interaction,mate choice and fitness when we caged male and female rat-like hamsters Tscheskia triton in pair,a solitary species. We found that females paired with nonsibling males became heavier than the females paired with sibling males,but both agonistic and amicable behavior between paired males and females did not differ between sibling and nonsibling groups. This indicated that kinship might reduce females' obesity in response to forced cohabitation,and dissociation might exist between physiological and behavioral responses. Furthermore,binary choice tests revealed that social familiarity between either siblings or nonsiblings decreased their investigating time spent in opposite sex conspecific of cage mates and/or their scents as compared with those of nonmates,suggesting effects of social association on mate and kin selection of the hamsters. On the other side,both females and males caged in pair with siblings show a preference between unfamiliar siblings or their scents and the counterparts of nonsiblings after two month separation,indicating that the kin recognition of the hamsters might also rely on phenotype matching. In addition,cohabitation (or permanent presence of fathers) elicited a lower survival of pups in nonsibling pairs than sibling pairs,but did not affect litter size,suggesting that kinship affects fitness when housing male and female ratlike hamsters together. Therefore,inbreeding might be adapted for rare and endangered animals.

  10. Influence of hormonal environment in induction of hepatic, mammary and pituitary tumors in male rats treated with radiation or chemical carcinogen

    International Nuclear Information System (INIS)

    Diethylstilbestrol (DES) pellets (5 mg) were implanted in the backs of Wistar Furch strain rats castrated 40 days after birth. Two weeks after the implantation, the rat were treated for carcinogenesis with either a single dose of 200 rad of 14.1 MeV fast neutrons or with N-nitrosobutylurea (NBU) (5 mg/day) for 30 days. Moreover, a prolactin-secreting pituitary tumor was grafted in some of the rats. Both mammary and hepatic tumors occurred in 3 of 7 irradiated rats given DES. Pituitary tumor also occurred in 5 of 7 rats. Mammary, hepatic, and pituitary tumors occurred simultaneously in half of the rats given prolactin. The same results as those obtained in the rats irradiated with fast neutrons were obtained in the rats treated with NBU. These results suggest that only the mammary gland in the rats treated previously with DES was subject to malignant transformation as the target of radiation and a chemical carcinogen and that transformed cells reacted to the high levels of prolactin proliferated, and formed gross carcinoma. (Tsunoda, M.)

  11. A combined dietary chronic toxicity and two-year carcinogenicity study of (2R,4R)-monatin salt in Sprague-Dawley rats.

    Science.gov (United States)

    Brathwaite, Witty A; Crincoli, Christine M; Eapen, Alex K; Rihner, Marisa O; Nikiforov, Andrey I; Remick, Amera K

    2016-05-01

    In a combined chronic toxicity/carcinogenicity study, groups of Crl:CD(SD) rats were fed 0 (2 control groups), 5000, 20,000, or 40,000 ppm (2R,4R)-monatin salt (hereafter "R,R-monatin") in the diet for up to one year in the chronic toxicity phase and up to two years in the carcinogenicity phase. There were no adverse effects on survival, incidence of palpable masses, neoplasms, organ weights, or ophthalmic examinations. The only notable effect was statistically significantly lower mean body weights and body weight gains in all treated groups generally throughout the study, which were most likely a result of caloric dilution of the test diets. Effects of long-term R,R-monatin ingestion by rats were predominantly focused on the urinary system (i.e., clinical pathology alterations indicative of electrolyte and pH imbalances, increased incidence of renal calculi, mineralization and bone hyperostosis, and increased severity of chronic progressive nephropathy). The no-observed-adverse-effect level (NOAEL) for R,R-monatin from the chronic toxicity phase was 20,000 ppm (equivalent to an exposure level of 1080 mg/kg bw/day for males and 1425 mg/kg/day for females) and from the carcinogenicity phase was 5000 ppm (equivalent to an exposure level of 238 and 302 mg/kg bw/day for males and females, respectively). PMID:26747978

  12. Concordance between Results of Medium-term Liver Carcinogenesis Bioassays and Long-term Findings for Carcinogenic 2-Nitropropane and Non-carcinogenic1-Nitropropane in F344 Rats.

    Science.gov (United States)

    Doi, Yuko; Tamano, Seiko; Kawabe, Mayumi; Sano, Masashi; Imai, Norio; Nakashima, Hironao; Furukawa, Fumio; Hagiwara, Akihiro; Otsuka, Masanori; Shirai, Tomoyuki

    2011-12-01

    This study was conducted to determine the concordance of results for a pair of structural isomers, 2-nitropropane (2-NP) and 1-nitropropane (1-NP), using the rat medium-term liver carcinogenesis bioassay (Ito test) and previously published long-term carcinogenicity tests. Male F344 rats were given a single intraperitoneal injection of DEN (200 mg/kg b.w.) to initiate hepatocarcinogenesis. After 2 weeks, they received per os 0, 0.8, 4 or 20 mg/kg/day of 2-NP or 1-NP six times a week and were subjected to two-thirds partial hepatectomy at week 3. Non-initiated groups receiving 0 or 20 mg/kg/day were also included. The animals were sacrificed for quantitative analysis of GST-P-positive foci at week 8. With the highest dose of 2-NP, significantly increased numbers and areas of GST-P-positive foci were demonstrated as compared with the respective control but were not noted with 1-NP. In the non-DEN-initiated groups, many small GST-P-positive foci of less than 0.2 mm in diameter were also induced in the rats treated with 2-NP at 20 mg/kg/day but were lacking with 1-NP. These results strongly support that 2-NP is a complete hepatocarcinogen with a potent initiation activity, whereas 1-NP is not. PMID:22319232

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

    International Nuclear Information System (INIS)

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

  14. Is nitrous oxide a genotoxic carcinogen?

    Science.gov (United States)

    O'Donovan, Michael R; Hammond, Timothy G

    2015-07-01

    Nitrous oxide (N2O) has been widely used as a dental and surgical anaesthetic for over 150 years. However, results from a recent study suggested that increased DNA damage was seen in lymphocytes from surgical patients and this led to its continued clinical use to be questioned. The data can be challenged on technical grounds and must be considered with other studies in order to assess any possible risk. There are other studies indicating that N2O has weak genotoxicity in man, but these are confused by exposure of the populations to other anaesthetic gases including isoflurane and sevoflurane, both of which have also been reported to increase DNA damage. It should be noted that the suggested genotoxic mechanisms are all indirect, including folate deficiency, oxidative stress and homocysteine toxicity. Further, results from in vitro studies indicate that N2O has no direct DNA reactivity as negative results were obtained in a bacterial mutation (Ames) test and an assay for mutation at the hprt locus in Chinese hamster lung cells. Although not performed to definitive study designs, no evidence of carcinogenicity was seen in two long-term tests in mice and another in rats. Although there is some evidence that N2O is weakly genotoxic in humans, this appears to be similar to that reported for isoflurane and sevoflurane and all the postulated mechanisms have clear thresholds with no evidence of direct DNA reactivity. Because any potential genotoxic mechanism would have a threshold, it seems reasonable to conclude that neither occasional high exposure to patients as an anaesthetic nor low-level exposure to staff within published recommended exposure limits presents any significant carcinogenic risk. PMID:25852088

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

    OpenAIRE

    Boudreau, Mary D.; Mellick, Paul W.; Olson, Greg R.; Felton, Robert P.; Thorn, Brett T.; Beland, Frederick A.

    2012-01-01

    Aloe barbadensis Miller (Aloe vera) is an herbal remedy promoted to treat a variety of illnesses; however, only limited data are available on the safety of this dietary supplement. Drinking water exposure of F344/N rats and B6C3F1 mice to an Aloe vera whole-leaf extract (1, 2, and 3%) for 13 weeks resulted in goblet cell hyperplasia of the large intestine in both species. Based upon this observation, 2-year drinking water studies were conducted to assess the carcinogenic potential of an Aloe ...

  16. Low Doses of the Carcinogen Furan Alter Cell Cycle and Apoptosis Gene Expression in Rat Liver Independent of DNA Methylation

    OpenAIRE

    Tao CHEN; Mally, Angela; Ozden, Sibel; Chipman, J. Kevin

    2010-01-01

    Background Evidence of potent rodent carcinogenicity via an unclear mechanism suggests that furan in various foods [leading to an intake of up to 3.5 μg/kg body weight (bw)/day] may present a potential risk to human health. Objectives We tested the hypothesis that altered expression of genes related to cell cycle control, apoptosis, and DNA damage may contribute to the carcinogenicity of furan in rodents. In addition, we investigated the reversibility of such changes and the potential role of...

  17. DNA Adduct Formation from Metabolic 5'-Hydroxylation of the Tobacco-Specific Carcinogen N'-Nitrosonornicotine in Human Enzyme Systems and in Rats.

    Science.gov (United States)

    Zarth, Adam T; Upadhyaya, Pramod; Yang, Jing; Hecht, Stephen S

    2016-03-21

    N'-Nitrosonornicotine (NNN) is carcinogenic in multiple animal models and has been evaluated as a human carcinogen. NNN can be metabolized by cytochrome P450s through two activation pathways: 2'-hydroxylation and 5'-hydroxylation. While most previous studies have focused on 2'-hydroxylation in target tissues of rats, available evidence suggests that 5'-hydroxylation is a major activation pathway in human enzyme systems, in nonhuman primates, and in target tissues of some other rodent carcinogenicity models. In the study reported here, we investigated DNA damage resulting from NNN 5'-hydroxylation by quantifying the adduct 2-(2-(3-pyridyl)-N-pyrrolidinyl)-2'-deoxyinosine (py-py-dI). In rats treated with NNN in the drinking water (7-500 ppm), py-py-dI was the major DNA adduct resulting from 5'-hydroxylation of NNN in vivo. Levels of py-py-dI in the lung and nasal cavity were the highest, consistent with the tissue distribution of CYP2A3. In rats treated with (S)-NNN or (R)-NNN, the ratios of formation of (R)-py-py-dI to (S)-py-py-dI were not the expected mirror image, suggesting that there may be a carrier for one of the unstable intermediates formed upon 5'-hydroxylation of NNN. Rat hepatocytes treated with (S)- or (R)-NNN or (2'S)- or (2'R)-5'-acetoxyNNN exhibited a pattern of adduct formation similar to that of live rats. In vitro studies with human liver S9 fraction or human hepatocytes incubated with NNN (2-500 μM) demonstrated that py-py-dI formation was greater than the formation of pyridyloxobutyl-DNA adducts resulting from 2'-hydroxylation of NNN. (S)-NNN formed more total py-py-dI adducts than (R)-NNN in human liver enzyme systems, which is consistent with the critical role of CYP2A6 in the 5'-hydroxylation of NNN in human liver. The results of this study demonstrate that the major DNA adduct resulting from NNN metabolism by human enzymes is py-py-dI and provide potentially important new insights into the metabolic activation of NNN in rodents and humans

  18. In vivo mutagenicity studies in rats mice and Chinese hamsters fed irradiated foodstuffs - chicken, fish, dates, pulses, mangoes and cocoa beans

    International Nuclear Information System (INIS)

    Three in vivo genetic toxicity tests were performed in rats, mice and Chinese hamsters to detect possible mutagenic effects of irradiated chicken, dried dates, fish, cocoa beans, pulses and mangoes. The tests employed were the micronucleus test and sister-chromatid exchange (SCE) test for irradiated and unirradiated samples of all foodstuffs listed, and the spermatogonia test, (including SCE technique) in mice for irradiated and unirradiated chicken, fish and dates only. In the case of cocoa beans, the mutagenicity tests were performed on an additional test group fed beans fumigated with ethylene oxide. The different mammalian species used for the various experiments are given below. None of the tests provided any evidence of mutagenicity induced by irradiation in any of the foodstuffs studied. Moreover, these tests are currently considered to be the most sensitive in vivo mutagenicity tests in mammals. (orig.)

  19. Toxicity and carcinogenicity of methyl isobutyl ketone in F344N rats and B6C3F1 mice following 2-year inhalation exposure

    International Nuclear Information System (INIS)

    Methyl isobutyl ketone (MIBK) is primarily used as a denaturant for rubbing alcohol, as a solvent and in the manufacture of methyl amyl alcohol. Inhalation of vapors is the most likely route of exposure in the work place. In order to evaluate the potential of MIBK to induce toxic and carcinogenic effects following chronic exposure, groups of 50 male and 50 female F344/N rats and B6C3F1 mice were exposed to MIBK at concentrations of 0, 450, 900, or 1800 ppm by inhalation, 6 h/day, 5 days per week for 2 years. Survival was decreased in male rats at 1800 ppm. Body weight gains were decreased in male rats at 900 and 1800 ppm and in female mice at 1800 ppm. The primary targets of MIBK toxicity and carcinogenicity were the kidney in rats and the liver in mice. In male rats, there was increased mineralization of the renal papilla at all exposure concentrations. The incidence of chronic progressive nephropathy (CPN) was increased at 1800 ppm and the severity was increased in all exposed groups. There were also increases in renal tubule hyperplasia at all exposure concentrations, and in adenoma and adenoma or carcinoma (combined) at 1800 ppm; these lesions are thought to represent a continuum in the progression of proliferative lesions in renal tubule epithelium. These increases may have resulted from the increased severity of CPN, either through α2μ-globulin-dependent or -independent mechanisms. An increase in mononuclear cell leukemia at 1800 ppm was an uncertain finding. Adrenal medulla hyperplasia was increased at 1800 ppm, and there was a positive trend for increases in benign or malignant pheochromocytomas (combined). In female rats, there were increases in the incidence of CPN in all exposure concentrations and in the severity at 1800 ppm, indicating that CPN was increased by mechanisms in addition to those related to α2μ-globulin. There were renal mesenchymal tumors, which have not been observed in historical control animals, in two female rats at 1800 ppm. The

  20. Toxicity and carcinogenicity of methyl isobutyl ketone in F344N rats and B6C3F1 mice following 2-year inhalation exposure.

    Science.gov (United States)

    Stout, Matthew D; Herbert, Ronald A; Kissling, Grace E; Suarez, Fernando; Roycroft, Joseph H; Chhabra, Rajendra S; Bucher, John R

    2008-02-28

    Methyl isobutyl ketone (MIBK) is primarily used as a denaturant for rubbing alcohol, as a solvent and in the manufacture of methyl amyl alcohol. Inhalation of vapors is the most likely route of exposure in the work place. In order to evaluate the potential of MIBK to induce toxic and carcinogenic effects following chronic exposure, groups of 50 male and 50 female F344/N rats and B6C3F1 mice were exposed to MIBK at concentrations of 0, 450, 900, or 1800ppm by inhalation, 6h/day, 5 days per week for 2 years. Survival was decreased in male rats at 1800ppm. Body weight gains were decreased in male rats at 900 and 1800ppm and in female mice at 1800ppm. The primary targets of MIBK toxicity and carcinogenicity were the kidney in rats and the liver in mice. In male rats, there was increased mineralization of the renal papilla at all exposure concentrations. The incidence of chronic progressive nephropathy (CPN) was increased at 1800ppm and the severity was increased in all exposed groups. There were also increases in renal tubule hyperplasia at all exposure concentrations, and in adenoma and adenoma or carcinoma (combined) at 1800ppm; these lesions are thought to represent a continuum in the progression of proliferative lesions in renal tubule epithelium. These increases may have resulted from the increased severity of CPN, either through alpha2micro-globulin-dependent or -independent mechanisms. An increase in mononuclear cell leukemia at 1800ppm was an uncertain finding. Adrenal medulla hyperplasia was increased at 1800ppm, and there was a positive trend for increases in benign or malignant pheochromocytomas (combined). In female rats, there were increases in the incidence of CPN in all exposure concentrations and in the severity at 1800ppm, indicating that CPN was increased by mechanisms in addition to those related to alpha2micro-globulin. There were renal mesenchymal tumors, which have not been observed in historical control animals, in two female rats at 1800ppm. The

  1. Multigeneration reproduction and carcinogenicity studies in Sprague-Dawley rats exposed topically to oxidative hair-colouring formulations containing p-phenylenediamine and other aromatic amines.

    Science.gov (United States)

    Burnett, C M; Goldenthal, E I

    1988-05-01

    Two-generation reproduction and chronic toxicity-carcinogenicity studies were conducted in Sprague-Dawley rats receiving topical applications of six oxidative hair-colouring formulations. These formulations were prepared as prototypes of permanent hair colourings using the base ingredients and primary intermediates and couplers most often used in this kind of product. Among the dyes included in the various formulations were p-phenylenediamine, p-toluenediamine, p-aminophenol, resorcinol, m-aminophenol, 1-naphthol, 2-amino-4-nitrophenol, 4-chlororesorcinol, p-aminodiphenylamine hydrochloride and N-methyl-p-aminophenol sulphate. The dye solutions were mixed with an equal volume of 6% hydrogen peroxide prior to application. In the reproduction study the samples were applied topically twice weekly throughout the growth, mating, gestation and lactation phases of the F0 parents to the weaning of the F1a and F2b litters. Fertility, gestation and foetal viability indices and body weights were evaluated for the six treatment groups and these were compared with the values for the three concurrent control groups. Weanlings selected from the F1a litters were the subjects for the lifetime carcinogenesis study. For 24 months they received twice-weekly topical applications of the same dyes as were administered to their parents. Clinical chemistry, haematological and urinalysis studies were performed at months 3, 12, 18 and 24, and five animals/sex/group were killed at month 12 and autopsied for histological examination of the rat tissues. All animals in the chronic study were evaluated for incidence of neoplastic and non-neoplastic lesions. In the reproduction phase the application of hair dyes had no adverse effect on the fertility of the males or females, or on gestation, lactation and weaning indices. The average number weaned per litter and the mean body weights of the weanlings were comparable among the treated and control groups. No treatment-related gross lesions were

  2. Overleeft de hamster?

    NARCIS (Netherlands)

    Apeldoorn, van R.C.; Klein Douwel, C.; Thomas, P.

    1999-01-01

    Een analyse van de achteruitgang van de hamster (Cricetus cricetus) in Europa en Limburg, de oorzaken (veranderingen in de landbouw; versnippering van leefgebieden), en oplossingsrichtingen voor een duurzaam overleven van de hamster in Limburg (kernpopulaties in duurzame populatienetwerken)

  3. Molecular biomarkers of oxidative stress associated with bromate carcinogenicity

    International Nuclear Information System (INIS)

    Potassium bromate (KBrO3) is a chemical oxidizing agent found in drinking water as a disinfection byproduct of surface water ozonation. Chronic exposures to KBrO3 cause renal cell tumors in rats, hamsters and mice and thyroid and testicular mesothelial tumors in rats. Experimental evidence indicates that bromate mediates toxicological effects via the induction of oxidative stress. To investigate the contribution of oxidative stress in KBrO3-induced cancer, male F344 rats were administered KBrO3 in their drinking water at multiple concentrations for 2-100 weeks. Gene expression analyses were performed on kidney, thyroid and mesothelial cell RNA. Families of mRNA transcripts differentially expressed with respect to bromate treatment included multiple cancer, cell death, ion transport and oxidative stress genes. Multiple glutathione metabolism genes were up-regulated in kidney following carcinogenic (400 mg/L) but not non-carcinogenic (20 mg/L) bromate exposures. 8-Oxodeoxyguanosine glycosylase (Ogg1) mRNA was up-regulated in response to bromate treatment in kidney but not thyroid. A dramatic decrease in global gene expression changes was observed following 1 mg/L compared to 20 mg/L bromate exposures. In a separate study oxygen-18 (18O) labeled KBrO3 was administered to male rats by oral gavage and tissues were analyzed for 18O deposition. Tissue enrichment of 18O was observed at 5 and 24 h post-KBr18O3 exposure with the highest enrichment occurring in the liver followed by the kidney, thyroid and testes. The kidney dose response observed was biphasic showing similar statistical increases in 18O deposition between 0.25 and 50 mg/L (equivalent dose) KBr18O3 followed by a much greater increase above 50 mg/L. These results suggest that carcinogenic doses of potassium bromate require attainment of a threshold at which oxidation of tissues occurs and that gene expression profiles may be predictive of these physiological changes in renal homeostasis

  4. Prepubertal exposure to cow’s milk reduces susceptibility to carcinogen-induced mammary tumorigenesis in rats

    OpenAIRE

    Nielsen, Tina S.; Khan, Galam; Davis, Jennifer; Michels, Karin B; Hilakivi-Clarke, Leena

    2011-01-01

    Cow’s milk contains high levels of estrogens, progesterone and insulin-like growth factor 1 (IGF-1), all of which are associated with breast cancer. We investigated whether prepubertal milk exposure affects mammary gland development and carcinogenesis in rats. Sprague Dawley rats were given either whole milk or tap water to drink from postnatal day (PND) 14 to PND 35, and thereafter normal tap water. Mammary tumorigenesis was induced by administering 7,12-dimethylbenz[a]anthracene (DMBA) on P...

  5. Inhibition of Rat 5α-Reductase Activity and Testosterone-Induced Sebum Synthesis in Hamster Sebocytes by an Extract of Quercus acutissima Cortex

    Directory of Open Access Journals (Sweden)

    Junichi Koseki

    2015-01-01

    Full Text Available Objective. Bokusoku (BK is an extract from the Quercus cortex used in folk medicine for treatment of skin disorders and convergence, and is present in jumihaidokuto, a traditional Japanese medicine that is prescribed for purulent skin diseases like acne vulgaris. The excess of sebum production induced by androgen is involved in the development of acne. Our aim is to examine whether BK and its constituents inhibit testosterone metabolism and testosterone-induced sebum synthesis. Methods. Measurements of 5α-reductase activity and lipogenesis were performed using rat liver microsomes and hamster sebocytes, respectively. Results. BK dose-dependently reduced the conversion of testosterone to a more active androgen, dihydrotestosterone in a 5α-reductase enzymatic reaction. Twenty polyphenols in BK categorized as gallotannin, ellagitannin, and flavonoid were identified by LC-MS/MS. Nine polyphenols with gallate group, tetragalloyl glucose, pentagalloyl glucose, eugeniin, 1-desgalloyl eugeniin, casuarinin, castalagin, stenophyllanin C, (−-epicatechin gallate, and (−-epigallocatechin gallate, inhibited testosterone metabolism. In particular, pentagalloyl glucose showed the strongest activity. BK and pentagalloyl glucose suppressed testosterone-induced lipogenesis, whereas they weakly inhibited the lipogenic action of insulin. Conclusions. BK inhibited androgen-related pathogenesis of acne, testosterone conversion, and sebum synthesis, partially through 5α-reductase inhibition, and has potential to be a useful agent in the therapeutic strategy of acne.

  6. Benzo[a]pyrene metabolites: formation in rat liver cell-culture lines, binding to macromolecules, and mutagenesis in V79 hamster cells

    International Nuclear Information System (INIS)

    Benzo[a]pyrene was metabolized in liver cell lines derived from BD-IV and BD-VI rats which included several chemically-transformed lines (IAR-6-1; IAR-19; IAR-28), one spontaneous transformant (IAR-27) as well as one nonmalignant line (IAR-20). Cultures were treated with tritiated benzo[a]pyrene over a 5-day period. The cells and medium were extracted with ethyl acetate and the distribution between organic-soluble and water-soluble metabolites determined. Organic-soluble metabolites consisting of dihydrodiols, phenols and quinones were determined by high-pressure liquid chromatography, and macromolecular binding of BP to each cell line was measured over a 24-h period. Comparisons between binding and overall metabolism were not directly proportional in these liver cell lines. However, there was a positive correlation for benzo[a]pyrene mutagenesis in the V-79 hamster cell assay with 8-azaguanine as a marker when the cell lines with the highest (IAR-20) and lowest (IAR-27) metabolic competence were used as activating cell layers

  7. Intrinsic denervation of the colon is associated with a decrease of some colonic preneoplastic markers in rats treated with a chemical carcinogen

    Directory of Open Access Journals (Sweden)

    M.V.O. Vespúcio

    2008-04-01

    Full Text Available Denervation of the colon is protective against the colon cancer; however, the mechanisms involved are unknown. We tested the hypothesis that the denervated colonic mucosa could be less responsive to the action of the chemical carcinogen dimethylhydrazine (DMH. Three groups of 32 male Wistar rats were treated as follows: group 1 (G1 had the colon denervated with 0.3 mL 1.5 mM benzyldimethyltetradecylammonium (benzalkonium chloride, BAC; G2 received a single ip injection of 125 mg/kg DMH; G3 was treated with BAC + the same dose and route of DMH. A control group (Sham, N = 32 did not receive any treatment. Each group was subdivided into four groups according to the sacrifice time (1, 2, 6, and 12 weeks after DMH. Crypt fission index, ß-catenin accumulated crypts, aberrant crypt foci, and cell proliferation were evaluated and analyzed by ANOVA and the Student t-test. G3 animals presented a small number of aberrant crypt foci and low crypt fission index compared to G2 animals after 2 and 12 weeks, respectively. From the second week on, the index of ß-catenin crypt in G3 animals increased slower than in G2 animals. From the 12th week on, G2 animals presented a significant increase in cell proliferation when compared to the other groups. Colonic denervation plays an anticarcinogenic role from early stages of colon cancer development. This finding can be of importance for the study of the role of the enteric nervous system in the carcinogenic process.

  8. Kinetic study on the metabolismofstyrol and styrol-7,8-oxide in hepatocytes of the rat, mouse and man as well as investigations into the carcinogenic effects of styrol and impulse ''white'' radiation in the rat

    International Nuclear Information System (INIS)

    In the first part of the study, comparative evaluations were carried out for kinetic parameters of the ST and SO metabolism in recently isolated hepatocytes from the rat, mouse and man. In order to additionally ascertain stereochemical influences on the metabolism studied, those kinetic parameters were determined for both the toxicologically more potent R(+)-SO and for racemic SO. It was also of interest whether data obtained in hepatocytes would be more suitable for calculations of the in vivo pharmacokinetics than the results from determinations in subcellular fractions. To elucidate this question, comparisons were carried out between kinetic parameters measured in hepatocytes and those examined in subcellular fractions and a physiologic model validated on the basis of in vivo data. In the second part, ST was investigated for carcinogenic effects using the ''Rat-Liver-Foci-Bioassay'' as a short-term carcinogenicity test. Tests of the initiating effects of ST were performed using a modified method adapted from the initiator-promoter model developed by Oesterle and Deml. Parallel irradiation experiments were carried out to obtain data for comparisons with the ''RAD equivalence concept''. (orig./MG)

  9. Combined effect of carcinogenic n-nitrosodimethylamine precursors and fractioned γ-irradiation on tumor development in rats

    International Nuclear Information System (INIS)

    The influence of combined action of N-nitrosodimethylamine (NDMA) and fractioned γ-irradiation on tumor development in rats was investigated. Both the tumor frequency and tumor plurality coefficient have been studied for two types of treatment: precursors of NDMA (amidopyrine and/or sodium nitrite (SN)) alone and the combination 'precursors plus radiation'. Tumor frequency decreased by about 11% after combination of γ-irradiation and precursors in comparison with precursors alone. Nevertheless, treatment with SN and γ-irradiation did not change tumor frequency in comparison with SN alone. Irradiation of rats treated with precursors led to an increased tumor plurality coefficient

  10. Morphological findings relating to the problem of cortex and medulla in the pineal glands of rat and hamster.

    OpenAIRE

    Heidbüchel, U; Vollrath, L.

    1983-01-01

    Because, in previous investigations on the rat pineal gland, karyometric studies of pinealocytes from cortical and medullary regions had yielded contradictory results, experiments were carried out to resolve this problem. In immersion-fixed, paraffin-embedded pineal glands, nuclear size of cortical regions was invariably larger than that in the medulla, the nuclear size clearly depending on the plane of sectioning. The differences between cortex and medulla were abolished in (a) pineal glands...

  11. Tissue distribution of the tobacco-specific carcinogen 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone and its metabolites in F344 rats

    International Nuclear Information System (INIS)

    The tissue distribution of the tobacco-specific N-nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), in the F344 rat was studied by whole-body autoradiography and high-performance liquid chromatography. The results of the wholebody autoradiography experiments indicate that the substance is able to freely cross biological membranes and reach all tissues of the body. A high level of tissue-bound metabolites occurred in the mucosa of the ethmoturbinates, in the lung, and the liver, which are the targets for the carcinogenicity of NNK in F344 rats. However, tissue-bound radioactivity was also present in non-target tissues such as the lateral nasal gland(Steno's gland), the tracheal mucosa, and the mucosa of the nasopharyngeal duct. A high level of unbound radioactivity occurred in the preputial gland, submaxillary and adrenal glands, and the urinary and gastrointestinal systems. High localization of unbound radioactivity was observed in the stomach lumen not only after p.o. but also after i.v. administration of NNK. Analysis of extracts of the stomach contents by high-performance liquid chromatography indicated that, due to their basicity, NNK and its metabolites were trapped in the gastric juice and later reabsorbed from the intestinal tract. Analysis of unbound metabolites in various tissues and in the urine after i.v. or p.o. administration of [carbonyl-14C]NNK indicated metabolism and excretion of products resulting from alpha-carbon hydroxylation, carbonyl reduction, and pyridine N-oxidation of NNK. In vitro autoradiography experiments showed that NNK is metabolized in the mucosa of the ethmoturbinates, the lung, and the liver, suggesting that the tumors are induced by metabolites formed locally in the target tissues. In the lung, the labeling was higher in the bronchial tree than in the lung parenchyma

  12. First Experimental Demonstration of the Multipotential Carcinogenic Effects of Aspartame Administered in the Feed to Sprague-Dawley Rats

    OpenAIRE

    Soffritti, Morando; Belpoggi, Fiorella; Esposti, Davide Degli; Lambertini, Luca; Tibaldi, Eva; Rigano, Anna

    2005-01-01

    The Cesare Maltoni Cancer Research Center of the European Ramazzini Foundation has conducted a long-term bioassay on aspartame (APM), a widely used artificial sweetener. APM was administered with feed to 8-week-old Sprague-Dawley rats (100–150/sex/group), at concentrations of 100,000, 50,000, 10,000, 2,000, 400, 80, or 0 ppm. The treatment lasted until natural death, at which time all deceased animals underwent complete necropsy. Histopathologic evaluation of all pathologic lesions and of all...

  13. Bioavailability of PCDDs and PCDFs adsorbed on fly ash in rat, guinea pig and Syrian golden hamster

    Energy Technology Data Exchange (ETDEWEB)

    van de Berg, M.; de Vroom, E.; van Greevenbroek, M.; Olie, K.

    1985-01-01

    In the environment PCDDs and PCDFs often occur in an adsorbed state in soil, sediment or combustion residues. Detailed information about physical, chemical and biological properties is available only for 2,3,7,8-TCDD and to a lesser extent for 2,3,7,8-TCDF. Information about the bioavailability of PCDDs and PCDFs in the adsorbed state is also very limited. The authors have reported earlier about the bioavailability of these compounds from fly ash in the rat. In this paper they report the bioavailability of these compounds from fly ash of a municipal incinerator in three animal species, during a one to three month feeding study.

  14. Androgen regulation of CYP4B1 responsible for mutagenic activation of bladder carcinogens in the rat bladder: detection of CYP4B1 mRNA by competitive reverse transcription-polymerase chain reaction.

    Science.gov (United States)

    Imaoka, S; Yoneda, Y; Sugimoto, T; Ikemoto, S; Hiroi, T; Yamamoto, K; Nakatani, T; Funae, Y

    2001-05-26

    Significant sex differences exist among cases of bladder cancer in humans as well as in experimental animals such as rats. Aromatic amines such as benzidine and 2-naphthylamine are known to induce bladder cancer. These carcinogenic amines are activated to genotoxic substances by cytochrome P 450 CYP4B1, which is present in bladder mucosa. In this study, regulation of CYP4B1 was investigated to elucidate sex difference in bladder carcinogenesis. Competitive reverse transcription-polymerase chain reaction was used to investigate the expression of rat CYP4B1 mRNA occurring in small amounts of tissue such as bladder tissue. Expression of CYP4B1 in the bladder of male rats increased with development but not in that of female rats. Moreover, mature male rats exhibited higher expression of CYP4B1 in the bladder than did mature female rats. Castration of male rats decreased CYP4B1 levels and treatment with testosterone led to a partial recovery of CYP4B1 levels. These results indicate that CYP4B1 levels in the rat bladder are partly regulated by androgens. Furthermore, the present findings suggest that the sex difference observed in bladder carcinogenesis was due to sex-different expression of CYP4B1 in bladder tissue. PMID:11311483

  15. Mode-of-Action Uncertainty for Dual-Mode Carcinogens: A Bounding Approach for Naphthalene-Induced Nasal Tumors in Rats Based on PBPK and 2-Stage Stochastic Cancer Risk Models

    Energy Technology Data Exchange (ETDEWEB)

    Bogen, K T

    2007-05-11

    A relatively simple, quantitative approach is proposed to address a specific, important gap in the appr approach recommended by the USEPA Guidelines for Cancer Risk Assessment to oach address uncertainty in carcinogenic mode of action of certain chemicals when risk is extrapolated from bioassay data. These Guidelines recognize that some chemical carcinogens may have a site-specific mode of action (MOA) that is dual, involving mutation in addition to cell-killing induced hyperplasia. Although genotoxicity may contribute to increased risk at all doses, the Guidelines imply that for dual MOA (DMOA) carcinogens, judgment be used to compare and assess results obtained using separate 'linear' (genotoxic) vs. 'nonlinear' (nongenotoxic) approaches to low low-level risk extrapolation. However, the Guidelines allow the latter approach to be used only when evidence is sufficient t to parameterize a biologically based model that reliably o extrapolates risk to low levels of concern. The Guidelines thus effectively prevent MOA uncertainty from being characterized and addressed when data are insufficient to parameterize such a model, but otherwise clearly support a DMOA. A bounding factor approach - similar to that used in reference dose procedures for classic toxicity endpoints - can address MOA uncertainty in a way that avoids explicit modeling of low low-dose risk as a function of administere administered or internal dose. Even when a 'nonlinear' toxicokinetic model cannot be fully validated, implications of DMOA uncertainty on low low-dose risk may be bounded with reasonable confidence when target tumor types happen to be extremely rare. This concept was i illustrated llustrated for a likely DMOA rodent carcinogen naphthalene, specifically to the issue of risk extrapolation from bioassay data on naphthalene naphthalene-induced nasal tumors in rats. Bioassay data, supplemental toxicokinetic data, and related physiologically based p

  16. Rodent Carcinogenicity Dataset

    OpenAIRE

    Fjodorova, Natalja; Novič, Marjana

    2013-01-01

    The rodent carcinogenicity dataset was compiled from the Carcinogenic Potency Database (CPDBAS) and was applied for the classification of quantitative structure-activity relationship (QSAR) models for the prediction of carcinogenicity based on the counter-propagation artificial neural network (CP ANN) algorithm. The models were developed within EU-funded project CAESAR for regulatory use. The dataset contains the following information: common information about chemicals (ID, chemical name, an...

  17. Studies on rat liver nuclear DNA damaged by chemical carcinogen (3'-Me DAB) and AP DNA endonuclease. II. Kinetic properties of AP DNA endonucleases in rat liver chromatin.

    OpenAIRE

    Y. S. Kim; Kim, J. W.; Lee, S. E.; Oh, S.H.(Department of Physics, Duke University, Durham, NC, United States)

    1990-01-01

    An experiment was designed to investigate the reaction mechanism of AP (apurinic or apyrimidinic) DNA endonucleases (APcI, APcII, APcIII) purified from rat liver chromatin. Sulfhydryl compounds (2-mercaptoethanol, dithiothreitol) brought about optimal activities of AP DNA endonucleases and N-ethylmaleimide or HgCl2 inhibited the enzyme activities, indicating the presence of sulfhydryl group at or near the active sites of the enzymes. Mg2+ was essential and 4mM of Mg2+ was sufficient for the o...

  18. Researchers exploring faster alternatives to 2-year test for carcinogenicity.

    OpenAIRE

    Schmidt, Charlie

    2006-01-01

    KEYWORDS - CLASSIFICATION: Animals;Animals,Laboratory;biomarkers of exposure & effect: validation;Carcinogenicity Tests;Carcinogens;Female;metabolism;methods;Male;Mice;Pharmaceutical Preparations;Predictive Value of Tests;Prognosis;Rats;standards;Species Specificity;trends;Time Factors;Tumor Markers,Biological;United States;United States Environmental Protection Agency;United States Food and Drug Administration.

  19. 3,2'-Dimethyl-4-aminobiphenyl-DNA adduct formation in tumor target and nontarget organs of rapid and slow acetylator Syrian hamsters cogenic at the NAT2 locus.

    Science.gov (United States)

    Feng, Y; Jiang, W; Deitz, A C; Hein, D W

    1996-10-01

    DNA adduct formation is an important step in initiation of the carcinogenic process. 3,2'-Dimethyl-4-aminobiphenyl (DMABP) is a well-documented multiorgan carcinogenic aromatic amine in rodents. In the present study, DMABP-DNA adduct levels were measured in rapid (Bio. 82.73/H-Pat(r)) and slow (Bio. 82.73/H-Pat(s)) acetylator Syrian hamsters congenic at the NAT2 locus following a single injection of 33 or 100 mg/kg body wt DMABP. Two DNA adducts, N-(deoxyguanosin-8-yl)-DMABP and 5-(deoxyguanosin-N2-yl)-DMABP, were identified and quantitated by 32P-postlabeling assay. After injection of 33 mg/kg, DMABP-DNA adducts were detected in urinary bladder at 6, 18, 24, and 48 hr with adduct levels increasing up to 48 hr postinjection. DMABP-DNA adducts were not detected in liver, colon, and heart. After injection of 100 mg/kg, DMABP-DNA adducts were detected in urinary bladder, liver, prostate, colon, and heart at 48 hr postinjection. DMABP-DNA adduct levels were significantly higher in urinary bladder (primary tumor target organ) than in the other organs of both rapid and slow acetylator congenic hamsters. N-(deoxyguanosin-8-yl)-DMABP levels were significantly higher in liver and prostate than in colon and heart of rapid and slow acetylator congenic hamsters, whereas 5-(deoxyguanosin-N2-yl)-DMABP levels were significantly higher in prostate than in colon and heart of rapid and slow acetylator congenic hamsters. DMABP-DNA adduct levels in each tissue examined did not differ significantly between rapid and slow acetylator hamsters following either 33 or 100 mg/kg injection. The tissue-dependent differences in DMABP-DNA adduct levels observed in the Syrian hamster differ from those reported in the rat and are consistent with previous studies that show DMABP induces primarily urinary bladder tumors in the Syrian hamster. PMID:8887447

  20. Lung Carcinogenic Bioassay of CuO and TiO2 Nanoparticles with Intratracheal Instillation Using F344 Male Rats

    OpenAIRE

    YOKOHIRA, MASANAO; Hashimoto, Nozomi; YAMAKAWA, KEIKO; Suzuki, Satoshi; Saoo, Kousuke; KUNO, TOSHIYA; Imaida, Katsumi

    2009-01-01

    Toxicity assessment of nanoparticles, now widespread in our environment, is an important issue. We have focused attention on the carcinogenic potential of copper oxide (CuO) and titanium dioxide (TiO2). In experiment 1, a sequential pilot study, the effectiveness of a carcinogenic bioassay featuring intraperitoneal injection (i.p.) of 20 mg 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) or 0.1% N-bis(2-hydroxypropyl)nitrosamine (DHPN) in drinking water for 2 weeks was examined. Based on...

  1. Subchronic inhalation of carbon tetrachloride alters the tissue retention of acutely inhaled plutonium-239 nitrate in F344 rats and syrian golden hamsters

    International Nuclear Information System (INIS)

    Carbon tetrachloride (CCl4) has been used extensively in the nuclear weapons industry, so it is likely that nuclear plant workers have been exposed to both CCl4 and plutonium compounds. Future exposures may occur during open-quotes cleanupclose quotes operations at weapons productions sites such as the Hanford, Washington, and Rocky Flats, Colorado, facilities. Inhalation of 20 and 100 ppm CCl4 by hamsters reduces uptake of 239Pu solubilized from lung, shunting the 239Pu to the skeleton

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

    DEFF Research Database (Denmark)

    1978-01-01

    was found in Chinese hamster V-79 cells when they were cocultivated with bronchial explants in the presence of BzaP. The proximate carcinogenic form of BzaP, the 7,8-diol [(+/-)-r7,t8-dihyroxy-7,8-dihydrobenzo[a]pyrene], was 5-fold more potent as a promutagen than the parent compound. Neither BzaP nor...

  3. Mode-of-Action Uncertainty for Dual-Mode Carcinogens:Lower Bounds for Naphthalene-Induced Nasal Tumors in Rats Implied byPBPK and 2-Stage Stochastic Cancer Risk Models

    Energy Technology Data Exchange (ETDEWEB)

    Bogen, K T

    2007-01-30

    As reflected in the 2005 USEPA Guidelines for Cancer Risk Assessment, some chemical carcinogens may have a site-specific mode of action (MOA) that is dual, involving mutation in addition to cell-killing induced hyperplasia. Although genotoxicity may contribute to increased risk at all doses, the Guidelines imply that for dual MOA (DMOA) carcinogens, judgment be used to compare and assess results obtained using separate ''linear'' (genotoxic) vs. ''nonlinear'' (nongenotoxic) approaches to low-level risk extrapolation. However, the Guidelines allow the latter approach to be used only when evidence is sufficient to parameterize a biologically based model that reliably extrapolates risk to low levels of concern. The Guidelines thus effectively prevent MOA uncertainty from being characterized and addressed when data are insufficient to parameterize such a model, but otherwise clearly support a DMOA. A bounding factor approach--similar to that used in reference dose procedures for classic toxicity endpoints--can address MOA uncertainty in a way that avoids explicit modeling of low-dose risk as a function of administered or internal dose. Even when a ''nonlinear'' toxicokinetic model cannot be fully validated, implications of DMOA uncertainty on low-dose risk may be bounded with reasonable confidence when target tumor types happen to be extremely rare. This concept was illustrated for the rodent carcinogen naphthalene. Bioassay data, supplemental toxicokinetic data, and related physiologically based pharmacokinetic and 2-stage stochastic carcinogenesis modeling results all clearly indicate that naphthalene is a DMOA carcinogen. Plausibility bounds on rat-tumor-type specific DMOA-related uncertainty were obtained using a 2-stage model adapted to reflect the empirical link between genotoxic and cytotoxic effects of the most potent identified genotoxic naphthalene metabolites, 1,2- and 1,4-naphthoquinone. Resulting

  4. Subchronic inhalation of carbon tetrachloride alters the tissue retention of acutely inhaled plutonium-239 nitrate in F344 rats and syrian golden hamsters

    Energy Technology Data Exchange (ETDEWEB)

    Benson, J.M.; Barr, E.B.; Lundgren, D.L. [and others

    1995-12-01

    Carbon tetrachloride (CCl{sub 4}) has been used extensively in the nuclear weapons industry, so it is likely that nuclear plant workers have been exposed to both CCl{sub 4} and plutonium compounds. Future exposures may occur during {open_quotes}cleanup{close_quotes} operations at weapons productions sites such as the Hanford, Washington, and Rocky Flats, Colorado, facilities. Inhalation of 20 and 100 ppm CCl{sub 4} by hamsters reduces uptake of {sup 239}Pu solubilized from lung, shunting the {sup 239}Pu to the skeleton.

  5. Critical analysis of carcinogenicity study outcomes. Relationship with pharmacological properties.

    Science.gov (United States)

    van der Laan, Jan Willem; Kasper, Peter; Silva Lima, Beatriz; Jones, David R; Pasanen, Markku

    2016-08-01

    Predicting the outcome of life-time carcinogenicity studies in rats based on chronic (6-month) toxicity studies in this species is possible in some instances. This should reduce the number of such studies and hence have a significant impact on the total number of animals used in safety assessment of new medicines. From a regulatory perspective, this should be sufficient to grant a waiver for a carcinogenicity study in those cases where there is confidence in the outcome of the prediction. Pharmacological properties are a frequent key factor for the carcinogenic mode of action of some pharmaceuticals, but data-analysis on a large dataset has never been formally conducted. We have conducted an analysis of a dataset based on the perspective of the pharmacology of 255 compounds from industrial and regulatory sources. It is proposed that a pharmacological, class-specific, model may consist of an overall causal relationship between the pharmacological class and the histopathology findings in rats after 6 months treatment, leading to carcinogenicity outcome after 2 years. Knowledge of the intended drug target and pathway pharmacology should enhance the prediction of either positive or negative outcomes of rat carcinogenicity studies. The goal of this analysis is to review the pharmacological properties of compounds together with the histopathology findings from the chronic toxicity study in rodents in order to introduce an integrated approach to estimate the risk of human carcinogenicity of pharmaceuticals. This approach would allow scientists to define conditions under which 2-year rat carcinogenicity studies will or will not add value to such an assessment. We have demonstrated the possibility of a regulatory waiver for a carcinogenicity study in rats, as currently discussed in the International Council for Harmonization (ICH) - formerly known as the International Conference on Harmonization (ICH), by applying the proposed prediction approach in a number of case studies

  6. Influence of normal epithelial cells on the development and expression of the neoplastic phenotype in carcinogen exposed rat tracheal epithelial cells

    International Nuclear Information System (INIS)

    An inhibitory effect of normal epithelial cells on both preneoplastic and neoplastic tracheal epithelial cells using a cell culture as well as an in vivo model has been demonstrated. It is not clear at present whether inhibition observed in vivo in reconstructed tracheal mucosa occurs via the same mechanism as that occurring in intact carcinogen-exposed tracheal transplants, or whether the inhibition observed in cell culture shares any common mechanism with inhibition observed in cell co-cultures or in conditioned medium experiments. They are currently carrying out experiments designed to examine and elucidate these unresolved questions

  7. Histomorphological and histomorphometrical investigations of early bone damage following incorporation of optimal carcinogenic doses of 239-plutonium in male rats of different age

    International Nuclear Information System (INIS)

    There is early damage to bone at small carcinogenic amounts of the nuclide, including heavy defects of bone structure and bone marrow osteoporotic features of trabecular bone and only histomorphometrically detectable changes in bone metabolism. The dependence of radiation dose to skeleton and the spacial distribution of the nuclide on age and growth of the experimental animals is demonstrated and correlated to the histological findings. It is also shown that growth and metabolism parameters of bone influence the decorporation performance of the chelating agent Zn-DTPA. (orig.)

  8. Understanding arsenic carcinogenicity by the use of animal models

    International Nuclear Information System (INIS)

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

  9. Beryllium: genotoxicity and carcinogenicity

    International Nuclear Information System (INIS)

    Beryllium (Be) has physical-chemical properties, including low density and high tensile strength, which make it useful in the manufacture of products ranging from space shuttles to golf clubs. Despite its utility, a number of standard setting agencies have determined that beryllium is a carcinogen. Only a limited number of studies, however, have addressed the underlying mechanisms of the carcinogenicity and mutagenicity of beryllium. Importantly, mutation and chromosomal aberration assays have yielded somewhat contradictory results for beryllium compounds and whereas bacterial tests were largely negative, mammalian test systems showed evidence of beryllium-induced mutations, chromosomal aberrations, and cell transformation. Although inter-laboratory differences may play a role in the variability observed in genotoxicity assays, it is more likely that the different chemical forms of beryllium have a significant effect on mutagenicity and carcinogenicity. Because workers are predominantly exposed to airborne particles which are generated during the machining of beryllium metal, ceramics, or alloys, testing of the mechanisms of the mutagenic and carcinogenic activity of beryllium should be performed with relevant chemical forms of beryllium

  10. Carcinogenic risks of radiations

    International Nuclear Information System (INIS)

    Ionising radiations are known since the end of the 19th century. Early, after being discovered, they were applied in Medicine and the association with an increased number of different malignant tumors was proved. This paper presents a literature review concerning epidemiological proof of radiation induced cancer, molecular mechanisms and factors that increase or decrease the carcinogenic action of ionizing radiations

  11. Carcinogens formed when Meat is Cooked

    Energy Technology Data Exchange (ETDEWEB)

    Felton, J S; Salmon, C P; Knize, M G

    2003-05-30

    Diet has been associated with varying cancer rates in human populations for many years, yet the causes of the observed variation in cancer patterns have not been adequately explained (Wynder et al. 1977). Along with the effect of diet on human cancer incidence is the strong evidence that mutations are the initiating events in the cancer process (Vogelstein et al. 1992). Foods, when heated, are a good source of genotoxic carcinogens that very likely are a cause for some of these events(Doll et al. 1981). These carcinogens fall into two chemical classes: heterocyclic aromatic amines (HAA) and polycyclic aromatic hydrocarbons (PAH). There is ample evidence that many of these compounds are complete carcinogens in rodents(El-Bayoumy et al. 1995; Ohgaki et al. 1991). Heterocyclic aromatic amines are among the most potent mutagenic substances ever tested in the Ames/Salmonella mutagenicity test (Wakabayashi et al. 1992). Both classes of carcinogen cause tumors in rodents at multiple sites, (El-Bayoumy et al. 1995; Ohgaki et al. 1991) many of which are common tumor sites in people on a Western diet. An HAA, PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine), and a PAH, B[a]P (benzo[a]pyrene), of comparable carcinogenic potency caused mammary gland tumors in a feeding study in female rats (El-Bayoumy et al. 1995). In addition, PhIP has recently been shown to cause carcinomas in the prostate of the male rat (Shirai et al. 1997). Complementing the rodent cancer studies are numerous human case-control and prospective studies suggesting a relationship between overheated beef, chicken, and lamb, and cancer of the colon, breast, prostate, and stomach (Sinha et al. 1999; Ward et al. 1997; Zheng et al. 1998).

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

    DEFF Research Database (Denmark)

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

    2011-01-01

    We investigated whether maternal exposure during pregnancy to cow's milk containing endogenous estrogens and insulin like growth factor 1 (IGF-1) and either high or low levels of isoflavones from dietary legumes (HIM and LIM, respectively) affected carcinogen-induced mammary carcinogenesis in......, offspring exposed to LIM in utero, did not exhibit increased breast cancer risk, despite having higher estradiol and IGF-1 environment and consequently earlier puberty onset. These results indicate that the phytochemical content in the cow's milk, consumed by a pregnant dam, determines how milk affects the...... differences in maternal serum estradiol (P = 0.19) and IGF-1 levels (P = 0.15) at GD 19 or birth weight among the milk and water groups were seen, but estradiol, and IGF-1 levels and birth weight were numerically higher in the LIM than in the HIM group. Puberty onset occurred earlier in the LIM offspring than...

  13. Modifying effects of 1,2-dichloropropane on N-nitrosobis(2-oxopropyl)amine-induced cholangiocarcinogenesis in male Syrian hamsters.

    Science.gov (United States)

    Gi, Min; Fujioka, Masaki; Yamano, Shotaro; Shimomura, Eri; Kanki, Masayuki; Kawachi, Satoko; Tachibana, Hirokazu; Tatsumi, Kumiko; Fang, He; Ishii, Naomi; Kakehashi, Anna; Wanibuchi, Hideki

    2015-01-01

    Based on the findings of epidemiological studies in Japan that occupational exposure to 1,2-dichloropropane (1,2-DCP) was associated with increased cholangiocarcinomas, 1,2-DCP has recently been classified as being carcinogenic to humans (Group 1). However, the cholangiocarcinogenicity of 1,2-DCP has not been demonstrated experimentally, and it was negative for cholangiocarcinogenicity in rats and mice. The present study determined the effects of 1,2-DCP on N-nitrosobis(2-oxopropyl)amine (BOP)-induced cholangiocarcinogenesis in male hamsters. We found that 1,2-DCP did not enhance the development of BOP-induced atypical biliary hyperplasia and did not induce any lesions in liver bile duct when administered alone. Notably, 1,2-DCP had no effect on the proliferative activity of bile duct epithelial cells regardless of BOP-initiation. These results demonstrate that 1,2-DCP lacks promoting effects on BOP-induced cholangiocarcinogenesis and suggest the possibility that 1,2-DCP is not cholangiocarcinogenic to the hamster in the present model. In addition, 1,2-DCP also lacks promoting effects on pancreatic, lung, and renal carcinogenesis. As the occurrence of occupational cholangiocarcinomas in Japan might be attributed to exposure to multiple chemicals, the results of the present study indicate that it will be necessary to determine the cholangiocarcinogenic effects of concurrent exposure of 1,2-DCP and the other halogen solvents to which workers with cholangiocarcinomas were exposed. PMID:26354381

  14. Chemistry of carcinogenic metals.

    OpenAIRE

    Martell, A E

    1981-01-01

    The periodic distribution of known and suspected carcinogenic metal ions is described, and the chemical behavior of various types of metal ions is explained in terms of the general theory of hard and soft acids and bases. The chelate effect is elucidated, and the relatively high stability of metal chelates in very dilute solutions is discussed. The concepts employed for the chelate effect are extended to explain the high stabilities of macrocyclic and cryptate complexes. Procedures for the us...

  15. The carcinogenicity of chromium

    OpenAIRE

    Norseth, Tor

    1981-01-01

    The carcinogenicity of chromium compounds is reviewed with specific attention to the gaps in knowledge for risk estimation and research needs. The most important problems at present are whether trivalent chromium compounds cause cancer, and whether there is a difference in cancer causing effects between the soluble and the slightly soluble hexavalent compounds in the practical exposure situation. Dose estimates for risk estimation based on epidemiological investigations are also lacking. Pres...

  16. Carcinogen risk assessment

    International Nuclear Information System (INIS)

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

  17. EFFECTS OF STRAIN, SEX, ROUTE OF ADMINISTRATION AND PARTIAL HEPATECTOMY ON THE INDUCTION BY CHEMICAL CARCINOGENS OF GAMMA-GLUTAMYLTRANSPEPTIDASE FOCI IN RAT LIVER

    Science.gov (United States)

    The incidence of gamma-glutamyltranspeptidase (GGT)-positive foci induced by 0.3 mmol/kg diethylnitrosamine (DENA) followed by promotion with 500 ppm sodium phenobarbital in drinking water and was the same in Fischer 344, Sprague-Dawley and Wistar-Lewis rats. There was no differe...

  18. Covalent binding of food carcinogens MeIQx, MeIQ and IQ to DNA and protein in microsomal incubations and isolated rat hepatocytes

    Energy Technology Data Exchange (ETDEWEB)

    Wallin, H.; Holme, J.A.; Alexander, J. (National Institute of Public Health, Department of Environmental Medicine, Oslo (Norway))

    1992-01-01

    The metabolic activation of {sup 14}C-labelled food carcinogens 2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline (MeIQx),2-amino-3,4-dimethylimidazo(4,5-f)quinoline(MeIQ) and 2-amino-3-methylimidazo(4,5-f)quinoline (IQ) to macromolecular bound species was studied in microsomal and hepatocellular incubations. Several data indicated that the covalent binding was dependent on P450 enzymes: It was dependent on NADPH, it was induced many times by the P450 IA1 and IA2 upregulators {beta}-naphthoflavone and polychlorinated biphenyls, and was inhibited by the P450 IA1 and IA2 inhibitor {alpha}-naphtoflavone. In both hepatocellular and microsomal incubations the three compounds bound with similar efficiency, with IQ being somewhat more potent compared to MeIQx and MeIQ. The binding appeared to follow saturation kinetics with K{sub m} values less than 20 {mu}M. In incubations with hepatocytes the compounds bound to both cellular DNA and to bovine serum albumin in the medium. The fact that 13-26% of total adducts were formed with bovine serum albumin, indicates that reactive metabolites of the compounds may be transported and react at distant sites from their formation without any further activation. (au).

  19. Covalent binding of food carcinogens MeIQx, MeIQ and IQ to DNA and protein in microsomal incubations and isolated rat hepatocytes

    International Nuclear Information System (INIS)

    The metabolic activation of 14C-labelled food carcinogens 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx),2-amino-3,4-dimethylimidazo[4,5-f]quinoline(MeIQ) and 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) to macromolecular bound species was studied in microsomal and hepatocellular incubations. Several data indicated that the covalent binding was dependent on P450 enzymes: It was dependent on NADPH, it was induced many times by the P450 IA1 and IA2 upregulators β-naphthoflavone and polychlorinated biphenyls, and was inhibited by the P450 IA1 and IA2 inhibitor α-naphtoflavone. In both hepatocellular and microsomal incubations the three compounds bound with similar efficiency, with IQ being somewhat more potent compared to MeIQx and MeIQ. The binding appeared to follow saturation kinetics with Km values less than 20 μM. In incubations with hepatocytes the compounds bound to both cellular DNA and to bovine serum albumin in the medium. The fact that 13-26% of total adducts were formed with bovine serum albumin, indicates that reactive metabolites of the compounds may be transported and react at distant sites from their formation without any further activation. (au)

  20. Effects of a probiotic soy product and physical exercise on formation of pre-neoplastic lesions in rat colons in a short-term model of carcinogenic

    Directory of Open Access Journals (Sweden)

    Rossi Elizeu A

    2009-08-01

    Full Text Available Abstract Purpose In this study the influence of moderate or intense physical exercise, alone or in combination with the consumption of a soya product fermented with Enterococcus faecium, on the development of colon cancer induced chemically in rats with 1,2-dimethylhydrazine (DMH, was investigated. Methods Eighty male Wistar SPF rats were randomly allocated to 8 groups (n = 10. One week after the start of the program of product ingestion and/or physical activity, all animals except the controls (group I were injected subcutaneously with 50 mg/kg b.w. of 1,2-dimethylhydrazine (DMH. This procedure was repeated at the end of the second week. At the end of the 6-week experiment, all the animals were euthanized; the colons were removed and numbers of ACF was estimated. Results Twenty-four days after the induction of pre-neoplastic lesions, it was evident that the formation of ACF was not significantly reduced by the ingestion of the fermented product, by intense or moderate physical activity or by a combination of these factors, in comparison with the positive control group of rats (p Conclusion The results reported in this article show that consumption of the fermented soy product described here and the practice of physical exercise (intense or moderate were incapable, separately or combined, of inhibiting the formation of ACF in DMH-induced rats. The intense physical exercise led to an increased number of foci in the colons of these rats and, probably, to greater susceptibility to colorectal cancer.

  1. Food derived carcinogenic amnoimidazoazaarenes

    DEFF Research Database (Denmark)

    Frandsen, Henrik

    Carcinogenic aminoimidazoazaarenes are formed during cooking of meat and fish. Important factors for the formation of these compounds are meat type, cooking temperature and time. The compounds are genotoxic in bacterial and mammalian cells. In animal feeding studies the compounds tested so far were...... adducts with DNA. Adducts with 2-deoxyguanosine have been characterized for a number of aminoimidazoazaarenes. Adducts with DNA have also been found in animals after exposure to these compounds. In \\:iw major metabolic detoxification pathways are ring hydroxylation followed by conjugation and conjugation...... of the exocyclic amino group. Estimations of human cancer risk have indicated that ingestion of food containing aminoimidazoazaarenes are of importance....

  2. Expression of thioredoxin during progression of hamster and human cholangiocarcinoma.

    Science.gov (United States)

    Yoon, Byung-Il; Kim, Yeong-Hun; Yi, Jung-Yeon; Kang, Min-Soo; Jang, Ja-June; Joo, Kyoung-Hwan; Kim, Yongbaek; McHugh Law, J; Kim, Dae-Yong

    2010-01-01

    Thioredoxin (Trx) is a multifunctional redox protein that has growth-promoting and anti-apoptotic effects on cells and protects cells from endogenous and exogenous free radicals. Recently, altered expression of Trx has been reported in various cancers. In the present study, we investigated altered expression of Trx at the precancerous and carcinogenic phases during cholangiocarcinogenesis in a hamster cholangiocarcinoma (ChC) model, using semiquantitative immunohistochemical and Western blot analyses. Moreover, to determine if the results correlated well with those in human ChCs, we carried out a comparative immunohistochemical study for Trx in tissue-arrayed human ChCs with different grades of tumor cell differentiation. Trx was found highly expressed in the cytoplasm of dysplastic bile ducts with highly abnormal growth patterns and ChCs irrespective of tumor type or tumor cell differentiation. Overexpression of Trx at the precancerous and carcinogenic phases was further supported by significant elevation of Trx protein in Western blotting. The results from the hamster ChCs were in good agreement with those from human ChCs. Our results strongly suggested that the redox regulatory function of Trx plays an important role in bile duct cell transformation and tumor progression during cholangiocarcinogenesis. PMID:19799607

  3. Conversion of Suspected Food Carcinogen 5-Hydroxymethylfurfural by Sulfotransferases and Aldehyde Dehydrogenases in Postmitochondrial Tissue Preparations of Humans, Mice, and Rats.

    Science.gov (United States)

    Sachse, Benjamin; Meinl, Walter; Glatt, Hansruedi; Monien, Bernhard H

    2016-01-01

    The food contaminant 5-hydroxymethylfurfural (HMF) is formed by heat- and acid-catalyzed reactions from carbohydrates. More than 80% of HMF is metabolized by oxidation of the aldehyde group in mice and rats. Sulfo conjugation yields mutagenic 5-sulfoxymethylfurfural, the probable cause for the neoplastic effects observed in HMF-treated rodents. Considerable metabolic differences between species hinder assessing the tumorigenic risk associated with human dietary HMF uptake. Here, we assayed HMF turnover catalyzed by sulfotransferases or by aldehyde dehydrogenases (ALDHs) in postmitochondrial preparations from liver, kidney, colon, and lung of humans, mice, and rats. The tissues-specific clearance capacities of HMF sulfo conjugation (CL(SC)) and ALDH-catalyzed oxidation (CL(OX)) were concentrated to the liver. The hepatic clearance CL(SC) in mice (males: 487 µl/min/kg bw, females: 2520 µl/min/kg bw) and rats (males: 430 µl/min/kg bw, females: 198 µl/min/kg bw) were considerably higher than those in humans (males: 21.2 µl/min/kg bw, females: 32.2 µl/min/kg bw). The ALDH-related clearance rates CLOX in mice (males: 3400 ml/min/kg bw, females: 1410 ml/min/kg bw) were higher than those of humans (males: 436 ml/min/kg bw, females: 646 ml/min/kg bw) and rats (males: 627 ml/min/kg bw, females: 679 ml/min/kg bw). The ratio of CL(OX) to CL(SC) was lowest in female mice. This finding indicated that HMF sulfo conjugation was most substantial in the liver of female mice, a target tissue for HMF-induced neoplastic effects, and that humans may be less sensitive regarding HMF sulfo conjugation compared with the rodent models. PMID:26454887

  4. Experimental pathologic observation on chronic toxicity and carcinogenicity of pesticide pyraflufen-ethyl in rats%吡草醚原药大鼠慢性毒性与致癌试验病理观察

    Institute of Scientific and Technical Information of China (English)

    裴兰洁; 郑艳华; 杨文祥; 刘瑶; 郏自明

    2013-01-01

    目的 通过病理学观察探讨吡草醚原药对大鼠的慢性毒性与致癌作用.方法 按照GB15670-1995《农药登记毒理学试验方法》进行大鼠慢性毒性与致癌性合并试验,样本经10%中性福尔马林固定,脱水,石蜡包埋,切片,HE染色,树胶封固,光镜检查.结果 慢性毒性实验高剂量组肾小管上皮细胞变性高于对照组,与对照组之间有极显著性差异(P≤0.01);中剂量组肾脏间质炎高于对照组,与对照组之间有显著性差异(P≤0.05);低剂量组肾脏病理变化与对照组之间无显著性差异.其他病变各组之间均无显著性差异.致癌性试验,肿瘤发生率统计学上无显著性差异.该受试物对肿瘤的潜伏期没有影响;多发性肿瘤的发生各组之间没有差异.结论 未发现该药物对SD大鼠的致癌性.慢性毒性表现出一定的雌雄差异,肾脏是其主要靶器官.%Objective To explore the chronic toxicity and carcinogenicity of pesticide pyraflufen-ethyl in rats.Methods According to National Standards of "Toxicological Methods of Pesticides for Registration" (GB15670-1995 of PRC),chronic toxicity tests and carcinogenicity tests were conducted.These samples were fixed in 10% neutral formalin firstly.Then the samples were embedded in paraffin after dehydration process.Afterward,the samples were sectioned and stained by hematoxylin-eosin(HE) staining.Finally,the sections were cemented by gum and observed in light microscope.Results Chronic toxicity tests revealed that the degeneration ratio of renal tubular epithelial cells in high dosage group was significantly increased comparing to control group (P ≤ 0.01).Furthermore,the middle dosage group results showed there was a similar increasing in the proportion of tubulointerstitial nephritis (P≤0.05),however,there were no evident renal pathology differences between low dosage group and control group.In addition,other pathological changes in any dosage group were not

  5. The hamster cheek pouch model for field cancerization studies.

    Science.gov (United States)

    Monti-Hughes, Andrea; Aromando, Romina F; Pérez, Miguel A; Schwint, Amanda E; Itoiz, Maria E

    2015-02-01

    External carcinogens, such as tobacco and alcohol, induce molecular changes in large areas of oral mucosa, which increase the risk of malignant transformation. This condition, known as 'field cancerization', can be detected in biopsy specimens using histochemical techniques, even before histological alterations are identified. The efficacy of these histochemical techniques as biomarkers of early cancerization must be demonstrated in appropriate models. The hamster cheek pouch oral cancer model, universally employed in biological studies and in studies for the prevention and treatment of oral cancer, is also an excellent model of field cancerization. The carcinogen is applied in solution to the surface of the mucosa and induces alterations that recapitulate the stages of cancerization in human oral mucosa. We have demonstrated that the following can be used for the early detection of cancerized tissue: silver staining of nucleolar organizer regions; the Feulgen reaction to stain DNA followed by ploidy analysis; immunohistochemical analysis of fibroblast growth factor-2, immunohistochemical labeling of proliferating cells to demonstrate an increase of epithelial cell proliferation in the absence of inflammation; and changes in markers of angiogenesis (i.e. those indicating vascular endothelial growth factor activity, endothelial cell proliferation and vascular density). The hamster cheek pouch model of oral cancer was also proposed and validated by our group for boron neutron capture therapy studies for the treatment of oral cancer. Clinical trials of this novel treatment modality have been performed and are underway for certain tumor types and localizations. Having demonstrated the efficacy of boron neutron capture therapy to control tumors in the hamster cheek pouch oral cancer model, we adapted the model for the long-term study of field cancerized tissue. We demonstrated the inhibitory effect of boron neutron capture therapy on tumor development in field

  6. In vitro metabolism of 2,2',3,4',5,5',6-heptachlorobiphenyl(CB187) with liver microsomes of rats, hamsters and guinea pigs

    Energy Technology Data Exchange (ETDEWEB)

    Koga, N.; Ohta, C.; Kanamaru, T. [Nakamura Gakuen Univ., Fukuoka (Japan); Haraguchi, K. [Daiichi Coll. of Pharmaceutical Sciences, Fukuoka (Japan); Kato, Y.; Yamada, S. [Univ. of Shizuoka, Shizuoka (Japan)

    2004-09-15

    PCB congeners possess extremely high lipophilicity and biological stability, and as a result they are not easily eliminated from the body once ingested. In particular, not only 2,4,5-trichlorosubstituted but also 6 or more chlorine-substituted PCBs such as 2,2',3',4,4',5-hexa-chlorobiphenyl (hexaCB) (CB138), 2,2',4,4',5,5'-hexaCB (CB153), 2,2',3,4,4',5,5'-heptachloro-biphenyl (heptaCB) (CB180) and 2,2',3,4',5,5',6-heptaCB (CB187) have been detected in blood and adipose tissues of mammals and human mother's milk at higher concentration. In addition, the 4-hydroxy (OH)-metabolite of CB187 has been reported to be present in human blood at the highest concentration of that derived from other PCB congeners. Although CB187, a tri-ortho-PCB, is one of the minor component in the commercial PCB preparations such as Clophen, Aroclor and Kanechlor, the toxic equivalency factor (TEF) which is used for dioxin-like PCB congeners including coplanar-PCBs and mono-ortho-PCBs to assess the potency of the toxicity has not been set up for di- and tri-ortho-PCB congeners. These facts indicate that 4-OH-PCB187 become more persistent and more important toxicologically than the parent CB187. However, there is little report about biotransformation in vivo or in vitro of CB187 in animals. Therefore, we examined CB187 metabolism by liver microsomes of rats, hamsters and guinea pigs.

  7. Different effects of short- and long-chained fructans on large intestinal physiology and carcinogen-induced aberrant crypt foci in rats

    DEFF Research Database (Denmark)

    Poulsen, Morten; Molck, Anne-Marie; Jacobsen, Bodil Lund

    2002-01-01

    the development of ACF: microflora, short-chain fatty acids, pH, and cell proliferation. A 3-wk pretreatment period with both fructans was included. Feeding the long-chained fructan (5% or 15%) significantly inhibited the numbers of small and total ACF after 5 and 10 wk. The short-chained fructan (15......-type fructan on 1,2-dimethylhydrazine dihydrochloride-induced aberrant crypt foci (ACF) in the rat colon. In addition, the present study investigated the influence of chain length, dietary level (5% or 15%), and duration of feeding (5 or 10 wk) on the following intestinal parameters supposed to be involved in...

  8. COMPLEMENTARITY OF GENOTOXIC AND NONGENOTOXIC PREDICTORS OF RODENT CARCINOGENICITY

    Science.gov (United States)

    Twenty-one chemicals known to be carcinogenic in rodent bioassays were selected for study. he chemicals were administered by gavage in two dose levels to female Sprague-Dawley rats. he effects of these 21 chemicals on four biochemical assays (hepatic DNA damage by alkaline elutio...

  9. Arsenic Is A Genotoxic Carcinogen

    Science.gov (United States)

    Arsenic is a recognized human carcinogen; however, there is controversy over whether or not it should be considered a genotoxic carcinogen. Many possible modes of action have been proposed on how arsenic induces cancer, including inhibiting DNA repair, altering methylation patter...

  10. Different effects of short- and long-chained fructans on large intestinal physiology and carcinogen-induced aberrant crypt foci in rats.

    Science.gov (United States)

    Poulsen, Morten; Mølck, Anne-Marie; Jacobsen, Bodil Lund

    2002-01-01

    Inulin-type fructans, which are nondigestible carbohydrates, have been shown to modulate the number of induced preneoplastic lesions in the colon as well as the colonic microflora in laboratory animals. The present study was designed to investigate the effect of a short- and long-chained inulin-type fructan on 1,2-dimethylhydrazine dihydrochloride-induced aberrant crypt foci (ACF) in the rat colon. In addition, the present study investigated the influence of chain length, dietary level (5% or 15%), and duration of feeding (5 or 10 wk) on the following intestinal parameters supposed to be involved in the development of ACF: microflora, short-chain fatty acids, pH, and cell proliferation. A 3-wk pretreatment period with both fructans was included. Feeding the long-chained fructan (5% or 15%) significantly inhibited the numbers of small and total ACF after 5 and 10 wk. The short-chained fructan (15%) inhibited the number of small and total ACF after 5 and 10 wk but significantly increased the numbers of medium and large ACF after 10 wk. In conclusion, the effect on ACF outcome was influenced by the chain length of the fructans. PMID:12416260

  11. Oxidative Stress in the Carcinogenicity of Chemical Carcinogens

    Directory of Open Access Journals (Sweden)

    Hideki Wanibuchi

    2013-10-01

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

  12. Oxidative Stress in the Carcinogenicity of Chemical Carcinogens

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-10-28

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

  13. Oxidative Stress in the Carcinogenicity of Chemical Carcinogens

    International Nuclear Information System (INIS)

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

  14. New clues on carcinogenicity-related substructures derived from mining two large datasets of chemical compounds.

    Science.gov (United States)

    Golbamaki, Azadi; Benfenati, Emilio; Golbamaki, Nazanin; Manganaro, Alberto; Merdivan, Erinc; Roncaglioni, Alessandra; Gini, Giuseppina

    2016-04-01

    In this study, new molecular fragments associated with genotoxic and nongenotoxic carcinogens are introduced to estimate the carcinogenic potential of compounds. Two rule-based carcinogenesis models were developed with the aid of SARpy: model R (from rodents' experimental data) and model E (from human carcinogenicity data). Structural alert extraction method of SARpy uses a completely automated and unbiased manner with statistical significance. The carcinogenicity models developed in this study are collections of carcinogenic potential fragments that were extracted from two carcinogenicity databases: the ANTARES carcinogenicity dataset with information from bioassay on rats and the combination of ISSCAN and CGX datasets, which take into accounts human-based assessment. The performance of these two models was evaluated in terms of cross-validation and external validation using a 258 compound case study dataset. Combining R and H predictions and scoring a positive or negative result when both models are concordant on a prediction, increased accuracy to 72% and specificity to 79% on the external test set. The carcinogenic fragments present in the two models were compared and analyzed from the point of view of chemical class. The results of this study show that the developed rule sets will be a useful tool to identify some new structural alerts of carcinogenicity and provide effective information on the molecular structures of carcinogenic chemicals. PMID:26986491

  15. Is peroxisome proliferation an obligatory precursor step in the carcinogenicity of di(2-ethylhexyl)phthalate (DEHP)?

    OpenAIRE

    Melnick, R L

    2001-01-01

    Di(2-ethylhexyl)phthalate (DEHP), a peroxisome proliferator, has been listed by the International Agency for Research on Cancer (IARC) and by the National Toxicology Program as a possible or reasonably anticipated human carcinogen because it induces dose-related increases in liver tumors in both sexes of rats and mice. Recently, the suggestion has been advanced that DEHP should be considered unlikely to be a human carcinogen because it is claimed that the carcinogenic effects of this agent in...

  16. Carcinogenicity/tumour promotion by NDL PCB

    Energy Technology Data Exchange (ETDEWEB)

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

    2004-09-15

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

  17. N,N'-dimethylnitrosourea-induced tumors in mice and Syrian hamsters

    Directory of Open Access Journals (Sweden)

    Hiraki,Shunkichi

    1974-10-01

    Full Text Available Carcinogenic effect of N, N'-dimethylnitrosourea (DMNU on mice and hamsters was studied. Repeated subcutaneous injections of DMNU resulted in the induction of malignant lymphomas with an incidence of 100 per cent in adult C3HjBifBjKi mice and induced malignant tumors of forestomach, mammary gland and uterus with a high incidence in adult hamsters. Control animals showed no pathological changes. Electron microscopy revealed the presence of murine type C virus particles in some of the tissues examined. Many type C virus particles were found in a transplant of DMNU.induced malig. nant lymphoma. Some type C virus particles were shown in malignant lymphomas and lymph nodes of malignant lymphoma-bearing mice. A very small number of type C virus particles were observed in thymus of control mice and bone marrow of a malignant lymphoma.bearing mouse. A few particles, quite similar to murine type C virus particles, were detected in DMNU.induced mammary adenocarcinoma of hamster. No virus-like particles were seen in mammary glands of control hamsters. Whether these particles are merely passengers or are playing a significant role in the carcinogenesis of these tumors remains to be determined.

  18. Hepatic metabolism of carcinogenic β-asarone.

    Science.gov (United States)

    Cartus, Alexander T; Stegmüller, Simone; Simson, Nadine; Wahl, Andrea; Neef, Sylvia; Kelm, Harald; Schrenk, Dieter

    2015-09-21

    β-Asarone (1) belongs to the group of naturally occurring phenylpropenes like eugenol or anethole. Compound 1 is found in several plants, e.g., Acorus calamus or Asarum europaeum. Compound 1-containing plant materials and essential oils thereof are used to flavor foods and alcoholic beverages and as ingredients of many drugs in traditional phytomedicines. Although 1 has been claimed to have several positive pharmacological effects, it was found to be genotoxic and carcinogenic in rodents (liver and small intestine). The mechanism of action of carcinogenic allylic phenylpropenes consists of the metabolic activation via cytochrome P450 enzymes and sulfotransferases. In vivo experiments suggested that this pathway does not play a major role in the carcinogenicity of the propenylic compound 1 as is the case for other propenylic compounds, e.g., anethole. Since the metabolic pathways of 1 have not been investigated and its carcinogenic mode of action is unknown, we investigated the metabolism of 1 in liver microsomes of rats, bovines, porcines, and humans using (1)H NMR, HPLC-DAD, and LC-ESI-MS/MS techniques. We synthesized the majority of identified metabolites which were used as reference compounds for the quantification and final verification of metabolites. Microsomal epoxidation of the side chain of 1 presumably yielded (Z)-asarone-1',2'-epoxide (8a) which instantly was hydrolyzed to the corresponding erythro- and threo-configurated diols (9b, 9a) and the ketone 2,4,5-trimethoxyphenylacetone (13). This was the main metabolic pathway in the metabolism of 1 in all investigated liver microsomes. Hydroxylation of the side chain of 1 led to the formation of three alcohols at total yields of less than 30%: 1'-hydroxyasarone (2), (E)- and (Z)-3'-hydroxyasarone (4 and 6), with 6 being the mainly formed alcohol and 2 being detectable only in liver microsomes of Aroclor 1254-pretreated rats. Small amounts of 4 and 6 were further oxidized to the corresponding carbonyl

  19. The in vivo rodent test systems for assessment of carcinogenic potential

    DEFF Research Database (Denmark)

    van der Laan, Jan-Willem; Spindler, Per

    2002-01-01

    mouse models, the RasH2 and Tg.AC transgenic mouse models, and the neonatal mouse model. The "ICH Guideline S1B on Testing for Carcinogenicity of Pharmaceuticals" advocates that carcinogenicity testing of pharmaceuticals, when needed, might be carried out choosing one 2-year rodent carcinogenicity study...... (rat) plus one other study that supplements the 2-year study and providing additional information that is not readily available from the 2-year study: either (1) a short- or medium-term in vivo rodent test system or (2) a 2-year carcinogenicity study in a second rodent species (mouse). Another topic of...... end of 2001. The use of the short- and medium-term rodent test systems were not considered appropriate for the assessment of carcinogenic potential of biotechnology-derived medicinal products....

  20. Goitre and wasting induced in hamsters by hexachlorobenzene

    International Nuclear Information System (INIS)

    Male Syrian hamsters were treated with hexachlorobenzene (HCB) in their diet at levels of 100 ppm for 28 weeks, 200 ppm for 18 and 28 weeks, and 500 ppm for 6 weeks. All treatments caused at least a 2.5- to 3-fold increase in thyroid size, mainly by enlargement of some follicles. Serum thyroxine (T4) levels were unchanged, whereas levels of triiodothyronine (T3) eventually became depressed by >60%. Uptake of 131I into thyroids was induced approximately 3-fold when estimated after feeding HCB (500 ppm) for 3 or 6 weeks. Hamsters also lost weight by depletion of adipose tissue, leading to 50% mortality in longer experiments. Results were distinct from the effects of the known antithyroid agent 3-aminotriazole or amitrole (200 ppm for 28 weeks), which did not affect survival and although causing thyroid enlargement depressed serum T4 and significantly elevated T3. The effects of HCB in hamsters were also different from those in rats (500 ppm HCB for 6 weeks) in which there was only a small increase in thyroid size (1.3-fold), serum levels of T3 were only slightly depressed but T4 levels were reduced by 74%. These studies are discussed with reference to the effects of other polyhalogenated aromatic chemicals on the thyroid, serum thyroid hormone levels and lethality. (orig.)

  1. Existence of an Endogenous Glutamate and Aspartate Transporter in Chinese Hamster Ovary Cells

    Institute of Scientific and Technical Information of China (English)

    Xunhe JI; Yuhua JIN; Yaoyue CHEN; Chongyong LI; Lihe GUO

    2007-01-01

    Chinese hamster ovary cells show endogenous high-affinity Na+-dependent glutamate transport activity. This transport activity is kinetically similar to a glutamate transporter family strategically expressed in the central nervous system and is pharmacologically unlike glutamate transporter-1 or excitatory amino acid carrier 1. The cDNA of a glutamate/aspartate transporter (GLAST)-like transporter was obtained and analyzed. The deduced amino acid sequence showed high similarity to human, mouse, and rat GLAST. We concluded that a GLAST-like glutamate transporter exists in Chinese hamster ovary cells that might confer the endogenous high-affinity Na+-dependent glutamate transport activity evident in these cells.

  2. Carcinogenic effects of the combined action of /sup 241/Am and. gamma. -radiation

    Energy Technology Data Exchange (ETDEWEB)

    Filippova, L.G.; Buldakov, L.A.; Nifatov, A.P. (Institut Biofiziki, Moscow (USSR))

    In experiments on Wistar rats a study was made of the carcinogenic effects of the combined exposure to /sup 241/Am administered intrapertioneally (6.7 to 229.4 kBq/kg body weight) and external ..gamma..-radiation (/sup 137/Cs, 175 cGy). The occurrence of osteosarcoma, leucosis, skin and mammary tumors increased in the exposed animals. The combined irradiation produced an additive carcinogenic effect.

  3. Carcinogenic effects of the combined action of 241Am and γ-radiation

    International Nuclear Information System (INIS)

    In experiments on Wistar rats a study was made of the carcinogenic effects of the combined exposure to 241Am administered intrapertioneally (6.7 to 229.4 kBq/kg body weight) and external γ-radiation (137Cs, 175 cGy). The occurrence of osteosarcoma, leucosis, skin and mammary tumors increased in the exposed animals. The combined irradiation prodUced an additive carcinogenic effect

  4. EVALUATION OF THE POTENTIAL CARCINOGENICITY OF CYCLOPHOSPHAMIDE

    Science.gov (United States)

    Cyclophosphamide is a probable human carcinogen, classified as weight-of-evidence Group B1 under the EPA Guidelines for Carcinogen Risk Assessment (U.S. EPA, 1986a).Evidence on potential carcinogenicity from animal studies is "Sufficient," and the evidence from human studies is "...

  5. Experimental pancreatic carcinogenesis. II. Lifetime carcinogenesis studies in the outbred Syrian golden hamster with N-nitroso-bis(2-hydroxypropyl)amine.

    Science.gov (United States)

    Levitt, M; Harris, C; Squire, R; Wenk, M; Mollelo, C; Springer, S

    1978-03-01

    A high incidence of pancreatic duct neoplasms was induced in outbred male Syrian golden hamsters following weekly sc injection of N-nitroso-bis(2-hydroxypropyl)amine for life. The first such tumors appeared as early as 16 experimental weeks; the maximum incidence reached 100% by the termination of the study. Tumors in the respiratory tracts and angiosarcomas of the livers of the hamsters were also observed in high frequency. Latency of the induced neoplasms was significantly decreased by the substitution of distilled water for olive oil as the vehicle for the carcinogen. PMID:625072

  6. In vitro comet and micronucleus assays do not predict morphological transforming effects of silica particles in Syrian Hamster Embryo cells.

    Science.gov (United States)

    Darne, Christian; Coulais, Catherine; Terzetti, Francine; Fontana, Caroline; Binet, Stéphane; Gaté, Laurent; Guichard, Yves

    2016-01-15

    Crystalline silica particles and asbestos have both been classified as carcinogenic by the International Agency for Research on Cancer (IARC). However, because of the limited data available, amorphous silica was not classifiable. In vitro, the carcinogenic potential of natural crystalline and amorphous silica particles has been revealed by the Syrian Hamster Embryo (SHE) cell transformation assay. On the other hand, the genotoxic potential of those substances has not been investigated in SHE cells. And yet, genotoxicity assays are commonly used for hazard evaluation and they are often used as in vitro assays of reference to predict a possible carcinogenic potential. The main objective of this study was to compare the genotoxic potential and the carcinogenic potential of different crystalline and amorphous silica particles in SHE cells. Three silica samples of different crystallinity were used: natural amorphous silica, partially crystallized silica and quartz silica particles. Their genotoxicity were tested through the in vitro micronucleus assay and the comet assay in SHE, and their carcinogenic potential through the SHE transformation assay. In addition, silica samples were also tested with the same genotoxicity assays in V79 hamster-lung cells, a common in vitro model for particle exposure. Results obtained in the micronucleus and the comet assays show that none of the silica was capable of inducing genotoxic effects in SHE cells and only the amorphous silica induced genotoxic effects in V79 cells. However in the SHE cell transformation assays, the partially crystallized and quartz silica were able to induce morphological cell transformation. Together, these data suggest that, in vitro, the short-term genotoxic assays alone are not sufficient to predict the hazard and the carcinogenic potential of this type of particles; SHE transformation assay appears a more reliable tool for this purpose and should be included in the "in vitro battery assays" for hazard

  7. Thermogenin amount and activity in hamster brown fat mitochondria: effect of cold acclimation

    Energy Technology Data Exchange (ETDEWEB)

    Sundin, U.; Moore, G.; Nedergaard, J.; Cannon, B.

    1987-05-01

    To investigate the acclimation process in a hibernator, four different parameters of thermogenin amount and activity were investigated in brown adipose tissue mitochondria from cold-exposed and cold-acclimated Syrian hamsters. Hamsters, which are hibernators, have been considered to be primed for thermogenesis and thus not to show cold-acclimation effects, but here a significant increase in (/sup 3/H)GDP-binding capacity was observed, and this increase was paralleled by an increase in thermogenin antigen amount, as measured in an enzyme-linked immunosorbent assay. The transient nature of the effect of cold exposure on (/sup 3/H)GDP binding, characteristically observed with rat mitochondria, was not observed with hamster mitochondria, and the increase in (/sup 3/H)GDP binding occurred without a change in the dissociation constant. The increase in thermogenin amount was paralleled by an increase both in GDP-sensitive Cl/sup -/ permeability of the mitochondria and in GDP-sensitive respiration. It was established that it is the maximal activity of thermogenin that is rate limiting for thermogenesis in isolated mitochondria, provided that an optimal substrate is used (such as palmitoyl carnitine). Cold acclimation also increased the total amount of mitochondria in the tissue, leading totally to a sixfold increase in thermogenin content of the hamster. It is concluded that hamsters show the expected physiological, pharmacological, and biochemical signs of cold acclimation.

  8. Thermogenin amount and activity in hamster brown fat mitochondria: effect of cold acclimation

    International Nuclear Information System (INIS)

    To investigate the acclimation process in a hibernator, four different parameters of thermogenin amount and activity were investigated in brown adipose tissue mitochondria from cold-exposed and cold-acclimated Syrian hamsters. Hamsters, which are hibernators, have been considered to be primed for thermogenesis and thus not to show cold-acclimation effects, but here a significant increase in [3H]GDP-binding capacity was observed, and this increase was paralleled by an increase in thermogenin antigen amount, as measured in an enzyme-linked immunosorbent assay. The transient nature of the effect of cold exposure on [3H]GDP binding, characteristically observed with rat mitochondria, was not observed with hamster mitochondria, and the increase in [3H]GDP binding occurred without a change in the dissociation constant. The increase in thermogenin amount was paralleled by an increase both in GDP-sensitive Cl- permeability of the mitochondria and in GDP-sensitive respiration. It was established that it is the maximal activity of thermogenin that is rate limiting for thermogenesis in isolated mitochondria, provided that an optimal substrate is used (such as palmitoyl carnitine). Cold acclimation also increased the total amount of mitochondria in the tissue, leading totally to a sixfold increase in thermogenin content of the hamster. It is concluded that hamsters show the expected physiological, pharmacological, and biochemical signs of cold acclimation

  9. Rift Valley fever virus infection in golden Syrian hamsters.

    Directory of Open Access Journals (Sweden)

    Dionna Scharton

    Full Text Available Rift Valley fever virus (RVFV is a formidable pathogen that causes severe disease and abortion in a variety of livestock species and a range of disease in humans that includes hemorrhagic fever, fulminant hepatitis, encephalitis and blindness. The natural transmission cycle involves mosquito vectors, but exposure can also occur through contact with infected fluids and tissues. The lack of approved antiviral therapies and vaccines for human use underlies the importance of small animal models for proof-of-concept efficacy studies. Several mouse and rat models of RVFV infection have been well characterized and provide useful systems for the study of certain aspects of pathogenesis, as well as antiviral drug and vaccine development. However, certain host-directed therapeutics may not act on mouse or rat pathways. Here, we describe the natural history of disease in golden Syrian hamsters challenged subcutaneously with the pathogenic ZH501 strain of RVFV. Peracute disease resulted in rapid lethality within 2 to 3 days of RVFV challenge. High titer viremia and substantial viral loads were observed in most tissues examined; however, histopathology and immunostaining for RVFV antigen were largely restricted to the liver. Acute hepatocellular necrosis associated with a strong presence of viral antigen in the hepatocytes indicates that fulminant hepatitis is the likely cause of mortality. Further studies to assess the susceptibility and disease progression following respiratory route exposure are warranted. The use of the hamsters to model RVFV infection is suitable for early stage antiviral drug and vaccine development studies.

  10. Distinct mechanisms of oxidative DNA damage induced by carcinogenic nickel subsulfide and nickel oxides.

    OpenAIRE

    Kawanishi, Shosuke; Oikawa, Shinji; Inoue, Sumiko; Nishino, Kohsuke

    2002-01-01

    The U.S. National Toxicology Program has shown clear evidence of carcinogenicity of nickel subsulfide (Ni(3)S(2)) and some evidence of carcinogenicity of NiO (green) in rats. In the present study, DNA damage in cultured cells and in lungs of rats induced by nickel compounds was investigated to clarify the mechanism of nickel carcinogenesis. In cultured HeLa cells, Ni(3)S(2) induced a significant increase in 8-hydroxydeoxyguanosine (8-OH-dG) formation, whereas NiO (black), NiO (green), and NiS...

  11. Establishment of a hamster lymphoma cell line

    Directory of Open Access Journals (Sweden)

    Abe,Shinji

    1974-08-01

    Full Text Available The establishment of a hamster lymphoma cell line was attempted. Simple mincing and trypsinization of lymphoma tissue resulted in a high degree of cell degeneration. The ascitic tumor cells produced by intraperitoneal transplantation of lymphoma tissue gave a better result. These ascitic cells grew and were cultured successively in medium consisting of RPMI 1640 and 20% fetal calf serum. Cells were round and grew in suspension. Accelerated cell growth was observed one month after starting the culture. In the stained preparations, cells were lymphoblastic. Cells were transplantable into new-born hamsters and produced tumors, but not in young adult hamsters.

  12. Protection of signal processing at low temperature in baroreceptive neurons in the nucleus tractus solitarius of Syrian hamsters, a hibernating species

    Science.gov (United States)

    Sekizawa, Shin-Ichi; Horwitz, Barbara A.; Horowitz, John M.

    2013-01-01

    We previously described synaptic currents between baroreceptor fibers and second-order neurons in the nucleus tractus solitarius (NTS) that were larger in Syrian hamsters than in rats. This suggested that although electrical activity throughout the hamster brain decreased as brain temperature declined, the greater synaptic input to its NTS would support continued operation of cardiorespiratory reflexes at low body temperatures. Here, we focused on properties that would protect these neurons against potential damage from the larger synaptic inputs, testing the hypotheses that hamster NTS neurons exhibit: 1) intrinsic N-methyl-d-aspartate receptor (NMDAR) properties that limit Ca2+ influx to a greater degree than do rat NTS neurons and 2) properties that reduce gating signals to NMDARs to a greater degree than in rat NTS neurons. Whole cell patch-clamp recordings on anatomically identified second-order NTS baroreceptive neurons showed that NMDAR-mediated synaptic currents between sensory fibers and second-order NTS neurons were larger in hamsters than in rats at 33°C and 15°C, with no difference in their permeability to Ca2+. However, at 15°C, but not at 33°C, non-NMDAR currents evoked by glutamate released from baroreceptor fibers had significantly shorter durations in hamsters than in rats. Thus, hamster NMDARs did not exhibit lower Ca2+ influx than did rats (negating hypothesis 1), but they did exhibit significant differences in non-NMDAR neuronal properties at low temperature (consistent with hypothesis 2). The latter (shorter duration of non-NMDAR currents) would likely limit NMDAR coincidence gating and may help protect hamster NTS neurons, enabling them to contribute to signal processing at low body temperatures. PMID:24068050

  13. 12-O-Tetradecanoyl-phorbol-13-acetate and its relationship to SCE induction in Syrian and Chinese hamster cells

    International Nuclear Information System (INIS)

    12-O-Tetradecanoyl-phorbol-13-acetate (TPA) in conditions that produce enhancement of ultraviolet light (UV) and x-irradiation Syrian hamster embryo cell (HEC) transformation did not cause further increase in the sister chromatid exchange (SCE) frequency induced by UV and x-irradiation, two physical carcinogens that differ in their mode of DNA interaction and efficiency of SCE induction. Several factors which might influence SCE induction by TPA were studied on HEC and Chinese hamster V79-4 cells. Heat-inactivated serum was used because of the possibility that a serum component may interfere with TPA ability to cause SCE. TPA effect on SCE was determined at the first and second division post treatment on cells exposed to different 5-bromodeoxyuridine (BrdUrd) concentrations. Independent of BrdUrd concentration (1-10μg/ml medium) and the number of cells divisions post treatment, TPA (0.01-2μg/ml medium) was ineffective in inducing SCE in exponentially and stationary HEC cultures cultivated in medium supplemented with heat-inactivated serum. Also, TPA did not increase the SCE frequency in V79-4 Chinese hamster cells cultured in heat-activated or noninactivated serum. Although SCE induction, a cellular response to carcinogen-induced DNA damage, may be important for the induction of transformation by environmental agents, the enhancement of transformation frequency caused by TPA occurs without further DNA alterations involved in SCE formation

  14. Genotoxicity, carcinogenicity, and mode of action of the fried food mutagen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ).

    OpenAIRE

    Weisburger, J H; Barnes, W S; Lovelette, C A; Tong, C; Tanaka, T; Williams, G.M.

    1986-01-01

    Because mutagens typified by 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) observed in cooked foods are widely consumed, detailed studies of their biochemical and biological properties including carcinogenicity are most important. IQ induces unscheduled DNA synthesis in liver cells, which when taken together with its powerful mutagenicity in the Salmonella typhimurium test system, predicts carcinogenicity. In female Sprague-Dawley rats, IQ did exhibit potent carcinogenicity for the mammary gla...

  15. In vivo Comet assay on isolated kidney cells to distinguish genotoxic carcinogens from epigenetic carcinogens or cytotoxic compounds.

    Science.gov (United States)

    Nesslany, Fabrice; Zennouche, Nadia; Simar-Meintières, Sophie; Talahari, Ismaïl; Nkili-Mboui, Esther-Nadège; Marzin, Daniel

    2007-06-15

    The objective of this study was to determine the ability of the alkaline in vivo Comet assay (pH>13) to distinguish genotoxic carcinogens from epigenetic carcinogens when performed on freshly isolated kidney cells and to determine the possible interference of cytotoxicity by assessing DNA damage induced by renal genotoxic, epigenetic or toxic compounds after enzymatic isolation of kidney cells from OFA Sprague-Dawley male rats. The ability of the Comet assay to distinguish (1) genotoxicity versus cytotoxicity and (2) genotoxic versus non-genotoxic (epigenetic) carcinogens, was thus investigated by studying five known genotoxic renal carcinogens acting through diverse mechanisms of action, i.e. streptozotocin, aristolochic acids, 2-nitroanisole, potassium bromate and cisplatin, two rodent renal epigenetic carcinogens: d-limonene and ciclosporine and two nephrotoxic compounds: streptomycin and indomethacin. Animals were treated once with the test compound by the appropriate route of administration and genotoxic effects were measured at the two sampling times of 3-6 and 22-26h after treatment. Regarding the tissue processing, the limited background level of DNA migration observed in the negative control groups throughout all experiments demonstrated that the enzymatic isolation method implemented in the current study is appropriate. On the other hand, streptozotocin, 20mg/kg, used as positive reference control concurrently to each assay, caused a clear increase in the mean Olive Tail Moment median value, which allows validating the current methodology. Under these experimental conditions, the in vivo rodent Comet assay demonstrated good sensitivity and good specificity: all the five renal genotoxic carcinogens were clearly detected in at least one expression period either directly or indirectly, as in the case of cisplatin: for this cross-linking agent, the significant decrease in DNA migration observed under standard electrophoresis conditions was clearly amplified

  16. Induction of lyme arthritis in LSH hamsters

    Energy Technology Data Exchange (ETDEWEB)

    Schmitz, J.L.; Schell, R.F.; Hejka, A.; England, D.M.; Konick, L.

    1988-09-01

    In studies of experimental Lyme disease, a major obstacle has been the unavailability of a suitable animal model. We found that irradiated LSH/Ss Lak hamsters developed arthritis after injection of Borrelia burgdorferi in the hind paws. When nonirradiated hamsters were injected in the hind paws with B. burgdorferi, acute transient synovitis was present. A diffuse neutrophilic infiltrate involved the synovia and periarticular structures. The inflammation was associated with edema, hyperemia, and granulation tissue. Numerous spirochetes were seen in the synovial and subsynovial tissues. The histopathologic changes were enhanced in irradiated hamsters. The onset and duration of the induced swelling were dependent on the dose of radiation and the inoculum of spirochetes. Inoculation of irradiated hamsters with Formalin-killed spirochetes or medium in which B. burgdorferi had grown for 7 days failed to induce swelling. This animal model should prove useful for studies of the immune response to B. burgdorferi and the pathogenesis of Lyme arthritis.

  17. Induction of lyme arthritis in LSH hamsters

    International Nuclear Information System (INIS)

    In studies of experimental Lyme disease, a major obstacle has been the unavailability of a suitable animal model. We found that irradiated LSH/Ss Lak hamsters developed arthritis after injection of Borrelia burgdorferi in the hind paws. When nonirradiated hamsters were injected in the hind paws with B. burgdorferi, acute transient synovitis was present. A diffuse neutrophilic infiltrate involved the synovia and periarticular structures. The inflammation was associated with edema, hyperemia, and granulation tissue. Numerous spirochetes were seen in the synovial and subsynovial tissues. The histopathologic changes were enhanced in irradiated hamsters. The onset and duration of the induced swelling were dependent on the dose of radiation and the inoculum of spirochetes. Inoculation of irradiated hamsters with Formalin-killed spirochetes or medium in which B. burgdorferi had grown for 7 days failed to induce swelling. This animal model should prove useful for studies of the immune response to B. burgdorferi and the pathogenesis of Lyme arthritis

  18. Mycoplasma pneumoniae-induced hydrocephalus in hamsters.

    OpenAIRE

    Kohn, D F; Chinookoswong, N; Wang, J

    1984-01-01

    Hydrocephalus was induced in neonatal hamsters after intracerebral inoculation of Mycoplasma pneumoniae. Examination of the ependyma from affected animals by electron microscopy did not reveal mycoplasma. However, in an ependymal organ culture system, M. pneumoniae cytadsorbed to ependymal cells.

  19. Track segment studies with Chinese hamster cells

    International Nuclear Information System (INIS)

    Survival curves of near-diploid and near-tetraploid Chinese hamster cell cultures following irradiation by an 241Am α source indicate different growth rates for the two clones. Possible reasons for the difference are discussed

  20. Immunohistochemical localization of glutathione-S-transferase and glutathione peroxidase in adult Syrian hamster tissues and during kidney development.

    OpenAIRE

    Oberley, T. D.; Oberley, L. W.; Slattery, A. F.; Elwell, J. H.

    1991-01-01

    Tissues from adult Syrian hamsters were studied with immunoperoxidase techniques using polyclonal antibodies to glutathione-S-transferase (rat liver and human placental enzymes) and human erythrocyte glutathione peroxidase. Most tissues immunostained similarly with these antibodies. Most notable was the cytoplasmic staining of mesenchyme tissues, especially smooth muscle, by all three antibodies. Epithelial cells stained distinctively, but usually less intensely than mesenchyme. Epithelial ce...

  1. Artificial sweeteners--do they bear a carcinogenic risk?

    Science.gov (United States)

    Weihrauch, M R; Diehl, V

    2004-10-01

    Artificial sweeteners are added to a wide variety of food, drinks, drugs and hygiene products. Since their introduction, the mass media have reported about potential cancer risks, which has contributed to undermine the public's sense of security. It can be assumed that every citizen of Western countries uses artificial sweeteners, knowingly or not. A cancer-inducing activity of one of these substances would mean a health risk to an entire population. We performed several PubMed searches of the National Library of Medicine for articles in English about artificial sweeteners. These articles included 'first generation' sweeteners such as saccharin, cyclamate and aspartame, as well as 'new generation' sweeteners such as acesulfame-K, sucralose, alitame and neotame. Epidemiological studies in humans did not find the bladder cancer-inducing effects of saccharin and cyclamate that had been reported from animal studies in rats. Despite some rather unscientific assumptions, there is no evidence that aspartame is carcinogenic. Case-control studies showed an elevated relative risk of 1.3 for heavy artificial sweetener use (no specific substances specified) of >1.7 g/day. For new generation sweeteners, it is too early to establish any epidemiological evidence about possible carcinogenic risks. As many artificial sweeteners are combined in today's products, the carcinogenic risk of a single substance is difficult to assess. However, according to the current literature, the possible risk of artificial sweeteners to induce cancer seems to be negligible. PMID:15367404

  2. Carcinogenicity Tests and Interspecies Concordance

    OpenAIRE

    Lin, Tony; Gold, Lois Swirsky; Freedman, David

    1995-01-01

    According to current policy, chemicals are evaluated for possible cancer risk to humans at low dose by testing in bioassays, where high doses of the chemical are given to rodents. Thus, risk is extrapolated from high dose in rodents to low dose in humans. The accuracy of these extrapolations is generally unverifiable, since data on humans are limited. However, it is feasible to examine the accuracy of extrapolations from mice to rats. If mice and rats are similar with respect to carcinogenesi...

  3. Methods for modeling chinese hamster ovary (cho) cell metabolism

    DEFF Research Database (Denmark)

    2015-01-01

    Embodiments of the present invention generally relate to the computational analysis and characterization biological networks at the cellular level in Chinese Hamster Ovary (CHO) cells. Based on computational methods utilizing a hamster reference genome, the invention provides methods for...

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

    Science.gov (United States)

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

    2015-03-01

    Abstract Glyphosate, an herbicidal derivative of the amino acid glycine, was introduced to agriculture in the 1970s. Glyphosate targets and blocks a plant metabolic pathway not found in animals, the shikimate pathway, required for the synthesis of aromatic amino acids in plants. After almost forty years of commercial use, and multiple regulatory approvals including toxicology evaluations, literature reviews, and numerous human health risk assessments, the clear and consistent conclusions are that glyphosate is of low toxicological concern, and no concerns exist with respect to glyphosate use and cancer in humans. This manuscript discusses the basis for these conclusions. Most toxicological studies informing regulatory evaluations are of commercial interest and are proprietary in nature. Given the widespread attention to this molecule, the authors gained access to carcinogenicity data submitted to regulatory agencies and present overviews of each study, followed by a weight of evidence evaluation of tumor incidence data. Fourteen carcinogenicity studies (nine rat and five mouse) are evaluated for their individual reliability, and select neoplasms are identified for further evaluation across the data base. The original tumor incidence data from study reports are presented in the online data supplement. There was no evidence of a carcinogenic effect related to glyphosate treatment. The lack of a plausible mechanism, along with published epidemiology studies, which fail to demonstrate clear, statistically significant, unbiased and non-confounded associations between glyphosate and cancer of any single etiology, and a compelling weight of evidence, support the conclusion that glyphosate does not present concern with respect to carcinogenic potential in humans. PMID:25716480

  5. Molecular basis of carcinogenicity of tungsten alloy particles

    International Nuclear Information System (INIS)

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

  6. Molecular basis of carcinogenicity of tungsten alloy particles

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-03-15

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

  7. Predicting carcinogenicity of organic compounds based on CPDB.

    Science.gov (United States)

    Wu, Xiuchao; Zhang, Qingzhu; Wang, Hui; Hu, Jingtian

    2015-11-01

    Cancer is a major killer of human health and predictions for the carcinogenicity of chemicals are of great importance. In this article, predictive models for the carcinogenicity of organic compounds using QSAR methods for rats and mice were developed based on the data from CPDB. The models was developed based on the data of specific target site liver and classified according to sex of rats and mice. Meanwhile, models were also classified according to whether there is a ring in the molecular structure in order to reduce the diversity of molecular structure. Therefore, eight local models were developed in the final. Taking into account the complexity of carcinogenesis and in order to obtain as much information, DRAGON descriptors were selected as the variables used to develop models. Fitting ability, robustness and predictive power of the models were assessed according to the OECD principles. The external predictive coefficients for validation sets of each model were in the range of 0.711-0.906, and for the whole data in each model were all greater than 0.8, which represents that all models have good predictivity. In order to study the mechanism of carcinogenesis, standardized regression coefficients were calculated for all predictor variables. In addition, the effect of animal sex on carcinogenesis was compared and a trend that female showed stronger tolerance for cancerogen than male in both species was appeared. PMID:26070146

  8. Histopathology of Lyme arthritis in LSH hamsters

    Energy Technology Data Exchange (ETDEWEB)

    Hejka, A.; Schmitz, J.L.; England, D.M.; Callister, S.M.; Schell, R.F.

    1989-05-01

    The authors studied the histopathologic evolution of arthritis in nonirradiated and irradiated hamsters infected with Borrelia burgdorferi. Nonirradiated hamsters injected in the hind paws with B. burgdorferi developed an acute inflammatory reaction involving the synovium, periarticular soft tissues, and dermis. This acute inflammatory reaction was short-lived and was replaced by a mild chronic synovitis as the number of detectable spirochetes in the synovium, periarticular soft tissues, and perineurovascular areas diminished. Exposing hamsters to radiation before inoculation with B. burgdorferi exacerbated and prolonged the acute inflammatory phase. Spirochetes also persisted longer in the periarticular soft tissues. A major histopathologic finding was destructive and erosive bone changes of the hind paws, which resulted in deformation of the joints. These studies should be helpful in defining the immune mechanism participating in the onset, progression, and resolution of Lyme arthritis.

  9. Decreased adult neurogenesis in hibernating Syrian hamster.

    Science.gov (United States)

    León-Espinosa, Gonzalo; García, Esther; Gómez-Pinedo, Ulises; Hernández, Félix; DeFelipe, Javier; Ávila, Jesús

    2016-10-01

    Generation of new neurons from adult neural stem cells occurs in the dentate gyrus (DG) of the hippocampus and the lateral walls of the lateral ventricles. In this article, we study the neurogenesis that takes place during the hibernation of the Syrian hamster (Mesocricetus auratus). Using a variety of standard neurogenesis markers and 5-bromo-2-deoxyuridine (BrdU) incorporation, we describe a preferential decrease in the proliferation of newborn neurons in the subventricular zone (SVZ) of the hibernating hamsters (torpor) rather than in the hippocampus. Furthermore, we demonstrate that the proliferative capacity is recovered after 3-4days of torpor when arousal is triggered under natural conditions (i.e., not artificially provoked). In addition, we show that tau3R, a tau isoform with three microtubule-binding domains, is a suitable marker to study neurogenesis both in the SVZ and subgranular zone (SGZ) of the Syrian hamster brain. PMID:27436535

  10. Histopathology of Lyme arthritis in LSH hamsters

    International Nuclear Information System (INIS)

    The authors studied the histopathologic evolution of arthritis in nonirradiated and irradiated hamsters infected with Borrelia burgdorferi. Nonirradiated hamsters injected in the hind paws with B. burgdorferi developed an acute inflammatory reaction involving the synovium, periarticular soft tissues, and dermis. This acute inflammatory reaction was short-lived and was replaced by a mild chronic synovitis as the number of detectable spirochetes in the synovium, periarticular soft tissues, and perineurovascular areas diminished. Exposing hamsters to radiation before inoculation with B. burgdorferi exacerbated and prolonged the acute inflammatory phase. Spirochetes also persisted longer in the periarticular soft tissues. A major histopathologic finding was destructive and erosive bone changes of the hind paws, which resulted in deformation of the joints. These studies should be helpful in defining the immune mechanism participating in the onset, progression, and resolution of Lyme arthritis

  11. Human follicular fluid adverses hamster spermatozoa motility.

    Science.gov (United States)

    Wetzels, A; Goverde, H J; Bastiaans, L A; Rolland, R

    1989-01-01

    To determine the optimal conditions for in vitro spermatozoa vitality, human and hamster spermatozoa were incubated at 37 degrees C in T6 medium supplemented with different biologic fluids (10% v/v). The fluids tested were human serum (HUS), hamster serum (HAS), and human follicular fluid (HUF). After incubation the spermatozoa were investigated for their qualitative and quantitative motility. Human spermatozoa maintained a good vitality in all fluids tested (approximately 25% motility after 18-h incubation). The hamster spermatozoa had after an incubation of 4 h a motility of 28.4% in HUS, 14.2% in HAS, and 2.2% in HUF. The quality of the motility was also extremely low in HUF, whereas it was adequate in HUS and in HAS. The presence of species-specific substances in mammalian follicular fluid is discussed. PMID:2589906

  12. Specific growth stimulation by linoleic acid in hepatoma cell lines transfected with the target protein of a liver carcinogen.

    OpenAIRE

    Keler, T; Barker, C. S.; Sorof, S

    1992-01-01

    The hepatic carcinogen N-2-fluorenylacetamide (2-acetylaminofluorene) was shown previously to interact specifically with its target protein, liver fatty acid binding protein (L-FABP), early during hepatocarcinogenesis in rats. In search of the significance of the interaction, rat L-FABP cDNA in the sense and antisense orientations was transfected into a subline of the rat hepatoma HTC cell line that did not express L-FABP. After the transfections, the basal doubling times of the cells were no...

  13. Identification of the Syrian hamster cardiomyopathy gene.

    Science.gov (United States)

    Nigro, V; Okazaki, Y; Belsito, A; Piluso, G; Matsuda, Y; Politano, L; Nigro, G; Ventura, C; Abbondanza, C; Molinari, A M; Acampora, D; Nishimura, M; Hayashizaki, Y; Puca, G A

    1997-04-01

    The BIO14.6 hamster is a widely used model for autosomal recessive cardiomyopathy. These animals die prematurely from progressive myocardial necrosis and heart failure. The primary genetic defect leading to the cardiomyopathy is still unknown. Recently, a genetic linkage map localized the cardiomyopathy locus on hamster chromosome 9qa2.1-b1, excluding several candidate genes. We now demonstrate that the cardiomyopathy results from a mutation in the delta-sarcoglycan gene that maps to the disease locus. This mutation was completely coincident with the disease in backcross and F2 pedigrees. This constitutes the first animal model identified for human sarcoglycan disorders. PMID:9097966

  14. Biomonitoring of exposure to chemical carcinogens

    Czech Academy of Sciences Publication Activity Database

    Šrám, Radim

    Poland : Institute of Nuclear Physics, 2002. s. -. [NATO advanced research workshop (Human monitoring for genetic effects). 23.06.2002-27.06.2002, Krakow - Poland] Institutional research plan: CEZ:AV0Z5039906 Keywords : carcinogens Subject RIV: FH - Neurology

  15. Mutagenic and carcinogenic properties of drinking water

    International Nuclear Information System (INIS)

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

  16. The kinetics of macrophage and phospholipid renewal in the hamster lung

    International Nuclear Information System (INIS)

    The amount of an inhaled plutonium dioxide aerosol removed from hamster lung by bronchopulmonary lavage has been found to be directly proportional to the number of pulmonary macrophages in the lavage fluid. Similar findings have been reported in both rats and monkeys. Lung lavage also removes some of the surface active phospholipid film (pulmonary surfactant) lining the alveoli. Removal of this surfactant material may lead to lung collapse and therefore reduce chances of survival following prolonged lung lavage. In this study the removal, by lung lavage, and the subsequent replenishment of both pulmonary surfactant and macrophages have been examined in hamsters. Figures show the phospholipid and macrophage content of each of ten successive washes with saline. The significance of the results is discussed. (author)

  17. Ahne hamster lõikuskuul/ Tambet Kaugema

    Index Scriptorium Estoniae

    Kaugema, Tambet

    2010-01-01

    Eesti Nuku- ja Noorsoteatri jõululavastusest "Ahne hamster ja värvilised jäälilled", autor Miloš Macourek, tõlkija Leo Metsar, lavastaja ja muusikaline kujundaja Virko Annus, mängib Tarmo Männard. Esietendus 21. novembril Köismäe tornis

  18. Morphological transformation of an established Syrian hamster dermal cell with the anti-tussive agent noscapine.

    Science.gov (United States)

    Porter, R; Parry, E M; Parry, J M

    1992-05-01

    Following exposure to the alkaloid noscapine hydrochloride over a concentration range of 10-120 micrograms/ml immortal cultures of Syrian hamster dermal fibroblasts were shown to undergo morphological transformation. The resultant transformed foci produced cultures which were anchorage independent as confirmed by soft agar tests. Karyotype analysis of a noscapine transformed colony demonstrated an increase in chromosome number compared to the immortal culture and the non-random duplication of a translocated chromosome 9 previously identified in the immortal culture. These data indicate that noscapine, which has previously been shown to be a spindle inhibitor and inducer of polyploidy in cultured cells, is capable of inducing in vitro cell transformation. Such data indicate a carcinogenic potential for this widely used cough suppressant. PMID:1602976

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

    Science.gov (United States)

    Papamokos, George; Silins, Ilona

    2016-01-01

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

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

    International Nuclear Information System (INIS)

    Determining the carcinogenicity and carcinogenic potency of new chemicals is both a labor-intensive and time-consuming process. In order to expedite the screening process, there is a need to identify alternative toxicity measures that may be used as surrogates for carcinogenic potency. Alternative toxicity measures for carcinogenic potency currently being used in the literature include lethal dose (dose that kills 50% of a study population [LD50]), lowest-observed-adverse-effect-level (LOAEL) and maximum tolerated dose (MTD). The purpose of this study was to investigate the correlation between tumor dose (TD50) and three alternative toxicity measures as an estimator of carcinogenic potency. A second aim of this study was to develop a Classification and Regression Tree (CART) between TD50 and estimated/experimental predictor variables to predict the carcinogenic potency of new chemicals. Rat TD50s of 590 structurally diverse chemicals were obtained from the Cancer Potency Database, and the three alternative toxicity measures considered in this study were estimated using TOPKAT, a toxicity estimation software. Though poor correlations were obtained between carcinogenic potency and the three alternative toxicity (both experimental and TOPKAT) measures for the CPDB chemicals, a CART developed using experimental data with no missing values as predictor variables provided reasonable estimates of TD50 for nine chemicals that were part of an external validation set. However, if experimental values for the three alternative measures, mutagenicity and logP are not available in the literature, then either the CART developed using missing experimental values or estimated values may be used for making a prediction

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

    International Nuclear Information System (INIS)

    Prevention of environmentally induced cancers is a major health problem of which solutions depend on the rapid and accurate screening of potential chemical hazards. Lately, theoretical approaches such as the one proposed here - Quantitative Structure-Activity Relationship (QSAR) - are increasingly used for assessing the risks of environmental chemicals, since they can markedly reduce costs, avoid animal testing, and speed up policy decisions. This paper reports a QSAR study based on the Topological Substructural Molecular Design (TOPS-MODE) approach, aiming at predicting the rodent carcinogenicity of a set of nitroso-compounds selected from the Carcinogenic Potency Data Base (CPDB). The set comprises nitrosoureas (14 chemicals), N-nitrosamines (18 chemicals) C-nitroso-compounds (1 chemical), nitrosourethane (1 chemical) and nitrosoguanidine (1 chemical), which have been bioassayed in male rat using gavage as the route of administration. Here we are especially concerned in gathering the role of both parameters on the carcinogenic activity of this family of compounds. First, the regression model was derived, upon removal of one identified nitrosamine outlier, and was able to account for more than 84% of the variance in the experimental activity. Second, the TOPS-MODE approach afforded the bond contributions - expressed as fragment contributions to the carcinogenic activity - that can be interpreted and provide tools for better understanding the mechanisms of carcinogenesis. Finally, and most importantly, we demonstrate the potentialities of this approach towards the recognition of structural alerts for carcinogenicity predictions

  2. The relevance of the rat lung response to particle overload for human risk assessment: a workshop consensus report.

    Science.gov (United States)

    2000-01-01

    On 23-24 March 1998, the International Life Sciences Institute (ILSI) Risk Science Institute convened a workshop entitled "Relevance of the Rat Lung Response to Particle Overload for Human Risk Assessment." The workshop addressed the numerous study reports of lung tumors in rats resulting from chronic inhalation exposures to poorly soluble, nonfibrous particles of low acute toxicity and not directly genotoxic. These poorly soluble particles, indicated by the acronym PSPs (e.g., carbon black, coal dust, diesel soot, nonasbestiform talc, and titanium dioxide), elicit tumors in rats when deposition overwhelms the clearance mechanisms of the lung resulting in a condition referred to as "overload." These PSPs have been shown not to induce tumors in mice and hamsters, and the available data in humans are consistently negative. The objectives were twofold: (1) to provide guidance for risk assessment on the interpretation of neoplastic and nonneoplastic responses of the rat lung to PSPs; and (2) to identify important data gaps in our understanding of the lung responses of rats and other species to PSPs. Utilizing the five critical reviews of relevant literature that follow herein and the combined expertise and experience of the 30 workshop participants, a number of questions were addressed. The consensus views of the workshop participants are presented in this report. Because it is still not known with certainty whether high lung burdens of PSPs can lead to lung cancer in humans via mechanisms similar to those of the rat, in the absence of mechanistic data to the contrary it must be assumed that the rat model can identify potential carcinogenic hazards to humans. Since the apparent responsiveness of the rat model at overload is dependent on coexistent chronic active inflammation and cell proliferation, at lower lung doses where chronic active inflammation and cell proliferation are not present, no lung cancer hazard is anticipated. PMID:10715616

  3. Refined carbohydrate enhancement of aberrant crypt foci (ACF) in rat colon induced by the food-borne carcinogen 2-amino-3-methyl-imidazo[4,5-f]quinoline (IQ)

    DEFF Research Database (Denmark)

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

    1996-01-01

    The aberrant crypt foci (ACF) bioassay has been used extensively to study the early effects of different dietary components on the colonic mucosa of laboratory rodents. ACF are proposed to represent preneoplastic lesions of colon cancer. Compared to the normally used initiators 1,2-dimethylhydraz......The aberrant crypt foci (ACF) bioassay has been used extensively to study the early effects of different dietary components on the colonic mucosa of laboratory rodents. ACF are proposed to represent preneoplastic lesions of colon cancer. Compared to the normally used initiators 1......,2-dimethylhydrazine dihydrochloride (DMH) and azoxymethane (AOM), the use of a diet-related colon cancer initiator, such as the heterocyclic amine 2-amino-3-methyl-imidazo[4,5-f]quinoline (IQ) formed during meat cooking, would probably give a more relevant insight into diet-related colon carcinogenesis. In the...... modulated by the amount of refined carbohydrates in the diet. Rats given a high sucrose/dextrin diet showed a significantly higher number of ACF compared to rats given a diet high in starches. The effect on tumor outcome will await the termination of a ongoing parallel study....

  4. Acetylator genotype-dependent formation of 2-aminofluorene-hemoglobin adducts in rapid and slow acetylator Syrian hamsters congenic at the NAT2 locus.

    Science.gov (United States)

    Feng, Y; Rustan, T D; Ferguson, R J; Doll, M A; Hein, D W

    1994-01-01

    Arylamine-hemoglobin adducts are a valuable dosimeter for assessing arylamine exposures and carcinogenic risk. The effects of age, sex, time-course, dose, and acetylator genotype on levels of 2-aminofluorene-hemoglobin adducts were investigated in homozygous rapid (Bio. 82.73/H-Patr) and slow (Bio. 82.73/H-Pats) acetylator hamsters congenic at the polymorphic (NAT2) acetylator locus. Following administration of a single ip dose of [3H]2-aminofluorene, peak 2-aminofluorene-hemoglobin adduct levels were achieved at 12-18 hr and retained a plateau up to 72 hr postinjection in both rapid and slow acetylator congenic hamsters. 2-Aminofluorene-hemoglobin adduct levels did not differ significantly between young (5-6 weeks) and old (32-49 weeks) hamsters or between male and female hamsters within either acetylator genotype. 2-Aminofluorene-hemoglobin adduct levels increased in a dose-dependent manner (r = 0.95, p = 0.0001) and were consistently higher in slow versus rapid acetylator congenic hamsters in studies of both time-course and dose-effect. The magnitude of the acetylator genotype-dependent difference was a function of dose; 2-aminofluorene-hemoglobin adduct levels were 1.5-fold higher in slow acetylator congenic hamsters following a 60 mg/kg 2-aminofluorene dose (p = 0.0013) but 2-fold higher following a 100 mg/kg 2-aminofluorene dose (p < 0.0001). These results show a specific and significant role for NAT2 acetylator genotype in formation of arylamine-hemoglobin adducts, which may reflect the relationship between acetylator genotype and the incidence of different cancers from arylamine exposures. PMID:8291051

  5. The multitude and diversity of environmental carcinogens

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1986-07-15

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

  8. Refined carbohydrate enhancement of aberrant crypt foci (ACF) in rat colon induced by the food-borne carcinogen 2-amino-3-methyl-imidazo[4,5-f]quinoline (IQ)

    DEFF Research Database (Denmark)

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

    1996-01-01

    ,2-dimethylhydrazine dihydrochloride (DMH) and azoxymethane (AOM), the use of a diet-related colon cancer initiator, such as the heterocyclic amine 2-amino-3-methyl-imidazo[4,5-f]quinoline (IQ) formed during meat cooking, would probably give a more relevant insight into diet-related colon carcinogenesis. In the...... present study it is shown that a feeding regimen with continuous low IQ doses (0.03% in the diet) throughout a study period of 10 weeks has a significant effect on the induction of ACF in the colon of male F344 rats. In addition, the study illustrates that the incidence of the IQ-induced ACF can be...

  9. Gene discovery in the hamster: a comparative genomics approach for gene annotation by sequencing of hamster testis cDNAs

    Directory of Open Access Journals (Sweden)

    Khan Shafiq A

    2003-06-01

    Full Text Available Abstract Background Complete genome annotation will likely be achieved through a combination of computer-based analysis of available genome sequences combined with direct experimental characterization of expressed regions of individual genomes. We have utilized a comparative genomics approach involving the sequencing of randomly selected hamster testis cDNAs to begin to identify genes not previously annotated on the human, mouse, rat and Fugu (pufferfish genomes. Results 735 distinct sequences were analyzed for their relatedness to known sequences in public databases. Eight of these sequences were derived from previously unidentified genes and expression of these genes in testis was confirmed by Northern blotting. The genomic locations of each sequence were mapped in human, mouse, rat and pufferfish, where applicable, and the structure of their cognate genes was derived using computer-based predictions, genomic comparisons and analysis of uncharacterized cDNA sequences from human and macaque. Conclusion The use of a comparative genomics approach resulted in the identification of eight cDNAs that correspond to previously uncharacterized genes in the human genome. The proteins encoded by these genes included a new member of the kinesin superfamily, a SET/MYND-domain protein, and six proteins for which no specific function could be predicted. Each gene was expressed primarily in testis, suggesting that they may play roles in the development and/or function of testicular cells.

  10. The ISS Carcinogens Data Bank (BDC)

    International Nuclear Information System (INIS)

    The Data Bank on Carcinogens (Banca Dati Cancerogeni, BDC) is a factual data bank, available on the Istituto Superiore di Sanita web site, aimed at supporting the risk management decision making of central and local administrators. It can also represent a valuable tool for industry. The available information on carcinogenicity evaluations/classifications produced by European Union and by other institutions (IARC, USEPA, NTP, CCTN) is presented in a concise form accompanied by bibliographic references enabling the users to consult the original sources and, in some cases, to be directly connected to the relevant web site. The classifications carried out by each organization in accordance with its own criteria assign the examined agents to specific qualitative categories and do not include quantitative assessment. BDC intends to provide an easy tool for experts, researchers and risk managers dealing with carcinogenic agents

  11. Carcinogenic potential of various energy sources

    International Nuclear Information System (INIS)

    Evaluation of the health impacts of different sources of energy should include a comparison of the potential carcinogenic effects of the radioactive and chemical substances produced by various sources. In general, these potential health effects are too small to be measured directly and are therefore estimated by extrapolation, on the basis of a linear dose-response model, from measurable effects at high dose levels. Estimates of the carcinogenic potential of various energy sources available in North America are given in this paper. For most if not all of the energy sources for which data are currently available, it would appear that the known biological benefits in terms of life expectancy greatly outweigh all the potential harm due to carcinogenic (and genetic) effects on human beings, when expressed in the same terms, i.e. life expectancy. (author)

  12. Bioactivation of diethylstilbestrol by the Syrian hamster kidney

    Energy Technology Data Exchange (ETDEWEB)

    Adams, S.P.

    1987-01-01

    Male Syrian golden hamsters chronically exposed to diethylstilbestrol (DES) develop renal adenocarcinomas with an incidence approaching 100%. The ability of the hamster kidney to bioactivate DES was assessed using hamster kidney slices. The male hamster renal cortex has a 2- to 5-fold greater capacity to irreversibly bind ({sup 3}H)DES as compared with female hamster renal cortex and with male hamster renal medulla. Incubation of the tissue under anaerobic conditions inhibited the metabolism and irreversible binding of ({sup 3}H)DES. Gel electrophoresis analysis of covalently modified proteins revealed several radioactive peaks indicating that specific adduct formation had occurred. The cytochrome P-450 inhibitors SKF 525-A, metyrapone, carbon monoxide, butylated hydroxytoluene, and dicumarol decreased the irreversible binding of ({sup 3}H)DES to renal cortical protein by 38 to 72%.

  13. Bioactivation of diethylstilbestrol by the Syrian hamster kidney

    International Nuclear Information System (INIS)

    Male Syrian golden hamsters chronically exposed to diethylstilbestrol (DES) develop renal adenocarcinomas with an incidence approaching 100%. The ability of the hamster kidney to bioactivate DES was assessed using hamster kidney slices. The male hamster renal cortex has a 2- to 5-fold greater capacity to irreversibly bind [3H]DES as compared with female hamster renal cortex and with male hamster renal medulla. Incubation of the tissue under anaerobic conditions inhibited the metabolism and irreversible binding of [3H]DES. Gel electrophoresis analysis of covalently modified proteins revealed several radioactive peaks indicating that specific adduct formation had occurred. The cytochrome P-450 inhibitors SKF 525-A, metyrapone, carbon monoxide, butylated hydroxytoluene, and dicumarol decreased the irreversible binding of [3H]DES to renal cortical protein by 38 to 72%

  14. Carcinogenicity tests of N-nitroso derivatives of two drugs, phenmetrazine and methylphenidate

    Energy Technology Data Exchange (ETDEWEB)

    Lijinsky, W.; Taylor, H.W.

    1976-01-01

    Two commonly used drugs that are derivatives of cyclic secondary amines, phenmetrazine and methylphenidate, were converted to their N-nitroso derivatives by reaction with nitrite in acid solution, and the products were tested by chronic administration to rats in doses comparable with those used to test the unsubstituted parent nitrosamines. No tumors were seen that could be attributed to these nitrosamines, and it is concluded that, under these conditions, neither compound is carcinogenic.

  15. 5-azacytidine induces micronuclei in and morphological transformation of Syrian hamster embryo fibroblasts in the absence of unscheduled DNA synthesis

    OpenAIRE

    Stopper, Helga; Pechan, R; Schiffmann, D

    2012-01-01

    lt is known that 5-azacytidine (5-AC) induces tumors in several organs of rats and mice. The mechanisms of these effects are still poorly understood although it is known that 5-AC can be incorporated into DNA. Furthermore, it can inhibit DNA methylation. The known data on its clastogenic andjor gene mutation-inducing potential are still controversial. Therefore, we have investigated the kinds of genotoxic effects caused by 5-AC in Syrian hamster embryo (SHE) fibroblasts. Three different endp6...

  16. Oxytocin inhibits aggression in female Syrian hamsters.

    Science.gov (United States)

    Harmon, A C; Huhman, K L; Moore, T O; Albers, H E

    2002-12-01

    Dominant subordinate relationships are formed as the result of social conflict and are maintained at least in part by communication. At this time, little is known about the neural mechanisms that are responsible for coordinating the social behaviours (e.g. aggression) that occur in association with the formation and maintenance of these relationships. The purpose of the present study was to investigate the role of oxytocin (OXT) within the medial preoptic anterior hypothalamic continuum (MPOA-AH) in the control of aggression in female hamsters. OXT injected into the MPOA-AH immediately before testing significantly reduced the duration of aggression in a dose-dependent manner. Injection of an OXT antagonist 30 min before testing significantly increased the duration of aggression. In contrast, the duration of aggression was not altered when hamsters were tested either 30 min after injection of OXT or immediately following injection of an OXT-antagonist. These data support the hypothesis that OXT release within the MPOA-AH regulates social behaviours important in the formation and maintenance of dominant subordinate relationships in female hamsters. PMID:12472877

  17. Inhibitory Effect of 1α-Hydroxyvitamin D3 on N-nitrosobis (2-oxopropyl)Amine-induced Cholangiocarcinogenesis in Syrian Hamsters

    OpenAIRE

    Kawaura, Akihiko; Tanida,Noritoshi; Akiyama, Junichi; Nonaka,Kouji; Mizutani,Masatoshi; Sawada, Kenji; Nakagawa, Kimie; Tsugawa,Naoko; Izumi, Keisuke; Ii,Kunio; Okano, Toshio; Takeda, Eiji

    2011-01-01

    Sixty-three male 5-week-old Syrian hamsters received the carcinogen N-nitrosobis(2-oxopropyl)amine (BOP) s.c. in 5 weekly injections (the first, 70mg/kg body, and the remaining, 20mg/kg each). The hamsters that received BOP were given intragastric administration of 0.2ml of medium chain triglyceride (MCT) with or without 0.04μg of 1α-hydroxyvitamin D3 [1α(OH)D3] through a feeding tube for 12 weeks. Thus, 3 groups were assigned:Group 1;BOP alone (n=20), Group 2;BOP+MCT (n=18) and Group 3;BOP+1...

  18. Tumor-related gene changes in immunosuppressive Syrian hamster cholangiocarcinoma.

    Science.gov (United States)

    Juasook, Amornrat; Aukkanimart, Ratchadawan; Boonmars, Thidarut; Sudsarn, Pakkayanee; Wonkchalee, Nadchanan; Laummaunwai, Porntip; Sriraj, Pranee

    2013-10-01

    The results of a previous study demonstrated that prednisolone enhanced cholangiocarcinogenesis. Therefore, to clarify molecular changes during immunosuppressive cholangiocarcinogenesis, Syrian hamsters were divided into 8 groups: uninfected controls; immunosuppressed Syrian hamsters using prednisolone (P); normal Syrian hamsters administered N-nitrosodimethylamine (ND); immunosuppressed Syrian hamsters administered N-nitrosodimethylamine (NDis); normal Syrian hamsters infected with Opisthorchis viverrini (OV); immunosuppressed Syrian hamsters infected with O. viverrini (OVis); normal Syrian hamsters infected with O. viverrini and administered N-nitrosodimethylamine (CCA); and immunosuppressed Syrian hamsters infected with O. viverrini and administered N-nitrosodimethylamine (CCAis). Syrian hamster livers were used for analysis of tumor-related gene expression and immunohistochemistry through cytokeratin 19 (CK19) and proliferating cell nuclear antigen (PCNA) staining. The tumor-related gene expression results show that CCAis groups at all time points exhibited upregulation of COX-2, IL-6, SOD1, CAT and iNOS and downregulation of p53, which correlated with the predominant expression of CK19 and PCNA in liver tissue. These results suggest that prednisolone enhances cholangiocarcinoma development, which was confirmed by molecular changes. PMID:23645518

  19. Mechanisms of cellular transformation by carcinogenic agents

    International Nuclear Information System (INIS)

    This book contains 14 chapters. Some of the chapter titles are: DNA Modification by Chemical Carcinogens; Role of DNA Lesions and Repair in the Transformation of Human Cells; The Induction and Regulation of Radiogenic Transformation In Vitro: Cellular and Molecular Mechanisms; Cellular Transformation by Adenoviruses; and The fos Gene

  20. Biomonitoring human exposure to environmental carcinogenic chemicals

    DEFF Research Database (Denmark)

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

    1996-01-01

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

  1. Mechanisms of cellular transformation by carcinogenic agents

    Energy Technology Data Exchange (ETDEWEB)

    Grunberger, D.; Goff, S.P.

    1987-01-01

    This book contains 14 chapters. Some of the chapter titles are: DNA Modification by Chemical Carcinogens; Role of DNA Lesions and Repair in the Transformation of Human Cells; The Induction and Regulation of Radiogenic Transformation In Vitro: Cellular and Molecular Mechanisms; Cellular Transformation by Adenoviruses; and The fos Gene.

  2. Carcinogenic effects of radiation-introduction

    International Nuclear Information System (INIS)

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2004-10-01

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

  4. Predictions for the outcome of rodent carcinogenicity bioassays: identification of trans-species carcinogens and noncarcinogens.

    OpenAIRE

    Tennant, R W; Spalding, J.

    1996-01-01

    Thirty chemicals or substances currently undergoing long-term carcinogenicity bioassays in rodents have been used in a project to further evaluate methods and information that may have the capability of predicting potential carcinogens. In our predictions the principal information used includes structural alerts and in vitro test results for Salmonella mutagenicity, relative subchronic toxicity, and the sites and types of pathology found in subchronic (90-day) studies. This group of chemicals...

  5. Multicomponent criteria for predicting carcinogenicity: dataset of 30 NTP chemicals.

    OpenAIRE

    Huff, J; Weisburger, E; Fung, V A

    1996-01-01

    This article is in response to the challenge issued to the scientific community by the National Toxicology Program to predict the carcinogenicity potential of 30 chemicals previously selected for long-term carcinogenicity testing. Utilizing the available toxicologic, genetic, and structural information on 30 chemicals previously selected for long-term carcinogenicity testing, we predict that 16 chemicals (53%) would induce some indication of carcinogenic activity in rodents; we further predic...

  6. EVALUATION OF THE POTENTIAL CARCINOGENICITY OF COKE OVEN EMISSIONS

    Science.gov (United States)

    Coke oven emissions are known human carcinogens, classified as weight-of-evidence Group A under the EPA Guidelines for Carcinogen Risk Assessment (U.S. EPA, 1986a). vidence on potential carcinogenicity from animal studies is "Sufficient,". and the evidence rom human studies is "S...

  7. EVALUATION OF THE POTENTIAL CARCINOGENICITY OF TRYPAN BLUE

    Science.gov (United States)

    Trypan blue is a probable human carcinogen, classified as weight-of-evidence Group B2 under the EPA Guidelines for Carcinogen Risk Assessment (U.S. EPA, 1986a). vidence on potential carcinogenicity from animal studies is "Sufficient," and the evidence from human studies is "No Da...

  8. Ochratoxin A: An overview on toxicity and carcinogenicity in animals and humans.

    Science.gov (United States)

    Pfohl-Leszkowicz, Annie; Manderville, Richard A

    2007-01-01

    Ochratoxin A (OTA) is a ubiquitous mycotoxin produced by fungi of improperly stored food products. OTA is nephrotoxic and is suspected of being the main etiological agent responsible for human Balkan endemic nephropathy (BEN) and associated urinary tract tumours. Striking similarities between OTA-induced porcine nephropathy in pigs and BEN in humans are observed. International Agency for Research on Cancer (IARC) has classified OTA as a possible human carcinogen (group 2B). Currently, the mode of carcinogenic action by OTA is unknown. OTA is genotoxic following oxidative metabolism. This activity is thought to play a central role in OTA-mediated carcinogenesis and may be divided into direct (covalent DNA adduction) and indirect (oxidative DNA damage) mechanisms of action. Evidence for a direct mode of genotoxicity has been derived from the sensitive 32P-postlabelling assay. OTA facilitates guanine-specific DNA adducts in vitro and in rat and pig kidney orally dosed, one adduct comigrates with a synthetic carbon (C)-bonded C8-dG OTA adduct standard. In this paper, our current understanding of OTA toxicity and carcinogenicity are reviewed. The available evidence suggests that OTA is a genotoxic carcinogen by induction of oxidative DNA lesions coupled with direct DNA adducts via quinone formation. This mechanism of action should be used to establish acceptable intake levels of OTA from human food sources. PMID:17195275

  9. Radiation-induced anorexia in Syrian hamsters

    International Nuclear Information System (INIS)

    The recovery of Syrian hamsters after split dose application (interval 11 days) was studied on the basis of the weight response and of food uptake. Two periods of weight loss and anorexia can be distinguished, an early one immediately after irradiation and a secondary one 6-10 days later. The secondary response is a function of the radiation dose and allows to distinguish survivors from non-survivors, since it is much more pronounced and longerlasting in the latter than in the former. The first response appears not to be influenced by a previous conditioning irradiation. (orig.)

  10. Radiation-induced anorexia in Syrian hamsters

    Energy Technology Data Exchange (ETDEWEB)

    Kindt, A.; Sattler, E.L.; Schraub, A.

    1980-10-01

    The recovery of Syrian hamsters after split dose application (interval 11 days) was studied on the basis of the weight response and of food uptake. Two periods of weight loss and anorexia can be distinguished, an early one immediately after irradiation and a secondary one 6-10 days later. The secondary response is a function of the radiation dose and allows to distinguish survivors from non-survivors, since it is much more pronounced and longerlasting in the latter than in the former. The first response appears not to be influenced by a previous conditioning irradiation.

  11. The multitude and diversity of environmental carcinogens.

    OpenAIRE

    Belpomme, Dominique; Irigaray, Philippe; Hardell, Lennart; Clapp, Richard; Montagnier, Luc; Epstein, Slava; Sasco, Annie

    2007-01-01

    We have recently proposed that lifestyle-related factors, screening and aging cannot fully account for the present overall growing incidence of cancer. In order to propose the concept that in addition to lifestyle related factors, exogenous environmental factors may play a more important role in carcinogenesis than it is expected, and may therefore account for the growing incidence of cancer, we overview herein environmental factors, rated as certainly or potentially carcinogenic by the Inter...

  12. RADON AND CARCINOGENIC RISK IN MOSCOW

    Directory of Open Access Journals (Sweden)

    S. M. Golovanev

    2015-01-01

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

  13. Carcinogenic risk of hot-particle exposures

    International Nuclear Information System (INIS)

    It has been suggested that spatially non-uniform radiation exposures, such as those from small radioactive particles ('hot particles'), may be very much more carcinogenic than when the same amount of energy is deposited uniformly throughout a tissue volume. This review provides a brief summary of in vivo and in vitro experimental findings, and human epidemiology data, which can be used to evaluate the veracity of this suggestion. Overall, this supports the contrary view and indicates that average dose, as advocated by the ICRP, is likely to provide a reasonable estimate of carcinogenic risk (within a factor of ∼ ±3). There are few human data with which to address this issue. The limited data on lung cancer mortality following occupational inhalation of plutonium aerosols, and the incidence of liver cancer and leukaemia due to thorotrast administration for clinical diagnosis, do not appear to support a significant enhancement factor. Very few animal studies, including mainly lung and skin exposures, provide any indication of a hot-particle enhancement for carcinogenicity. Some recent in vitro malignant transformation experiments provide evidence for an enhanced cell transformation for hot-particle exposures but, properly interpreted, the effect is modest. Few studies extend below absorbed doses of ∼ 0.1 Gy. (review)

  14. Metabolism, genotoxicity, and carcinogenicity of comfrey.

    Science.gov (United States)

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

    2010-10-01

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

  15. Impact and compliance: OSHA Carcinogen Policy

    Energy Technology Data Exchange (ETDEWEB)

    Meyer, A.F. Jr.; Crowder, C.; Wisniewski, S.; Russell, T.; Senn, K.

    1980-06-26

    This document provides an examination of various aspects of the Occupational Safety and Health Administration (OSHA)Carcinogen Policy. To satisfy the dimensions of the Policy's broad, general nature, a two-fold approach was taken. Throughout, the focus is on the possible effects of the Policy's implementation, but this is first approached as it generally will effect research and compliance activities across broad industry sectors, while specific impacts on DOE are addressed separately. To overview and integrate these approaches, and to provide a quick reference for further information, an outline of information is presented. General or industry-wide applications are addressed both in the Summary and Overview of the Policy (Chapters I and II) and in the discussion of the Model Standard (Chapter V). Also included is a copy of the Policy itself in the General Industry Standards and interpretations Change 10. Sections specifically addressed to the major concerns of DOE and its contractors are a discussion of implications for action regarding the synthetic fuels program, a comparison of the OSHA Model Regulations and the FE OSH Manual Standards for Carcinogens, and finally, a list of known carcinogens in coal gasification/liquefaction. Together, these elements illustrate the broad scope of the policy's impact, which economic and other constraining consequences begin to become visible. Measures to minimize these consequences are a common underlying theme to each of the sections.

  16. Carcinogenic potential of hydrotreated petroleum aromatic extracts.

    Science.gov (United States)

    Doak, S M; Hend, R W; van der Wiel, A; Hunt, P F

    1985-06-01

    Five experimental petroleum extracts were produced from luboil distillates derived from Middle East paraffinic crude by solvent extraction and severe hydrotreatment. The polycyclic aromatic content (PCA) of the extracts was determined by dimethyl sulphoxide extraction and ranged from 3.7-9.2% w/w. The five extracts were evaluated for their potential to induce cutaneous and systemic neoplasia in female mice derived from Carworth Farm No 1 strain (CF1). The test substances were applied undiluted (0.2 ml per application) to the shorn dorsal skin twice weekly for up to 78 weeks, with 48 mice in each treatment group and 96 in the untreated control group; two further groups, each of 48 mice, were similarly treated either with a non-hydrotreated commercial aromatic extract (PCA content, 19.7% w/v) or with a low dose of benzo(a)pyrene (12.5 micrograms/ml acetone). The mice were housed individually in polypropylene cages in specified pathogen free conditions. The incidence of cutaneous and systemic tumours was determined from histological analysis of haematoxylin and eosin stained tissue sections. The results were correlated with the PCA content of the extracts and compared with those from female mice exposed to a non-hydrotreated commercial aromatic extract. Four of the hydrotreated extracts were carcinogenic for murine skin; the two products with the lower PCA contents were less carcinogenic than the products with the higher PCA contents and all were less carcinogenic than the commercial extract. One extract with the lowest PCA content was non-carcinogenic. Thus refining by severe hydrotreatment was an effective method of reducing the carcinogenic potential of petroleum aromatic extracts. Although other physicochemical properties may influence the biological activity of oil products, the PCA content determined by dimethyl sulphoxide extraction may be a useful indicator of the potential of oil products to induce cutaneous tumours in experimental animals. There was no

  17. Cultivation of hamster bone marrow haematopoietic stem and progenitor cells

    Directory of Open Access Journals (Sweden)

    Kovačević-Filipović Milica

    2010-01-01

    Full Text Available Hamster, a hibernating animal, is an important experimental model in research on the influence of hypothermia on different physiological processes. A simple procedure for cultivation and identification of hamster hematopoetic stem cells (HSC and hematopoetic progenitor cells (HPC is a premise for a successful investigation upon hypothermia effects on hematopoiesis. The aim of this work was to evaluate the utilization of commercially available methylcellulose media (MC and recombinant mouse and human cytokines for hamster HSC and HPC assays, in order to enable further studies on these cells. Hamster bone marrow mononuclear cells (BMMNC were plated in MC containing cytokines that support mouse or human HPC growth. Also, BMMNC were resuspended in cytokine supplemented liquid media and incubated for 5 weeks with a four day monitoring of viable cell number. We demonstrated that hamster hematopoietic progenitor cells committed for erythroid lineage and myeloid lineage successfully formed recognizable colonies in both mouse and human MC, while multipotent progenitor cells formed colonies only in mouse MC. We also defined conditions for the evaluation of hamster HSC activity in liquid cultures, based on continuous 5 weeks HSC proliferation. The obtained results verify the utilization of mouse specific MC for further research on hamster HPC biology during hypothermia.

  18. Radiation equivalency: A conceptual relationship for indexing the carcinogenic properties of radiation and environmental pollutants

    International Nuclear Information System (INIS)

    A Tier-Two type of bioassay complimentary to the National Cancer Institute whole-animal protocol has been proposed based upon relating the antitumor cell-mediated immune responses induced by the test substance to those immune effects induced by a localized exposure to X-rays, a concept which termed the substance's Radiation Equivalency. The conceptual principle for the Radiation Equivalency entails the hypothesis that a mutagenic/carcinogenic insult results in the development of transformed ''foreign-like'' cells which then initiate their specific recognition by the host's immune system. This immune sensitization can then be quantitated by measuring the increased injury and killing of cultured tumor cells by the now so-called educated peripheral blood lymphoid-cells obtained from the exposed animals. The authors proposed that all carcinogenic agents will interact with their particular organoismal components in a constant fashion to induce such antitumor immune responses, thus permitting the experimental results to be interpreted according to the Law of Mass Action. The findings have been accordingly described in terms of Michaelis-Menton kinetics with specific experimental comparisons in the rate presented between the colon carcinogen, 1,2-dimethylhydrazine (DMH), and the X-irradiation effects upon the localized hypoxic small bowel to obtain a Radiation Equivalency value for the chemical. Similar measurements have also been utilized for the analysis of mutagens/carcinogens present in the urine obtained from DMH-exposed rats such to arrive at its Radiation Equivalency. Previous findings have been summarized together, all of which suggest that the Radiation Equivalency concept may readily serve as a method for indexing the carcinogenic properties of various environmental pollutants

  19. Mutagenicity of comfrey (Symphytum Officinale) in rat liver.

    Science.gov (United States)

    Mei, N; Guo, L; Fu, P P; Heflich, R H; Chen, T

    2005-03-14

    Comfrey is a rat liver toxin and carcinogen that has been used as a vegetable and herbal remedy by humans. In order to evaluate the mechanisms underlying its carcinogenicity, we examined the mutagenicity of comfrey in the transgenic Big Blue rat model. Our results indicate that comfrey is mutagenic in rat liver and the types of mutations induced by comfrey suggest that its tumorigenicity results from the genotoxicity of pyrrolizidine alkaloids in the plant. PMID:15726100

  20. Mutagenicity of comfrey (Symphytum Officinale) in rat liver

    OpenAIRE

    MEI, N.; Guo, L.; Fu, P P; Heflich, R H; Chen, T.

    2005-01-01

    Comfrey is a rat liver toxin and carcinogen that has been used as a vegetable and herbal remedy by humans. In order to evaluate the mechanisms underlying its carcinogenicity, we examined the mutagenicity of comfrey in the transgenic Big Blue rat model. Our results indicate that comfrey is mutagenic in rat liver and the types of mutations induced by comfrey suggest that its tumorigenicity results from the genotoxicity of pyrrolizidine alkaloids in the plant.

  1. Susceptibility of Djungarian hamsters (Phodopus sungorus) to Neospora caninum infection.

    Science.gov (United States)

    Uchida, Yuko; Ike, Kazunori; Kurotaki, Tetsuro; Takeshi, Midori; Imai, Soichi

    2003-03-01

    Djungarian hamsters were examined for the susceptibility to Neospora caninum infection. After 29 Djungarian hamsters were intraperitoneally inoculated with 5 x 10(6) N. caninum tachyzoites of JPA1 strain, some animals showed symptoms such as ataxia, and many tissue cysts were detected in the brain and a cyst in the muscular tunics of stomach. Especially, more than 100 cysts per head were observed after 5 weeks post inoculation. It is suggested that the Djungarian hamster is a model useful to examine neosporosis. PMID:12679575

  2. Golden hamsters are nocturnal in captivity but diurnal in nature.

    Science.gov (United States)

    Gattermann, Rolf; Johnston, Robert E; Yigit, Nuri; Fritzsche, Peter; Larimer, Samantha; Ozkurt, Sakir; Neumann, Karsten; Song, Zhimin; Colak, Ercüment; Johnston, Joan; McPhee, M Elsbeth

    2008-06-23

    Daily activity rhythms are nearly universal among animals and their specific pattern is an adaptation of each species to its ecological niche. Owing to the extremely consistent nocturnal patterns of activity shown by golden hamsters (Mesocricetus auratus) in the laboratory, this species is a prime model for studying the mechanisms controlling circadian rhythms. In contrast to laboratory data, we discovered that female hamsters in the wild were almost exclusively diurnal. These results raise many questions about the ecological variables that shape the activity patterns in golden hamsters and the differences between laboratory and field results. PMID:18397863

  3. Remarkable Anticancer Activity of Teucrium polium on Hepatocellular Carcinogenic Rats

    Directory of Open Access Journals (Sweden)

    Ariyo Movahedi

    2014-01-01

    Full Text Available The term cancer has been concomitant with despair, agony, and dreadful death. Like many other diseases, herbal therapy has been used to prevent or suppress cancer. The present study investigated the capability of the decoction of Teucrium polium L. from Lamiaceae family to protect liver cells against hepatocellular carcinoma in carcinogenesis-induced animal model. After 28 weeks of treatment with decoction of Teucrium polium L., serum biochemical markers including ALT, AST, AFP, GGT, ALP, HCY, TNF-α, α2MG, and CBG have been regulated auspiciously. Total antioxidant status also has been increased intensely. Liver lesion score in treated group was lessened and glucocorticoid activity has been intensified significantly. In conclusion, Teucrium polium L. decoction might inhibit or suppress liver cancer development.

  4. Carcinogen-induced damage to DNA

    International Nuclear Information System (INIS)

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

  5. RADON AND CARCINOGENIC RISK IN MOSCOW

    OpenAIRE

    S. M. Golovanev

    2015-01-01

    Objective: comparative evaluation of carcinogenic risk inMoscowfrom radon in indoor and atmospheric pollutants.Materials and methods: the lung cancer incidence in Moscow; radiation-hygienic passport of the territory; .U.S. EPA estimated average age at all and radon induced deaths, years of life lost; Report of UNSCEAR 2006 and WHO handbook on indoor radon, 2009. Trend analysis of incidence; evaluation of the excess relative risk; assessment of ratio radon-induced population risk and published...

  6. Inhibitory Effect of 1α-Hydroxyvitamin D3 on N-nitrosobis (2-oxopropylAmine-induced Cholangiocarcinogenesis in Syrian Hamsters

    Directory of Open Access Journals (Sweden)

    Kawaura,Akihiko

    2011-06-01

    Full Text Available Sixty-three male 5-week-old Syrian hamsters received the carcinogen N-nitrosobis(2-oxopropylamine (BOP s.c. in 5 weekly injections (the first, 70mg/kg body, and the remaining, 20mg/kg each. The hamsters that received BOP were given intragastric administration of 0.2ml of medium chain triglyceride (MCT with or without 0.04μg of 1α-hydroxyvitamin D3 [1α(OHD3] through a feeding tube for 12 weeks. Thus, 3 groups were assigned:Group 1;BOP alone (n=20, Group 2;BOP+MCT (n=18 and Group 3;BOP+1α(OHD3 (n=25. The mean body weight of Group 3 was lower than those of Groups 1 and 2 at the end of the experiment (p<0.001,Tukey-Kramer HSD test. At the end of week 12, all surviving hamsters were put to sleep. The incidences of liver tumors were 80%, 72% and 32% in Groups 1, 2 and 3, respectively. The incidence of tumors in Group 3 was significantly lower than in Group 1 and Group 2 (p<0.05, χ2-test. All tumors were cholangiocarcinoma. These results indicated that BOP-induced cholangiocarcinogenesis was suppressed by the supplemental administration of 1α(OHD3.

  7. Inhibitory effect of 1α-hydroxyvitamin D3 on N-nitrosobis(2-oxopropyl)amine-induced cholangiocarcinogenesis in Syrian hamsters.

    Science.gov (United States)

    Kawaura, Akihiko; Tanida, Noritoshi; Akiyama, Junichi; Nonaka, Kouji; Mizutani, Masatoshi; Sawada, Kenji; Nakagawa, Kimie; Tsugawa, Naoko; Izumi, Keisuke; Ii, Kunio; Okano, Toshio; Takeda, Eiji

    2011-06-01

    Sixty-three male 5-week-old Syrian hamsters received the carcinogen N-nitrosobis(2-oxopropyl)amine (BOP) s.c. in 5 weekly injections (the first, 70 mg/kg body, and the remaining, 20mg/kg each). The hamsters that received BOP were given intragastric administration of 0.2 ml of medium chain triglyceride (MCT) with or without 0.04 μg of 1α-hydroxyvitamin D3 [1α(OH)D3] through a feeding tube for 12 weeks. Thus, 3 groups were assigned:Group 1;BOP alone (n=20), Group 2;BOP+MCT (n=18) and Group 3;BOP+1α(OH)D3 (n=25). The mean body weight of Group 3 was lower than those of Groups 1 and 2 at the end of the experiment (p<0.001,Tukey-Kramer HSD test). At the end of week 12, all surviving hamsters were put to sleep. The incidences of liver tumors were 80%, 72% and 32% in Groups 1, 2 and 3, respectively. The incidence of tumors in Group 3 was significantly lower than in Group 1 and Group 2 (p<0.05, χ2-test). All tumors were cholangiocarcinoma. These results indicated that BOP-induced cholangiocarcinogenesis was suppressed by the supplemental administration of 1α(OH)D3. PMID:21709717

  8. Lipids of hamster cheek pouch epithelium.

    Science.gov (United States)

    Whittle, S; Swartzendruber, D C; Kremer, M; Squier, C A; Wertz, P W

    1997-09-01

    The hamster cheek pouch is a much used but incompletely understood experimental model. In particular, the cheek pouch epithelial lipids, which are important for permeability barrier function as well as other aspects of epithelial biology, have not been completely characterized. In the present study, the complete lipid class composition has been determined by thin-layer chromatography in conjunction with photodensitometry. The major lipid classes were phospholipids, free sterols, and ceramides. Minor amounts of monohexosylceramides, sterol esters, fatty acids, and triglycerides were also present. Significant amounts of covalently bound omega-hydroxyceramide was also detected. Transmission electron micrographs reveal extensive, largely paired, lipid bilayers in the intercellular spaces of the stratum corneum. PMID:9307937

  9. Proteomic Analysis of Chinese Hamster Ovary Cells

    DEFF Research Database (Denmark)

    Baycin-Hizal, Deniz; Tabb, David L.; Chaerkady, Raghothama; Chen, Lily; Lewis, Nathan; Nagarajan, Harish; Sarkaria, Vishaldeep; Kumar, Amit; Wolozny, Daniel; Colao, Joe; Jacobson, Elena; Tian, Yuan; O’Meally, Robert N.; Krag, Sharon S.; Cole, Robert N.; Palsson, Bernhard; Zhang, Hui; Betenbaugh, Michael

    2012-01-01

    this analysis, the CHO codon frequency was determined and found to be distinct from humans, which will facilitate expression of human proteins in CHO cells. Analysis of the combined proteomic and mRNA data sets indicated the enrichment of a number of pathways including protein processing and apoptosis......To complement the recent genomic sequencing of Chinese hamster ovary (CHO) cells, proteomic analysis was performed on CHO cells including the cellular proteome, secretome, and glycoproteome using tandem mass spectrometry (MS/MS) of multiple fractions obtained from gel electrophoresis...... identified from both glycoproteome and proteome analysis, representing an 8-fold increase in the number of proteins currently identified in the CHO proteome. Furthermore, this is the first proteomic study done using the CHO genome exclusively, which provides for more accurate identification of proteins. From...

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

    International Nuclear Information System (INIS)

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

  11. Trace elements and carcinogenicity: a subject in review

    OpenAIRE

    Mulware, Stephen Juma

    2012-01-01

    Cancer is known to be a multi-step process, which involves different stages including initiation, promotion, progression and metastasis. Chemical carcinogens including most trace elements can change any of these processes to induce their carcinogenic effects. Various studies confirm that cancer arises from the accumulation of irreversible DNA damage, which results from multiple mutations in critical genes in the body organ. Chemical carcinogens most often directly or after xenobiotic metaboli...

  12. A review of mechanisms of acrylamide carcinogenicity.

    Science.gov (United States)

    Besaratinia, Ahmad; Pfeifer, Gerd P

    2007-03-01

    The fact that acrylamide, a proven rodent carcinogen, is present in significant quantities (up to several mg/kg of foodstuff) in a wide range of commonly consumed human foods is alarming. Attempts to determine a possible involvement of dietary acrylamide in human cancers have not been conclusive, however. To resolve the carcinogenicity of acrylamide to humans, the as yet unknown mechanism of action of acrylamide needs to be unraveled. The present review is a synopsis of research on the known and hypothetical modes of action of acrylamide of relevance for carcinogenesis. Both genotoxic and non-genotoxic modes of action of acrylamide are discussed with special emphasis on DNA adduct-targeted mutagenesis. Mechanistic data are presented from various experimental systems including in vitro experiments and in vivo rodent and human studies with special focus on mouse models. Human exposure data, including estimates of daily intake of dietary acrylamide in different populations and the corresponding cancer risk assessments are provided. The significant gaps in knowledge, which currently preclude a more definitive evaluation of human cancer risk due to exposure to dietary acrylamide, are highlighted. Future directions for research on acrylamide and cancer are outlined, and potential challenges are underscored. PMID:17234719

  13. Estimation of carcinogenicity using molecular fragments tree.

    Science.gov (United States)

    Wang, Yong; Lu, Jing; Wang, Fei; Shen, Qiancheng; Zheng, Mingyue; Luo, Xiaomin; Zhu, Weiliang; Jiang, Hualiang; Chen, Kaixian

    2012-08-27

    Carcinogenicity is an important toxicological endpoint that poses high concern to drug discovery. In this study, we developed a method to extract structural alerts (SAs) and modulating factors of carcinogens on the basis of statistical analyses. First, the Gaston algorithm, a frequent subgraph mining method, was used to detect substructures that occurred at least six times. Then, a molecular fragments tree was built and pruned to select high-quality SAs. The p-value of the parent node in the tree and that of its children nodes were compared, and the nodes that had a higher statistical significance in binomial tests were retained. Finally, modulating factors that suppressed the toxic effects of SAs were extracted by three self-defining rules. The accuracy of the 77 SAs plus four SA/modulating factor pairs model for the training set, and the test set was 0.70 and 0.65, respectively. Our model has higher predictive ability than Benigni's model, especially in the test set. The results highlight that this method is preferable in terms of prediction accuracy, and the selected SAs are useful for prediction as well as interpretation. Moreover, our method is convenient to users in that it can extract SAs from a database using an automated and unbiased manner that does not rely on a priori knowledge of mechanism of action. PMID:22834690

  14. Experimental Models in Syrian Golden Hamster Replicate Human Acute Pancreatitis

    OpenAIRE

    Yunan Wang; Abudurexiti Kayoumu; Guotao Lu; Pengfei Xu; Xu Qiu; Liye Chen; Rong Qi; Shouxiong Huang; Weiqin Li; Yuhui Wang; George Liu

    2016-01-01

    The hamster has been shown to share a variety of metabolic similarities with humans. To replicate human acute pancreatitis with hamsters, we comparatively studied the efficacy of common methods, such as the peritoneal injections of caerulein, L-arginine, the retrograde infusion of sodium taurocholate, and another novel model with concomitant administration of ethanol and fatty acid. The severity of pancreatitis was evaluated by serum amylase activity, pathological scores, myeloperoxidase acti...

  15. Clozapine chronically suppresses alcohol drinking in Syrian golden hamsters

    OpenAIRE

    Chau, David T; Gulick, Danielle; Xie, Haiyi; Dawson, Ree; Green, Alan I.

    2009-01-01

    Alcohol use disorder is common in patients with schizophrenia and is associated with poor clinical outcomes. Preliminary reports from our group and others suggest that the atypical antipsychotic clozapine may decrease alcohol use in these patients. We have previously shown that clozapine suppresses alcohol consumption for 9 days in Syrian golden hamsters. Here, we assessed the effects of clozapine on alcohol consumption in hamsters over a 27-day period, using a continuous access, 2-bottle (15...

  16. Asymmetric learning to avoid heterospecific males in Mesocricetus hamsters

    OpenAIRE

    delBarco-Trillo, Javier; Johnston, Robert E.

    2012-01-01

    If a female mates with a male of a closely related species, her fitness is likely to decline. Consequently, females may develop behavioral mechanisms to avoid mating with heterospecific males. In some species, one such mechanism is for adult females to learn to discriminate against heterospecific males after exposure to such males. We have previously shown that adult, female Syrian hamsters (Mesocricetus auratus) learn to discriminate against male Turkish hamsters (Mesocricetus brandti) after...

  17. Experience-Independent Development of the Hamster Circadian Visual System

    OpenAIRE

    Kampf-Lassin, August; Wei, Jenny; Galang, Jerome; Prendergast, Brian J

    2011-01-01

    Experience-dependent functional plasticity is a hallmark of the primary visual system, but it is not known if analogous mechanisms govern development of the circadian visual system. Here we investigated molecular, anatomical, and behavioral consequences of complete monocular light deprivation during extended intervals of postnatal development in Syrian hamsters. Hamsters were raised in constant darkness and opaque contact lenses were applied shortly after eye opening and prior to the introduc...

  18. Cultivation of hamster bone marrow haematopoietic stem and progenitor cells

    OpenAIRE

    Kovačević-Filipović Milica; Okić Ivana; Petrićević Tanja; Mojsilović S.; Krstić Aleksandra; Jovčić Gordana; Bugarski Diana; Milenković P.; Petakov Marijana; Radovanović Anita; Božić Tatjana; Ivanović Z.

    2010-01-01

    Hamster, a hibernating animal, is an important experimental model in research on the influence of hypothermia on different physiological processes. A simple procedure for cultivation and identification of hamster hematopoetic stem cells (HSC) and hematopoetic progenitor cells (HPC) is a premise for a successful investigation upon hypothermia effects on hematopoiesis. The aim of this work was to evaluate the utilization of commercially available methylcellulose media (MC) and recombinant mouse...

  19. Fasting-induced daily torpor in desert hamsters (Phodopus roborovskii).

    Science.gov (United States)

    Chi, Qing-Sheng; Wan, Xin-Rong; Geiser, Fritz; Wang, De-Hua

    2016-09-01

    Daily torpor is frequently expressed in small rodents when facing energetically unfavorable ambient conditions. Desert hamsters (Phodopus roborovskii, ~20g) appear to be an exception as they have been described as homeothermic. However, we hypothesized that they can use torpor because we observed reversible decreases of body temperature (Tb) in fasted hamsters. To test this hypothesis we (i) randomly exposed fasted summer-acclimated hamsters to ambient temperatures (Tas) ranging from 5 to 30°C or (ii) supplied them with different rations of food at Ta 23°C. All desert hamsters showed heterothermy with the lowest mean Tb of 31.4±1.9°C (minimum, 29.0°C) and 31.8±2.0°C (minimum, 29.0°C) when fasted at Ta of 23°C and 19°C, respectively. Below Ta 19°C, the lowest Tb and metabolic rate increased and the proportion of hamsters using heterothermy declined. At Ta 5°C, nearly all hamsters remained normothermic by increasing heat production, suggesting that the heterothermy only occurs in moderately cold conditions, perhaps to avoid freezing at extremely low Tas. During heterothermy, Tbs below 31°C with metabolic rates below 25% of those during normothermia were detected in four individuals at Ta of 19°C and 23°C. Consequently, by definition, our observations confirm that fasted desert hamsters are capable of shallow daily torpor. The negative correlation between the lowest Tbs and amount of food supply shows that heterothermy was mainly triggered by food shortage. Our data indicate that summer-acclimated desert hamsters can express fasting-induced shallow daily torpor, which may be of significance for energy conservation and survival in the wild. PMID:27215346

  20. Golden hamsters are nocturnal in captivity but diurnal in nature

    OpenAIRE

    GATTERMANN, Rolf; Johnston, Robert E; Yigit, Nuri; Fritzsche, Peter; Larimer, Samantha; Özkurt, Sakir; Neumann, Karsten; Song, Zhimin; Colak, Ercüment; Johnston, Joan; McPhee, M. Elsbeth

    2008-01-01

    Daily activity rhythms are nearly universal among animals and their specific pattern is an adaptation of each species to its ecological niche. Owing to the extremely consistent nocturnal patterns of activity shown by golden hamsters (Mesocricetus auratus) in the laboratory, this species is a prime model for studying the mechanisms controlling circadian rhythms. In contrast to laboratory data, we discovered that female hamsters in the wild were almost exclusively diurnal. These results raise m...

  1. Fluoxetine does not prevent interspecific mating between two hamster species

    OpenAIRE

    delBarco-Trillo, Javier; Johnston, Robert E.

    2010-01-01

    In a recent study we showed that female Syrian hamsters (Mesocricetus auratus) from a laboratory stock readily mated with male Turkish hamsters (M. brandti). We hypothesized that captivity and/or unconscious selection of the most receptive females by researchers or animal caretakers results in heightened female sexual receptivity and reduces the tendency to reject heterospecific males. To test this hypothesis, we decided to decrease female receptivity by injection of fluoxetine, which increas...

  2. Seasonal aspects of sleep in the Djungarian hamster

    OpenAIRE

    Deboer Tom; Palchykova Svitlana; Tobler Irene

    2003-01-01

    Abstract Background Changes in photoperiod and ambient temperature trigger seasonal adaptations in the physiology and behaviour of many species, including the Djungarian hamster. Exposure of the hamsters to a short photoperiod and low ambient temperature leads to a reduction of the polyphasic distribution of sleep and waking over the light and dark period. In contrast, a long photoperiod enhances the daily sleep-wake amplitude leading to a decline of slow-wave activity in NREM sleep within th...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1990-12-01

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

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

    International Nuclear Information System (INIS)

    Liver fatty acid binding protein (L-FABP) is the principal target protein of the hepatic carcinogen N-(2-fluorenyl)acetamide (2-acetylaminofluorene) in rat liver. In addition, the cyclopentenone prostaglandins (PG), PGA, PGJ2, and Δ12-PGJ2, inhibit the growth of many cell types in vitro. This report describes the preferential binding of the growth inhibitory prostaglandins by L-FABP and the reversible inhibition of thymidine incorporation into DNA by PGA2 and Δ12-PGJ2 in primary cultures of purified rat hepatocytes. As a model ligand, [3H]PGA1 bound to L-FABP specifically, reversibly, rapidly, and with high affinity. Its dissociation constants were 134 nM (high affinity) and 3.6 μM (low affinity). The high-affinity finding of [3H]PGA1 correlated with their growth inhibitory activities reported previously and here. The in vitro actions of L-FABP are compatible with those of a specific and dissociable carrier of growth inhibitory prostaglandins in rat hepatocytes and suggest that the carcinogen may usurp the cellular machinery of the growth inhibitory prostaglandins

  5. A Hamster Model of Diet-Induced Obesity for Preclinical Evaluation of Anti-Obesity, Anti-Diabetic and Lipid Modulating Agents.

    Directory of Open Access Journals (Sweden)

    Louise S Dalbøge

    Full Text Available Unlike rats and mice, hamsters develop hypercholesterolemia, and hypertriglyceridemia when fed a cholesterol-rich diet. Because hyperlipidemia is a hallmark of human obesity, we aimed to develop and characterize a novel diet-induced obesity (DIO and hypercholesterolemia Golden Syrian hamster model.Hamsters fed a highly palatable fat- and sugar-rich diet (HPFS for 12 weeks showed significant body weight gain, body fat accumulation and impaired glucose tolerance. Cholesterol supplementation to the diet evoked additional hypercholesterolemia. Chronic treatment with the GLP-1 analogue, liraglutide (0.2 mg/kg, SC, BID, 27 days, normalized body weight and glucose tolerance, and lowered blood lipids in the DIO-hamster. The dipeptidyl peptidase-4 (DPP-4 inhibitor, linagliptin (3.0 mg/kg, PO, QD also improved glucose tolerance. Treatment with peptide YY3-36 (PYY3-36, 1.0 mg/kg/day or neuromedin U (NMU, 1.5 mg/kg/day, continuously infused via a subcutaneous osmotic minipump for 14 days, reduced body weight and energy intake and changed food preference from HPFS diet towards chow. Co-treatment with liraglutide and PYY3-36 evoked a pronounced synergistic decrease in body weight and food intake with no lower plateau established. Treatment with the cholesterol uptake inhibitor ezetimibe (10 mg/kg, PO, QD for 14 days lowered plasma total cholesterol with a more marked reduction of LDL levels, as compared to HDL, indicating additional sensitivity to cholesterol modulating drugs in the hyperlipidemic DIO-hamster. In conclusion, the features of combined obesity, impaired glucose tolerance and hypercholesterolemia in the DIO-hamster make this animal model useful for preclinical evaluation of novel anti-obesity, anti-diabetic and lipid modulating agents.

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

    OpenAIRE

    S H Khan; Sorof, S

    1990-01-01

    Liver fatty acid binding protein (L-FABP) is the principal target protein of the hepatic carcinogen N-(2-fluorenyl)acetamide (2-acetylaminofluorene) in rat liver. In addition, the cyclopentenone prostaglandins (PG), PGA, PGJ2, and delta 12-PGJ2, inhibit the growth of many cell types in vitro. This report describes the preferential binding of the growth inhibitory prostaglandins by L-FABP and the reversible inhibition of thymidine incorporation into DNA by PGA2 and delta 12-PGJ2 in primary cul...

  7. Studies on the biological effects of internal exposure of alpha emitters. Carcinogenicity test of plutonium

    International Nuclear Information System (INIS)

    Outlines of carcinogenicity tests in animals given with injected or inhaled plutonium (Pu) were described. Insoluble 239PuO2 particles were nasally inhaled in rats maintained for life. The dose response relationship between incidence of their lung tumor and absorbed radiation dose in the lung revealed that>1 Gy dose increased the incidence of malignant lung tumors, which differed from findings in the U.S. probably due to the difference between particle sizes. Further, a carcinogenic mechanism specific for alpha-ray was suggested based on tumor-related gene analysis. After soluble 239Pu (citrate salt) was injected in mice, significant reduction of lifetime and early tumor- or non-tumor-death were observed when the bone dose exceeded 3 Gy. Tumors were mostly osteosarcoma, lymphoma and other soft tissue solid cancers and were different from those induced by gamma-ray, X-ray and neutron irradiation. Studies on the strain difference, on the carcinogenic mechanism and alpha-ray induced mutation and transformation are in progress, which may lead to elucidation of the biological effects of internal exposure of alpha-emitters. (K.H.)

  8. An update on direct genotoxicity as a molecular mechanism of ochratoxin a carcinogenicity.

    Science.gov (United States)

    Pfohl-Leszkowicz, Annie; Manderville, Richard A

    2012-02-20

    Ochratoxin A (OTA) is a naturally occurring chlorophenolic fungal toxin that contaminates a wide range of food products and poses a cancer threat to humans. The mechanism of action (MOA) for OTA renal carcinogenicity is a controversial issue. In 2005, direct genotoxicity (covalent DNA adduct formation) was proposed as a MOA for OTA-mediated carcinogenicity [ Manderville , R. A. ( 2005 ) Chem. Res. Toxicol. 18 , 1091 - 1097 ]. At that time, inconsistent results had been published on OTA genotoxicity/mutagenicity, and conclusive evidence for OTA-mediated DNA adduction had been lacking. In this update, published data from the past 6-7 years are presented that provide new hypotheses for the MOA of OTA-mediated carcinogenicity. While direct genotoxicity remains a controversial issue for OTA, new findings from the Umemura and Nohmi laboratories provide definitive results for the mutagenicity of OTA in the target tissue (outer medulla) of male rat kidney that rules out oxidative DNA damage. These findings, coupled with our own efforts that provide new structural evidence for DNA adduction by OTA, has strengthened the argument for involvement of direct genotoxicity in OTA-mediated renal carcinogenesis. This MOA should be taken into consideration for OTA human risk assessment. PMID:22054007

  9. CHLOROFORM INDUCTION OF ORNITHINE DECARBOXYLASE ACTIVITY IN RATS

    Science.gov (United States)

    Chloroform is a drinking water contaminant that has been demonstrated to be carcinogenic to mice and rats resulting in an increased incidence of liver and kidney tumors, respectively. The mechanism of chloroform carcinogenicity might be by tumor initiation and/or promotion. Since...

  10. Large scale isolation of DNA repair mutants of Chinese hamster ovary cells

    International Nuclear Information System (INIS)

    A semiautomated procedure has been designed and used successfully to permit the isolation of a large number of uv (ultraviolet light) sensitive mutant colonies of Chinese hamster ovary (CHO) cells. 149 uv sensitive mutants of CHO cells have been isolated to date by this procedure. This represents the largest in vitro isolation to date of uv sensitive mutants of mammalian cells The isolation of uv sensitive clones of EM9-1 represents the first stepwise isolation of double mutants of mammalian cells with sensitivity to an increased range of carcinogenic agents. Using a rapid screening test for complementation group assignment, 70 of these mutants have been assigned to a total of 5 complementation classes. Representatives of 4 of these classes have been studied for competence in repair replication following uv irradiation and have demonstrated a defective phenotype in uv repair. Representatives of 2 of these repair-deficient classes have been studies for uv mutagenic response for three selective markers, and have demonstrated an approximately ninefold enhancement in mutant yield per unit uv exposure relative to the parental cels. The sensitivity, repair phenotype, and mutational response ofthe isolates studied resemble that of human mutant xeroderma pigmentosum cells

  11. Chemical mechanisms of the interaction between radiation and chemical carcinogens

    International Nuclear Information System (INIS)

    There is evidence to suggest that ionizing radiation and chemical carcinogens can act synergistically to produce deleterious biological effects. In addition, many carcinogens undergo metabolic activation in vivo. This activation, initiated by biochemical redox reactions, can be simulated chemically, electrochemically, photochemically and radiation chemically. The principal reactive species formed by the action of ionizing radiation on aqueous solutions of macromolecules and mammalian cells, are hydroxyl radicals and superoxide anions. Pulse and steady-state radiolysis studies of model chemical systems have established that these species can 'activate' chemical carcinogens by a radical oxidation process, and that the resulting activated carcinogens can subsequently react with nucleophilic sites on DNA and other potential target macromolecules. Rate constants for some of the fast reactions involved in the radiation activation of carcinogens and in the subsequent carcinogen-DNA interactions have been determined, together with the yields of radiation-induced covalent DNA-carcinogen binding. A redox models for radiation-induced chemical carcinogenesis is proposed which describes a possible mechanism of action involving free radical species generated in the aqueous cellular milieu, which diffuse to and react with carcinogens located within the micro-environment of the cell. Preliminary experiments suggest that protection against radiation and chemical carcinogenesis can be achieved by radical scavenging or by competitive free radical inhibition

  12. Carcinogens in the Workplace: A Scientific, Political and Social Problem

    OpenAIRE

    Atherley, Gordon; Whiting, Robert

    1982-01-01

    Investigation, assessment, and management of carcinogenic risks are not only scientific but also political responsibilities. In Canada, this becomes cumbersome, since local, provincial and federal policies are involved. The process also involves workers and management. This article outlines Canadian legislative experience, the principles involved, the methods of risk assessment, and the classification of carcinogens in the workplace.

  13. Workshop on problem areas associated with developing carcinogen guidelines

    Energy Technology Data Exchange (ETDEWEB)

    1984-06-01

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

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

    International Nuclear Information System (INIS)

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

  15. 29 CFR 1926.1103 - 13 carcinogens (4-Nitrobiphenyl, etc.).

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 8 2010-07-01 2010-07-01 false 13 carcinogens (4-Nitrobiphenyl, etc.). 1926.1103 Section 1926.1103 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION... § 1926.1103 13 carcinogens (4-Nitrobiphenyl, etc.). Note: The requirements applicable to...

  16. 29 CFR 1915.1003 - 13 carcinogens (4-Nitrobiphenyl, etc.).

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 7 2010-07-01 2010-07-01 false 13 carcinogens (4-Nitrobiphenyl, etc.). 1915.1003 Section 1915.1003 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION... Hazardous Substances § 1915.1003 13 carcinogens (4-Nitrobiphenyl, etc.). Note: The requirements...

  17. 29 CFR 1910.1003 - 13 Carcinogens (4-Nitrobiphenyl, etc.).

    Science.gov (United States)

    2010-07-01

    ... employees, designated representatives, and the Assistant Secretary in accordance with 29 CFR 1910.1020 (a... 29 Labor 6 2010-07-01 2010-07-01 false 13 Carcinogens (4-Nitrobiphenyl, etc.). 1910.1003 Section... Substances § 1910.1003 13 Carcinogens (4-Nitrobiphenyl, etc.). (a) Scope and application. (1) This...

  18. Rats

    Directory of Open Access Journals (Sweden)

    Alexey Kondrashov

    2012-01-01

    Full Text Available We aimed to perform a chemical analysis of both Alibernet red wine and an alcohol-free Alibernet red wine extract (AWE and to investigate the effects of AWE on nitric oxide and reactive oxygen species production as well as blood pressure development in normotensive Wistar Kyoto (WKY and spontaneously hypertensive rats (SHRs. Total antioxidant capacity together with total phenolic and selected mineral content was measured in wine and AWE. Young 6-week-old male WKY and SHR were treated with AWE (24,2 mg/kg/day for 3 weeks. Total NOS and SOD activities, eNOS and SOD1 protein expressions, and superoxide production were determined in the tissues. Both antioxidant capacity and phenolic content were significantly higher in AWE compared to wine. The AWE increased NOS activity in the left ventricle, aorta, and kidney of SHR, while it did not change NOS activity in WKY rats. Similarly, increased SOD activity in the plasma and left ventricle was observed in SHR only. There were no changes in eNOS and SOD1 expressions. In conclusion, phenolics and minerals included in AWE may contribute directly to increased NOS and SOD activities of SHR. Nevertheless, 3 weeks of AWE treatment failed to affect blood pressure of SHR.

  19. Effect of non-steroidal anti-inflammatory drugs and the pro-carcinogen 1, 2 dimethylhydrazine on the rat intestinal membrane structure and function Efecto de los fármacos antiinflmatorios no esteroideos y del procarcinógeno 1,2-dimetilhidracina sobre la estructura y función de la membrana intestinal de la rata

    Directory of Open Access Journals (Sweden)

    N. Mittal

    2008-10-01

    Full Text Available The present study was designed to evaluate the effects of three non-steroidal anti-inflammatory drugs (NSAIDs with varying cycloxygenase selectivities on the small intestinal biochemical composition, function and histology during 1, 2-dimethylhydrazine (DMH administration. Sprague Dawley male rats were divided into five different groups viz: Group 1 (control, vehicle treated, Group 2 (DMH-treated, 30 mg/kg body weight/week in 1 mM EDTA-saline, subcutaneously, Group 3 (DMH + aspirin-60 mg/kg body weight, Group 4 (DMH + celecoxib-6 mg/kg body weight, Group 5 (DMH + etoricoxib-0.64 mg/kg body weight. After six weeks of treatment, brush border membrane was isolated from the jejunum segment of all the groups and changes in the associated enzymes such as sucrase, lactase, maltase, alkaline phosphatase, membrane lipid composition, fluorescence polarizations of diphenylhexatriene, pyrene excimer formation, histological changes and surface characteristics were studied. The results indicated a significant alteration in the enzyme activity as well as changes in the structure and function of the intestine in the presence of the pro-carcinogen, DMH, which suggests the possible chemopreventive efficacy of NSAIDs against the intestinal cancer.El presente estudio se diseñó para evaluar los efectos de tres fármacos antiinflamatorios no esteroideos (AINE con diferente selectividad por la ciclooxigenasa sobre la composición bioquímica, la función y la histología del intestino delgado durante la administración de 1,2-dimetilhidracina (DMH. Se distribuyó a ratas macho Sprague Dawley en grupos distintos: Grupo 1 (control, tratado con vehículo, Grupo 2 (tratado con DMH, 30 mg/kg de peso /semana en 1 mM de EDTA-salino, subcutáneo, Grupo 3 (DMH + aspirina-60 mg/kg de peso, Grupo 4 (DMH + celecoxib-6 mg/kg de peso, Grupo 5 (DMH + etoricoxib-0,64 mg/kg de peso. Tras seis semanas de tratamiento, se aisló la membrana en cepillo de un segmento del yeyuno en todos

  20. Copulatory and agonistic behavior in Syrian hamsters following social defeat.

    Science.gov (United States)

    Jeffress, Elizabeth C; Huhman, Kim L

    2013-01-01

    Syrian hamsters are highly aggressive animals that reliably defend their home territory. After social defeat, however, hamsters no longer defend their home cage but instead display submissive and defensive behavior toward an intruder, a response that we have termed conditioned defeat. Plasma testosterone is significantly reduced in Syrian hamsters following repeated defeat suggesting that social defeat might also impair copulatory behavior. The present study aimed to determine whether copulatory behavior in male Syrian hamsters is suppressed following repeated social defeats and additionally whether exposure to a hormone-primed stimulus female after social defeat reduces the behavioral response to defeat. Hamsters were paired with an aggressive opponent for one or nine defeats using a resident-intruder model, while controls were placed into the empty cage of a resident aggressor. On the day after the last treatment, half of the hamsters were paired with a receptive female for 10 min. There were no significant differences in the copulatory behavior of defeated versus non-defeated hamsters, and the opportunity to copulate had no effect on subsequent conditioned defeat testing, as defeated animals displayed significantly more submissive behavior than did non-defeated animals. The current data suggest that conditioned defeat is not necessarily a maladaptive response to social stress, at least in terms of reproductive behavior, but may instead represent a viable behavioral strategy adopted by losing animals following social defeat. Further, these data indicate that conditioned defeat is relatively persistent and stable, as the opportunity to copulate does not reduce the subsequent display of submissive behavior. PMID:23382023

  1. Lymphocyte reactivity of workers exposed to carcinogenic and non-carcinogenic chemicals.

    OpenAIRE

    Kumar, S.; Taylor, G; Hurst, W; Wilson, P.; Costello, C B

    1981-01-01

    Immunological studies have shown an increased lymphocyte reactivity in patients with early stage bladder cancer and individuals with pre-stage T1 exposed to bladder carcinogens (2-naphthylamine and industrial 1-naphthylamine containing 4-8% 2-naphthylamine) before 1952-that is, those at high risk of developing bladder cancer. Because of the close chemical similarity of Tobias acid (2-naphthylamine-1 sulphonic acid) to 2-naphthylamine, the lymphocytotoxicity of workers exposed to this chemical...

  2. 2-(/sup 125/I)iodomelatonin binding sites in hamster brain membranes: pharmacological characteristics and regional distribution

    Energy Technology Data Exchange (ETDEWEB)

    Duncan, M.J.; Takahashi, J.S.; Dubocovich, M.L.

    1988-05-01

    Studies in a variety of seasonally breeding mammals have shown that melatonin mediates photoperiodic effects on reproduction. Relatively little is known, however, about the site(s) or mechanisms of action of this hormone for inducing reproductive effects. Although binding sites for (3H)melatonin have been reported previously in bovine, rat, and hamster brain, the pharmacological selectivity of these sites was never demonstrated. In the present study, we have characterized binding sites for a new radioligand, 2-(125I)iodomelatonin, in brains from a photoperiodic species, the Syrian hamster. 2-(125I)Iodomelatonin labels a high affinity binding site in hamster brain membranes. Specific binding of 2-(125I)iodomelatonin is rapid, stable, saturable, and reversible. Saturation studies demonstrated that 2-(125I)iodomelatonin binds to a single class of sites with an affinity constant (Kd) of 3.3 +/- 0.5 nM and a total binding capacity (Bmax) of 110.2 +/- 13.4 fmol/mg protein (n = 4). The Kd value determined from kinetic analysis (3.1 +/- 0.9 nM; n = 5) was very similar to that obtained from saturation experiments. Competition experiments showed that the relative order of potency of a variety of indoles for inhibition of 2-(125I)iodomelatonin binding site to hamster brain membranes was as follows: 6-chloromelatonin greater than or equal to 2-iodomelatonin greater than N-acetylserotonin greater than or equal to 6-methoxymelatonin greater than or equal to melatonin greater than 6-hydroxymelatonin greater than or equal to 6,7-dichloro-2-methylmelatonin greater than 5-methoxytryptophol greater than 5-methoxytryptamine greater than or equal to 5-methoxy-N,N-dimethyltryptamine greater than N-acetyltryptamine greater than serotonin greater than 5-methoxyindole (inactive).

  3. 2-[125I]iodomelatonin binding sites in hamster brain membranes: pharmacological characteristics and regional distribution

    International Nuclear Information System (INIS)

    Studies in a variety of seasonally breeding mammals have shown that melatonin mediates photoperiodic effects on reproduction. Relatively little is known, however, about the site(s) or mechanisms of action of this hormone for inducing reproductive effects. Although binding sites for [3H]melatonin have been reported previously in bovine, rat, and hamster brain, the pharmacological selectivity of these sites was never demonstrated. In the present study, we have characterized binding sites for a new radioligand, 2-[125I]iodomelatonin, in brains from a photoperiodic species, the Syrian hamster. 2-[125I]Iodomelatonin labels a high affinity binding site in hamster brain membranes. Specific binding of 2-[125I]iodomelatonin is rapid, stable, saturable, and reversible. Saturation studies demonstrated that 2-[125I]iodomelatonin binds to a single class of sites with an affinity constant (Kd) of 3.3 +/- 0.5 nM and a total binding capacity (Bmax) of 110.2 +/- 13.4 fmol/mg protein (n = 4). The Kd value determined from kinetic analysis (3.1 +/- 0.9 nM; n = 5) was very similar to that obtained from saturation experiments. Competition experiments showed that the relative order of potency of a variety of indoles for inhibition of 2-[125I]iodomelatonin binding site to hamster brain membranes was as follows: 6-chloromelatonin greater than or equal to 2-iodomelatonin greater than N-acetylserotonin greater than or equal to 6-methoxymelatonin greater than or equal to melatonin greater than 6-hydroxymelatonin greater than or equal to 6,7-dichloro-2-methylmelatonin greater than 5-methoxytryptophol greater than 5-methoxytryptamine greater than or equal to 5-methoxy-N,N-dimethyltryptamine greater than N-acetyltryptamine greater than serotonin greater than 5-methoxyindole (inactive)

  4. Proteomic analysis of Chinese hamster ovary cells.

    Science.gov (United States)

    Baycin-Hizal, Deniz; Tabb, David L; Chaerkady, Raghothama; Chen, Lily; Lewis, Nathan E; Nagarajan, Harish; Sarkaria, Vishaldeep; Kumar, Amit; Wolozny, Daniel; Colao, Joe; Jacobson, Elena; Tian, Yuan; O'Meally, Robert N; Krag, Sharon S; Cole, Robert N; Palsson, Bernhard O; Zhang, Hui; Betenbaugh, Michael

    2012-11-01

    To complement the recent genomic sequencing of Chinese hamster ovary (CHO) cells, proteomic analysis was performed on CHO cells including the cellular proteome, secretome, and glycoproteome using tandem mass spectrometry (MS/MS) of multiple fractions obtained from gel electrophoresis, multidimensional liquid chromatography, and solid phase extraction of glycopeptides (SPEG). From the 120 different mass spectrometry analyses generating 682,097 MS/MS spectra, 93,548 unique peptide sequences were identified with at most 0.02 false discovery rate (FDR). A total of 6164 grouped proteins were identified from both glycoproteome and proteome analysis, representing an 8-fold increase in the number of proteins currently identified in the CHO proteome. Furthermore, this is the first proteomic study done using the CHO genome exclusively, which provides for more accurate identification of proteins. From this analysis, the CHO codon frequency was determined and found to be distinct from humans, which will facilitate expression of human proteins in CHO cells. Analysis of the combined proteomic and mRNA data sets indicated the enrichment of a number of pathways including protein processing and apoptosis but depletion of proteins involved in steroid hormone and glycosphingolipid metabolism. Five-hundred four of the detected proteins included N-acetylation modifications, and 1292 different proteins were observed to be N-glycosylated. This first large-scale proteomic analysis will enhance the knowledge base about CHO capabilities for recombinant expression and provide information useful in cell engineering efforts aimed at modifying CHO cellular functions. PMID:22971049

  5. Malignancy of transplanted hamster lung lesions induced by inhaled 239PuO2

    International Nuclear Information System (INIS)

    Selected sites from the lungs of hamsters that had inhaled 239PuO2 aerosol were serially transplanted into the cheek pouches of recipient hamsters. Up to 13 mo postexposure, no evidence of malignancy has appeared

  6. The hamster flank organ model: Is it relevant to man

    International Nuclear Information System (INIS)

    The critical role that androgens play in the etiology of acne has led to a search for topically active antiandrogens and the frequent use of the flank organ of the golden Syrian hamster as an animal model. 17-alpha-propyltestosterone (17-PT) has been identified as having potent antiandrogenic activity in the hamster model, and this report describes its clinical evaluation. Two double-blind placebo controlled studies comparing 4% 17-PT in 80% alcohol versus vehicle alone were conducted. One study examined 17-PT sebosuppressive activity in 20 subjects. The second study examined its efficacy in 44 subjects having mild to moderate acne. A third study measured in vitro percutaneous absorption of 17-PT through hamster flank and monkey skin, and human face skin in-vivo, using radioactive drug. 17-PT was found to be ineffective in reducing either the sebum excretion rate or the number of inflammatory acne lesions. Failure of 17-PT to show clinical activity was not a result of poor percutaneous absorption. Total absorption in man was 7.7% of the dose and only 1.0% in the hamster. The sebaceous gland of hamster flank organ is apparently more sensitive to antiandrogens than the human sebaceous gland

  7. A combination of 3D-QSAR, docking, local-binding energy (LBE) and GRID study of the species differences in the carcinogenicity of benzene derivatives chemicals.

    Science.gov (United States)

    Fratev, Filip; Benfenati, Emilio

    2008-09-01

    A combination of 3D-QSAR, docking, local-binding energy (LBE) and GRID methods was applied as a tool to study and predict the mechanism of action of 100 carcinogenic benzene derivatives. Two 3D-QSAR models were obtained: (i) model of mouse carcinogenicity on the basis of 100 chemicals (model 1) and (ii) model of the differences in mouse and rat carcinogenicity on the basis of 73 compounds (model 2). 3D-QSAR regression maps indicated the important differences in species carcinogenicity, and the molecular positions associated with them. In order to evaluate the role of P450 metabolic process in carcinogenicity, the following approaches were used. The 3D models of CYP2E1 for mouse and rat were built up. A docking study was applied and the important ligand-protein residues interactions and oxidation positions of the molecules were identified. A new approach for quantitative assessment of metabolism pathways was developed, which enabled us to describe the species differences in CYP2E1 metabolism, and how it can be related to differences in the carcinogenic potential for a subset of compounds. The binding energies of the important substituents (local-binding energy-LBE) were calculated, in order to quantitatively demonstrate the contribution of the substituents in metabolic processes. Furthermore, a computational procedure was used for determining energetically favourable binding sites (GRID examination) of the enzymes. The GRID procedure allowed the identification of some important differences, related to species metabolism in CYP2E1. Comparing GRID, 3D-QSAR maps and LBE results, a similarity was identified, indicating a relationship between P450 metabolic processes and the differences in the carcinogenicity. PMID:18495507

  8. 32P-Postlabeling test for covalent DNA binding of chemicals in vivo: Application to a variety of aromatic carcinogens and methylating agents

    International Nuclear Information System (INIS)

    Carcinogen--DNA adducts were detected and determined by 32P-postlabeling assay after exposure of mouse or rat tissues in vivo to a total of 28 compounds comprising 7 arylamines and derivatives, 3 azo compounds, 2 nitroaromatics, 12 polycyclic aromatic hydrocarbons, and 4 methylating agents. DNA was isolated from mouse skin, mouse liver, and rat liver after treatment with the individual carcinogens, then digested enzymatically to deoxyribonucleoside 3'-monophosphates, which were converted to 5'-32P-labeled deoxyribonucleoside 3',5'-bisphosphates by T4 polynucleotide kinase-catalyzed [32P]phosphate transfer from [gamma-32P]ATP. The nucleotides were resolved by anion-exchange t.l.c. on polyethyleneimine-cellulose and detected by autoradiography. The determination of low levels of DNA binding of the aromatic carcinogens entailed the removal of normal nucleotides prior to the resolution of adduct nucleotides. For this purpose, an alternative procedure employing reversed-phase t.l.c. was devised which offered advantages for the detection of quantitatively minor adducts. The procedures described enabled the detection of 1 aromatic DNA adduct in approximately 10(8) normal nucleotides, while the limit of detection of methylated adducts was 1 adduct in approximately 6 X 10(5) nucleotides. The results show that a great number of carcinogen-DNA adducts of diverse structure are substrates for 32P-labeling by polynucleotide kinase-catalyzed phosphorylation. Because covalent DNA adduct formation in vivo appears to be an essential property of the majority of chemical carcinogens, 32P-postlabeling analysis of carcinogen--DNA adducts in mammalian tissues may serve as a test for the screening of chemicals for potential carcinogenicity

  9. Role of caloric homeostasis and reward in alcohol intake in Syrian golden hamsters

    OpenAIRE

    Gulick, Danielle; Green, Alan I.

    2010-01-01

    The Syrian golden hamster drinks alcohol readily, but only achieves moderate blood alcohol levels, and does not go through withdrawal from alcohol. Because the hamster is a model of caloric homeostasis, both caloric content and reward value may contribute to the hamster’s alcohol consumption. The current study examines alcohol consumption in the hamster when a caloric or non-caloric sweet solution is concurrently available and caloric intake in the hamster before, during, and after exposure t...

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

    Science.gov (United States)

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

    2015-05-01

    Numerous epidemiological studies have demonstrated a link between excessive meat consumption and the incidence of various cancers, especially colorectal cancer, and it has been suggested that environmental carcinogens present in meat might be related to the increased risk of cancer associated with this food. However, there are no studies evaluating the carcinogenic potential of meat in relation to its content of carcinogens. Our purpose was to emphasize the relevance of environmental carcinogens existing in meat as a determinant of the association between cancer and meat consumption. Because within Europe, Spain shows high consumption of meat and charcuterie, we performed this study focusing on Spanish population. Based on the preferences of consumers we acquired 100 samples of meat and charcuterie that reflect the variety available in the European market. We quantified in these samples the concentration of 33 chemicals with calculated carcinogenic potential (PAHs, organochlorine pesticides, and dioxin-like PCBs). The carcinogenic risk of these contaminants was assessed for each food using a risk ratio based on the current consumption of meat and charcuterie and the maximum tolerable intake of these foods depending on the level of contamination by the carcinogens they contain. Our results indicate that the current consumption of beef, pork, lamb, chicken, and "chorizo", represents a relevant carcinogenic risk for consumers (carcinogenic risk quotient between 1.33 and 13.98). In order to reduce carcinogenic risk, the study population should halve the monthly consumption of these foods, and also not to surpass the number of 5 servings of beef/pork/chicken (considered together). PMID:25659303

  11. Metabolic activation of chemical carcinogens to reactive electrophiles

    International Nuclear Information System (INIS)

    Ionizing radiations and ultraviolet light constitute the principal known physical carcinogens. Likewise, a great variety and large number of chemicals and over 50 DNA and RNA viruses comprise the known chemical and viral carcinogens. These three categories of carcinogenic agents include the great majority of extrinsic agents known to induce cancer in mammals. Man is clearly susceptible to the action of physical and chemical carcinogens and, indeed, was the first species in which the activities of some of these agents were demonstated. It seems certain that viral carcinogenic information is involved in the etiology of at least some human tumors, but ethical and methodological problems have made it difficult to obtain unequivocal data. Given the long availability of experimental carcinogens of these three classes, there is surprisingly little known of their interrelationships in the production of cancer in experimental animals. The objective of this brief review is to present some salient aspects of experimental chemical carcinogenesis and an analysis of how some of these features relate to the mechanisms of action of radiation carcinogens

  12. Carcinogens in Israeli milk: a study in regulatory failure.

    Science.gov (United States)

    Westin, J B

    1993-01-01

    The potential danger to humans of exposure to chemicals shown to be carcinogenic in animals has become increasingly clear in the last 20 years. A gap still exists, however, between the appreciation of the risk by scientists and the willingness of public health authorities to reduce it. Three pesticides, shown repeatedly to produce over a dozen different types of cancer in rats and mice, were discovered in inordinately high concentrations in Israeli milk and dairy products. The three pesticides--alpha-BHC, gamma-BHC (lindane), and DDT--had been shown to be present for ten years or more at mean concentrations up to 100 times those found in U.S. dairy products--with resultant concentrations in breast milk being possibly 800 times greater than those in the United States--yet neither the Ministry of Health nor the Israel Cancer Association made any apparent moves either to warn the public or to rectify the situation. A small consumer organization, Consumer Shield, brought the issue into the open. Through public pressure, court action, and the threat of further legal redress--and despite repeated attacks in the media by the milk producers, the Ministry, and the Cancer Association--Consumer Shield forced the authorities to outlaw the use of alpha-BHC and lindane (DDT no longer being in general use). The ban resulted in a precipitous drop in the concentrations of these substances in Israeli milk. Recent epidemiological and laboratory findings suggest that the dramatic drop in breast cancer mortality rates subsequent to the pesticide ban could be a direct result of that ban. PMID:8375952

  13. Chloroform induction of ornithine decarboxylase activity in rats.

    OpenAIRE

    Savage, R E; Westrich, C; Guion, C; M. A. PEREIRA

    1982-01-01

    Chloroform is a drinking water contaminant that has been demonstrated to be carcinogenic to mice and rats resulting in an increased incidence of liver and kidney tumors, respectively. The mechanism of chloroform carcinogenicity might be by tumor initiation and/or promotion. Since induction of ornithine decarboxylase (ODC) activity has been proposed as a molecular marker for tumor promoters, we have investigated the effect of chloroform on ODC activity in rats. Chloroform induced a dose-depend...

  14. Identification and monitoring of non-radiological carcinogens

    International Nuclear Information System (INIS)

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

  15. Genitourinary changes in hamsters infected and reinfected with Trypanosoma cruzi

    Directory of Open Access Journals (Sweden)

    Cabrine-Santos Marlene

    2003-01-01

    Full Text Available Authors describe genitourinary changes in male hamsters infected and reinfected with Trypanosoma cruzi. Changes in genital organs have been described in human and in experimental chagasic infection. Genital dysfunctions in chronic chagasic patients affect ejaculation, libido and sexual potency, and testis biopsies may show arrested maturation of germ cells, oligozoospermia and azoospermia. Sixty-five male hamsters were inoculated and reinoculated with 2x10³ trypomastigotes of T. cruzi VIC strain, and 22 non-infected animals constituted the control group. Animals were necropsied and fragments from testis, epididymis, seminal vesicle and bladder were collected and stained with hematoxylin-eosin. Peroxidase anti-peroxidase procedure was utilized to detect tissue parasitism. T. cruzi nests were found in testis, epididymis and seminal vesicle of these hamsters. Such parasitism plays a role in the origin of genital lesions observed in humans and laboratory animals during chronic chagasic infection.

  16. Asbestos cement dust inhalation by hamsters

    Energy Technology Data Exchange (ETDEWEB)

    Wehner, A.P.; Dagle, G.E.; Cannon, W.C.; Buschbom, R.L. (Pacific Northwest Laboratories, Richland, WA (USA))

    1978-12-01

    Two groups of 96 male Syrian golden hamsters were exposed to respirable asbestos cement aerosol at concentrations of approximately 1 and approximately 10 micrograms/liter, respectively, 3 hours/day, 5 days/week. Average fiber counts ranged from 5 to about 120 fibers/cm3. Each group was randomly divided into six subgroups of 16 animals. The first subgroup was sacrificed after 3 months of exposure, the second after 6 months, and the third after 15 months. The fourth subgroup was withdrawn from exposure after 3 months, observed for an additional 3 months, and then sacrificed. The fifth and sixth subgroups were withdrawn after 3 and 6 months of exposure, respectively, and maintained for observation up to the 15-month exposure point of the third subgroup at which time all surviving animals were sacrificed. All other experimental procedures were similar to those delineated in a previous publication describing the development of an animal model, techniques, and an exposure system for asbestos cement dust inhalation. The asbestos cement exposures had no significant effect on body weight and mortality of the animals. Higher aerosol concentration and longer exposure times increased the number of macrophages and ferruginous bodies found in the lungs of the exposed animals. Recovery periods had no effect on the incidence of macrophages and ferruginous bodies. The incidence of very slight to slight fibrosis in the animals sacrificed after 15 months of exposure shows a significant (P less than 0.01) trend when the untreated control group and the 1 and 10 microgram/liter dose level groups are compared, indicating a dose-response relationship. Development of minimal fibrosis continued in animals withdrawn from exposure. No primary carcinomas of the lung and respiratory tract and no mesotheliomas were found.

  17. Hamster thecal cells express muscle characteristics

    International Nuclear Information System (INIS)

    Contraction of the follicular wall about the time of ovulation appears to be a coordinated event; however, the cells that mediate it remain poorly studied. We examined the theca externa cells in the wall of hamster follicles for the presence of a functional actomyosin system, both in developing follicles and in culture. We used a monoclonal antibody (HHF35) that recognizes the alpha and gamma isoelectric variants of actin normally found in muscle, but not the beta variant associated with non-muscle sources, to evaluate large preovulatory follicles for actin content and composition. Antibody staining of sectioned ovaries showed intense circumferential reactivity in the outermost wall of developing follicles. Immunoblots from two-dimensional gels of theca externa lysates demonstrated the presence of the two muscle-specific isozymes of actin. Immunofluorescence of cultured follicular cells pulse-labeled with [3H] thymidine (for autoradiographic detection of DNA replication) revealed the presence, in many dividing cells, of actin filaments aligned primarily along the longitudinal axis of the cells. In cultures exposed to the calcium ionophore A23187 (10(-4) M) for varying periods (5 min to 1 h), contraction of many individual muscle-actin-positive cells was observed. Immunofluorescence of these cells, fixed immediately after ionophore-induced contraction, revealed compaction of the actin filaments. Our findings demonstrate that the cells of the theca externa contain muscle actins from an early stage and that these cells are capable of contraction even while proliferating in subconfluent cultures. They suggest that follicular growth may include a naturally occurring developmental sequence in which a contractile cell type proliferates in the differentiated state

  18. Biologic markers in risk assessment for environmental carcinogens

    Energy Technology Data Exchange (ETDEWEB)

    Perera, F.; Mayer, J.; Santella, R.M.; Brenner, D.; Jeffrey, A.; Latriano, L.; Smith, S.; Warburton, D.; Young, T.L.; Tsai, W.Y.; Brandt-Rauf, P. (Columbia Univ. School of Public Health, New York, NY (United States)); Hemminki, K. (Finnish School of Occupational Health, Helsinki (Finland))

    1991-01-01

    The potential of biologic markers to provide more timely and precise risk assessments for environmental carcinogens is viewed against the current state-of-the-art in biological monitoring/molecular epidemiology. Biologic markers such as carcinogen-DNA adducts and oncogene activation are currently considered valid qualitative indicators of potential risk, but for most chemical exposures research is needed to establish their validity as quantitative predictors of cancer risk. Biologic markers have, however, already provided valuable insights into the magnitude of interindividual variation in response to carcinogenic exposures, with major implications for risk assessment.

  19. Biologic markers in risk assessment for environmental carcinogens

    International Nuclear Information System (INIS)

    The potential of biologic markers to provide more timely and precise risk assessments for environmental carcinogens is viewed against the current state-of-the-art in biological monitoring/molecular epidemiology. Biologic markers such as carcinogen-DNA adducts and oncogene activation are currently considered valid qualitative indicators of potential risk, but for most chemical exposures research is needed to establish their validity as quantitative predictors of cancer risk. Biologic markers have, however, already provided valuable insights into the magnitude of interindividual variation in response to carcinogenic exposures, with major implications for risk assessment

  20. Autonomic nervous dysfunction in hamsters infected with West Nile virus.

    Directory of Open Access Journals (Sweden)

    Hong Wang

    Full Text Available Clinical studies and case reports clearly document that West Nile virus (WNV can cause respiratory and gastrointestinal (GI complications. Other functions controlled by the autonomic nervous system may also be directly affected by WNV, such as bladder and cardiac functions. To investigate how WNV can cause autonomic dysfunctions, we focused on the cardiac and GI dysfunctions of rodents infected with WNV. Infected hamsters had distension of the stomach and intestines at day 9 after viral challenge. GI motility was detected by a dye retention assay; phenol red dye was retained more in the stomachs of infected hamsters as compared to sham-infected hamsters. The amplitudes of electromygraphs (EMGs of intestinal muscles were significantly reduced. Myenteric neurons that innervate the intestines, in addition to neurons in the brain stem, were identified to be infected with WNV. These data suggest that infected neurons controlling autonomic function were the cause of GI dysfunction in WNV-infected hamsters. Using radiotelemetry to record electrocardiograms and to measure heart rate variability (HRV, a well-accepted readout for autonomic function, we determined that HRV and autonomic function were suppressed in WNV-infected hamsters. Cardiac histopathology was observed at day 9 only in the right atrium, which was coincident with WNV staining. A subset of WNV infected cells was identified among cells with hyperpolarization-activated cyclic nucleotide-gated potassium channel 4 (HCN4 as a marker for cells in the sinoatrial (SA and atrioventricular (AV nodes. The unique contribution of this study is the discovery that WNV infection of hamsters can lead to autonomic dysfunction as determined by reduced HRV and reduced EMG amplitudes of the GI tract. These data may model autonomic dysfunction of the human West Nile neurological disease.

  1. Use of CB hamsters in the study of Treponema pertenue.

    Science.gov (United States)

    Schell, R F; Le Frock, J L; Babu, J P; Chan, J K

    1979-10-01

    The CB/Ss LAK strain of inbred hamster was used as a model for studies of infection with Treponema pertenue and of acquired resistance to it. When infected, this strain developed cutaneous lesions which lasted for six to seven months, even in the presence of peak titres of antitreponemal antibody. The rate of appearance and resolution of these lesions varied with the size of the inoculum. The infected hamsters' inguinal lymph nodes increased significantly in weight and teemed with treponemes for several weeks. Animals infected for eight or 10 weeks obtained quick resolution of their lesions by treatment with penicillin and were thereafter resistant to reinfection. PMID:509189

  2. Trichloroethylene: Mechanistic, Epidemiologic and Other Supporting Evidence of Carcinogenic Hazard

    OpenAIRE

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

    2013-01-01

    The chlorinated solvent trichloroethylene (TCE) is a ubiquitous environmental pollutant. The carcinogenic hazard of TCE was the subject of a 2012 evaluation by a Working Group of the International Agency for Research on Cancer (IARC). Information on exposures, relevant data from epidemiologic studies, bioassays in experimental animals, and toxicity and mechanism of action studies was used to conclude that TCE is carcinogenic to humans (Group 1). This article summarizes the key evidence formin...

  3. Biologic markers in risk assessment for environmental carcinogens

    OpenAIRE

    Perera, F.; Mayer, J.; Santella, R. M.; Brenner, D; Jeffrey, A.; Latriano, L; Smith, S.; Warburton, D; Young, T. L.; Tsai, W. Y.; Hemminki, K; Brandt-Rauf, P

    1991-01-01

    The potential of biologic markers to provide more timely and precise risk assessments for environmental carcinogens is viewed against the current state-of-the-art in biological monitoring/molecular epidemiology. Biologic markers such as carcinogen-DNA adducts and oncogene activation are currently considered valid qualitative indicators of potential risk, but for most chemical exposures research is needed to establish their validity as quantitative predictors of cancer risk. Biologic markers h...

  4. Carcinogenicity evaluations and ongoing studies: the IARC databases.

    OpenAIRE

    Vainio, H.; Coleman, M.; Wilbourn, J

    1991-01-01

    Many thousands of chemicals are produced industrially and many more occur naturally. Information on the toxicology of these chemicals is often minimal or absent. The International Agency for Research on Cancer (IARC) has published evaluations of the carcinogenic risk to humans of over 700 chemicals, groups of chemicals, and complex mixtures as a regular series of monographs. A database has been created containing summaries of all the relevant epidemiological, animal carcinogenicity, and other...

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

    Science.gov (United States)

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

    2014-01-01

    The chlorinated solvent trichloroethylene (TCE) is a ubiquitous environmental pollutant. The carcinogenic hazard of TCE was the subject of a 2012 evaluation by a Working Group of the International Agency for Research on Cancer (IARC). Information on exposures, relevant data from epidemiologic studies, bioassays in experimental animals, and toxicity and mechanism of action studies was used to conclude that TCE is carcinogenic to humans (Group 1). This article summarizes the key evidence forming the scientific bases for the IARC classification. Exposure to TCE from environmental sources (including hazardous waste sites and contaminated water) is common throughout the world. While workplace use of TCE has been declining, occupational exposures remain of concern, especially in developing countries. The strongest human evidence is from studies of occupational TCE exposure and kidney cancer. Positive, although less consistent, associations were reported for liver cancer and non-Hodgkin lymphoma. TCE is carcinogenic at multiple sites in multiple species and strains of experimental animals. The mechanistic evidence includes extensive data on the toxicokinetics and genotoxicity of TCE and its metabolites. Together, available evidence provided a cohesive database supporting the human cancer hazard of TCE, particularly in the kidney. For other target sites of carcinogenicity, mechanistic and other data were found to be more limited. Important sources of susceptibility to TCE toxicity and carcinogenicity were also reviewed by the Working Group. In all, consideration of the multiple evidence streams presented herein informed the IARC conclusions regarding the carcinogenicity of TCE. PMID:23973663

  6. Induction of active melanocytes in mouse skin by carcinogens: a new method for detection of skin carcinogens.

    Science.gov (United States)

    Iwata, K; Inui, N; Takeuchi, T

    1981-01-01

    Application of potent skin carcinogens, such as 7,12-dimethylbenz[a]anthracene, 3-methylcholanthrene, benzo[a]pyrene and 4-nitroquinoline-1-oxide, induced numerous dihydroxyphenylalanine (dopa)-positive cells in the interfollicular epidermis of C57BL/6 mice in a dose- and time-dependent fashion. Chrysene, a weak skin carcinogen, and croton oil, a tumor promoter, also induced 3--4 times more dopa-positive cells than acetone. Liver carcinogens, such as 3'-methyl-4-dimethylaminoazobenzene and N-2-acetylaminofluorene, and non-carcinogenic aromatic hydrocarbons, such as anthracene, fluoranthene, fluorene and pyrene, did not induce increase in these cells. These results indicate that increase in the number of dopa-positive cells after application of chemicals is well correlated with the abilities of these compounds to induce skin carcinogenesis and suppress sebaceous glands. PMID:7273337

  7. Development of Taenia pisiformis in golden hamster (Mesocricetus auratus

    Directory of Open Access Journals (Sweden)

    Maravilla Pablo

    2011-07-01

    Full Text Available Abstract The life cycle of Taenia pisiformis includes canines as definitive hosts and rabbits as intermediate hosts. Golden hamster (Mesocricetus auratus is a rodent that has been successfully used as experimental model of Taenia solium taeniosis. In the present study we describe the course of T. pisiformis infection in experimentally infected golden hamsters. Ten females, treated with methyl-prednisolone acetate were infected with three T. pisiformis cysticerci each one excised from one rabbit. Proglottids released in faeces and adults recovered during necropsy showed that all animals were infected. Eggs obtained from the hamsters' tapeworms, were assessed for viability using trypan blue or propidium iodide stains. Afterwards, some rabbits were inoculated with eggs, necropsy was performed after seven weeks and viable cysticerci were obtained. Our results demonstrate that the experimental model of adult Taenia pisiformis in golden hamster can replace the use of canines in order to study this parasite and to provide eggs and adult tapeworms to be used in different types of experiments.

  8. Matrix population modelling of the Common hamster life history

    Czech Academy of Sciences Publication Activity Database

    Damugi, I. E. D.; Petrová, I.; Bendová, M.; Losík, J.; Tkadlec, Emil

    Brno: Ústav biologie obratlovců AV ČR, 2016 - (Bryja, J.; Sedláček, F.; Fuchs, R.). s. 52 ISBN 978-80-87189-20-7. [Zoologické dny. 11.02.2016-12.02.2016, České Budějovice] Institutional support: RVO:68081766 Keywords : common hamster Subject RIV: EG - Zoology

  9. DOSE RESPONSE OF ELASTASE-INDUCED EMPHYSEMA IN HAMSTERS

    Science.gov (United States)

    Elastase-induced emhysema in hamsters was studied using pulmonary function tests in an effort to develop techniques for determining the effects of air pollutants on the progression of this disease. It appears that as little as 6 units of elastase produces mild emphysema in hamste...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-07-30

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

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

    International Nuclear Information System (INIS)

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

  12. Asbestos and benzo[a]pyrene act synergistically to induce squamous metaplasia and incorporation of [3H]thymidine in hamster tracheal epithelium

    International Nuclear Information System (INIS)

    When exposed to either crocidolite asbestos (single 1-h exposure to 0.4 mg/ml medium) or the polycyclic aromatic hydrocarbon, benzo[a]pyrene (BaP) (less than or equal to 2.5 micrograms/ml medium, 1x weekly for 4 weeks), the epithelium of hamster tracheal explants exhibits insignificant amounts of squamous metaplasia, an atypical lesion, in comparison to amounts observed in untreated tissues. Incorporation of [3H]thymidine, an indication of DNA synthesis by epithelial cells, likewise is unchanged. However, the extent of squamous metaplasia and numbers of labeled basal and suprabasal cells are increased substantially when BaP and asbestos are added in combination. These results suggest an important mechanism of co-carcinogenesis involving chemical and physical carcinogens and support epidemiologic observations documenting an increased risk of bronchogenic carcinoma in asbestos workers who smoke

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

    Science.gov (United States)

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

    2014-07-30

    Conazoles are a class of imidazole- or triazole-containing drugs commonly used as fungicides in agriculture and medicine. The broad application of azole drugs has led to the contamination of surface aquifers receiving the effluent of municipal or hospital wastewater or agricultural runoff. Several triazoles are rodent carcinogens; azole pollution is a concern to environmental safety and human health. However, the carcinogenic mechanisms associated with cytochrome P450 enzymes (CYPs) of conazoles remain unclear. We exposed adult medaka fish (Oryzias latipes) to continuous aqueous solutions of carcinogenic triadimefon and non-carcinogenic myclobutanil for 7 to 20 days at sub-lethal or environmentally relevant concentrations and assessed hepatic CYP activity and gene expression associated with CYP-mediated toxicity. Both triadimefon and myclobutanil induced hepatic CYP3A activity, but only triadimefon enhanced CYP1A activity. The gene expression of cyp3a38, cyp3a40, pregnane x receptor (pxr), cyp26b, retinoid acid receptor γ1 (rarγ1) and p53 was higher with triadimefon than myclobutanil. As well, yeast-based reporter gene assay revealed that 4 tested conazoles were weak agonists of aryl hydrocarbon receptor (AhR). We reveal differential CYP gene expression with carcinogenic and non-carcinogenic conazoles in a lower vertebrate, medaka fish. Liver CYP-enzyme induction may be a key event in conazole-induced tumorigenesis. This information is essential to evaluate the potential threat of conazoles to human health and fish populations in the aquatic environment. PMID:24962053

  14. Seasonal aspects of sleep in the Djungarian hamster

    Directory of Open Access Journals (Sweden)

    Deboer Tom

    2003-05-01

    Full Text Available Abstract Background Changes in photoperiod and ambient temperature trigger seasonal adaptations in the physiology and behaviour of many species, including the Djungarian hamster. Exposure of the hamsters to a short photoperiod and low ambient temperature leads to a reduction of the polyphasic distribution of sleep and waking over the light and dark period. In contrast, a long photoperiod enhances the daily sleep-wake amplitude leading to a decline of slow-wave activity in NREM sleep within the light period. It is unknown whether these changes can be attributed specifically to photoperiod and/or ambient temperature, or whether endogenous components are contributing factors. The influence of endogenous factors was investigated by recording sleep in Djungarian hamsters invariably maintained at a low ambient temperature and fully adapted to a short photoperiod. The second recording was performed when they had returned to summer physiology, despite the maintenance of the 'winter' conditions. Results Clear winter-summer differences were seen in sleep distribution, while total sleep time was unchanged. A significantly higher light-dark cycle modulation in NREM sleep, REM sleep and waking was observed in hamsters in the summer physiological state compared to those in the winter state. Moreover, only in summer, REM sleep episodes were longer and waking bouts were shorter during the light period compared to the dark period. EEG power in the slow-wave range (0.75–4.0 Hz in both NREM sleep and REM sleep was higher in animals in the summer physiological state than in those in the 'winter' state. In winter SWA in NREM sleep was evenly distributed over the 24 h, while in summer it decreased during the light period and increased during the dark period. Conclusion Endogenous changes in the organism underlie the differences in sleep-wake redistribution we have observed previously in hamsters recorded in a short and long photoperiod.

  15. Effects of pegylated hamster red blood cells on microcirculation.

    Science.gov (United States)

    Chen, Peter C Y; Huang, Wei; Stassinopoulos, Adonis; Cheung, Anthony T W

    2008-01-01

    The objective of this study was to examine the effects of polyethylene glycol (PEG) treated red blood cells (RBCs) on the microcirculation in a hamster back skin window chamber model. Donor hamster RBCs were PEGylated through an incubation with an activated PEG solution, washed, resuspended, and infused through a 10% volume top loading procedure into the carotid artery in an awake Syrian Golden hamster. Eight hamster groups were treated with activated PEG different sizes and concentrations: 0.05 mM-5 kDa PEG, 0.5 mM-5 kDa PEG, 1.1 mM-5 kDa PEG, 2.2 mM-5 kDa PEG, 22 mM-5 kDa PEG, 0.05 mM-20 kDa PEG, 0.5 mM-20 kDa PEG, and 5 mM-20 kDa PEG. Non-treated RBCs were used as control. The microvascular bed under observation was videotaped 30 min before the infusion and followed for 30 min post infusion. The diameter of individual blood vessels and blood flow velocities in selected vessels was measured. Hematocrit and hemoglobin concentration were recorded before infusion and at the end of experiment. Tissue pO(2) was also monitored. Results showed the hamsters tolerated the PEGylated RBCs without apparent ill effects. No significant changes were recorded for the hematocrit, the hemoglobin concentration, the blood vessel diameters, blood flow velocities, and the interstitial partial oxygen pressure (pO(2)) before, during, and after the injections of PEG-RBCs (P > 0.05). Unlike most hemoglobin-based oxygen carrying compounds, which can cause vasoconstriction, the PEGylated RBCs did not produce any measurable vasoactivity. Together with the absence of rouleaux formation and the fact that PEG molecules can mask the surface antigens on RBCs, PEGylation appeared promising as a circulation enhancement treatment. PMID:18649167

  16. Mutagenic and carcinogenic effect of sulfur-35

    International Nuclear Information System (INIS)

    In experiments with metaphase plates from blood lymphocytes, conducted during rats' lifetime, a study was made of the mutagenic effect of 35S. Various tumors were diagnosed in the experimental animals after their death. The competitive analysis of the number of stable cytogenetic changes in lymphocytes of the experimental animals at the remote times and tumor occurrence has revealed a highly positive correlation between these indices. Both effects were severest at the highest absorbed 35S dose of less than 10 cGy

  17. Effects of long-term administration of cancer-promoting substances on oral subepithelial mast cells in the rat.

    Science.gov (United States)

    Sand, L; Hilliges, M; Larsson, P A; Wallstrom, M; Hirsch, J M

    2002-01-01

    The role of oral subepithelial mast cells in the defence against tumours is a matter of controversy. The effect of established and suggested carcinogens, such as the carcinogen 4-nitroquinoline-N-oxide (4-NQO) and Herpes simplex virus type 1 (HSV-1), in combination with oral snuff on lower lip subepithelial mast cells (MC) was studied in rats. The rats were exposed to prolonged use of oral snuff. The test substances were administered in a surgically created canal in the lower lip of the rats. There were 15 rats in each test group and 10 rats in the control group. The amount of countable subepithelial mast cells decreased significantly when the rat oral mucosa was exposed to the oral carcinogen 4-NQO but the effect of oral snuff and HSV-1 infection was weak. Our findings suggest that mast cells play a role in immunological cell defence against chemical carcinogens. Further studies are needed to clarify the mechanisms. PMID:12529973

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

    International Nuclear Information System (INIS)

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

  19. Impact of Environmental Exposures on the Mutagenicity/Carcinogenicity of Heterocyclic Amines

    Energy Technology Data Exchange (ETDEWEB)

    Felton, J S; Knize, M G; Bennett, L M; Malfatti, M A; Colvin, M E; Kulp, K S

    2003-12-19

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

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

    International Nuclear Information System (INIS)

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

  1. Food Additives of Public Concern for their Carcinogenicity

    Directory of Open Access Journals (Sweden)

    Fatih Gultekin

    2015-08-01

    Full Text Available No-Observed-Adverse Effect Level (NOAEL of food additives has been long determined on the basis of toxicological studies. Acceptable Daily Intake (ADI levels of food additives for human are derived from these NOAEL, and their legal limits are then established for the food products, intentionally added with food additives. However, recent studies demonstrated that consumption of some processed food containing certain food additives might have increased the risk of cancer in human although the legal limits of these additives in processed foods are well respected by the manufacturers. Possible reasons for increased carcinogenicity risk in processed foods containing these additives can be due to various factors: -interaction of additives with some food ingredients, -food processing may change the chemical formula of food additive to a formula to be acting similarly as carcinogenic compound, -a negative synergistic effects when combined with other additives, -improper storage conditions, and -unknown carcinogenic by-products occurring during the food processing. Due to the above mentioned factors we recommend that an additive, intentionally added to the food during processing must be traced officially for its carcinogenicity. In this review, we overviewed all of the food additives authorized in European Union. Therefore, the traceability issues of processed foods containing certain food additives, which have a negligible probability of carcinogenicity in legal limits, must be reinforced in the perspective of public health concerns.

  2. Sensibility of the hamster (Cricetus auratus to the Treponema pertenue

    Directory of Open Access Journals (Sweden)

    F. Nery-Guimarães

    1955-05-01

    Full Text Available In two experiments, 8 Hamsters inoculated with material from yaws lesions (Treponema pertenue, developed skin lesions considered specific by their clinical and histopathological aspects and by the presence of treponemae. These lesions appeared on the scrotumm, testicle, prepuce, anus, tail, muzzle, back and hinders paws (palm surface. In the internal organs no treponemae were found in direct examinations and inoculation of brain, spleen and lymph node. The incubation period was of 35 days for the testicle, 55 days for the scrotum and 107 days for peritoneal cavity inoculation. Positive sub-inoculations were obtained. The serum reactions (Qasserman's and Kahn's were negative in all 5 tested Hamsters. Out of 4 normal females matched to infected males two developed nasal lesions resulting from direct contact. Apparently the genital lesions hindered copulation. Hamsters are very well suited for an experimental study of yaws.Em 2 experiências, 8 Hamsters inoculados com material direto de lesões boubáticas (Treponema pertenue, desenvolveram lesões cutâneas consideradas específicas, pelo aspecto clínico e histopatológico e pela presentça de treponemas. Essas lesões se manifestaram no escrôto, testículo, prepúcio, anus, cauda, focinho, dorso e patas posteriores (face palmar. Nos órgãos internos não foram vistos treponemas ao exame direto e, uma vez, por inoculação de cérebro, baço e gânglio linfático. O período incubativo foi de 35 dias pela via testicular, 55 dias pela via escrotal e 107 dias pela via peritonial. Foram obtidas sub-inoculações positivas para Hamsters normais. As experiências continuam. De 4 fêmeas normais, acasaladas com 4 hamsters infectados apenas 2 mostraram lesões positivas resultantes de contágio direto. Aparentemente, não houve copulação e, se esta ocorreu, não determinou fecundação.

  3. Expression of a fms-related oncogene in carcinogen-induced neoplastic epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Walker, C.; Nettesheim, P.; Barrett, J.C.; Gilmer, T.M.

    1987-04-01

    Following carcinogen exposure in vitro, normal rat tracheal epithelial cells are transformed in a multistage process in which the cultured cells become immortal and ultimately, neoplastic. Five cell lines derived from tumors produced by neoplastically transformed rat tracheal epithelial cells were examined for the expression of 11 cellular oncogenes previously implicated in pulmonary or epithelial carcinogenesis. RNA homologous to fms was expressed at a level 5-19 times higher than normal tracheal epithelial cells in three of five of the tumor-derived lines. All three lines expressing high levels of fms-related RNA gave rise to invasive tumors of epithelial origin when injected into nude mice. Increased expression of the fms-related mRNA was not due to gene amplification, and no gene rearrangement was detected by Southern analyses. RNA blot analysis using a 3' v-fms probe detected a 9.5-kilobase message in the three tumor-derived lines, whereas both normal rat aveolar macrophages and the human choriocarcinoma line BeWo expressed a fms transcript of approx. = 4 kilobases. The authors conclude from these data that the gene expressed as a 9.5-kilobase transcript in these neoplastic epithelial cells is a member of a fms-related gene family but may be distinct from the gene that encodes the macrophage colony-stimulating factor (CSF-1) receptor.

  4. Species and diet related resistance to chemical carcinogens: biochemical mechanisms of aflatoxin B1 detoxification

    International Nuclear Information System (INIS)

    To provide insight into the biochemical mechanisms mediating species and diet related resistance to chemical carcinogens, the biotransformation and covalent binding to DNA of the potent hepatocarcinogen aflatoxin B1(AFB) was investigated in resistant and susceptible species fed standard and butylated hydroxyanisole (BHA)-supplemented diets. The rat is sensitive to the hepatocarcinogenic effects of AFB, whereas the mouse, and rats fed BHA-supplemented diet, are resistant. To differentiate between enzyme induction and direct antioxidant effects, BHA was administered to rats for 9 days, or as a single dose 4-7 hrs prior to i.p. injection of 3H-AFB. Long-term treatment with BHA doubled the biliary excretion of the glutathione conjugate of AFB and the AFP1-glucuronide, and reduced the binding of AFB to hepatic DNA to 16% of control. Single-dose BHA treatment had no effect. To determine if glutathione S-transferase (GST) activity towards the AFB-epoxide mediates both treatment and species related resistance to AFB carcinogenesis, a method was developed to measure the rate of formation of the AFB-epoxide, and the rate of inactivation of the epoxide via GST. To demonstrate the importance of GST-mediated detoxification of the AFB-epoxide in the mouse in vivo, depletion of hepatic GSH was accomplished by administration of L-buthionine-S,R-sulfoximine and diethyl maleate, prior to administration of AFB. GSH depletion was associated with a 30-fold increase in AFB-DNA binding

  5. Heat and cold acclimation in helium-cold hypothermia in the hamster.

    Science.gov (United States)

    Musacchia, X. J.

    1972-01-01

    A study was made of the effects of acclimation of hamsters to high (34-35 C) and low (4-5 C) temperatures for periods up to 6 weeks on the induction of hypothermia in hamsters. Hypothermia was achieved by exposing hamsters to a helox mixture of 80% helium and 20% oxygen at 0 C. Hypothermic induction was most rapid (2-3 hr) in heat-acclimated hamsters and slowest (6-12 hr) in cold-acclimated hamsters. The induction period was intermediate (5-8 hr) in room temperature nonacclimated animals (controls). Survival time in hypothermia was relatable to previous temperature acclimations. The hypothesis that thermogenesis in cold-acclimated hamsters would accentuate resistance to induction of hypothermia was substantiated.

  6. TELOMERASE ACTIVITY DURING 7, 12-DIMETHYLBENZ [a] ANTHRACENE-INDUCED HAMSTER BUCCAL POUCH CARCINOGENESIS

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective: To investigate the roles of telomerase activity (TA) in relation to hamster buccal pouch tumor progression. Methods: male hamster were treated three times weekly with 0.5% of 7, 12-dimethyl- benzanthracene (DMBA) over a 15 weeks experimental period. Hamsters were sacrificed at 3, 6, 9, 12 and 15 weeks after treatment. Telomerase activity of hamster buccal pouch tissue were measured along with the analyses of the formation of DMBA-induced hamster buccal pouch tumors. Results: DMBA-induced squamous cell carcinomas were found at the 6th week after dosing. Telomerase activity elevation began at the 3rd week and was increasing to a plateau at the 12th week. Conclusion: Our results show that telomerase activity in the target tissue may be detected at the early stage of the DMBA-induced hamster buccal pouch tumor formation and suggests that telomerase activity may be used as a biomarker for an early clinical detection of buccal pouch cancer.

  7. Cystolithiasis in a Syrian hamster: a different outcome

    Directory of Open Access Journals (Sweden)

    D. Petrini

    2016-08-01

    Full Text Available A 14-month-old intact male Syrian hamster was admitted for lethargy and hematuria. A total body radiographic image and abdominal ultrasonography showed the presence of a vesical calculus. During cystotomy, a sterile urine sample was obtained and sent to the diagnostic laboratory along with the urolith for analysis. Urine culture was found negative for bacterial growth, and the urolith was identified as a calcium-oxalate stone. Diet supplementation with palmitoylethanolamide, glucosamine and hesperidin was adopted the day after discharge. One year follow up revealed no presence of vesical calculi. Although this is the report of a single clinical case, this outcome differs from the results reported in the literature characterized by recurrences after few months. Considering the positive outcome and the beneficial properties of palmitoylethanolamide, glucosamine, and hesperidin, these nutritional elements in Syrian hamsters, are recommended to reduce recurrence after surgical treatment of urolithiasis.

  8. Current issues in carcinogenic effect of low-dose radiation

    International Nuclear Information System (INIS)

    A review of publications dealing with study of radiation sources and biological evaluation of increasing doses of people irradiation under occupational and usual living conditions is presented. The existing natural and artifial irradiation sources are considered. It is noted that all types of ionizing radiations are characterized by high carcinogenic efficiency and can induce benign and malignant tumors practically in all organs. Statistically reliable data in experimental and epidemiological investigations were recorded under the effect of large and mean doses. Minor radiation doses not responsible for visible functional and morphological changes in early periods can cause pathological changes in delayed periods. The data on carcinogenic effect of relatively small radiation doses are available

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

    International Nuclear Information System (INIS)

    We have accumulated more experimental evidences that demonstrated the comparative approaches with human cells will allow us to predict human risk with good accuracy following exposure to toxic chemicals. We also synthesized several carcinogenic DNA adducts, i.e., the major benzo[a]pyrene DNA adduct, 06-methyldeoxyguanosine, 7-methyl- deoxyguanosine and 2-methyl-deoxyguanosine to be used as standards for quantitating DNA adduct formation in carcinogen exposed cells. A simple synthetic method was developed for preparation of the major B[a]p DNA adduct with yields better than those reported. The main accomplishments related to the originally stated objectives are summarized. 8 refs., 2 figs., 1 tab

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

    Science.gov (United States)

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

    2013-05-01

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

  11. Photoperiodic regulation of adrenal hormone secretion and aggression in female Syrian hamsters

    OpenAIRE

    Gutzler, Stephanie J.; Karom, Mary; Erwin, W. Daniel; ALBERS, H. Elliott

    2009-01-01

    Seasonal changes in the length of the daily photoperiod induce significant changes in social behavior. Hamsters housed in winter-like short photoperiods (SP) can express significantly higher levels of aggression than hamsters housed in long photoperiods (LP) that mimic summer. The mechanisms responsible for increasing aggressiveness in SP-exposed female hamsters are not well understood but may involve seasonal changes in the endocrine system. In experiment 1, the effects of SP exposure on the...

  12. Acquired resistance of hamsters to challenge with homologous and heterologous virulent treponemes.

    OpenAIRE

    Schell, R F; Azadegan, A A; Nitskansky, S G; LeFrock, J L

    1982-01-01

    Hamsters infected with Treponema pallidum Nichols (venereal syphilis), T. pallidum Bosnia A (endemic syphilis), or T. pertenue (frambesia, or yaws) developed substantial resistance to homologous reinfection. Hamsters infected for 10 weeks developed no lesions, and their lymph nodes contained fewer treponemes after reinfection with the same strain. The degree of cross-resistance among the treponemes correlated well with pathological changes occurring in infected hamsters and with the persisten...

  13. Oral implantation of Bacteroides asaccharolyticus and Eikenella corrodens in conventional hamsters.

    OpenAIRE

    Nagahata, T; Kiyoshige, T; Tomono, S; Abe, R; Sasaki, S.; Takazoe, I

    1982-01-01

    Oral implantation of Bacteroides asaccharolyticus 381-R' and Eikenella corrodens 1073S-R, which are highly resistant to streptomycin, was examined in conventional hamsters. The hamsters' first molars were ligatured with cotton threads preimmersed in bacterial suspensions. Bacterial inoculation was performed daily for 1 week, followed by a single weekly inoculation for 7 more weeks. Hamsters were fed Keyes' diet no. 2000 or ordinary powdered diet. Bacterial recovery, gingival histological chan...

  14. Hibernation, stress, intestinal functions, and catecholoamine turnover rate in hamsters and gerbils

    Science.gov (United States)

    Musacchia, X. J.

    1973-01-01

    Bioenergetic studies on hamsters during depressed metabolic states are reported. External support of blood glucose extended the survival times of hibernating animals. Radioresistance increased in hibernating as well as in hypothermic hamsters. Marked changes in hamster catecholamine turnover rates were observed during acclimatization to high temperature stress. High radioresistance levels of the gerbil gastrointestinal system were attributed in part to the ability of the gut to maintain functional integrity.

  15. Inhibition of caries in hamsters treated with staphylococcin 1580.

    OpenAIRE

    Fitzgerald, R J; Morhart, R E; Marquez, C; Adams, B. O.

    1986-01-01

    Littermate hamsters were infected orally with cariogenic Streptococcus mutans NS-50S and maintained on a high-sucrose diet to induce dental caries. Individual groups of animals were treated by single daily instillation of staphylococcin 1580 (100 micrograms) in the cheek pouches. Other groups were treated similarly with bacitracin (60 or 120 U) or saline. After 35 days on the caries test regimen, animals treated with staphylococcin 1580 had 49 or 60% less caries than the saline controls in tw...

  16. Kinetic differences between fed and starved Chinese hamster ovary cells

    International Nuclear Information System (INIS)

    When Chinese hamster ovary (CHO) cells are grown as monolayer cultures, they eventually reach a population-density plateau after which no net increase in cell numbers occurs. A manuscript has recently been published which draws attention to the important, and perhaps unexpected, differences in the kinetic status of different types of plateau-phase CHO cells (Nelson, Todd and Metting 1984). The essence of this manuscript and the most significant findings are summarized in this paper

  17. X-ray epilation and hair detriments in chinese hamsters

    International Nuclear Information System (INIS)

    Chinese hamsters were exposed to an acute dose of whole-body x radiation. Survivors displayed a wave-like pattern of epilation and hair-graying that has not previously been reported in the literature. The pigment score, length, and width of individual graying hairs from the haunch and shoulder of the surviving animals were statistically analyzed to demonstrate x radiation damage to and recovery of the follicle and pigment cells

  18. Autoradiographic images in the hamster cheek pouch oral cancer model

    International Nuclear Information System (INIS)

    The aim of this work is to summarize the autoradiographic study performed to samples from different protocols of the hamster cheek pouch oral cancer model. The qualitative analysis of histological and autoradiographic images, together with the determination of the boron concentration in the different structures of tumor, premalignant tissue and normal tissue contributed to the knowledge of the microdistribution of boron compounds. Besides, the study led to the optimization of the autoradiography technique applied to BNCT (Boron Neutron Capture Therapy). (author)

  19. Effects of hyperthermia on the hamster immune system

    International Nuclear Information System (INIS)

    In previous studies, the authors have shown that hyperthermia can enhance antibody-complement chytotoxicity of hamster and human tumor cells. Moreover, whole body microwave exposure of hamsters resulted in activation of peritoneal macrophages to a viricidal state and transient suppression of natural killer (NK) cell activity. In this study, the authors compare the effects of whole body heating by microwaves or by an environmental chamber (hot air) on the hamster immune system. Microwave exposure (25mW/cm/sup 2/; 1 hr) caused viricidal activation of peritoneal macrophages which resulted in restriction of vaccinia and vesicular stomatitis virs (VSV) growth. However, heating in an environmental chamber (410C; 1 hr) did not activate macrophages to a viricidal state. Both microwave and hot air hyperthermia caused significant augmentation of antibody producing spleen cell response to sheep red blood cells (SRBC), using the Jerne hymolytic plaque assay, four days post exposure and immunization with SRBC. Natural killer spleen cell cytotoxicity was suppressed by microwave and hot air hyperthermia showing that NK lymphocytes are extremely sensitive to changes in temperature. These alterations in cellular immune response due to hyperthermia could be of significance in treatment of tumors and viral infections

  20. Teratogenicity and embryotoxicity of nickel carbonyl in Syrian hamsters

    Energy Technology Data Exchange (ETDEWEB)

    Sunderman, F.W. Jr.; Shen, S.K.; Reid, M.C.; Allpass, P.R.

    1980-01-01

    Nickel carbonyl was administered to groups of pregnant hamsters by inhalation on days 4, 5, 6, 7, or 8 of gestation. The dams were killed on day 15 of gestation, and the fetuses were examined for malformations. Exposure to Ni(CO)/sub 4/ on days 4 or 5 of gestation resulted in malformation in 5.5% and 5.8% of the progeny, respectively. Progeny included 9 fetuses with cystic lungs, 7 fetuses with exencephaly, 1 fetus with exencephaly plus fused rib and 1 fetus with anophthalmia plus cleft palate. Hemorrhages into serious cavities were found. In progeny of dams exposed to Ni(CO)/sub 4/ on days 6 or 7 of gestation, there was 1 fetus with fused ribs and there were 2 fetuses with hydronephrosis. In another experiment, pregnant hamsters were exposed to inhalation of Ni(CO)/sub 4/ on day 5 of gestation; these dams were permitted to deliver their litters and to nurse their pups. There was no significant difference in the average number of live pups in the Ni(CO)/sub 4/-exposed litters compared to control litters. Neonatal mortality was increased in Ni(CO)/sub 4/-exposed litters. This study demonstrates that Ni(CO)/sub 4/ is teratogenic and embryotoxic in Syrian hamsters.

  1. Suppression of Clostridium difficile by Normal Hamster Cecal Flora and Prevention of Antibiotic-Associated Cecitis

    OpenAIRE

    Wilson, Kenneth H.; Silva, Joseph; Fekety, F. Robert

    1981-01-01

    Administration of normal cecal homogenates decreased numbers of viable Clostridium difficile and prevented cecitis in antibiotic-challenged hamsters. Cecal anaerobes appeared to suppress C. difficile.

  2. DNA (deoxyribonucleic acid) synthesis following microinjection of heterologous sperm and somatic cell nuclei into hamster oocytes

    International Nuclear Information System (INIS)

    The authors investigated the ability of the hamster oocyte to initiate DNA synthesis in nuclei differing in basic protein content. DNA synthesis was studied by autoradiography in oocytes that had been incubated in 3H-thymidine after being parthenogenetically activated by sham microinjection, or microinjected with hamster, mouse, rabbit, or fish sperm nuclei, or hamster hepatocyte nuclei. Within 6 hr of sham or nucleus microinjection, nuclei of each type underwent transformation into pronuclei and synthesized DNA. These results demonstrated that the hamster egg can access and utilize its own and each type of template provided, whether homologous or heterologous. However, pronuclei derived from hamster sperm nuclei were more likely to be synthesizing DNA at 6 hr than pronuclei derived from sperm nuclei of other species. The authors conclude that the mechanisms employed by the hamster oocyte to transform hamster sperm nuclei into pronuclei and to effect DNA synthesis in these nuclei are not specific for the hamster sperm nucleus. Nevertheless, these mechanisms apparently operate more efficiently when the hamster sperm nucleus, rather than a heterologous sperm nucleus, is present

  3. Potential neoplastic effects of parathion-methyl on rat liver

    Institute of Scientific and Technical Information of China (English)

    M. Nisa UNALDI CORAL; Sonay UCMAN; Hasan YILDIZ; Haydar OZTAS; Semih DALKILIC

    2009-01-01

    The mutagenic and carcinogenic effects of parathion-methyl were examined by bacterial reverse assay and a long term experiment with Wistar rats. The potential mutagenic effect of parathion-methyl in Salmonella typhimurium TA100 bacterial cells was observed without rat liver S9 metabolic activation. Parathion-methyl was further investigated for pathological changes in rat pancreas and liver. The long-term rat experiments showed that parathion-methyl exposure for 3 months can cause pathological changes in rat pancreases acinar cells and pancreatic hepatocytes. Atypical acinar cell focuses (AACF) were determined in the liver and pancreas of the rats. The results from short-term Ames test and long-term rat experiments suggest that parathion-methyl would be potential carcinogenic.

  4. An assessment of the carcinogenic potential of ezetimibe using nonclinical data in a weight-of-evidence approach

    International Nuclear Information System (INIS)

    Ezetimibe blocks intestinal absorption of sterols via interaction with the Neimann-Pick C1-Like 1 (NPC1L1) transporter and is approved for use in the treatment of primary hyperlipidemia (heterozygous familial and non-familial), homozygous familial hypercholesterolemia, and homozygous sitosterolemia. A recently completed randomized clinical trial [simvastatin and ezetimibe in aortic stenosis (SEAS)] testing the effectiveness of VytorinTM (a combination of simvastatin and ezetimibe) in patients with aortic stenosis reported an unexpected safety finding: an increase in overall cancer incidence and cancer-associated mortality (all types) in the treated groups relative to the placebo control. A subsequent meta-analysis utilizing a much larger database from two ongoing clinical trials indicated that the observed findings in the SEAS trial were likely due to chance and not a true drug-induced effect. Nonetheless, it has been suggested by various commentators on the SEAS trial that ezetimibe may be carcinogenic. The extensive nonclinical database for ezetimibe was used to test the hypothesis that ezetimibe may be a direct or indirect carcinogen. Using two different in silico approaches, ezetimibe showed no structural alerts for genetic toxicity or carcinogenicity. Ezetimibe was not genotoxic in two reverse mutation assays, one in vitro clastogenicity assay, and two mouse micronucleus assays. No evidence of proliferative lesions was observed in three species in studies of 1-12 months in duration. Ezetimibe was not carcinogenic in standard 2-year bioassays in mice and rats. Additionally, in these 2-year bioassays, no drug-related non-neoplastic lesions were noted. The absence of drug-induced non-neoplastic or proliferative lesions in these studies indicates that ezetimibe treatment was not associated with findings characteristic of carcinogens (i.e., DNA reactivity or cell proliferation) Administration of pharmacologic doses of ezetimibe to mice did not alter hepatic

  5. Genetic determinants of growth phase-dependent and adenovirus 5-responsive expression of the Chinese hamster thymidine kinase gene are contained within thymidine kinase mRNA sequences.

    OpenAIRE

    Lewis, J. A.; Matkovich, D A

    1986-01-01

    We have constructed a chimeric thymidine kinase (TK) minigene, pHe delta 6Ha, which combines the complete coding and 3' noncoding regions of a Chinese hamster TK cDNA with the promoter region and 5' untranslated region of the TK gene of herpes simplex virus type 1. We have transformed rat 4 cells to Tk+ with this gene and analyzed the pattern of TK gene expression in these transformants under various conditions of in vitro cell culture. We find that TK gene expression in these Tk+ transforman...

  6. Social play in juvenile hamsters alters dendritic morphology in the medial prefrontal cortex and attenuates effects of social stress in adulthood.

    Science.gov (United States)

    Burleson, Cody A; Pedersen, Robert W; Seddighi, Sahba; DeBusk, Lauren E; Burghardt, Gordon M; Cooper, Matthew A

    2016-08-01

    Social play is a fundamental aspect of behavioral development in many species. Social play deprivation in rats alters dendritic morphology in the ventromedial prefrontal cortex (vmPFC) and we have shown that this brain region regulates responses to social defeat stress in Syrian hamsters. In this study, we tested whether play deprivation during the juvenile period disrupts dendritic morphology in the prefrontal cortex and potentiates the effects of social defeat stress. At weaning, male hamsters were either group-housed with peers or pair-housed with their mother, with whom they do not play. In adulthood, animals received acute social defeat stress or no-defeat control treatment. The hamsters were then tested for a conditioned defeat response in a social interaction test with a novel intruder, and were also tested for social avoidance of a familiar opponent. Brains were collected for Golgi-Cox staining and analysis of dendritic morphology in the infralimbic (IL), prelimbic (PL), and orbitofrontal cortex (OFC). Play-deprived animals showed an increased conditioned defeat response and elevated avoidance of a familiar opponent compared with play-exposed animals. Furthermore, play-deprived animals showed increased total length and branch points in apical dendrites of pyramidal neurons in the IL and PL cortices, but not in the OFC. These findings suggest that social play deprivation in juvenile hamsters disrupts neuronal development in the vmPFC and increases vulnerability to the effects of social stress in adulthood. Overall, these results suggest that social play is necessary for the natural dendritic pruning process during adolescence and promotes coping with stress in adulthood. (PsycINFO Database Record PMID:27176563

  7. 18. Adduct detection in human monitoring for carcinogen exposure

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    @@Determination of the covalently bound products (adducts) of carcinogens with DNA or proteins may be used for the monitoring of exposure to these compounds. Protein adducts are generally stable and are not enzymatically repaired, and the use of these for cxposure monitoring is normally carried out with globin or albumin, because

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

    NARCIS (Netherlands)

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

    2015-01-01

    BACKGROUND: Recently the International Agency for Research on Cancer (IARC) Programme for the Evaluation of Carcinogenic Risks to Humans has been criticized for several of its evaluations, and also the approach used to perform these evaluations. Some critics have claimed that IARC Working Groups' fa

  9. Modern Electrochemical Methods for Monitoring of Chemical Carcinogens

    OpenAIRE

    Zima, J; Moreira, J.; J. Barek

    2005-01-01

    This contribution is based on our presentation at the 1st International Symposium on Sensor Science, Paris, 16-20 June 2003. It presents recent results regarding the electrochemical determination of submicromolar and nanomolar concentrations of various carcinogenic substances (nitrated polycyclic aromatic hydrocarbons, heterocyclic compounds, azo compounds, aromatic amino compounds, etc.) using both traditional (classical dropping mercury electrode, static mercury drop electrode, hanging merc...

  10. DETECTION OF CARCINOGENICITY BASED ON MUTAGENICITY IN ARABIDOPSIS

    Science.gov (United States)

    Thirty-seven synthetic chemicals plus two mycotoxins were tested for mutagenicity in an Arabidopsis embryo system. The results of this test, prokaryotic repair tests, bacterial mutation assays, eukaryotic cell systems, and in vivo tests were compared to the carcinogenicity classi...

  11. Non—Genotoxic Carcinogens.Approaches to Their Rish Assessment

    Institute of Scientific and Technical Information of China (English)

    J.A.CASTRO; M.I.DiazGomez; 等

    1993-01-01

    Epidemiological studies support the idea that most human cancers are related to chemicals present in the human environment.In turn,chemicals are believed to cause cancer via either genotoxic or non-genotoxic mechanisms.There were described in literature several simple rapid and inexpensive short term ests to reasonably predict the genotoxic nature of chemicals but in contrast,there is no reliable test or battery of tests available to predict the carcinogenicity of non-genotoxic compounds and this poses a major problem to their rish assessment.In addition,there are conflictive opinions about rish assessment needs for both classes of carcinogens.Some workers elieve that for non-genotoxic carcinogens,thresholds for exposure can be drawn while others do not.In this review,the reasons behind both of these opinions and the present hypotheses about the mechanism of action of non-genotoxic carcinogens are described and analyzed in relation to future needs.

  12. Flavonoids and alkenylbenzenes: mechanisms of mutagenic action and carcinogenic risk

    NARCIS (Netherlands)

    Rietjens, I.M.C.M.; Boersma, M.G.; Woude, van der H.; Jeurissen, S.M.F.; Schutte, M.E.; Alink, G.M.

    2005-01-01

    The present review focuses on the mechanisms of mutagenic action and the carcinogenic risk of two categories of botanical ingredients, namely the flavonoids with quercetin as an important bioactive representative, and the alkenylbenzenes, namely safrole, methyleugenol and estragole. For quercetin a

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

    NARCIS (Netherlands)

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

    2014-01-01

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

  14. Vinyl carbamate epoxide, a major strong electrophilic, mutagenic and carcinogenic metabolite of vinyl carbamate and ethyl carbamate (urethane).

    Science.gov (United States)

    Park, K K; Liem, A; Stewart, B C; Miller, J A

    1993-03-01

    Vinyl carbamate epoxide (VCO) was found to possess strong electrophilic, mutagenic and carcinogenic activities. It reacted with water at 37 degrees C and pH 7.4 (phosphate buffer) to form glycolaldehyde and several related reducing compounds; none of these products were mutagenic for Salmonella typhimurium TA1535. Under these conditions VCO had a half-life (determined chemically and mutagenically) of approximately 10.5 min. This half-life was progressively lowered by increasing concentrations of chloride ion (liver, serum and isotonic levels). This ion reacted with VCO to form chloroacetaldehyde. VCO also reacted with other nucleophiles such as glutathione, DNA and its constituent guanine and adenine bases. The purine adducts formed by VCO in DNA in vitro and in vivo were released by weak acid treatment and consisted of 7-(2'-oxoethyl)guanine and N2,3-ethenoguanine as major products with 1,N6-ethenoadenine as a minor product. VCO was a strong direct mutagen in Salmonella typhimurium TA1535 and TA100 but was only weakly active in the TA98 mutant. VCO was a stronger initiator of carcinogenesis in the skin of CD-1 mice and in the liver of infant male B6C3F1 mice than its metabolic precursors vinyl carbamate (VC) and ethyl carbamate (EC). Unlike VC and EC, VCO was a strong complete carcinogen in the skin of CD-1 mice and induced papillomas and carcinomas following repetitive administration of sub-ulcerogenic doses. VCO also exhibited some carcinogenic activity in the lungs of mice and in the s.c. and mammary tissue of female Sprague-Dawley rats. These data and those from other recent studies support the conclusion that VCO is a major strong electrophilic, mutagenic and carcinogenic metabolite of EC and VC in the mouse. PMID:8453720

  15. Inverse relationship of tumors and mononuclear cell leukemia infiltration in the lungs of F344 rats

    Energy Technology Data Exchange (ETDEWEB)

    Lundgren, D.L.; Griffith, W.C.; Hahn, F.F.

    1995-12-01

    In 1970 and F344 rat, along with the B6C3F{sub 1} mouse, were selected as the standard rodents for the National Cancer Institute Carcinogenic Bioassay program for studies of potentially carcinogenic chemicals. The F344 rat has also been used in a variety of other carcinogenesis studies, including numerous studies at ITRI. A major concern to be considered in evaluating carcinogenic bioassay studies using the F344 rat is the relatively high background incidence of mononuclear cell leukemia (MCL) (also referred to as large granular lymphocytic leukemia, Fischer rat leukemia, or monocytic leukemia). Incidences of MCL ranging from 10 to 72% in male F344 rats to 6 to 31% in female F344 rats have been reported. Gaining the understanding of the mechanisms involved in the negative correlations noted should enhance our understanding of the mechanisms involved in the development of lung cancer.

  16. How well can in vitro data predict in vivo effects of chemicals? Rodent carcinogenicity as a case study.

    Science.gov (United States)

    Anthony Tony Cox, Louis; Popken, Douglas A; Kaplan, A Michael; Plunkett, Laura M; Becker, Richard A

    2016-06-01

    A recent research article by the National Center for Computational Toxicology (NCCT) (Kleinstreuer et al., 2013), indicated that high throughput screening (HTS) data from assays linked to hallmarks and presumed pathways of carcinogenesis could be used to predict classification of pesticides as either (a) possible, probable or likely rodent carcinogens; or (b) not likely carcinogens or evidence of non-carcinogenicity. Using independently developed software to validate the computational results, we replicated the majority of the results reported. We also found that the prediction model correlating cancer pathway bioactivity scores with in vivo carcinogenic effects in rodents was not robust. A change of classification of a single chemical in the test set was capable of changing the overall study conclusion about the statistical significance of the correlation. Furthermore, in the subset of pesticide compounds used in model validation, the accuracy of prediction was no better than chance for about three quarters of the chemicals (those with fewer than 7 positive outcomes in HTS assays representing the 11 histopathological endpoints used in model development), suggesting that the prediction model was not adequate to predict cancer hazard for most of these chemicals. Although the utility of the model for humans is also unclear because a number of the rodent responses modeled (e.g., mouse liver tumors, rat thyroid tumors, rat testicular tumors, etc.) are not considered biologically relevant to human responses, the data examined imply the need for further research with HTS assays and improved models, which might help to predict classifications of in vivo carcinogenic responses in rodents for the pesticide considered, and thus reduce the need for testing in laboratory animals. PMID:26879462

  17. Risk assessment of DNA-reactive carcinogens in food

    International Nuclear Information System (INIS)

    Risk assessment of DNA-reactive carcinogens in food requires knowledge of the extent of DNA damage in the target organ which results from the competition between DNA adduct formation and repair. Estimates of DNA adduct levels can be made by direct measurement or indirectly as a consequence of their presence, for example, by tumor formation in animal models or exposed populations epidemiologically. Food-borne DNA-reactive carcinogens are present from a variety of sources. They are generally not intrinsically DNA-reactive but require bioactivation to DNA-reactive metabolites a process which may be modulated by the compound itself or the presence of other xenobiotics. A single DNA reactant may form several distinct DNA adducts each undergoing different rates of repair. Some DNA reactants may be photochemically activated or produce reactive oxygen species and thus indirect oxidative DNA damage. The levels of DNA adducts arising from exposures influenced by variations in the doses, the frequency with which an individual is exposed, and rates of DNA repair for specific adducts. Each adduct has a characteristic efficiency with which it induces mutations. Based on experience with the well-studied DNA-reactive food carcinogen aflatoxin B1 (AFB1), a limit of 20 ppb or ∼30 μg/day has been set and is considered a tolerable daily intake (TDI). Since AFB1 is considered a potent carcinogen, doses of 32P-postlabeling or the use of surrogates such as hemoglobin adducts, together with approaches to evaluate the results. A discussion of approaches to estimating possible threshold effects for DNA-reactive carcinogens is made

  18. Carcinogenicity of the insulation wools: reassessment of the IARC evaluation.

    Science.gov (United States)

    Brown, R C; Davis, J M; Douglas, D; Gruber, U F; Hoskins, J A; Ilgren, E B; Johnson, N F; Rossiter, C E; Wagner, J C

    1991-08-01

    In assessing the health evidence concerning man-made mineral fibers, the chemical composition, surface activity, durability, and size of fibers have to be taken into account. Special-purpose fine glass fibers need to be separated from the insulation wools (glass, rock, and slag wool). The epidemiological evidence is sufficient to conclude that there has been no mesothelioma risk to workers producing or using glass wool, rock wool, or slag wool. The epidemiological studies have been large and powerful, and they show no evidence of a cause-effect relationship between lung cancer and exposure to glass wool, rock wool, or slag wool fibers. There is some evidence of a small cancer hazard attached to the manufacturing process in slag wool plants 20 to 50 years ago, when asbestos was used in some products and other carcinogenic substances were present. However, this hazard is not associated with any index of exposure to slag wool itself. Animal inhalation studies of ordinary insulation wools also show that there is no evidence of hazard associated with exposure to these relatively coarse, soluble fibers. The evidence of carcinogenicity is limited to experiments with special-purpose fine durable glass fibers or experimental fibers, and only when these fibers are injected directly into the pleural or peritoneal cavity. Multiple chronic inhalation studies of these same special-purpose fine glass fibers have not produced evidence of carcinogenicity. It is suggested that the present IARC evaluation of the carcinogenic risk of insulation wools should be revised to Category 3: not classifiable as to carcinogenicity to humans. PMID:1947241

  19. Developmental Changes in the ECG of a Hamster Model of Muscular Dystrophy and Heart Failure

    Directory of Open Access Journals (Sweden)

    Thomas Gerard Hampton

    2012-05-01

    Full Text Available Aberrant autonomic signaling is being increasingly recognized as an important symptom in neuromuscular disorders. The delta-sarcoglycan-deficient BIO TO-2 hamster is recognized as a good model for studying mechanistic pathways and sequelae in muscular dystrophy and heart failure, including autonomic nervous system dysfunction. Recent studies using the TO-2 hamster model have provided promising preclinical results demonstrating the efficacy of gene therapy to treat skeletal muscle weakness and heart failure. Methods to accelerate preclinical testing of gene therapy and new drugs for neuromuscular diseases are urgently needed. The purpose of this investigation was to demonstrate a rapid non-invasive screen for characterizing the autonomic nervous system imbalance in dystrophic TO-2 hamsters. Electrocardiograms were recorded non-invasively in conscious ~9-month old TO-2 hamsters (n=10 and non-myopathic F1B control hamsters (n=10. Heart rate was higher in TO-2 hamsters than controls (453 ± 12 bpm vs. 311 ± 25 bpm, P<0.01. Time domain heart rate variability, an index of parasympathetic tone, was lower in TO-2 hamsters (12.2 ± 3.7 bpm vs. 38.2 ± 6.8, P<0.05, as was the coefficient of variance of the RR interval (2.8 ± 0.9 % vs. 16.2 ± 3.4 %, P<0.05 compared to control hamsters. Power spectral analysis demonstrated reduced high frequency and low frequency contributions, indicating autonomic imbalance with increased sympathetic tone and decreased parasympathetic tone in dystrophic TO-2 hamsters. Similar observations in newborn hamsters indicate autonomic nervous dysfunction may occur quite early in life in neuromuscular diseases. Our findings of autonomic abnormalities in newborn hamsters with a mutation in the delta-sarcoglycan gene suggest approaches to correct modulation of the heart rate as prevention or therapy for muscular dystrophies.

  20. The presence of opioidergic pinealocytes in the pineal gland of the European hamster (Cricetus cricetus): an immunocytochemical study

    DEFF Research Database (Denmark)

    Coto-Montes, A.; Masson-Pévet, M.; Pévet, P.;

    1994-01-01

    Neurobiologi, pineal gland, leu-enkephalin, Met-enkephalin, synaptic contacts, paracrine regulation, European hamster, cricetus cricetus (rodents)......Neurobiologi, pineal gland, leu-enkephalin, Met-enkephalin, synaptic contacts, paracrine regulation, European hamster, cricetus cricetus (rodents)...

  1. Biodistribution study with combined administration of BPA and BSH for BNCT in the hamster cheek pouch oral cancer model

    International Nuclear Information System (INIS)

    We previously proved the therapeutic potential of the chemically non-selective boron compound decahydrodecaborate (GB-10) as a stand-alone boron carrier for BNCT in the hamster cheek pouch oral cancer model with no toxic effects in normal or precancerous tissue. Although GB-10 is not taken up selectively by oral tumor tissue, selective tumor lethality would result from selective aberrant tumor blood vessel damage. Furthermore, BNCT efficacy was enhanced when GB-10 and boronophenylalanine (BPA) were administered jointly. The fact that sodium mercaptoundecahydro-closo-dodecaborate (BSH) is being investigated clinically as a stand-alone boron agent for BNCT of brain tumors and in combination with BPA for recurrent head and neck malignancies makes it a particularly interesting boron compound to explore. Based on the working hypothesis that BSH would conceivably behave similarly to GB-10 in oral cancer, we previously performed biodistribution studies with BSH alone in the hamster cheek pouch oral cancer model. The aim of the present study was to perform biodistribution studies of BSH + BPA administered jointly in the hamster cheek pouch oral cancer model as a starting point to contribute to the knowledge of (BSH+BPA)-BNCT radiobiology and optimize therapeutic efficacy. The right cheek pouch of Syrian hamsters was subjected to topical administration of a carcinogen twice a week for 12 weeks. Once the exophytic tumors, i.e. squamous cell carcinomas, had developed, the animals were used for biodistribution studies with BSH + BPA. Three administration protocols with different proportions of each of the compounds were assessed: 1. BSH, 50 mg 10B/kg, iv + BPA, 15.5 mg 10B/kg, ip; 2. BSH, 34.5 mg 10B/kg, iv + BPA, 31 mg 10B/kg, ip; 3. BSH, 20 mg 10B/kg, iv + BPA, 46.5 mg 10B/kg, ip. Groups of animals were euthanized 4 h after the administration of BSH and 3 h after the administration of BPA. Samples of blood, tumor, precancerous and normal pouch and other tissues with clinical

  2. Biostatistical issues in the design and analysis of animal carcinogenicity experiments.

    OpenAIRE

    Portier, C.J.

    1994-01-01

    Two-year animal carcinogenicity experiments are used to evaluate the potential carcinogenicity from exposure to chemicals. The choice of exposure levels, the allocation of animals to doses, the length of exposure, and the choice of interim sacrifice times all affect the power of statistical tests for carcinogenic effects and the variance of interpolated estimates of carcinogenic risk. In this paper, one aspect of this problems is considered: the ability of tumor incidence data to provide info...

  3. Multiple mechanisms for the carcinogenic effects of asbestos and other mineral fibers.

    OpenAIRE

    Barrett, J C; Lamb, P W; Wiseman, R. W.

    1989-01-01

    Asbestos and other mineral fibers are carcinogenic to humans and animals but differ from many carcinogens in that they do not induce gene mutations. An understanding of these interesting human carcinogens, therefore, is an important problem in cancer research. Asbestos and other fibers induce predominantly two types of cancers: mesotheliomas and bronchogenic carcinomas. Fiber size is an important factor in the carcinogenic activity of these substances as has been shown for mesothelioma induct...

  4. A Lethal Disease Model for Hantavirus Pulmonary Syndrome in Immunosuppressed Syrian Hamsters Infected with Sin Nombre Virus

    OpenAIRE

    Brocato, Rebecca L.; Hammerbeck, Christopher D.; Bell, Todd M.; Wells, Jay B.; Queen, Laurie A.; Hooper, Jay W.

    2014-01-01

    Sin Nombre virus (SNV) is a rodent-borne hantavirus that causes hantavirus pulmonary syndrome (HPS) predominantly in North America. SNV infection of immunocompetent hamsters results in an asymptomatic infection; the only lethal disease model for a pathogenic hantavirus is Andes virus (ANDV) infection of Syrian hamsters. Efforts to create a lethal SNV disease model in hamsters by repeatedly passaging virus through the hamster have demonstrated increased dissemination of the virus but no signs ...

  5. CARBENDAZIM (MBC) DISRUPTS OOCYTE SPINDLE FUNCTION AND INDUCES ANEUPLOIDY IN HAMSTERS EXPOSED DURING FERTILIZATION (MEIOSIS II)

    Science.gov (United States)

    Peri-fertilization exposure to Carbendazim (MBC; a microtubule poison) induces infertility and early pregnancy loss (EPL) in hamsters. resently, both in vivo and in vitro techniques were employed to characterize the effects of MBC on cellular aspects of fertilization in hamsters....

  6. Lack of negative effects on Syrian hamsters and Mongolian gerbils housed in the same secondary enclosure.

    Science.gov (United States)

    Pritchett-Corning, Kathleen R; Gaskill, Brianna N

    2015-05-01

    In cases where different species might be housed in the same room or secondary enclosure, the Guide for the Care and Use of Laboratory Animals recommends that the animals should be behaviorally compatible and have the same health status. Syrian hamsters and Mongolian gerbils, both desert-dwelling rodents, appear to be reasonable candidates for such a combination. This study was undertaken to evaluate whether housing hamsters and gerbils in the same secondary enclosure is an acceptable practice. Weanling and breeding-age hamsters and gerbils were housed in open-topped cages in an isolator for 5 mo; the isolator also contained with nude and haired mice, which acted as sentinels. Cages housing hamsters and gerbils were rotated between species, and dirty bedding was exchanged between species in an effort to transmit microorganisms. In addition, sentinel mice housed in the isolator were supplied with dirty bedding from both hamsters and gerbils. Neither species showed clinical signs of illness, the health status of neither the hamsters nor the gerbils changed significantly, and the sentinel mice acquired only 2 infectious organisms, a Helicobacter species and Staphylococcus aureus. Both hamsters and gerbils bred successfully when housed together in the same isolator, and no infanticide or mortality was seen. Breeding performance did not differ between isolator breeding and barrier breeding. This study supports the housing of hamsters and gerbils in the same secondary enclosure. PMID:26045450

  7. Hamster endogenous retrovirus (HaER) - distinct properties of structural proteins and DNA polymerase

    International Nuclear Information System (INIS)

    The structural proteins as well as some features of the RNA-dependent DNA polymerase of the hamster endogenous retrovirus (HaER) were examined. The polypeptide pattern of this virus is substantially different from that of other known retroviruses in containing major polypeptides with molecular weights of 68000, 59000, 27000, 24000 daltons. Double antibody competitive radioimmunoassays showed that the HaER particles do not share any detectable antigenic relatedness with the murine viruses' p30, but manifest a considerable relatedness with the feline leukemia virus p27 and a slight cross-reactivity with the rat virus major protein. The RNA-dependent DNA polymerase of HaER virus has a molecular size of approximately 73000 daltons and in contrast to other mammalian retroviruses shows no significant preference for Mn2+ over Mg2+. Apart from the lack of antigenic relatedness between the HaER virus proteins and the p30 protein of murine viruses, there is also no antigenic relatedness between HaER and murine viruses insofar as their DNA polymerase is concerned. (Author)

  8. Immunological detection and quantification of DNA components structurally modified by alkylating carcinogens, mutagens and chemotherapeutic agents

    International Nuclear Information System (INIS)

    The detection and quantification of defined reaction products of chemical mutagens and carcinogens (and of many cancer chemotherapeutic agents) with DNA require highly sensitive analytical techniques. The exceptional capability of immunoglobulins to recognize subtle alterations of molecular structure (especially when monoclonal antibodies are used to maximize specificity), outstanding sensitivity of immunoanalysis by high-affinity antibodies, and the fact that radioactively-labelled agents are not required suggest the utility of a radioimmunoassay to recognize and quantitate alkylated DNA products. We have recently developed a set of high-affinity monoclonal antibodies (secreted by mouse x mouse as well as by rat x rat hybridomas; antibody affinity constants, 109 to > 1010 lmol) specifically directed against several DNA alkylation products with possible relevance in relation to both mutagenesis and malignant transformation of mammalian cells. These alkylation products include 06-N-butyldeoxyguanosine, and 04-ethyldeoxythymidine. When used in a radioimmunassay, an antibody specific for 06-ethyldeoxyguanosine, for example, will detect this product at an 06-ethyldeoxyguanosine/deoxyguanosine molar ratio of approx. 3 x 10-7 in a hydrolysate of 100 ug of DNA. The limit of detection can be lowered further if the respective alkyldeoxynucleosides are separated by HPLC from the DNA hydrolysate prior to the RIA. The anti-alkyldeoxynucleoside monoclonal antibodies can also be used to visualize, by immunostaining and fluorescence microscopy combined with electronic image intensification, specific alkylation products in the nuclear DNA of individual cells, and to localize structurally modified bases in double-stranded DNA molecules by transmission electron microscopy

  9. Exposure and Metabolic Activation Biomarkers of Carcinogenic Tobacco-Specific Nitrosamines.

    Science.gov (United States)

    Hecht, Stephen S; Stepanov, Irina; Carmella, Steven G

    2016-01-19

    , blood, and toenails. Urinary and serum NNAL have been related to lung cancer risk, and urinary NNN has been related to esophageal cancer risk in prospective epidemiology studies. These results are consistent with carcinogenicity studies of NNK, NNAL, and NNN in rats, which show that NNK and NNAL induce mainly lung tumors, while NNN causes tumors of the esophagus and oral cavity. Biomarkers of metabolic activation of NNK and NNN applied in human studies include the metabolism of deuterium labeled substrates to distinguish NNK and NNN metabolism from that of nicotine and the determination of DNA and hemoglobin adducts in tissues, blood, and oral cells from people exposed to tobacco products. As these methods are continually improved in parallel with the ever increasing sensitivity and selectivity of mass spectrometers, development of a comprehensive biomarker panel for identifying tobacco users at high risk for cancer appears to be a realistic goal. Targeting high risk individuals for smoking cessation and cancer surveillance can potentially decrease the risk of developing fatal cancers. PMID:26678241

  10. Experience from a long-term carcinogenicity study with intraperitoneal injection of biosoluble synthetic mineral fibers.

    Science.gov (United States)

    Grimm, Hans G; Bernstein, David M; Attia, Mahmoud; Richard, Jacques; De Reydellet, Aymon

    2002-08-01

    The carcinogenic potential in the intraperitoneal cavity of three newly developed biosoluble insulation glass wool fibers (M, P, and V) and one newly developed biosoluble insulation stone wool fiber (O) was investigated and compared to that of a previously developed soluble glass fiber (B). The in vitro dissolution coefficient of the three glass wool fibers ranged from 450 to 1037 ng/cm(2) x h and was 523 ng/cm(2) x h for the stone wool fiber. The in vitro dissolution coefficient of the B fiber was 580 ng/cm(2) x h. Groups of female Wistar rats (strain Crl: Wi BR) were exposed by repeated injections to doses of 0.5, 2, and 5 x 10(9) WHO fibers, which corresponds to between 41 mg to 724 mg fiber injected. In addition, 2 groups of crocidolite were used as positive controls at doses of 0.1 x 10(9) and 1 x 10(9) WHO fibers (0.5 and 5 mg). The in vitro dissolution coefficient of crocidolite is estimated to be approximately 1 ng/cm(2) x h. The protocol of the study and the size distribution of the test samples conformed to the European Commission Protocol EUR 18748 EN, and the study was executed under Good Laboratory Practice conditions. Two of the new insulation wools, fibers M and 0, showed no statistically significant tumorigenic response even at the very high dose of 5 x 10(9) WHO fibers injected. Fibers P and V showed a small tumorigenic response in the ip cavity similar in magnitude to the B fiber, which has been declared in the German fiber regulations as a noncarcinogenic fiber. The response to the soluble insulation fibers was notably different from that of the known carcinogen crocidolite, which produced 53% tumors at a comparatively low dose of 0.1 x 10(9) WHO fibers. The incidence of mesothelioma was found to be highly correlated to the incidence of intra-abdominal nodules and masses at different sites. The incidence of abdominal nodules and masses was highly correlated to the number of animals with ascites. The incidence of chronic peritonitis with fibrotic

  11. Toxicology and Carcinogenesis Studies of Quercetin (CAS No. 117-39-5) in F344 Rats (Feed Studies).

    Science.gov (United States)

    1992-09-01

    exchanges and chromosomal aberrations in Chinese hamster ovary cells. Conclusions: Under the conditionslls. Conclusions: Under the conditions of these 2-year feed studies there was some evidence of carcinogenic activity of quercetin in male F344/N rats based on an increased incidence of renal tubule cell adenomas. There was no evidence of carcinogenic activity of quercetin in female F344/N rats receiving 1,000, 10,000 or 40,000 ppm. The incidence of renal tubule hyperplasia and the severity of nephropathy were increased in exposed male rats. Synonyms: C.I. Natural Yellow 10; C.I. 75670; Cyanidelonon 1522; Flavin Meletin; Quercetine; Quercetol; Quertin; Quertine; Sophoretin; Xanthaurine; 3,3',4',5,7-Pentahydroxyflavone; 3,5,7,3',4'-Pentahydroxyflavone; 2-(3,4-Dihydroxyphenyl)-3,5,7-trihydroxy-4H-1-benzopyran-4-one PMID:12621521

  12. [Update on benzene: from industrial toxicant to environmental carcinogen].

    Science.gov (United States)

    Manno, Maurizio

    2013-01-01

    Benzene, an industrial chemical myelotoxic at high doses in workers, is now an almost ubiquitous pollutant. It is also a no-threshold genotoxic carcinogen causing acute leukemia and other lymphoaematological tumours. Although its mechanism of action has not been fully clarified, benzene toxicity and carcinogenicity depend on metabolic activation. Polymorphism of activating and detoxifying enzymes (CYP, GST, NQO1) may be critical, therefore, in modulating individual susceptibility to benzene. Further uncertainty factors in assessing low level benzene exposure are the limited sensitivity and specificity of most exposure biomarkers, the frequent coexposure to other volatile organic chemicals (VOC), and the presence of non occupational sources of exposure, such as cigarette smoke and veicular traffic. The aim of this presentation is to introduce the main current critical issues in the risk assessment and the biological monitoring of occupational exposure to benzene at low doses. PMID:24303704

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

    International Nuclear Information System (INIS)

    This book contains nine sections, each consisting of several papers. The section titles are: Molecular Changes in Cell Transformation; Differentiation, Growth Control, and Cell Transformation; Mutagenesis and Cell Transformation; Tumor Promotion and Cell Transformation; Mechanisms of Transformation of Human Fibroblasts; Mechanisms of Transformation of Epithelial Cells; Mechanisms of C3H 10T12 Cell Transformation; Mechanisms of Radiation-Induced Cell Transformation; and Use of Cell Transformation Assays for Carcinogen Testing

  14. Cannabis and tobacco smoke are not equally carcinogenic

    OpenAIRE

    Melamede Robert

    2005-01-01

    Abstract More people are using the cannabis plant as modern basic and clinical science reaffirms and extends its medicinal uses. Concomitantly, concern and opposition to smoked medicine has occurred, in part due to the known carcinogenic consequences of smoking tobacco. Are these reactions justified? While chemically very similar, there are fundamental differences in the pharmacological properties between cannabis and tobacco smoke. Cannabis smoke contains cannabinoids whereas tobacco smoke c...

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

    OpenAIRE

    Gasser Robin B; Smout Michael J; Sripa Manop; Sripa Banchob; Mulvenna Jason; Pinlaor Porntip; Laha Thewarach; Brindley Paul J; Loukas Alex

    2007-01-01

    Abstract Background Cholangiocarcinoma (CCA) – cancer of the bile ducts – is associated with chronic infection with the liver fluke, Opisthorchis viverrini. Despite being the only eukaryote that is designated as a 'class I carcinogen' by the International Agency for Research on Cancer, little is known about its genome. Results Approximately 5,000 randomly selected cDNAs from the adult stage of O. viverrini were characterized and accounted for 1,932 contigs, representing ~14% of the entire tra...

  16. Pulmonary toxicity of components of textile paint linked to the Ardystil syndrome: intratracheal administration in hamsters.

    Science.gov (United States)

    Clottens, F L; Verbeken, E K; Demedts, M; Nemery, B

    1997-01-01

    OBJECTIVES: It was hypothesised from an epidemiological investigation that a formula change from Acramin FWR (a polyurea) to Acramin FWN (a polyamide-amine) had led to severe pulmonary disease in textile printing sprayers in SPAIN AND ALGERIA. To verify this, the pulmonary toxicity of the components of the paint systems involved was assessed in experimental animals. METHODS: Individual components and relevant mixtures, diluted in phosphate buttered saline, were given by intratracheal instillation of 2 ml/kg to hamsters. Pulmonary toxicity was assessed on days 3, 7, 14, 28, and 92 after a single intratracheal instillation, by histology and by measuring wet and dry lung weight, protein concentration, the activities of lactate dehydrogenase, alkaline phosphatase, beta-N-acetyl-glucosaminidase, and gamma-glutamyltransferase, inflammatory cell number and distribution in bronchoalveolar lavage fluid (BALF), and hydroxyproline content in dried lung tissue. RESULTS: Based on the doses that killed 50% of the animals (LD50s), the various components were found to be 10 to 1250 times more toxic when given intratracheally than when given orally (according to reported oral LD50s in rats). Acramin FWN, Acramin FWR, Acrafix FHN, or their mixtures caused lung damage. Protein concentration, enzyme activities, total cell number, and percentage of polymorphonuclear neutrophils were increased in BALF during the first week after intratracheal instillation. Lung weights remained high for at least a month. Histology showed inflammatory cell infiltration and subsequent fibrosis with collagen deposition. This finding was confirmed by an increased hydroxyproline content in dried lung tissue. Acramoll W did not show toxic effects. CONCLUSIONS: The study suggests that there is no major difference, in hamsters, between the acute intratracheal toxicity of Acramin FWR and that of Acramin FWN. Consequently, there is no simple toxicological explanation for the epidemiological hypothesis. However

  17. Cellular-signaling pathways unveil the carcinogenic potential of chemicals.

    Science.gov (United States)

    Hendriks, Giel; van de Water, Bob; Schoonen, Willem; Vrieling, Harry

    2013-06-01

    Most of the current in vitro carcinogenicity assays assess the potential carcinogenic properties of chemicals through the detection of inflicted DNA damage or subsequent chromosome damage and gene mutations. Unfortunately, these assays generally do not provide mechanistic insight into the reactive properties of a chemical. Upon chemical-induced damage of biomolecules, molecular sensors will activate general and damage-specific cellular response pathways that provide protection against the (geno)toxic and potential carcinogenic properties of chemicals. These cellular defense mechanisms include activation of cell-cycle checkpoints, DNA repair systems and induction of apoptosis or necrosis. Visualization of activated cellular-signaling pathways forms a powerful means to readily detect the genotoxic potential of chemical compounds and simultaneously gain insight into their reactive properties. Over the past years, various in vitro reporter assays have been developed that monitor activation of general and more specific cellular-signaling pathways, including the GreenScreen HC and ToxTracker assays. In this review we provide a perspective on how we can exploit activation of cellular signaling pathways to shed light on the mode of action of the chemical exposure and to develop sophisticated mechanism-based in vitro assays for cancer risk assessment. PMID:23339022

  18. Workplace carcinogen and pesticide exposures in Costa Rica.

    Science.gov (United States)

    Partanen, Timo; Chaves, Jorge; Wesseling, Catharina; Chaverri, Fabio; Monge, Patricia; Ruepert, Clemens; Aragón, Aurora; Kogevinas, Manolis; Hogstedt, Christer; Kauppinen, Timo

    2003-01-01

    The CAREX data system converts national workforce volumes and proportions of workers exposed to workplace carcinogens into numbers of exposed in 55 industrial categories. CAREX was adapted for Costa Rica for 27 carcinogens and seven groups of pesticides. Widespread workplace carcinogens in the 1.3 million workforce of Costa Rica are solar radiation (333,000 workers), diesel engine exhaust (278,000), environmental tobacco smoke (71,000), hexavalent chromium compounds (55,000), benzene (52,000), wood dust (32,000), silica dust (27,000), lead and inorganic lead compounds (19,000), and polycyclic aromatic compounds (17,000). The most ubiquitous pesticides were paraquat and diquat (175,000), mancozeb, maneb, and zineb (49,000), chlorothalonil (38,000), benomyl (19,000), and chlorophenoxy herbicides (11,000). Among women, formaldehyde, radon, and methylene chloride overrode pesticides, chromium, wood dust, and silica dust in numbers of exposed. High-risk sectors included agriculture, construction, personal and household services, land and water transport and allied services, pottery and similar industries, woodworks, mining, forestry and logging, fishing, manufacturing of electrical machinery, and bar and restaurant personnel. PMID:12848237

  19. Potential co-carcinogens in the uranium mine environment

    International Nuclear Information System (INIS)

    Studies of increased incidence of lung cancer in uranium miners have focussed on the relationship between lung cancer and miners' exposure to radon daughters and smoking. However, epidemiologic analyses of uranium miner populations also include the effects of exposure to external gamma rays, long-lived alpha emitters and other non-radioactive workplace contaminants. The diversity and variability of miner exposures to potentially carcinogenic substances and combinations of substances, and the natural difficulties involved in the study of lung cancer in human populations, make the assessment of the relative effects of causative agents difficult if not impossible. Moreover, concentrations of most of the substances have rarely been measured in mine environments, and data on human response to these substances is sparse. Nonetheless, research on the potential effects of such substances is required to understand the potential hazards in the mining environment. This paper examines the potential carcinogenic and co-carcinogenic effects of agents other than ionizing radiation, which may currently be present in uranium mine atmospheres

  20. [Mutagenic activation and carcinogenicity of aminoazo dyes of ortho-aminoazotoluene and 3'-methyl-4-dimethylaminoazobenzene in experiments on suckling mice].

    Science.gov (United States)

    Kaledin, V I; Il'nitskaia, S I; Ovchinnikova, L P; Popova, N A; Bogdanova, L A; Morozkova, T S

    2014-01-01

    It is found that after administration of 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB,) which was hepatocarcinogenic to rats, in suckling mice, the number of neoplastic lesions in the liver of mice was 3 times higher than after analogous administration of equimolar dose of ortho-aminoazotoluene (OAT)). However, in the Ames test (TA-98 strain of Salmonella typhimurium) with activation by hepatic enzymes (S-9 fraction) of both intact and Aroclor-1254-induced mice and rats OAT contributed by an order of magnitude to revertant colonies compared to 3'-Me-DAB. In vivo inhibition of sulfotransferase activity, the enzyme which catalyzes the final stage of the mutagenic activation of aminoazo dyes, had no effect on carcinogenicity of 3'-Me-DAB but more than 4 times elevated that of OAT. It was concluded that the mechanism of carcinogenic action of aminoazo dyes studied is not genotoxic and that the carcinogenic potential of OAT is lost in the process of mutagenic activation. PMID:25715596

  1. The benzodiazepine diazepam demonstrates the usefulness of Syrian hamsters as a model for anxiety testing: evaluation of other classes of anxiolytics in comparison to diazepam.

    Science.gov (United States)

    Gannon, Robert L; Lungwitz, Elizabeth; Batista, Natalia; Hester, Ian; Huntley, Christina; Peacock, Alyssa; Delagrange, Philippe; Millan, Mark J

    2011-03-17

    Clinical evidence in humans suggests that there is some linkage between dysfunction in the timing of circadian rhythms and certain types of depression. In animal models, Syrian hamsters have been used extensively to study the pharmacology of circadian rhythms, while rats and mice are used to screen putative anxiolytics/antidepressant compounds. It would be beneficial to be able to test anxiolytic/antidepressant compounds in hamsters in conjunction with circadian rhythm studies. Therefore, in this study, Syrian hamsters were used in three experimental paradigms to evaluate anxiety: the elevated plus maze, the t-tube, and the open field Thatcher-Britton conflict test. Diazepam, tested with 2mg/kg and 5mg/kg intraperitoneal injections, was found to induce anxiolytic activity in each of the three tests. Hamsters were more likely to spend time in the open arms in the plus maze, displayed more exploratory behavior in the t-tube, and were quicker to enter a brightly lit exposed field in the Thatcher-Britton conflict test following injections of diazepam. Diazepam (2mg/kg) was also tested at three times during the 24-h day in the elevated plus maze: at the beginning and end of the lights-on period (Zeitgeber times 23 and 11, respectively) and once in the dark just before the room lights came on (Zeitgeber time 20). Diazepam induced anxiolytic activity only at Zeitgeber 23. Therefore, the following known and putative anxiolytic compounds were also evaluated in each of the three tests at Zeitgeber 23: citalopram, the neurokinin(1) receptor antagonists GR205171 and vestipitant, the corticotropin releasing factor(1) receptor antagonist CP154526, the cannabinoid receptor(1) agonist CP55940, the serotonin(6) receptor antagonist SB399885, and the metabotropic glutamate receptor(5) antagonists fenobam and MTEP. Vestipitant displayed some anxiolytic activity in the elevated plus maze, but this effect was not confirmed with GR205171. None of the other compounds displayed any

  2. Determination of elements in blood of golden hamster by NAA

    International Nuclear Information System (INIS)

    In the present study Neutron Activation Analysis technique has been used to determine, simultaneously, some element concentrations of clinical relevance in whole blood samples of golden hamster. The normal range for Br, Ca, Cl K, Mg, Na and S considering 2 σ (Two Standard deviations) was 0.011 0.047 gL-1 (Br); 0.11 0.35 gL-1 (Ca); 2.11 3.75 gL-1 (Cl); 1.35 2.79 gL-1 (K), 0.026 0.090 gL-1 (Mg), 1.03 2.51 gL-1 (Na) e 0.97 2.01 gL-1 (S). The knowledge of these limits became possible to perform clinical investigation in this animal model using whole blood. The comparison with the results from human being whole blood estimation (Hamster and human) became possible to check the similarities or physiologic differences, an important data for animal experimentation. (author)

  3. Carcinogenic and Non-Carcinogenic Assessment of Phthalates Exposure Through Consumption of Bottled Water During the Storage Time

    OpenAIRE

    M Zare Jeddi; Rastkari, N.; R Ahmadkhaniha; M Alimohammadi; M. Yunesian

    2015-01-01

    Background and Objectives: Bottles for packaging drinking water represent one of the most popular uses of plastic and polymer additives. Recently, public concerns related to possibility of exposure to chemicals through the consumption of polyethylene terephthalate bottled water has caused great concern to consumers. Phthalate esters, as a class of these compounds, are often classified as endocrine disruptors and one of them is a possible carcinogen for human. The aim of this study was to dete...

  4. Comparison of hepatocarcinogen-induced gene expression profiles in conventional primary rat hepatocytes with in vivo rat liver.

    Science.gov (United States)

    Doktorova, Tatyana Y; Ellinger-Ziegelbauer, Heidrun; Vinken, Mathieu; Vanhaecke, Tamara; van Delft, Joost; Kleinjans, Jos; Ahr, Hans-Juergen; Rogiers, Vera

    2012-09-01

    At present, substantial efforts are focused on the development of in vitro assays coupled with "omics" technologies for the identification of carcinogenic substances as an alternative to the classical 2-year rodent carcinogenicity bioassay. A prerequisite for the eventual regulatory acceptance of such assays, however, is the in vivo relevance of the observed in vitro findings. In the current study, hepatocarcinogen-induced gene expression profiles generated after the exposure of conventional cultures of primary rat hepatocytes to three non-genotoxic carcinogens (methapyrilene hydrochloride, piperonyl butoxide, and Wy-14643), three genotoxic carcinogens (aflatoxin B1, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, and 2-nitrofluorene), and two non-carcinogens (nifedipine and clonidine) are compared with previously obtained in vivo data after oral administration for up to 14 days of the same hepatocarcinogens to rats. In addition to the comparison of deregulated genes and functions per compound between in vivo and in vitro models, the major discriminating cellular pathways found in vivo in livers of exposed rats were examined for deregulation in vitro. Further, in vivo-derived gene signatures for the identification of genotoxic versus non-genotoxic carcinogens are used to classify in vitro-tested hepatocarcinogens and non-carcinogens. In the primary hepatocyte cultures, two out of the three tested genotoxic carcinogens mimicked the in vivo-relevant DNA damage response and were correctly assessed. Exposure to the non-genotoxic hepatocarcinogens, however, triggered a relatively weak response in the in vitro system, with no clear similarities to in vivo. This study contributes to the further optimization of toxicogenomics predictive tools when applied in in vitro settings. PMID:22484513

  5. Nontoxigenic Clostridium difficile Protects Hamsters against Challenge with Historic and Epidemic Strains of Toxigenic BI/NAP1/027 C. difficile

    OpenAIRE

    Nagaro, Kristin J.; Phillips, S. Tyler; Cheknis, Adam K.; Sambol, Susan P.; Zukowski, Walter E.; Johnson, Stuart; Gerding, Dale N.

    2013-01-01

    Nontoxigenic Clostridium difficile (NTCD) has been shown to prevent fatal C. difficile infection in the hamster model when hamsters are challenged with standard toxigenic C. difficile strains. The purpose of this study was to determine if NTCD can prevent C. difficile infection in the hamster model when hamsters are challenged with restriction endonuclease analysis group BI C. difficile strains. Groups of 10 hamsters were given oral clindamycin, followed on day 2 by 106 CFU of spores of NTCD ...

  6. Determination of elements in blood of golden hamster by NAA; Determinacao de elementos em sangue de hamster dourado usando AAN

    Energy Technology Data Exchange (ETDEWEB)

    Aguiar, Rodrigo Oliveira de

    2009-07-01

    In the present study Neutron Activation Analysis technique has been used to determine, simultaneously, some element concentrations of clinical relevance in whole blood samples of golden hamster. The normal range for Br, Ca, Cl K, Mg, Na and S considering 2 {sigma} (Two Standard deviations) was 0.011 0.047 gL{sup -1} (Br); 0.11 0.35 gL{sup -1} (Ca); 2.11 3.75 gL{sup -1} (Cl); 1.35 2.79 gL{sup -1} (K), 0.026 0.090 gL{sup -1} (Mg), 1.03 2.51 gL{sup -1} (Na) e 0.97 2.01 gL{sup -1} (S). The knowledge of these limits became possible to perform clinical investigation in this animal model using whole blood. The comparison with the results from human being whole blood estimation (Hamster and human) became possible to check the similarities or physiologic differences, an important data for animal experimentation. (author)

  7. Lifelong persistent infection of hamster brain by human adenovirus type 6.

    Directory of Open Access Journals (Sweden)

    Yabe,Yoshiro

    1988-02-01

    Full Text Available To establish an experimental persistent infection of the brain with human adenoviruses, adenovirus type 6 (ad 6 was inoculated intracerebrally into young adult hamsters. Hamsters appeared languid for a few days after inoculation, but recovered rapidly. By cocultivation of tissue fragments with HeLa cells, ad 6 was always recovered from the brains of hamsters throughout their lives, as long as 29 months, indicating the establishment of a lifelong persistent infection. Except for the first few days after inoculation, however, attempts to recover virus by inoculation of tissue extracts onto HeLa cells or by cultivation of tissue fragments alone were unsuccessful.

  8. Effect of Radiation on the Functions of Carcinogenic Viruses

    International Nuclear Information System (INIS)

    When carcinogenic viruses are irradiated under suitable experimental conditions with ultra-violet rays or ionizing radiation, the various viral functions can be dissociated and virions defective in certain functions can be obtained. These defects are real mutations; they are passed on to subsequent generations provided the virions affected remain capable of reproduction. It has been possible to obtain various types of mutant, e.g. hyper producers of virions, non-productive transformers, non-transforming producers. The production of these mutants opens up certain experimental possibilities with regard to the transformation mechanism and the possible consequences of irradiation in vivo. Attention will be devoted in particular to the increased oncogenic capability in vivo which is sometimes observed in pre-irradiated viruses, and also to the consequences of this effect in the radiotherapy of certain malignant infections. These studies are also of interest for analysing the structure of the viral genome and throwing light on that fraction of the genome which is responsible for the transforming capacity. In the case of small viruses with a single DNA molecule (polyoma, SV-40) it has been possible to measure the fraction of the molecule responsible for the transforming capacity. In the case of the Rous virus the experiments suggest that the viral RNA is made up of sub-units capable of independent replication, the transforming capacity being possessed by only one of these sub-units. The induced defect may reveal the presence of transforming capacity in a virus considered as non- oncogenic because the transformed cells are usually eliminated by the infective process. In this way irradiation could render carcinogenic a virus which is not carcinogenic under normal conditions. The paper covers work done at the various viral radiobiology laboratories of the Radium Institute during the last two years. (author)

  9. Kisspeptin and the seasonal control of reproduction in hamsters

    DEFF Research Database (Denmark)

    Simonneaux, Valérie; Ansel, Laura; Revel, Florent G;

    2008-01-01

    Reproduction is a complex and energy demanding function. When internal and external conditions might impair reproductive success (negative energy balance, stress, harsh season) reproductive activity has to be repressed. Recent evidence suggests that these inhibitory mechanisms operate on Kiss1......-expressing neurons, which were recently shown to be implicated in the regulation of GnRH release. Hamsters are seasonal rodents which are sexually active in long photoperiod and quiescent in short photoperiod. The photoperiodic information is transmitted to the reproductive system by melatonin, a pineal...... hormone whose secretion is adjusted to night length. The photoperiodic variation in circulating melatonin has been shown to synchronize reproductive activity with seasons, but the mechanisms involved in this effect of melatonin were so far unknown. Recently we have observed that Kiss1 mRNA level in the...

  10. Estudios inmunologicos en hamsters (Cricetus auratus infectados con Schistosoma mansoni

    Directory of Open Access Journals (Sweden)

    Eduardo Monge

    1986-08-01

    Full Text Available Los resultados de este trabajo muestran que el hamster (Cricetus auratus puede ser utilizado como un modelo experimental para estudios inmunológicos en la infección por Schistosoma mansoni. Los datos obtenidos, relativos a inmunidad concomitante, producción de anticuerpo letal e inmunosupresión se asemejan a los conseguidos en otros modelos experimentales ya establecidos. Estas observaciones indican que el hámster, además de ser un hospedero satisfactorio para el mantenimiento del parásito en el laboratorio, puede ser considerado como un modelo experimental alterno cuyo crecimiento y mantenimiento son relativamente simples y además es un animal de fácil manejo.

  11. Photosensitized inactivation of Chinese hamster cells by phthalocyanines

    International Nuclear Information System (INIS)

    Chloroaluminum phthalocyanine was found to sensitize cultured Chinese hamster cells upon exposure to white fluorescent light. Elimination of wavelengths below 370 nm did not reduce the effect significantly, indicating that the effective wavelengths were those absorbed by the Q band (600-700 nm) of phthalocyanine. The magnitude of the photosensitizing effect increased with the dye concentration and the time of its contact with the cells prior to light exposure. Although photosensitization was drastically reduced in the absence of oxygen, the lack of effect of glycerol and D2O during exposure suggests that neither hydroxyl radicals nor 1O2 are responsible for the cytotoxic response. The efficiency of the photosensitized induced cell killing did not vary with the position of the cells in the cell cycle, in contrast to exposure to X-rays. The improved spectral properties, the reported low toxicity and the selective retention by neoplasms, make phthalocyanines promising candidates for use in photodynamic therapy of cancer. (author)

  12. Protective effect of propolis on radiation-induced chromosomal damage on Chinese hamster ovary cells (CHO-K1)

    Energy Technology Data Exchange (ETDEWEB)

    Spigoti, Geyza; Bartolini, Paolo; Okazaki, Kayo [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)], e-mail: kokazaki@ipen.br; Tsutsumi, Shiguetoshi [Amazon Food Ltd., Tokyo (Japan)], e-mail: fwip5138@mb.infoweb.ne.jp

    2009-07-01

    In the last years, particular interest has been given to investigations concerning natural, effective and nontoxic compounds with radioprotective capacity in concert with increasing utilization of different types of ionizing radiation for various applications. Among them, propolis, a resinous mixture of substances collected by honey bees (Apis mellifera) has been considered promising since it presents several advantageous characteristics, i.e., antiinflammatory, anticarcinogenic, antimicrobial and free radical scavenging action. It is, therefore, a direct antioxidant that protects cells and organisms from the adverse effects of ionizing radiation. These relevant biological activities are mainly mediated by the flavonoids, present at relatively high concentrations in the propolis. Considering that the chemical composition and, consequently, the biological activity of propolis is variable according to the environmental plant ecology, the present study was conducted in order to evaluate the radioprotective capacity of Brazilian propolis, collected in the State of Rio Grande do Sul, against genotoxic damages induced by {sup 60}Co {gamma}-radiation in Chinese hamster ovary cells (CHO-K1). for this purpose, micronucleus induction was analyzed concerning irreparable damage, specifically related to DNA double-strand breaks, that are potentially carcinogenic. CHO-K1 cells were submitted to different concentrations of propolis (3 - 33 {mu}g/ml), 1 h before irradiation, with 1 Gy of {gamma} radiation (0.722 Gy/min). The data obtained showed a decreasing tendency in the quantity of radioinduced damage on cells previously treated with propolis. The radioprotective effect was more prominent at higher propolis concentration. The treatment with propolis alone did not induce genotoxic effects on CHO-K1 cells. Beside that, the treatment with propolis, associated or not with radiation, did not influence the kinetics of cellular proliferation. (author)

  13. Protective effect of propolis on radiation-induced chromosomal damage on Chinese hamster ovary cells (CHO-K1)

    International Nuclear Information System (INIS)

    In the last years, particular interest has been given to investigations concerning natural, effective and nontoxic compounds with radioprotective capacity in concert with increasing utilization of different types of ionizing radiation for various applications. Among them, propolis, a resinous mixture of substances collected by honey bees (Apis mellifera) has been considered promising since it presents several advantageous characteristics, i.e., antiinflammatory, anticarcinogenic, antimicrobial and free radical scavenging action. It is, therefore, a direct antioxidant that protects cells and organisms from the adverse effects of ionizing radiation. These relevant biological activities are mainly mediated by the flavonoids, present at relatively high concentrations in the propolis. Considering that the chemical composition and, consequently, the biological activity of propolis is variable according to the environmental plant ecology, the present study was conducted in order to evaluate the radioprotective capacity of Brazilian propolis, collected in the State of Rio Grande do Sul, against genotoxic damages induced by 60Co γ-radiation in Chinese hamster ovary cells (CHO-K1). for this purpose, micronucleus induction was analyzed concerning irreparable damage, specifically related to DNA double-strand breaks, that are potentially carcinogenic. CHO-K1 cells were submitted to different concentrations of propolis (3 - 33 μg/ml), 1 h before irradiation, with 1 Gy of γ radiation (0.722 Gy/min). The data obtained showed a decreasing tendency in the quantity of radioinduced damage on cells previously treated with propolis. The radioprotective effect was more prominent at higher propolis concentration. The treatment with propolis alone did not induce genotoxic effects on CHO-K1 cells. Beside that, the treatment with propolis, associated or not with radiation, did not influence the kinetics of cellular proliferation. (author)

  14. Infection with the carcinogenic liver fluke Opisthorchis viverrini modifies intestinal and biliary microbiome

    OpenAIRE

    Plieskatt, Jordan L; Deenonpoe, Raksawan; Mulvenna, Jason P; Krause, Lutz; Sripa, Banchob; Bethony, Jeffrey M; Brindley, Paul J.

    2013-01-01

    Opisthorchis viverrini is a fish-borne trematode endemic in East Asia. Following ingestion, the flukes locate to the biliary treȩ where chronic infection frequently leads to cholangiocarcinoma (CCA). The mechanisms by which O. viverrini infection culminates in CCA remain unknown. An unexplored aspect is its influence on the host microbiome. In the hamster, infection with this pathogen reliably leads to CCA. Genomic DNAs of microbiota from colorectal contents and bile of hamsters and from whol...

  15. Fluoxetine disrupts motivation and GABAergic signaling in adolescent female hamsters.

    Science.gov (United States)

    Shannonhouse, John L; DuBois, Dustin W; Fincher, Annette S; Vela, Alejandra M; Henry, Morgan M; Wellman, Paul J; Frye, Gerald D; Morgan, Caurnel

    2016-08-01

    Initial antidepressant treatment can paradoxically worsen symptoms in depressed adolescents by undetermined mechanisms. Interestingly, antidepressants modulate GABAA receptors, which mediate paradoxical effects of other therapeutic drugs, particularly in females. Although the neuroanatomic site of action for this paradox is unknown, elevated GABAA receptor signaling in the nucleus accumbens can disrupt motivation. We assessed fluoxetine's effects on motivated behaviors in pubescent female hamsters - anhedonia in the reward investigational preference (RIP) test as well as anxiety in the anxiety-related feeding/exploration conflict (AFEC) test. We also assessed accumbal signaling by RT-PCR and electrophysiology. Fluoxetine initially worsened motivated behaviors at puberty, relative to adulthood. It also failed to improve these behaviors as pubescent hamsters transitioned into adulthood. Low accumbal mRNA levels of multiple GABAA receptor subunits and GABA-synthesizing enzyme, GAD67, assessed by RT-PCR, suggested low GABAergic tone at puberty. Nonetheless, rapid fluoxetine-induced reductions of α5GABAA receptor and BDNF mRNA levels at puberty were consistent with age-related differences in GABAergic responses to fluoxetine and disruption of the motivational state. Whole-cell patch clamping of accumbal slices also suggested low GABAergic tone by the low amplitude of miniature inhibitory postsynaptic currents (mIPSCs) at puberty. It also confirmed age-related differences in GABAergic responses to fluoxetine. Specifically, fluoxetine potentiated mIPSC amplitude and frequency at puberty, but attenuated the amplitude during adulthood. These results implicate GABAergic tone and GABAA receptor plasticity in adverse motivational responses and resistance to fluoxetine during adolescence. PMID:27068049

  16. Retention of inhaled particles in hamsters with pulmonary fibrosis

    International Nuclear Information System (INIS)

    Aerosol retention was studied in hamsters 30, 60, and 90 days after the initiation of interstitial pulmonary fibrosis by a combination of bleomycin (bleo), 0.16 U/100 g body weight given intratracheally, and O2, for 72 h. Groups of bleo-O2-treated and control animals were exposed (awake) for 25 min to a 99mTc-labeled insoluble aerosol (activity median aerodynamic diameter, 0.45 micron; geometric standard deviation, 1.3). Within 5 min after exposure, the hamsters were killed and their lungs were excised and dried at total lung capacity, and sliced into 1-mm sections. Slices were dissected into pieces, and an evenness index (EI) was calculated for each piece (formula: see text). With uniformity of retention, all Els would be 1. The distribution of Els in control animals had a mean of 1.0 and a SD of 0.27; 0% of the Els were less than or equal to 0.20. Total retention diminished and was less uniform in bleo-O2-treated animals. At 30 days, the SD increased to 0.62, and 6% of the Els were less than or equal to 0.20. At 60 and 90 days, nonuniformity decreased but was still greater than that in the control animals (SD60 . 0.42, SD90 . 0.36). When examined histologically, individual pieces with low Els had more disease than those with high Els. Local decreases in compliance caused by fibrosis may have altered regional ventilation and retention. Our data also correlate with the progression of fibrosis from a focal lesion at 30 days to a more diffuse lesion at 90 days

  17. Photoperiod Regulates vgf-Derived Peptide Processing in Siberian Hamsters.

    Directory of Open Access Journals (Sweden)

    Barbara Noli

    Full Text Available VGF mRNA is induced in specific hypothalamic areas of the Siberian hamster upon exposure to short photoperiods, which is associated with a seasonal decrease in appetite and weight loss. Processing of VGF generates multiple bioactive peptides, so the objective of this study was to determine the profile of the VGF-derived peptides in the brain, pituitary and plasma from Siberian hamsters, and to establish whether differential processing might occur in the short day lean state versus long day fat. Antisera against short sequences at the C- or N- termini of proVGF, as well as against NERP-1, TPGH and TLQP peptides, were used for analyses of tissues, and both immunohistochemistry and enzyme linked immunosorbent assay (ELISA coupled with high-performance liquid (HPLC or gel chromatography were carried out. VGF peptide immunoreactivity was found within cortex cholinergic perikarya, in multiple hypothalamic nuclei, including those containing vasopressin, and in pituitary gonadotrophs. ELISA revealed that exposure to short day photoperiod led to a down-regulation of VGF immunoreactivity in the cortex, and a less pronounced decrease in the hypothalamus and pituitary, while the plasma VGF levels were not affected by the photoperiod. HPLC and gel chromatography both confirmed the presence of multiple VGF-derived peptides in these tissues, while gel chromatography showed the presence of the VGF precursor in all tissues tested except for the cortex. These observations are consistent with the view that VGF-derived peptides have pleiotropic actions related to changing photoperiod, possibly by regulating cholinergic systems in the cortex, vasopressin hypothalamic pathways, and the reproductive axis.

  18. Study of radiation effects on DMBA induced hamster lingual carcinoma

    International Nuclear Information System (INIS)

    A morphological and histo-pathological study of DMBA-induced carcinoma of the tongue in hamsters was carried out. The tongues of eighty golden hamsters were coated with a 1% DMBA acetone solution three times a week to induce carcinoma. The ulceration rate was about 100% in three to five months, and the ulceration process was followed by microangiography using Hayashi's drawing ink. Papillomatous or carcinomatous tongues were irradiated once with 60Co-γ rays. The total absorption dosage was 2000 rad. Then 67Ga-citrate and 57Co-bleomycin (57Co-BLM), were injected into the abdominal cavity. The amount of uptake of the reagents by the tumor was clearly low on three days after irradiation and increased on ten days after irradiation. This variation was more remarkable in the case of carcinoma than in the case of papilloma. 67Ga-citrate concentration ratio of carcinoma-to-organ and of papilloma-to-organ was the same as 57Co-BLM concentration ratio of carcinoma-to-organ and of papilloma-to-organ. Vascular changes was observed by means of microangiography, and the ratio of vascular area was measured by an image analyzer. The ratio increased rapidly with expansion of the tumor vessel and the exuding of contrast media one day after irradiation, decreased with damage of the vessel neighboring the tumor two days after irradiation, slightly increased with the development of a minimal vessel in the neighborhood of tumor three days after irradiation, and slightly decreased with the death at the center of tumor on ten days. These morphological variations of the tumor vessel were closely related to those of labeled tumor seekers. (Nakanishi, T.)

  19. Results of screening NCI/NTP nongenotoxic carcinogens and genotoxic noncarcinogens with the ke test

    International Nuclear Information System (INIS)

    The interdependence of the electrophilic and carcinogenic properties of chemicals that was demonstrated two decades ago rekindled interest in the somatic mutation theory of carcinogenesis. Interest in this theory grew with the development of a reverse-mutation bacterial assay in the laboratory of B.N. Ames that permitted the mutagenic properties of the chemicals to be determined quickly and yielded results which indicated that ''carcinogens are mutagens.'' Subsequent validation studies of this bioassay, the Salmonella typhimurium/microsome or ''Ames test,'' by Ames' group and others provided additional support for the correlation between mutagenicity and carcinogenicity which led to the worldwide deployment of the Ames test in thousands of laboratories and to the development of more than 100 other short-term tests that continue to be used to identify potential carcinogens via various end-points of genotoxicity. This document discusses electrophilicity, mutagenicity, and carcinogenicity relationships as well as carcinogen-screening of chemicals. 28 refs., 4 tabs

  20. Calcium and α-tocopherol suppress cured-meat promotion of chemically induced colon carcinogenesis in rats and reduce associated biomarkers in human volunteers123

    OpenAIRE

    Pierre, Fabrice HF; Martin, Océane CB; Santarelli, Raphaelle L; Taché, Sylviane; Naud, Nathalie; Guéraud, Françoise; Audebert, Marc; Dupuy, Jacques; Meunier, Nathalie; Attaix, Didier; Vendeuvre, Jean-Luc; Mirvish, Sidney S; Kuhnle, Gunter CG; Cano, Noel; Corpet, Denis E

    2013-01-01

    Background: Processed meat intake has been associated with increased colorectal cancer risk. We have shown that cured meat promotes carcinogen-induced preneoplastic lesions and increases specific biomarkers in the colon of rats.

  1. Structure, function and carcinogenicity of metabolites of methylated and non-methylated polycyclic aromatic hydrocarbons: a comprehensive review.

    Science.gov (United States)

    Flesher, James W; Lehner, Andreas F

    2016-03-01

    The Unified Theory of PAH Carcinogenicity accommodates the activities of methylated and non-methylated polycyclic aromatic hydrocarbons (PAHs) and states that substitution of methyl groups on meso-methyl substituted PAHs with hydroxy, acetoxy, chloride, bromide or sulfuric acid ester groups imparts potent cancer producing properties. It incorporates specific predictions from past researchers on the mechanism of carcinogenesis by methyl-substituted hydrocarbons, including (1) requirement for metabolism to an ArCH2X type structure where X is a good leaving group and (2) biological substitution of a meso-methyl group at the most reactive center in non-methylated hydrocarbons. The Theory incorporates strong inferences of Fieser: (1) The mechanism of carcinogenesis involves a specific metabolic substitution of a hydrocarbon at its most reactive center and (2) Metabolic elimination of a carcinogen is a detoxifying process competitive with that of carcinogenesis and occurring by a different mechanism. According to this outlook, chemical or biochemical substitution of a methyl group at the reactive meso-position of non-methylated hydrocarbons is the first step in the mechanism of carcinogenesis for most, if not all, PAHs and the most potent metabolites of PAHs are to be found among the meso methyl-substituted hydrocarbons. Some PAHs and their known or potential metabolites and closely related compounds have been tested in rats for production of sarcomas at the site of subcutaneous injection and the results strongly support the specific predictions of the Unified Theory. PMID:26894797

  2. Familial incidence of mammary gland tumours in the Djungarian hamster (Phodopus sungaros): a case report

    Czech Academy of Sciences Publication Activity Database

    Jelínek, F.; Felsberg, Jürgen; Měšťan, M.

    2013-01-01

    Roč. 58, č. 8 (2013), s. 442-448. ISSN 0375-8427 Institutional support: RVO:61388971 Keywords : hamsters * neoplasias * atypical fibrosarcoma Subject RIV: EE - Microbiology, Virology Impact factor: 0.756, year: 2013

  3. INVESTIGATION OF POSSIBLE AGE EFFECTS ON MEIOTIC CHROMOSOMAL RECOMBINATION AND SEGREGATION IN ARMENIAN HAMSTER SPERMATOCYTES

    Science.gov (United States)

    Male Armenian hamsters (Cricetulus migratorius; 2N:22) were evaluated for age effects upon meiotic recombination and aneuploidy incidence. Primary spermatocytes from young and old animals revealed similar chiasma frequencies. The incidence of terminal-type chiasmata in sex bivale...

  4. Prostaglandin hydroperoxidase-catalyzed activation of certain N-substituted aryl renal and bladder carcinogens

    OpenAIRE

    Zenser, T V; Cohen, S M; Mattammal, M. B.; Wise, R. W.; Rapp, N. S.; Davis, B B

    1983-01-01

    Certain carcinogens are thought to induce renal and bladder cancer following metabolic activation. We propose a model system for this activation and provide supporting experimental evidence. This model proposes that renal and bladder carcinogens' entry into the urinary tract is facilitated, that carcinogens are activated by the prostaglandin hydroperoxidase activity of prostaglandin endoperoxide synthetase (PES), and that activation results in covalent binding to nucleic acids which can initi...

  5. Magnetic polyethyleneimine (PEI) microcapsules as retrievable traps for carcinogen electrophiles formed in the gastrointestinal tract

    International Nuclear Information System (INIS)

    Semi-permeable magnetic microcapsules containing polyethyleneimine (PEI) have been developed as retrievable carcinogen traps. In vitro, the soluble core PEI and membrane both bound reactive substances of limited aqueous stability, such as from [14C]N-methyl-N-nitrosourea ([14C]NMU), and aqueous stable dyes of molecular weight up to 1000. The core/membrane location ratio of binding was dependent upon membrane characteristics of the microcapsule batch used. Microcapsules administered intragastrically to rats bound up to 0.006% of [14C]dimethylhydrazine ([14C]DMH) and 1.4% of [14C]NMU administered i.p. or intrarectally, respectively. Time-dependency of [14C]DMH binding was consistent with labelling of microcapsules within the small intestine. There were no detectable metabolites from [14C]DMH trapped within the colon, whereas binding of [14C]NMU indicated that microcapsules could bind transient species present within the colon in competition with the faecal bulk. These results indicate that this approach could be used to detect highly unstable and possibly genotoxic substances in situ, hitherto unknown, formed within the intestinal lumen. (author). 20 refs

  6. Effects of propionyl-L-carnitine on ischemia-reperfusion injury in hamster cheek pouch microcirculation.

    OpenAIRE

    DomingaLapi; LinaSabatino; GiovannaAltobelli

    2010-01-01

    Background and Purpose Propionyl-L-carnitine (pLc) exerts protective effects in different experimental models of ischemia-reperfusion (I/R). The aim of the present study was to assess the effects of intravenously and topically applied pLc on microvascular permeability increase induced by I/R in the hamster check pouch preparation. Methods The hamster check pouch microcirculation was visualized by fluorescence microscopy. Microvascular permeability, leukocyte adhesion to venular walls, perfus...

  7. Seasonal pelage changes are synchronized by simulated natural photoperiods in Siberian hamsters (Phodopus sungorus)

    OpenAIRE

    Butler, Matthew P.; Zucker, Irving

    2009-01-01

    The extent to which changing day lengths synchronize the seasonal molt was assessed in nine cohorts of male and female Siberian hamsters (Phodopus sungorus) born into a simulated natural photoperiod (SNP) beginning 4 weeks before and ending 12 weeks after the summer solstice. Hamsters in early cohorts displayed rapid somatic and gonadal growth and early puberty, whereas those in later cohorts delayed puberty until the next spring. Despite the varying birth dates and puberty strategies, the se...

  8. Chronic Ethanol Intake Modulates Photic and Non-Photic Circadian Phase Responses in the Syrian Hamster

    OpenAIRE

    Seggio, Joseph A.; Logan, Ryan W.; Rosenwasser, Alan M.

    2007-01-01

    Chronic alcohol intake disrupts sleep and other circadian biological rhythms in both human alcoholics and in experimental animals. Recent studies from our laboratory indicate that these effects may be due, in part, to ethanol-induced alterations in fundamental properties of the circadian pacemaker. The present study explored the effects of chronic voluntary ethanol intake (25% v/v) on circadian phase responses to both photic and non-photic stimuli in Syrian hamsters. Hamsters were used in the...

  9. Gonadal Hormones Modulate the Display of Conditioned Defeat in Male Syrian Hamsters

    OpenAIRE

    Solomon, Matia B.; Karom, Mary C.; Norvelle, Alisa; Markham, Chris A; Erwin, W. Daniel; Huhman, Kim L.

    2009-01-01

    It has been widely reported that gonadal hormones influence the display of aggression in Syrian hamsters; conversely, much less is known about whether gonadal hormones modulate submissive/defensive behaviors in these animals. Following social defeat, male hamsters no longer display normal territorial aggression but instead display submissive/defensive behavior in the presence of a smaller opponent, a phenomenon we have termed conditioned defeat (CD). The purpose of the present study was to ex...

  10. Experimental infection of hamsters with avian paramyxovirus serotypes 1 to 9

    Directory of Open Access Journals (Sweden)

    Samuel Arthur S

    2011-02-01

    Full Text Available Abstract Avian paramyxoviruses (APMVs are frequently isolated from domestic and wild birds throughout the world and are separated into nine serotypes (APMV-1 to -9. Only in the case of APMV-1, the infection of non-avian species has been investigated. The APMVs presently are being considered as human vaccine vectors. In this study, we evaluated the replication and pathogenicity of all nine APMV serotypes in hamsters. The hamsters were inoculated intranasally with each virus and monitored for clinical disease, pathology, histopathology, virus replication, and seroconversion. On the basis of one or more of these criteria, each of the APMV serotypes was found to replicate in hamsters. The APMVs produced mild or inapparent clinical signs in hamsters except for APMV-9, which produced moderate disease. Gross lesions were observed over the pulmonary surface of hamsters infected with APMV-2 & -3, which showed petechial and ecchymotic hemorrhages, respectively. Replication of all of the APMVs except APMV-5 was confirmed in the nasal turbinates and lungs, indicating a tropism for the respiratory tract. Histologically, the infection resulted in lung lesions consistent with bronchointerstitial pneumonia of varying severity and nasal turbinates with blunting or loss of cilia of the epithelium lining the nasal septa. The majority of APMV-infected hamsters exhibited transient histological lesions that self resolved by 14 days post infection (dpi. All of the hamsters infected with the APMVs produced serotype-specific HI or neutralizing antibodies, confirming virus replication. Taken together, these results demonstrate that all nine known APMV serotypes are capable of replicating in hamsters with minimal disease and pathology.

  11. Use of hamster as a model to study diet-induced atherosclerosis

    Directory of Open Access Journals (Sweden)

    Lichtenstein Alice H

    2010-12-01

    Full Text Available Abstract Golden-Syrian hamsters have been used as an animal model to assess diet-induced atherosclerosis since the early 1980s. Advantages appeared to include a low rate of endogenous cholesterol synthesis, receptor-mediated uptake of LDL cholesterol, cholesteryl ester transfer protein activity, hepatic apoB-100 and intestinal apoB-48 secretion, and uptake of the majority of LDL cholesterol via the LDL receptor pathway. Early work suggested hamsters fed high cholesterol and saturated fat diets responded similarly to humans in terms of lipoprotein metabolism and aortic lesion morphology. Recent work has not consistently replicated these findings. Reviewed was the literature related to controlled hamster feeding studies that assessed the effect of strain, background diet (non-purified, semi-purified and dietary perturbation (cholesterol and/or fat on plasma lipoprotein profiles and atherosclerotic lesion formation. F1B hamsters fed a non-purified cholesterol/fat-supplemented diet had more atherogenic lipoprotein profiles (nHDL-C > HDL-C than other hamster strains or hamsters fed cholesterol/fat-supplemented semi-purified diets. However, fat type; saturated (SFA, monounsaturated or n-6 polyunsaturated (PUFA had less of an effect on plasma lipoprotein concentrations. Cholesterol- and fish oil-supplemented semi-purified diets yielded highly variable results when compared to SFA or n-6 PUFA, which were antithetical to responses observed in humans. Dietary cholesterol and fat resulted in inconsistent effects on aortic lipid accumulation. No hamster strain was reported to consistently develop lesions regardless of background diet, dietary cholesterol or dietary fat type amount. In conclusion, at this time the Golden-Syrian hamster does not appear to be a useful model to determine the mechanism(s of diet-induced development of atherosclerotic lesions.

  12. Developmental Changes in the ECG of a Hamster Model of Muscular Dystrophy and Heart Failure

    OpenAIRE

    ThomasGerardHampton; AjitKale; HemmiBhagavan

    2012-01-01

    Aberrant autonomic signaling is being increasingly recognized as an important symptom in neuromuscular disorders. The delta-sarcoglycan-deficient BIO TO-2 hamster is recognized as a good model for studying mechanistic pathways and sequelae in muscular dystrophy and heart failure, including autonomic nervous system dysfunction. Recent studies using the TO-2 hamster model have provided promising preclinical results demonstrating the efficacy of gene therapy to treat skeletal muscle weakness a...

  13. Dissociation of Ultradian and Circadian Phenotypes in Female and Male Siberian Hamsters

    OpenAIRE

    Prendergast, Brian J.; Cisse, Yasmine M.; Cable, Erin J.; Zucker, Irving

    2012-01-01

    Three experiments addressed whether pronounced alterations in the circadian system yielded concomitant changes in ultradian timing. Female Siberian hamsters were housed in a 16L:8D photoperiod after being subjected to a disruptive phase-shifting protocol that produced 3 distinct permanent circadian phenotypes: some hamsters entrained their circadian rhythms (CRs) with predominantly nocturnal locomotor activity (ENTR), others displayed free-running CRs (FR), and a third cohort was circadian ar...

  14. Male Syrian Hamsters Demonstrate a Conditioned Place Preference for Sexual Behavior and Female Chemosensory Stimuli

    OpenAIRE

    Bell, Margaret R.; Meerts, Sarah H.; Sisk, Cheryl L.

    2010-01-01

    Sexual behavior is a natural reward for many rodent species, and it often includes chemosensory-directed components. Chemosensory stimuli themselves may also be rewarding. Conditioned place preference (CPP) is one paradigm frequently used to test the rewarding properties of a range of stimuli. Males and females of several rodent species show a CPP for sexual behavior, however, it is currently unknown whether sexual behavior can induce a CPP in male Syrian hamsters. As male Syrian hamsters are...

  15. Adaptation to short photoperiods augments circadian food anticipatory activity in Siberian hamsters

    OpenAIRE

    Bradley, Sean P.; Prendergast, Brian J.

    2014-01-01

    Both the light-dark cycle and the timing of food intake can entrain circadian rhythms. Entrainment to food is mediated by a food entrainable circadian oscillator (FEO) that is formally and mechanistically separable from the hypothalamic light-entrainable oscillator. This experiment examined whether seasonal changes in day length affect the function of the FEO in male Siberian hamsters (Phodopus sungorus). Hamsters housed in long (LD; 15 h light/day) or short (SD; 9 h light/day) photoperiods w...

  16. Effects of Porcine Pancreatic Enzymes on the Pancreas of Hamsters. Part 2: Carcinogenesis Studies

    OpenAIRE

    Fumiaki Nozawa; Mehmet Yalniz; Murat Saruc; Jens Standop; Hiroshi Egami; Pour, Parviz M.

    2012-01-01

    Context Our previous study suggested that porcine pancreatic extract in hamsters with peripheral insulin resistance, normalizes insulin output, islet size and pancreatic DNA synthetic rate. It also inhibited the growth of human pancreatic cancer cells in nude mice. Objective To examine the potential value of the porcine pancreatic extract in controlling pancreatic carcinogenesis in this model, the present experiment was performed. Design Hamsters were fed a high fat diet and four wee...

  17. Regulation of Intestinal Immune Response by Selective Removal of the Anterior, Posterior, or Entire Pituitary Gland in Trichinella spiralis Infected Golden Hamsters

    Science.gov (United States)

    Hernández-Cervantes, Rosalía; Quintanar-Stephano, Andrés; Moreno-Méndoza, Norma; López-Griego, Lorena; López-Salazar, Valeria; Hernández-Bello, Romel; Carrero, Julio César; Morales-Montor, Jorge

    2013-01-01

    The influence of anterior pituitary hormones on the gastrointestinal tract of humans and animals has been previously reported. Hypophysectomy (HYPOX) in the rat causes atrophy of the intestinal mucosa, and reduction of gastric secretion and intestinal absorption, as well as increased susceptibility to bacterial and viral infections. However, to our knowledge, no findings have been published concerning the immune response following HYPOX during worm infection, particularly that which is caused by the nematode Trichinella spiralis. The aim of this work was to analyze the effects of total or partial HYPOX on colonization of T. spiralis in the intestinal lumen, together with duodenal and splenic cytokine expression. Our results indicate that 5 days post infection, only neurointermediate pituitary lobectomy (NIL) reduces the number of intestinally recovered T. spiralis larvae. Using semiquantitative inmunofluorescent laser confocal microscopy, we observed that the mean intensity of all tested Th1 cytokines was markedly diminished, even in the duodenum of infected controls. In contrast, a high level of expression of these cytokines was noted in the NIL infected hamsters. Likewise, a significant decrease in the fluorescence intensity of Th2 cytokines (with the exception of IL-4) was apparent in the duodenum of control and sham infected hamsters, compared to animals with NIL surgeries, which showed an increase in the expression of IL-5 and IL-13. Histology of duodenal mucosa from NIL hamsters showed an exacerbated inflammatory infiltrate located along the lamina propria, which was related to the presence of the parasite. We conclude that hormones from each pituitary lobe affect the gastrointestinal immune responses to T. spiralis through various mechanisms. PMID:23555042

  18. Regulation of intestinal immune response by selective removal of the anterior, posterior, or entire pituitary gland in Trichinella spiralis infected golden hamsters.

    Directory of Open Access Journals (Sweden)

    Rosalía Hernández-Cervantes

    Full Text Available The influence of anterior pituitary hormones on the gastrointestinal tract of humans and animals has been previously reported. Hypophysectomy (HYPOX in the rat causes atrophy of the intestinal mucosa, and reduction of gastric secretion and intestinal absorption, as well as increased susceptibility to bacterial and viral infections. However, to our knowledge, no findings have been published concerning the immune response following HYPOX during worm infection, particularly that which is caused by the nematode Trichinella spiralis. The aim of this work was to analyze the effects of total or partial HYPOX on colonization of T. spiralis in the intestinal lumen, together with duodenal and splenic cytokine expression. Our results indicate that 5 days post infection, only neurointermediate pituitary lobectomy (NIL reduces the number of intestinally recovered T. spiralis larvae. Using semiquantitative inmunofluorescent laser confocal microscopy, we observed that the mean intensity of all tested Th1 cytokines was markedly diminished, even in the duodenum of infected controls. In contrast, a high level of expression of these cytokines was noted in the NIL infected hamsters. Likewise, a significant decrease in the fluorescence intensity of Th2 cytokines (with the exception of IL-4 was apparent in the duodenum of control and sham infected hamsters, compared to animals with NIL surgeries, which showed an increase in the expression of IL-5 and IL-13. Histology of duodenal mucosa from NIL hamsters showed an exacerbated inflammatory infiltrate located along the lamina propria, which was related to the presence of the parasite. We conclude that hormones from each pituitary lobe affect the gastrointestinal immune responses to T. spiralis through various mechanisms.

  19. The induction of SCE and chromosomal aberrations with relation to specific base methylation of DNA in Chinese hamster cells by N-methyl-N-nitrosourea and dimethyl sulphate.

    Science.gov (United States)

    Connell, J R; Medcalf, A S

    1982-01-01

    Chinese hamster cells (V79) were treated, either as exponentially proliferating cultures or under conditions where they were density-inhibited, with various doses of the potent carcinogen N-methyl-N-nitrosourea (MNU) or the relatively weak carcinogen dimethylsulphate (DMS). The colony forming ability of these cells and the induced frequencies of sister chromatid exchanges (SCEs) and chromosomal aberrations were assayed. Following the exposure of density-inhibited cells to radio-labelled methylating agents (labelled in the methyl group) these phenomena were related to the levels of 7-methylguanine (7-meGua), O6-methylguanine (O6-meGua) and 3-methyladenine (3-me-Ade) in the DNA. At equitoxic doses MNU and DMS induced similar frequencies of SCEs and chromosomal aberrations. Since, at equitoxic doses, MNU produces approximately 20 times more O6-meGua in V79 cell DNA than does DMS, this indicates that the formation of O6-meGua in DNA is not a major cause of SCEs and chromosomal aberrations. DMS-induced SCEs may be mediated via the production of both 3-meAde and 7-meGua in the DNA; these two methylated purines may also be responsible for MNU-induced SCEs. Therefore, no one specific methylated purine was identified as being solely accountable for the formation of SCEs. Also, the repair of lesions in the DNA of non-replicating V79 cells leads to a reduction in the SCE frequency on their subsequent release from the density-inhibited state, suggesting that repair is not intimately responsible for their formation. No association was discernable between chromosomal aberrations and any of the three methylated purines studied. PMID:7094205

  20. Ochratoxin A carcinogenicity involves a complex network of epigenetic mechanisms.

    Science.gov (United States)

    Marin-Kuan, Maricel; Cavin, Christophe; Delatour, Thierry; Schilter, Benoît

    2008-08-01

    Ochratoxin A (OTA) is a mycotoxin occurring in a wide range of food products. Because of the limitation of human epidemiological data, the safety significance of OTA in food has to rely on animal data, with renal toxicity and carcinogenicity being considered the pivotal effects. The elucidation of the mechanism of action would improve the use of experimental animal data for risk assessment. Direct genotoxicity versus epigenetic mechanisms appears to be a key question. In the present review, the increasingly documented epigenetic cellular effects of OTA and their potential toxicological relevance are discussed. The information available suggests that OTA is unlikely to act through a single, well-defined mechanism of action. Instead, it is proposed that a network of interacting epigenetic mechanisms, including protein synthesis inhibition, oxidative stress and the activation of specific cell signalling pathways, is responsible for OTA carcinogenicity. From a risk assessment perspective, it has to be noted that the mechanisms proposed above depend mainly upon gene expression and enzyme activation, and are, therefore, likely to be thresholded. PMID:18649906

  1. Carcinogenic effects ofcircadian disruption:an epigenetic viewpoint

    Institute of Scientific and Technical Information of China (English)

    Abbas Salavaty

    2015-01-01

    Circadian rhythms refer to the endogenous rhythms that are generated to synchronize physiology and behavior with 24-h environmental cues. These rhythms are regulated by both external cues and molecular clock mechanisms in almost all cells. Disruption of circadian rhythms, which is called circadian disruption, affects many biological processes within the body and results in different long-term diseases, including cancer. Circadian regulatory pathways result in rhythmic epigenetic modiifcations and the formation of circadian epigenomes. Aberrant epigenetic modiifcations, such as hypermethylation, due to circadian disruption may be involved in the transformation of normal cells into cancer cells. Several studies have indicated an epigenetic basis for the carcinogenic effects of circadian disruption. In this review, I ifrst discuss some of the circadian genes and regulatory proteins. Then, I summarize the current evidence related to the epigenetic modiifcations that result in circadian disruption. In addition, I explain the carcinogenic effects of circadian disruption and highlight its potential role in different human cancers using an epigenetic view-point. Finally, the importance of chronotherapy in cancer treatment is highlighted.

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

    International Nuclear Information System (INIS)

    Studies indicate that being exposed to second hand smoke increases the chance of developing lung cancer. Understanding the deposition of carcinogenic particles present in second hand smoke is necessary to understand the development of specific histologic type cancers. In this study, a deposition model is presented for subjects of various ages exposed to sidestream smoke. The model included particle dynamics of coagulation, hygroscopic growth, charge and cloud behavior. Concentrations were varied from the maximum measured indoor concentrations (106 particles/cm3) to what would be expected from wisps of smoke (108 particles/cm3). Model results agreed well with experimental data taken from human subject deposition measurements (four studies). The model results were used to determine the dose intensity (dose per unit airway surface area) of Benzo[a]pyrene (BaP) in the respiratory tract for subjects of various ages. Model predictions for BaP surface concentration on the airway walls paralleled incident rates of tumors by location in the upper tracheobronchial region. Mass deposition efficiency was found to be larger for younger subjects, consistent with diffusion being the predominant mechanism for this particle size range. However, the actual dose intensity of BaP was found to be smaller for children than adults. This occurred due to the predominant effect of the smaller initial inhaled mass for children resulting from smaller tidal volumes. The resulting model is a useful tool to predict carcinogen specific particle deposition

  3. Systems biology perspectives on the carcinogenic potential of radiation

    International Nuclear Information System (INIS)

    This review focuses on recent experimental and modeling studies that attempt to define the physiological context in which high linear energy transfer (LET) radiation increases epithelial cancer risk and the efficiency with which it does so. Radiation carcinogenesis is a two-compartment problem: ionizing radiation can alter genomic sequence as a result of damage due to targeted effects (TE) from the interaction of energy and DNA; it can also alter phenotype and multicellular interactions that contribute to cancer by poorly understood non-targeted effects (NTE). Rather than being secondary to DNA damage and mutations that can initiate cancer, radiation NTE create the critical context in which to promote cancer. Systems biology modeling using comprehensive experimental data that integrates different levels of biological organization and time-scales is a means of identifying the key processes underlying the carcinogenic potential of high-LET radiation. We hypothesize that inflammation is a key process, and thus cancer susceptibility will depend on specific genetic predisposition to the type and duration of this response. Systems genetics using novel mouse models can be used to identify such determinants of susceptibility to cancer in radiation sensitive tissues following high-LET radiation. Improved understanding of radiation carcinogenesis achieved by defining the relative contribution of NTE carcinogenic effects and identifying the genetic determinants of the high-LET cancer susceptibility will help reduce uncertainties in radiation risk assessment

  4. Formaldehyde in dentistry: a review of mutagenic and carcinogenic potential

    Energy Technology Data Exchange (ETDEWEB)

    Lewis, B.B.; Chestner, S.B.

    1981-09-01

    For many years there has been controversy over the value of antimicrobial drugs for intracanal dressings in endodontics. Formocresol, a formaldehyde compound, has evolved as the preferred drug for routine endodontic procedures, as well as pediatric endodontics. The increase in the use of formaldehyde has been complicated by the introduction of paraformaldehyde pastes for filling root canals. Neither of these formulas has ever been standardized. The doses are arbitrary, and the common dose of formocresol has been shown to be many times greater than the minimum dose needed for effect. The efficacy of paraformaldehyde pastes is questionable and remains clouded by inconclusive evidence, conflicting research, inadequate terminology, and a lack of convincing statistical evidence. The clinical use and delivery of formocresol and paraformaldehyde pastes remain arbitrary and unscientific. Formaldehyde has a known toxic mutagenic and carcinogenic potential. Many investigations have been conducted to measure the risk of exposure to formaldehyde; it is clear that formaldehyde poses a carcinogenic risk in humans. There is a need to reevaluate the rationale underlying the use of formaldehyde in dentistry particularly in light of its deleterious effects.

  5. Neoplastic transformation of human diploid fibroblast cells by chemical carcinogens

    Science.gov (United States)

    Kakunaga, Takeo

    1978-01-01

    Cultured fibroblast cells derived from a skin biopsy sample taken from normal human adult were exposed to a potent carcinogen, 4-nitroquinoline 1-oxide. Alterations of cell growth pattern such as higher density and piling up of cells were noticed in some fractions of cultures that were successively subcultured after nitroquinoline oxide treatment. Morphologically altered cells retained this growth pattern and became established lines of transformed cells without showing the limited life-span characteristic of normal cells in culture. The transformed cells showed a higher saturation density and the ability to grow in soft agar, properties that are usually correlated with neoplastic transformation of cells in culture. Selection of preexisting transformed human cells as a mechanism of this observed transformation seemed unlikely because clones of these normal cells could also be used to assess the transforming effect of nitroquinoline oxide. Preliminary results suggest that numerous cell divisions were required for the development of the transformation after nitroquinoline oxide treatment of these human cells. When the transformed cell lines were injected subcutaneously into nude (athymic) mice, solid tumors were produced at the site of inoculation. Treatment with N-methyl-N′-nitro-N-nitrosoguanidine also induced cell transformation, in a manner similar to treatment with nitroquinoline oxide. However, transformation was not induced with (i) 4-aminoquinoline 1-oxide (a noncarcinogenic derivative of 4-nitroquinoline 1-oxide), (ii) 3-methylcholanthrene (a carcinogen that cannot be metabolically activated by the target cells employed), or (iii) the solvent dimethyl sulfoxide. Images PMID:418410

  6. Bioactivation of mitomycin antibiotics by aerobic and hypoxic Chinese hamster ovary cells overexpressing DT-diaphorase.

    Science.gov (United States)

    Belcourt, M F; Hodnick, W F; Rockwell, S; Sartorelli, A C

    1996-06-28

    DT-Diaphorase catalyzes a two-electron reduction of mitomycin C (MC) and porfiromycin (POR) to reactive species. Many cell lines that overexpress DT-diaphorase and are sensitive to the mitomycins are protected from the aerobic cytotoxicity of these drugs by the DT-diaphorase inhibitor dicumarol. The cytoprotective properties of this relatively non-specific inhibitor, however, vanish under hypoxic conditions. To ascertain the role of DT-diaphorase in mitomycin bioactivation and cytotoxicity in living cells, a rat liver DT-diaphorase cDNA was transfected into Chinese hamster ovary cells. MC was equitoxic to the parental cells under oxygenated and hypoxic conditions. In contrast, POR was less toxic than MC to these cells under aerobic conditions, but significantly more toxic than MC under hypoxia. Two DT-diaphorase-transfected clones displayed increases in DT-diaphorase activity of 126- and 133-fold over parental cells. The activities of other oxidoreductases implicated in mitomycin bioreduction were unchanged. MC was more toxic to both DT-diaphorase-transfected lines than to parental cells; the toxicity of MC to the transfected lines was similar in air and hypoxia. POR was also more toxic to the DT-diaphorase-elevated clones than to parental cells under oxygenated conditions. Under hypoxia, however, the toxicity of POR to the transfected clones was unchanged from that of parental cells. The findings implicate DT-diaphorase in mitomycin bioactivation in living cells, but suggest that this enzyme does not contribute to the differential toxicity of MC or POR in air and hypoxia. PMID:8687482

  7. Autoradiographic localization of tritiated dihydrotestosterone in the flank organ of the albino hamster

    International Nuclear Information System (INIS)

    In the hamster flank organ, the growth of hair and growth of sebaceous glands are androgen-dependent functions. Although dihydrotestosterone (DHT) is known to be a potent stimulator of flank organ growth, there is no information about localization of DHT receptor sites in this organ. The purpose of this study was to use steroid autoradiography to localize DHT receptors in the hamster flank organ. Because steroid hormones are functional when translocated to nuclear receptors, nuclear localization by autoradiography defines receptor sites. In order to be able to visualize autoradiographic grains from radiolabeled androgens around hair follicles, albino hamsters were studied to avoid confusion between the grains and pigment granules which are abundant in the more common Golden Syrian hamster. Mature male hamsters castrated 24 hours earlier were given tritium-labeled dihydrotestosterone ( [3H]DHT). Using the technique of thaw-mount steroid autoradiography, 4-micron unfixed frozen sections were mounted in the dark onto emulsion-coated glass slides and allowed to develop for 4-6 months. [3H]DHT was found to be concentrated over sebocyte nuclei. The label was present peripherally as well as in differentiating sebocytes. There was no nuclear localization of [3H]DHT in animals pretreated with excessive quantities of unlabeled DHT. Steroid metabolites of [3H] DHT were assessed by thin-layer chromatography in paired tissue samples. Most of the label remained with DHT. Uptake was inhibited in the flank organ of hamsters pretreated with unlabeled DHT

  8. Beneficial effects of noni (Morinda citrifolia L.) juice on livers of high-fat dietary hamsters.

    Science.gov (United States)

    Lin, Yi-Ling; Chang, Yuan-Yen; Yang, Deng-Jye; Tzang, Bor-Show; Chen, Yi-Chen

    2013-09-01

    Polyphenols in noni juice (NJ) are mainly composed of phenolic acids, mainly gentisic, p-hydroxybenoic, and chlorogenic acids. To investigate the beneficial effects of NJ on the liver, hamsters were fed with two diets, normal-fat and high-fat diets. Furthermore, high-fat dietary hamsters were received distilled water, and 3, 6, and 9 mL NJ/kg BW, respectively. After a 6-week feeding period, the increased (p<0.05) sizes of liver and visceral fat in high-fat dietary hamsters compared to the control hamsters were ameliorated (p<0.05) by NJ supplementation. NJ also decreased (p<0.05) serum/liver lipids but enhanced (p<0.05) daily faecal lipid/bile acid outputs in the high-fat dietary hamsters. High-fat dietary hamsters supplemented with NJ had higher (p<0.05) liver antioxidant capacities but lowered (p<0.05) liver iNOS, COX-2, TNF-α, and IL-1β expressions, gelatinolytic levels of MMP9, and serum ALT values compared to those without NJ. Hence, NJ protects liver against a high-fat dietary habit via regulations of antioxidative and anti-inflammatory responses. PMID:23578611

  9. Electroencephalography in the diagnosis of hydrocephalus in golden hamsters (Mesocricetus auratus).

    Science.gov (United States)

    Bali, M S; Gebhardt-Henrich, S; Keller, P; Steiger, A; Gattermann, R; Bergamasco, L; Kronen, P; Doherr, M G; Botteron, C; Tomek, A; Jaggy, A

    2008-04-01

    The golden hamster (Mesocricetus auratus) is a popular laboratory animal and is used in a multitude of behavioural studies. However, it has been shown that it suffers from different forms of hereditary hydrocephalus, which may result in behavioural changes. This prospective study was designed to look into the usefulness of electroencephalography (EEG) measurements in the diagnosis of hydrocephalus in hamsters. The EEGs of the hydrocephalic hamsters were evaluated double-blind and showed a high-voltage slow wave activity, with a fast activity superimposed onto it. This pattern has already been well described in other hydrocephalic species and differed significantly from the EEGs that were obtained from the normal hamsters. It was concluded from our study that a background activity with an amplitude over 50 muV in combination with a frequency of < or =5 Hz was highly indicative of hydrocephalus in young hamsters. We believe that the EEG could be a very useful diagnostic tool in the screening for hydrocephalus in hamsters. PMID:18435879

  10. Hamster-Adapted Sin Nombre Virus Causes Disseminated Infection and Efficiently Replicates in Pulmonary Endothelial Cells without Signs of Disease

    OpenAIRE

    Safronetz, David; Prescott, Joseph; Haddock, Elaine; Scott, Dana P.; Feldmann, Heinz; Ebihara, Hideki

    2013-01-01

    To date, a laboratory animal model for the study of Sin Nombre virus (SNV) infection or associated disease has not been described. Unlike infection with Andes virus, which causes lethal hantavirus pulmonary syndrome (HPS)-like disease in hamsters, SNV infection is short-lived, with no viremia and little dissemination. Here we investigated the effect of passaging SNV in hamsters. We found that a host-adapted SNV achieves prolonged and disseminated infection in hamsters, including efficient rep...

  11. Human cytochrome P-450PA (P-450IA2), the phenacetin O-deethylase, is primarily responsible for the hepatic 3-demethylation of caffeine and N-oxidation of carcinogenic arylamines.

    OpenAIRE

    Butler, M.A. (Mary A.); Iwasaki, M; Guengerich, F P; Kadlubar, F F

    1989-01-01

    Aromatic amines are well known as occupational carcinogens and are found in cooked foods, tobacco smoke, synthetic fuels, and agricultural chemicals. For the primary arylamines, metabolic N-oxidation by hepatic cytochromes P-450 is generally regarded as an initial activation step leading to carcinogenesis. The metabolic activation of 4-aminobiphenyl, 2-naphthylamine, and several heterocyclic amines has been shown recently to be catalyzed by rat cytochrome P-450ISF-G and by its human ortholog,...

  12. Photodynamic cytotoxicity of mammalian cells exposed to sunlight-simulating near ultraviolet light in the presence of the carcinogen 7, 12-dimethylbenz(a)anthracene

    International Nuclear Information System (INIS)

    The coal-derived carcinogen 7,12-dimethylbenz(a)anthracene (DMBA), added to cultures of V79 Chinese Hamster, C3H mouse 10T1/2, and human HeLa cells enhanced photolethality induced by the sunlight-simulating emission from Westinghouse Sun Lamps (approximately 290-400 nm) but only in the presence of 02. Treatment of cells with DMBA after irradiation was without lethal effect; the endoperoxide of DMBA was ineffective both before as well as after irradiation, and DMBA incubation before far-UV exposure (254 nm) was protective. Cells rendered photosensitive by incubation with DMBA rapidly lost their sensitivity (in 0C) if incubation in a DMBA-free solution containing serum, but maintained their sensitivity at least for several hours if a serum-free solution was used. Although DMBA enhanced light-induced killing of cells in all phases of the cycle, those undergoing DNA syntheses were preferentially sensitized. The data supported photodynamic lethality due to one or both of the following: (1) the reaction with DNA of either DMBA radicals followed by oxidation, or DMBA-produced single oxygen; or (2) the peroxidation of lysosomal membranes followed by the release of hydrolases including DNAses. As a model system of the combined effects of a fossil-fuel derived polycyclic aromatic hydrocarbon and sunlight, the results with DMBA + near-UV are discussed in the context of altered cell properties (e.g. neoplastic transformation) in sublethally affected cells. (author)

  13. DNA adducts in target and nontarget tissues of 3,2'-dimethyl-4-aminobiphenyl in rats.

    OpenAIRE

    Shirai, T; Tada, M; Kojima, M; Hasegawa, R.; Masui, T.; Ito, N.

    1994-01-01

    3,2'-Dimethyl-4-aminobiphenyl (DMAB) is a potent carcinogenic aromatic amine which demonstrates multiorgan tropism in rats. Using polyclonal antibodies against DMAB-DNA adducts, an immunohistochemical procedure as well as an ELISA were applied to investigate the relationship between DMAB-DNA adduct formation and tumorigenicity. Dose-related nuclear staining was observed 24 hr after application of the carcinogen but specificity in terms of sites of tumor development was lacking. No observable ...

  14. The impact of homologous recombination repair deficiency on depleted uranium clastogenicity in Chinese hamster ovary cells: XRCC3 protects cells from chromosome aberrations, but increases chromosome fragmentation.

    Science.gov (United States)

    Holmes, Amie L; Joyce, Kellie; Xie, Hong; Falank, Carolyne; Hinz, John M; Wise, John Pierce

    2014-04-01

    Depleted uranium (DU) is extensively used in both industry and military applications. The potential for civilian and military personnel exposure to DU is rising, but there are limited data on the potential health hazards of DU exposure. Previous laboratory research indicates DU is a potential carcinogen, but epidemiological studies remain inconclusive. DU is genotoxic, inducing DNA double strand breaks, chromosome damage and mutations, but the mechanisms of genotoxicity or repair pathways involved in protecting cells against DU-induced damage remain unknown. The purpose of this study was to investigate the effects of homologous recombination repair deficiency on DU-induced genotoxicity using RAD51D and XRCC3-deficient Chinese hamster ovary (CHO) cell lines. Cells deficient in XRCC3 (irs1SF) exhibited similar cytotoxicity after DU exposure compared to wild-type (AA8) and XRCC3-complemented (1SFwt8) cells, but DU induced more break-type and fusion-type lesions in XRCC3-deficient cells compared to wild-type and XRCC3-complemented cells. Surprisingly, loss of RAD51D did not affect DU-induced cytotoxicity or genotoxicity. DU induced selective X-chromosome fragmentation irrespective of RAD51D status, but loss of XRCC3 nearly eliminated fragmentation observed after DU exposure in wild-type and XRCC3-complemented cells. Thus, XRCC3, but not RAD51D, protects cells from DU-induced breaks and fusions and also plays a role in DU-induced chromosome fragmentation. PMID:24561002

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

    Science.gov (United States)

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

    2015-01-01

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

  16. Screening tests for determination of cytotoxic agent, mutagens and carcinogens

    Energy Technology Data Exchange (ETDEWEB)

    Spiegelberg, T.; Koerdel, W.; Goertz, T.; Thriemer, A.

    1983-01-01

    It is supposed that chemical substances are the primary factors responsible for the development of tumors and genetic damages. From this results the urgend demand to examine at least the frequently applied and suspicious substances on possibly health-affecting effects. The performance of these examinations with experimental animals requires a lot of time and financial support and has increasingly been criticised in public with regard to protection of animals. Experience gained in the U.S.A. revealed that the carcinogenicity test of one single substance performed with animal experiments takes approximately 3 years and costs about 300,000 Dollars. Therefore the application of cell cultures for such examinations and tests has been postulated and discussed for several years. Cell cultures require only little space and generally the observed effects develop after only a short time. Objectification and statistical assessment (due to high cell amounts per test) can be performed without any problems.

  17. Occurrence of the carcinogenic compound ptaquiloside in the soil environment

    DEFF Research Database (Denmark)

    Rasmussen, Lars Holm; Kroghsbo, Stine; Frisvad, Jens Christian;

    2003-01-01

    Bracken (Pteridium aquilinum (L.) Kuhn) is a common fern found on all continents except Antarctica. It is under suspicion of causing cancer among people who utilizes it as food. The main carcinogenic compound is thought to be the water-soluble compound ptaquiloside. Ptaquiloside-uptake may occur....... The ptaquiloside-content in the standing biomass, which could be transferred to the soil by the end of the growing season, ranged between 10 and 260 mgm2, with nine sites having ptaquiloside loads over 100 mgm2. The carbon-content in the O-horizon, the precipitation, the amount of Bracken-litter, the...... turnover rate and the size of Bracken-stands determined the ptaquiloside-content in the soil materials while the content in fronds was found to be a function of the frond-height and the light-exposure in the ecosystem....

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

    Science.gov (United States)

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

    2013-01-01

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

  19. A carcinogenicity study of sucralose in the CD-1 mouse.

    Science.gov (United States)

    Mann, S W; Yuschak, M M; Amyes, S J; Aughton, P; Finn, J P

    2000-01-01

    The potential carcinogenicity of sucralose was evaluated by feeding groups of 52 male and 52 female CD-1 mice a diet containing sucralose at 0.3% (3000 ppm), 1.0% (10,000 ppm) or 3.0% (30,000 ppm) for 104 weeks. A group of 72 male and 72 female mice received diet without sucralose and served as controls. Week 1 achieved doses ranging from 543 to 5870mg/kg body weight/day in the low-dose males and high-dose females, respectively. Sucralose had no adverse effect on survival. No significant changes attributable to sucralose were found in the clinical condition or behaviour of the mice. Organ weights and the gross appearance of tissues were unaffected by treatment. The mean erythrocyte counts of females receiving the highest dietary concentration were slightly, but statistically significantly, lower than those of the controls after 104 weeks of treatment. Group mean body weight gain at the highest dietary concentration of sucralose was significantly less than that of the control in mice of both sexes. Food consumption, after correction for sucralose content, was lower for female mice, but not statistically significant. Water consumption for male mice receiving the highest dietary concentration was approximately 9% higher than that of the controls. There were statistically significant increases in the incidence of several non-neoplastic findings, but these were not considered to be related to sucralose administration. Treatment with sucralose did not increase the incidence of any tumour or influence the types of tumours observed. It was concluded that sucralose is not carcinogenic in CD-1 mice. The body weight gain and erythrocyte observations at the 3.0% dietary level were of limited biological significance as they were not accompanied by any histopathologic finding and had no impact on survival. The remaining dose levels were judged to have no effects. PMID:10882820

  20. The carcinogenicity of dietary acrylamide intake: A comparative discussion of epidemiological and experimental animal research

    NARCIS (Netherlands)

    Hogervorst, J.G.F.; Baars, B.-J.; Schouten, L.J.; Konings, E.J.M.; Goldbohm, R.A.; Brandt, P.A. van den

    2010-01-01

    Since 2002, it is known that the probable human carcinogen acrylamide is present in commonly consumed carbohydrate-rich foods, such as French fries and potato chips. In this review, the authors discuss the body of evidence on acrylamide carcinogenicity from both epidemiological and rodent studies, i

  1. Study of isotopic tracing related with mechanism of cancer caused by carcinogenic substance

    International Nuclear Information System (INIS)

    In order to understand the mechanism of cancer caused by carcinogenic substance, a project using 41Ca as tracer and accelerator mass spectrometry (AMS) as measurement method to investigate the origin of the increased Ca2+ when the cells are exposed to carcinogenic substances is being undertaken. Several results as bellow have been obtained

  2. Transcriptomic effects of di-(2-ethylhexyl-phthalate in Syrian hamster embryo cells: an important role of early cytoskeleton disturbances in carcinogenesis?

    Directory of Open Access Journals (Sweden)

    Atienzar Franck

    2011-10-01

    Full Text Available Abstract Background Di-(2-ethylhexyl-phthalate (DEHP is a commonly used plasticizer in polyvinylchloride (PVC formulations and a potentially non-genotoxic carcinogen. The aim of this study was to identify genes whose level of expression is altered by DEHP by using a global wide-genome approach in Syrian hamster embryo (SHE cells, a model similar to human cells regarding their responses to this type of carcinogen. With mRNA Differential Display (DD, we analysed the transcriptional regulation of SHE cells exposed to 0, 12.5, 25 and 50 μM of DEHP for 24 hrs, conditions which induced neoplastic transformation of these cells. A real-time quantitative polymerase chain reaction (qPCR was used to confirm differential expression of genes identified by DD. Results Gene expression profiling showed 178 differentially-expressed fragments corresponding to 122 genes after tblastx comparisons, 79 up-regulated and 43 down-regulated. The genes of interest were involved in many biological pathways, including signal transduction, regulation of the cytoskeleton, xenobiotic metabolism, apoptosis, lipidogenesis, protein conformation, transport and cell cycle. We then focused particularly on genes involved in the regulation of the cytoskeleton, one of the processes occurring during carcinogenesis and in the early steps of neoplastic transformation. Twenty one cytoskeleton-related genes were studied by qPCR. The down-regulated genes were involved in focal adhesion or cell junction. The up-regulated genes were involved in the regulation of the actin cytoskeleton and this would suggest a role of cellular plasticity in the mechanism of chemical carcinogenesis. The gene expression changes identified in the present study were PPAR-independent. Conclusion This study identified a set of genes whose expression is altered by DEHP exposure in mammalian embryo cells. This is the first study that elucidates the genomic changes of DEHP involved in the organization of the

  3. DEVELOPMENT OF MICE AND HAMSTER EMBRYOS IN KSOMAA AND HECM-6 MEDIUM

    Directory of Open Access Journals (Sweden)

    Bayu Rosadi

    2008-12-01

    Full Text Available The purpose of the present study was to investigate the viability of mice and hamster embryos developed in Kalium Simplex Optimized Medium amino acid (KSOMaa and Hamster Embryo Culture Medium-6 (HECM-6 medium. Female DDY mice were superovulated by injection i.p. of 5 IU Pregnant Mare Serum Gonadotropine (PMSG and 5 IU Human Chorionic Gonadotropine (hCG in 48 h interval, hamster (Phodopus campbelli injected by 2.5 IU PMSG and 2.5 IU hCG 48 h later. Then females were mated with fertile males. Eight-cell embryos were recovered at day 3 after natural mating. The mice embryos were cultured in KSOMaa+5% NBCS (New Born Calf Serum (T1 and HECM-6+5% NBCS (T2, the hamster embryos were cultured in KSOMaa+5% NBCS (T3 and HECM-6 + 5% NBCS (T4 for further development at 37oC in a humidified atmosphere of 5% CO2 in air for 48 h. The examinations were replicated five times. The T1 embryos developed to compact morulla and early blastocyst 100% (140/140, 92.1% (129/140 to blastocyst and expanded blastocyst, and 22.9% (32/140 became hatching/hatched. The T3 reached 100% (60/60 to compact morulla and early blastocyst, 85.0% (51/60 blastocyst, and 48.3% (29/60 expanded blastocyst, no embryo observed hatching/hatced. The T2 embryos had more expanded blastocyst than T3 (P<0.05, hatching/hatched rate higher than T1 and T3 but lower than T4 (P<0.05. Shortly, KSOMaa enable to support 8-cell stage mice and hamster embryo, but the hamster embryo developed lower at expanded blastocyst stage. HECM-6 is more appropriate than KSOMaa to support 8-cell mice embryos development and suitable to develop 8-cell stage hamster embryos.

  4. LipL21 mRNA expression in lungs of hamsters infected with pathogenic Leptospira

    Institute of Scientific and Technical Information of China (English)

    Chintana Chirathaworn; Namo Suksomyos; Somchai Utivamek; Somboon Keelawat; Duangjai Suwancharoen; Duangporn Phulsuksombati; Yong Poovorawan

    2009-01-01

    Objective:Pulmonary haemorrhage is an increasing cause of death in leptospirosis patients.However,molecu-lar mechanism underlying pathologies in this organ is not clearly understood.It has been shown that sodium transport was disturbed following Leptospira infection.LipL21 is the second abundant outer membrane protein found only in pathogenic Leptospira.Its expression in vivo has been shown which suggests that this protein may be involved in survival in hosts or pathogenesis.However,the expression of this protein in host organs and its role in lung pathology has not been demonstrated.In this study we demonstrated the expression of LipL21 in lungs of hamsters infected with pathogenic Leptospira.Methods:Lung tissues were collected from Golden Syri-an hamsters injected with Leptospira interrogans serovar Pyrogenes at days 3,5 and 7 post-infection.Four ham-sters were used for each time point.Lungs from non-infected hamsters were collected as a control group.Li-pL21 mRNA expression in lung tissues was investigated by reverse transcription and nested PCR.Results:Li-pL21 mRNA expression was detected in all lung tissues from hamsters infected with pathogenic Leptospira.No PCR product was detected when tissues from non-infected hamsters were investigated.Conclusion:Our data demonstrated that LipL21 is expressed in lungs of hamsters infected with pathogenic Leptospira.Additional ex-periments such as quantitation and localization of LipL21 expression in lungs will provide further information whether this protein is involved in pathogenesis.

  5. Vomeronasal organ lesion disrupts social odor recognition, behaviors and fitness in golden hamsters.

    Science.gov (United States)

    Liu, Yingjuan; Zhang, Jinhua; Liu, Dingzhen; Zhang, Jianxu

    2014-06-01

    Most studies support the viewpoint that the vomeronasal organ has a profound effect on conspecific odor recognition, scent marking and mating behavior in the golden hamster (Mesocricetus auratus). However, the role of the vomeronasal organ in social odor recognition, social interaction and fitness is not well understood. Therefore, we conducted a series of behavioral and physiological tests to examine the referred points in golden hamster. We found that male hamsters with vomeronasal organ lesion showed no preference between a predator odor (the anal gland secretion of the Siberian weasels (Mustela sibirica) and putative female pheromone components (myristic acid and palmitic acid), but were still able to discriminate between these 2 kinds of odors. In behavioral tests of anxiety, we found that vomeronasal organ removal causes female hamsters to spend much less time in center grids and to cross fewer center grids and males to make fewer crossings between light and dark boxes than sham-operated controls. This indicates that a chronic vomeronasal organ lesion induced anxious responses in females. In aggressive behavioral tests, we found that a chronic vomeronasal organ lesion decreased agonistic behavior in female hamsters but not in males. The pup growth and litter size show no differences between the 2 groups. All together, our data suggested that vomeronasal organ ablation disrupted the olfactory recognition of social chemosignals in males, and induced anxiety-like and aggressive behavior changes in females. However, a vomeronasal organ lesion did not affect the reproductive capacity and fitness of hamsters. Our studies may have important implications concerning the role of the vomeronasal organ in golden hamsters and also in rodents. PMID:24952966

  6. Micro-total envelope system with silicon nanowire separator for safe carcinogenic chemistry

    Science.gov (United States)

    Singh, Ajay K.; Ko, Dong-Hyeon; Vishwakarma, Niraj K.; Jang, Seungwook; Min, Kyoung-Ik; Kim, Dong-Pyo

    2016-01-01

    Exploration and expansion of the chemistries involving toxic or carcinogenic reagents are severely limited by the health hazards their presence poses. Here, we present a micro-total envelope system (μ-TES) and an automated total process for the generation of the carcinogenic reagent, its purification and its utilization for a desired synthesis that is totally enveloped from being exposed to the carcinogen. A unique microseparator is developed on the basis of SiNWs structure to replace the usual exposure-prone distillation in separating the generated reagent. Chloromethyl methyl ether chemistry is explored as a carcinogenic model in demonstrating the efficiency of the μ-TES that is fully automated so that feeding the ingredients for the generation is all it takes to produce the desired product. Syntheses taking days can be accomplished safely in minutes with excellent yields, which bodes well for elevating the carcinogenic chemistry to new unexplored dimensions. PMID:26916423

  7. Micro-total envelope system with silicon nanowire separator for safe carcinogenic chemistry.

    Science.gov (United States)

    Singh, Ajay K; Ko, Dong-Hyeon; Vishwakarma, Niraj K; Jang, Seungwook; Min, Kyoung-Ik; Kim, Dong-Pyo

    2016-01-01

    Exploration and expansion of the chemistries involving toxic or carcinogenic reagents are severely limited by the health hazards their presence poses. Here, we present a micro-total envelope system (μ-TES) and an automated total process for the generation of the carcinogenic reagent, its purification and its utilization for a desired synthesis that is totally enveloped from being exposed to the carcinogen. A unique microseparator is developed on the basis of SiNWs structure to replace the usual exposure-prone distillation in separating the generated reagent. Chloromethyl methyl ether chemistry is explored as a carcinogenic model in demonstrating the efficiency of the μ-TES that is fully automated so that feeding the ingredients for the generation is all it takes to produce the desired product. Syntheses taking days can be accomplished safely in minutes with excellent yields, which bodes well for elevating the carcinogenic chemistry to new unexplored dimensions. PMID:26916423

  8. The carcinogenic action of crystalline silica: a review of the evidence supporting secondary inflammation-driven genotoxicity as a principal mechanism.

    Science.gov (United States)

    Borm, Paul J A; Tran, Lang; Donaldson, Ken

    2011-10-01

    the driving force for genotoxicity and that primary genotoxicity of deposited CS would play a role only at very high, possibly implausible, exposures and deposited doses. Although based on rat studies and in vitro studies, and therefore with caveats, the analysis supports the hypothesis that the mechanism of CS genotoxicity is via inflammation-driven secondary genotoxicity. This may have implications for setting of the CS standard in workplaces. During the writing of this review (in May 2009), IARC undertook a review of carcinogenic substances, including CS. The Working Group met to reassess 10 separate agents including CS. This was not a normal monograph working group published as a large single monograph, but was published as a two-page report. This review group reaffirmed the carcinogenicity of "silica dust, crystalline in the form of quartz or cristobalite" as a Group 1 agent, with the lung as the sole tumor site. Of special relevance to the present review is that the cited "established mechanism events" for CS are restricted to the words "impaired particle clearance leading to macrophage activation and persistent inflammation." The lack of mention of direct genotoxicity is in line with the conclusions reached in the present review. PMID:21923565

  9. Refeeding alters superoxide dismutase activity in Chinese hamster ovary cells

    International Nuclear Information System (INIS)

    The authors previously showed superoxide dismutase (SOD) activity is increased in heat shocked Chinese hamster ovary (CHO) and ovarian carcinoma (OvCa) cells during the time period when thermotolerance (TT) is observed (Ca Res 45,3029). SOD is also increased in OvCa cells following transient exposure to ethanol, carbonyl cyanide-N-chlorophenyl-hydrazone, or hypoxia; all treatments which induce TT (1986 Rad Res Abstr Co-2). As these experiments involved refeeding of cell cultures, the authors examined the effect of refeeding on SOD in CHO cells. Refeeding confluent CHO cells with fresh McCoy's 5A medium containing 10% FCS decreased SOD 0 to 6 hours after refeeding, which was due to loss of the mitochondrial or Mn SOD. Addition of glucose to the medium at the concentration originally found in the medium caused a similar decline in SOD. At 6-24 hours after refeeding or the addition of glucose an increase in Mn SOD was observed. These results suggest metabolic status can affect Mn SOD in the cell. The possible role of metabolic regulation of SOD in heat sensitivity is being investigated

  10. The dystrophic hamster: an animal model of alveolar hypoventilation.

    Science.gov (United States)

    Schlenker, E H; Burbach, J A

    1991-11-01

    The BIO 14.6 dystrophic hamster (DH) is a genetically determined animal model of alveolar hypoventilation (AH) that exhibits a ventilatory control pattern of compensation and then decompensation similar to that in progressive forms of muscular dystrophy and nonprogressive congenital myopathies in humans. Possible causes of AH in the DH include respiratory muscle weakness, ventilation-to-perfusion inequalities, and an inadequate drive to breathe. Histochemical and contractile abnormalities of the diaphragm, reduced lung surface area available for gas exchange, abnormal pulmonary microvascular reactivity to hypoxia, altered levels of neurochemicals, and abnormal cellular regulation of calcium are among the specific factors that may contribute to the development of AH. The potential role of hypothyroidism in the development of AH is reviewed because many hypothyroid patients exhibit AH and other ventilatory dysfunctions, hypothyroidism is present in human patients and animals with muscular dystrophy, and thyroid status is known to influence lung architecture, myocyte function, and neural activity. Additional studies linking neurohormonal signals, transcellular signal processing, and control of ventilation in the DH may help us understand the etiology of AH in human disease. PMID:1684789

  11. Red Yeast Rice Increases Excretion of Bile Acids in Hamsters

    Institute of Scientific and Technical Information of China (English)

    KA-YING MA; ZE-SHENG ZHANG; SHU-XIN ZHAO; QI CHANG; YIN-MEI WONG; SAI YING VENUS YEUNG; YU HUANG; ZHEN-YU CHEN

    2009-01-01

    Objectives To investigate the hypocholesterolemic activity of red yeast rice (RYR) and its underlying mechanism. Methods Three groups of hamsters were fed either the control diet or one of the two experimental diets containing by weight 0.1% RYR (0.1RYR) or 0.3% RYR (0.3RYR). Blood (0.5 mL) was collected from the retro-orbital sinus into a heparinized capillary tube at the end of week 0,3, and 6.Plasma lipoproteins were measured using enzymatic kits, while fecal neutral and acidic sterols were quantified using a gas-liquid chromatography. Results Plasma total cholesterol was reduced by 12% in 0.1RYR group and by 18% in 0.3RYR group compared with the control value. Similarly, plasma triacylglycerol was decreased by ll% in 0.1RYR group and by 24% in 0.3RYR group. Western blotting analysis demonstrated that RYR had no effect on sterol regulatory element binding protein 2, liver X receptor, 3-hydroxy-3-methylglutary-CoA reductase, LDL receptor, and cholesterol-7α-hydroxylase. HPLC analysis confirmed that RYR contained 0.88% monacolin K.It was recently found that RYR supplementation increased excretion of fecal acidic sterols by 3-4 folds compared with the control value. Conclusion Hypocholesterolemic activity of RYR is mediated at least partially by enhancement of acidic sterol excretion.

  12. Effect of neon ions on synchronized Chinese hamster cells

    International Nuclear Information System (INIS)

    The variation in radiosensitivity across the cell cycle after exposure to neon ions and 60Co γ-rays is reported for cultured hamster cells. The cells were first synchronized by mitotic selection, then resynchronized in the region of the G1/S boundary by treatment with 10-3 M hydroxyurea. Although the use of hydroxyurea improves the synchrony, it does sensitize cells at the G1/S boundary to some degree. The cells were exposed at the plateau and the distal peak position of a neon ion beam modified by a 10 cm wide ridge filter. The results indicate that the variation (ratio of maximum to minimum survival after fixed doses of radiation that are approximately matched to produce similar cell killing) was approximately 80 to 100-fold for 60Co γ-rays and neon ions at the plateau, and 25-fold for distal peak neon ions. While the r.b.e. of distal peak neon ions decreased rapidly with increasing dose for cells in late S-phase, the r.b.e. is independent of dose for cells at the G1/S boundary. (author)

  13. Vitamin K metabolism in Chinese Hamster Ovary cells

    International Nuclear Information System (INIS)

    Recent investigations suggest that vitamin K may have functions other than in blood coagulation and calcification. The present study was undertaken to investigate this hypothesis using cells in culture. Chinese Hamster Ovary (CHO) cells were chosen due to their active metabolism and growth and lack of similarity to liver and bone cells, in which vitamin K metabolism is well known. Cells were adapted to serum-free media, incubated in media containing the appropriate concentrations of vitamin K for specified times, scraped from plates, pelleted, extensively washed to remove adhering vitamin K, extracted with chloroform:methanol (2:1, v/v) and analyzed on C18 HPLC columns. Uptake of vitamin K by CHO cells follows saturation kinetics at vitamin K concentrations up to 25 μ M and is transported into cells at the rate of 10 pmol/min. 106 cells. After 24 hours, 3H vitamin K is metabolized by CHO cells to several compounds, the major of which was isolated and identified as vitamin K epoxide. In 3 experiments, after 24 hours, the average cellular uptake of vitamin K was 8% with approximately half being metabolized to vitamin K epoxide. These results demonstrate that vitamin K is metabolized in cells with widely different functions and suggest a generalized function for vitamin K which has yet to be elucidated

  14. Chlorpromazine distribution in hamsters and mice bearing transplantable melanoma

    International Nuclear Information System (INIS)

    Chlorpromazine (CPZ) distribution was measured in tissues of Syrian golden hamsters bearing Greene melanoma and in BALB/c mice bearing Harding-Passey melanoma. Distribution was evaluated as a function of time (0.5 to 14 days) and as a function of single and multiple doses (up to five) of from 5 to 50 mg CPZ per kg body weight. Routes of administration (i.p., i.v., p.o.) were compared. The physiological behavior of CPZ is of interest as it is used extensively as a tranquilizing drug (Thorazine). Further, since CPZ binds to the pigment melanin, the possibility exists of using CPZ to transport diagnostic or therapeutic agents to melanoma. It was found that, at 2 days postinjection, tumor/tissue concentration ratios exceeded 10 for metabolizing organs, such as liver, and 100 for background tissues, such as blood and muscle. Absolute concentrations of CPZ in tumor exceeding 100 μg CPZ per g tumor were obtained with both single and multiple doses. This selective high concentration in tumor would make CPZ an ideal vehicle for the transport of boron to tumor for use in neutron capture therapy via the 10B(n,α)7Li reaction

  15. HAMSTER: visualizing microarray experiments as a set of minimum spanning trees

    Directory of Open Access Journals (Sweden)

    Harada Hajime

    2009-11-01

    Full Text Available Abstract Background Visualization tools allow researchers to obtain a global view of the interrelationships between the probes or experiments of a gene expression (e.g. microarray data set. Some existing methods include hierarchical clustering and k-means. In recent years, others have proposed applying minimum spanning trees (MST for microarray clustering. Although MST-based clustering is formally equivalent to the dendrograms produced by hierarchical clustering under certain conditions; visually they can be quite different. Methods HAMSTER (Helpful Abstraction using Minimum Spanning Trees for Expression Relations is an open source system for generating a set of MSTs from the experiments of a microarray data set. While previous works have generated a single MST from a data set for data clustering, we recursively merge experiments and repeat this process to obtain a set of MSTs for data visualization. Depending on the parameters chosen, each tree is analogous to a snapshot of one step of the hierarchical clustering process. We scored and ranked these trees using one of three proposed schemes. HAMSTER is implemented in C++ and makes use of Graphviz for laying out each MST. Results We report on the running time of HAMSTER and demonstrate using data sets from the NCBI Gene Expression Omnibus (GEO that the images created by HAMSTER offer insights that differ from the dendrograms of hierarchical clustering. In addition to the C++ program which is available as open source, we also provided a web-based version (HAMSTER+ which allows users to apply our system through a web browser without any computer programming knowledge. Conclusion Researchers may find it helpful to include HAMSTER in their microarray analysis workflow as it can offer insights that differ from hierarchical clustering. We believe that HAMSTER would be useful for certain types of gradient data sets (e.g time-series data and data that indicate relationships between cells/tissues. Both

  16. The effect of dietary vitamin A on NO2 exposure on the hamster lung

    International Nuclear Information System (INIS)

    The effect of dietary vitamin A and NO2 exposure on the hamster lung was evaluated by histopathology, electron microscopy, and thymidine uptake studies. Hamsters were maintained on deficient (0 micrograms), adequate (100 micrograms), and high (200 micrograms) dose levels of vitamin A while being exposed repeatedly to 10 ppm of NO2 for 5 hours once a week over an 8-week period. Hamsters of the deficient group exhibited clinical and morphologic changes characteristic of vitamin A deficiency. Animals maintained on adequate and high dose levels of vitamin A were not affected by vitamin A deficiency. Hypertrophy and hyperplasia of the epithelial cells of the terminal bronchiolar alveolar region of lungs of adequately and highly dosed animals were greater than those observed in the deficient animals, when NO2 exposure was given. However, the extent of the lesions observed in all three groups was less than that seen in normal hamsters given a single, 5-hour NO2 exposure. Ultrastructural changes observed in vitamin A-deficient hamsters exposed to NO2 were hypertrophy and hyperplasia of bronchiolar epithelial cells, diffuse loss of cilia, membrane damage, and mitochondrial damage manifested by calcium deposition. Tritiated thymidine uptake studies of lungs of animals exposed repeatedly revealed a rather erratic cell renewal pattern following NO2 exposure in comparison to the group of animals exposed singly

  17. Propagation of Asian isolates of canine distemper virus (CDV in hamster cell lines

    Directory of Open Access Journals (Sweden)

    Yamaguchi Ryoji

    2009-10-01

    Full Text Available Abstract Backgrounds The aim of this study was to confirm the propagation of various canine distemper viruses (CDV in hamster cell lines of HmLu and BHK, since only a little is known about the possibility of propagation of CDV in rodent cells irrespective of their epidemiological importance. Methods The growth of CDV in hamster cell lines was monitored by titration using Vero.dogSLAMtag (Vero-DST cells that had been proven to be susceptible to almost all field isolates of CDV, with the preparations of cell-free and cell-associated virus from the cultures infected with recent Asian isolates of CDV (13 strains and by observing the development of cytopathic effect (CPE in infected cultures of hamster cell lines. Results Eleven of 13 strains grew in HmLu cells, and 12 of 13 strains grew in BHK cells with apparent CPE of cell fusion in the late stage of infection. Two strains and a strain of Asia 1 group could not grow in HmLu cells and BHK cells, respectively. Conclusion The present study demonstrates at the first time that hamster cell lines can propagate the majority of Asian field isolates of CDV. The usage of two hamster cell lines suggested to be useful to characterize the field isolates biologically.

  18. The Influence of Red Wine on Lipid of Golden Hamsters Plasma

    Institute of Scientific and Technical Information of China (English)

    GUO Jin-ying; LI Hua; WANG Hua; YUAN Chun-long; XIE Ren-ming

    2007-01-01

    This experiment was conducted on 50 male golden hamsters, which were divided into five groups. Each group contained 10 hamsters: red wine group, alcohol-free red wine group, alcohol group, hyperlipidemia group, and control group. During the four-week regime, all the hamsters were fed with a high cholesterol diet, except the control group. After completion of the trial, the plasma lipid levels and lipid peroxidation contents were determined in the golden hamsters, and the morphological variation in liver cells was investigated with electron microscopy. The results showed that concentrations of TC and TG in red wine, alcohol-free red wine, and alcohol groups had decreased dramatically. Compared with the hyperlipidemia group, the levels of LDL-C had significantly decreased in other groups, but not the HDL-C. Consumption of red wine,alcohol-free red wine, and alcohol, had no significant effects on Apo A1 and Apo B. Red wine, alcohol-free red wine, and alcohol significantly decreased the contents of MDA in hamsters. The experiment demonstrated that red wine could ameliorate the incidence of atherosclerosis (AS) via reducing serum TC, TG, LDL-C, and the compounds in red wine had synergic effects.

  19. Effects of short photoperiod on energy intake, thermogenesis, and reproduction in desert hamsters (Phodopus roborovskii).

    Science.gov (United States)

    Zhang, Xueying; Zhao, Zhijun; Vasilieva, Nina; Khrushchova, Anastasia; Wang, Dehua

    2015-03-01

    Desert hamsters (Phodopus roborovskii) are the least known species in the genus Phodopus with respect to ecology and physiology, and deserve scientific attention, particularly because of their small body size. Here, the responses of energy metabolism and reproductive function to short photoperiods in desert hamsters were investigated. Male and female desert hamsters were acclimated to either long day (LD) (L:D 16:8 h) or short day (SD) photoperiods (L:D 8:16 h) for three months, and then the females were transferred back to an LD photoperiod for a further five months, while at the end of the SD acclimation the males were killed and measurements were taken for serum leptin as well as molecular markers for thermogenesis. We found that like the other two species from the genus Phodopus, the desert hamsters under SD decreased body mass, increased adaptive thermogenesis as indicated by elevated mitochondrial protein content and uncoupling protein-1 content in brown adipose tissue, and suppressed reproduction compared to those under LD. However, different from the other two species, desert hamsters did not show any differences in energy intake or serum leptin concentration between LD and SD. These data suggest that different species from the same genus respond in different ways to the environmental signals, and the desert adapted species are not as sensitive to change in photoperiod as the other two species. PMID:25311843

  20. Pre-existing Immunity and Passive Immunity to Adenovirus 5 Prevents Toxicity Caused by an Oncolytic Adenovirus Vector in the Syrian Hamster Model

    OpenAIRE

    Dhar, Debanjan; Spencer, Jacqueline F.; Toth, Karoly; Wold, William SM

    2009-01-01

    We have used Syrian hamsters to examine the role of pre-existing immunity to adenovirus (Ad) 5 in the toxicity of the oncolytic Ad vector INGN 007. Groups of hamsters were or were not immunized with Ad5. Half the hamsters were immunosuppressed using cyclophosphamide (CP), then injected intravenously (i.v.) with 3× the maximum tolerated dose (MTD) of INGN 007 (in immunocompetent hamsters), and toxicity and vector replication in the liver were quantitated. In nonimmunized immunocompetent hamste...

  1. Enhanced replication of UV-damaged Simian virus 40 DNA in carcinogen-treated mammalian cells

    International Nuclear Information System (INIS)

    The replication of UV-damaged Simian virus 40 (SV40) in carcinogen-treated monkey cells has been studied to elucidate the mechanism of carcinogen-enhanced reactivation. Carcinogen enhanced reactivation is the observed increase in UV-irradiated virus survival in host cells treated with low doses of carcinogen compared to UV-irradiated virus survival in untreated hosts. Carcinogen treatment of monkey kidney cells with either N-acetoxy-2-acetylaminofluorene (AAAF) or UV radiation leads to an enhanced capacity to replicate UV-damaged virus during the first round of infection. To further define the mechanism leading to enhanced replication, a detailed biochemical analysis of replication intermediates in carcinogen-treated cells was performed. Several conclusions can be drawn. First enhanced replication can be observed in the first four rounds of replication after UV irradiation of viral templates. The second major finding is that the relaxed circular intermediate model proposed for the replication of UV-damaged templates in untreated cells appears valid for replication of UV-damaged templates in carcinogen-treated cells. Possible mechanisms and the supporting evidence are discussed and future experiments outlined

  2. Adapting to alcohol: Dwarf hamster (Phodopus campbelli) ethanol consumption, sensitivity, and hoard fermentation.

    Science.gov (United States)

    Lupfer, Gwen; Murphy, Eric S; Merculieff, Zoe; Radcliffe, Kori; Duddleston, Khrystyne N

    2015-06-01

    Ethanol consumption and sensitivity in many species are influenced by the frequency with which ethanol is encountered in their niches. In Experiment 1, dwarf hamsters (Phodopus campbelli) with ad libitum access to food and water consumed high amounts of unsweetened alcohol solutions. Their consumption of 15%, but not 30%, ethanol was reduced when they were fed a high-fat diet; a high carbohydrate diet did not affect ethanol consumption. In Experiment 2, intraperitoneal injections of ethanol caused significant dose-related motor impairment. Much larger doses administered orally, however, had no effect. In Experiment 3, ryegrass seeds, a common food source for wild dwarf hamsters, supported ethanol fermentation. Results of these experiments suggest that dwarf hamsters may have adapted to consume foods in which ethanol production naturally occurs. PMID:25712038

  3. Blood Vessel Normalization in the Hamster Oral Cancer Model for Experimental Cancer Therapy Studies

    Energy Technology Data Exchange (ETDEWEB)

    Ana J. Molinari; Romina F. Aromando; Maria E. Itoiz; Marcela A. Garabalino; Andrea Monti Hughes; Elisa M. Heber; Emiliano C. C. Pozzi; David W. Nigg; Veronica A. Trivillin; Amanda E. Schwint

    2012-07-01

    Normalization of tumor blood vessels improves drug and oxygen delivery to cancer cells. The aim of this study was to develop a technique to normalize blood vessels in the hamster cheek pouch model of oral cancer. Materials and Methods: Tumor-bearing hamsters were treated with thalidomide and were compared with controls. Results: Twenty eight hours after treatment with thalidomide, the blood vessels of premalignant tissue observable in vivo became narrower and less tortuous than those of controls; Evans Blue Dye extravasation in tumor was significantly reduced (indicating a reduction in aberrant tumor vascular hyperpermeability that compromises blood flow), and tumor blood vessel morphology in histological sections, labeled for Factor VIII, revealed a significant reduction in compressive forces. These findings indicated blood vessel normalization with a window of 48 h. Conclusion: The technique developed herein has rendered the hamster oral cancer model amenable to research, with the potential benefit of vascular normalization in head and neck cancer therapy.

  4. Genomic landscapes of Chinese hamster ovary cell lines as revealed by the Cricetulus griseus draft genome

    DEFF Research Database (Denmark)

    Lewis, Nathan E; Liu, Xin; Li, Yuxiang; Nagarajan, Harish; Yerganian, George; O'Brien, Edward; Bordbar, Aarash; Roth, Anne M; Rosenbloom, Jeffrey; Bian, Chao; Xie, Min; Chen, Wenbin; Li, Ning; Baycin-Hizal, Deniz; Latif, Haythem; Förster, Jochen; Betenbaugh, Michael; Famili, Iman; Xu, Xun; Wang, Jun; Palsson, Bernhard O

    2013-01-01

    Chinese hamster ovary (CHO) cells, first isolated in 1957, are the preferred production host for many therapeutic proteins. Although genetic heterogeneity among CHO cell lines has been well documented, a systematic, nucleotide-resolution characterization of their genotypic differences has been...... stymied by the lack of a unifying genomic resource for CHO cells. Here we report a 2.4-Gb draft genome sequence of a female Chinese hamster, Cricetulus griseus, harboring 24,044 genes. We also resequenced and analyzed the genomes of six CHO cell lines from the CHO-K1, DG44 and CHO-S lineages. This...... analysis identified hamster genes missing in different CHO cell lines, and detected >3.7 million single-nucleotide polymorphisms (SNPs), 551,240 indels and 7,063 copy number variations. Many mutations are located in genes with functions relevant to bioprocessing, such as apoptosis. The details of this...

  5. Stressors, including social conflict, decrease plasma prolactin in male golden hamsters.

    Science.gov (United States)

    Huhman, K L; Mougey, E H; Moore, T O; Meyerhoff, J L

    1995-12-01

    Following exposure to a stressor, plasma prolactin (PRL) rises in most species. The purpose of the present study was to examine the effect of social conflict or of footshock stress on PRL responsiveness in male Syrian hamsters. Contrary to expectations, PRL was significantly lower in subordinate hamsters than in their dominant opponents or in controls following one, five, or nine exposures to social conflict. Similarly, PRL was reduced in hamsters subjected to a mild footshock stressor. By contrast, adrenocorticotropin, another stress-responsive hormone, was elevated following exposure to each of these stressors. We also demonstrate that PRL release is inhibited by dopamine as it is in other species by showing that there is a dose-dependent increase in PRL release following treatment with the dopamine receptor blocker, domperidone. PMID:8748515

  6. X-ray induced dominant lethal mutations in mature and immature oocytes of guinea-pigs and golden hamsters

    International Nuclear Information System (INIS)

    The induction of dominant lethal mutations by doses of 100-400 rad X-rays in oocytes of the guinea-pig and golden hamster was studied using criteria of embryonic mortality. For both species higher yields were obtained from mature than from immature oocytes. Data on fertility indicated that in the golden hamster immature oocytes were more sensitive to killing by X-rays than mature oocytes but that the converse was true in the guinea-pig. The dose-response relationship for mutation to dominant lethals in pre-ovulatory oocytes of guinea-pigs and golden hamsters was linear, both when based on pre- and post-implantation loss only. The rate per unit dose was higher for the golden hamster, and the old golden hamsters were possibly slightly more sensitive than young ones

  7. Gender differences in the metabolism of 1,3-butadiene to butadiene diepoxide in Sprague-Dawley rats

    Energy Technology Data Exchange (ETDEWEB)

    Thornton-Manning, J.R.; Dahl, A.R.; Bechtold, W.E. [and others

    1995-12-01

    1,3-Butadiene (BD), a gaseous compound used in the production of rubber, is a potent carcinogen in mice and a weak carcinogen in rats. The mechanism of BD-induced carcinogenicity is thought to involve genotoxic effects of its reactive epoxide metabolites butadiene monoepoxide (BDO) and butadiene diepoxide (BDO{sub 2}). Studies in our laboratory have shown that levels of the epoxides, particularly BDO{sub 2}, are greater in mice-the more sensitive species-than rats. While both epoxides are genotoxic in a number of assays, BDO{sub 2} is mutagenic in TK6 human lymphoblastoid cells at concentrations approximately 100-fold lower than BDO. Species differences in carcinogenicity of BD have posed a dilemma to investigators deciding which animal model is most appropriate for BD risk assessment.

  8. Reversal of acetaminophen toxicity in isolated hamster hepatocytes by dithiothreitol

    International Nuclear Information System (INIS)

    The toxicity of acetaminophen in freshly isolated hamster hepatocytes was investigated. Cells exposed to 2.5 mM acetaminophen for 90 min, followed by washing to completely remove unbound acetaminophen, and resuspension in fresh buffer, showed a dramatic decrease in viability over the ensuing 4.5 hr by which time only 4% of the cells could still exclude trypan blue. During the initial 90-min incubation, there was a substantial depletion of glutathione, to 19% of control values, covalent binding of [14C]acetaminophen to cellular proteins, and evidence of morphological changes consistent with some disturbance of the plasma membrane. During subsequent incubation of these cells, covalent binding did not change nor did lipid peroxidation, despite the decrease in viability that occurred. Subsequent incubation of cells exposed to acetaminophen for 90 min in buffer containing 1.5 mM dithiothreitol (DTT), a disulfide-reducing agent, largely prevented the decrease in cell viability and reversed the morphological changes that occurred during the first 90-min incubation. However, there was no change in lipid peroxidation, glutathione content, or covalent binding. It is concluded that acetaminophen interacted with some critical target in the cell, and that this left unchecked, led eventually to the death of the cell. DTT prevented and reversed this effect. The toxicity of acetaminophen, and its reversal by DTT, appear independent of either covalent binding of acetaminophen or lipid peroxidation. In addition, the effect of DTT was independent of the concentration of glutathione, most probably acting by directly reducing oxidized SH-groups in critical enzymes, possibly membrane-bound ATP-dependent Ca2+ translocases

  9. A longitudinal study on BIO14.6 hamsters with dilated cardiomyopathy: micro-echocardiographic evaluation

    Directory of Open Access Journals (Sweden)

    Belfiore Maria

    2011-12-01

    Full Text Available Abstract Background In recent years, several new technologies for small-animal imaging have been developed. In particular, the use of ultrasound in animal imaging has focused on the investigation of accessible biological structures such as the heart, of which it provides a morphological and functional assessment. The purpose of this study was to investigate the role of micro-ultrasonography (μ-US in a longitudinal study on BIO14.6 cardiomyopathic hamsters treated with gene therapy. Methods Thirty hamsters were divided into three groups (n = 10: Group I, untreated BIO 14.6 hamsters; Group II, BIO 14.6 hamsters treated with gene therapy; Group III, untreated wild type (WT hamsters. All hamsters underwent serial μ-US sessions and were sacrificed at predetermined time points. Results μ-US revealed: in Group I, progressive dilation of the left ventricle with a change in heart morphology from an elliptical to a more spherical shape, altered configuration of the mitral valve and subvalvular apparatus, and severe reduction in ejection fraction; in Group II, mild decrease in contractile function and ejection fraction; in Group III, normal cardiac chamber morphology and function. There was a negative correlation between the percentage of fibrosis observed at histology and the ejection fraction obtained on μ-echocardiography (Spearman r: -0.839; p Conclusions Although histological examination remains indispensable for a conclusive diagnosis, high-frequency μ-echocardiography, thanks to the high spatial and contrast resolution, can be considered sufficient for monitoring therapeutic efficacy and/or the progression of dilated cardiomyopathy, providing an alternative tool for repeatable and noninvasive evaluation.

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

    Directory of Open Access Journals (Sweden)

    Buonaguro Franco M

    2009-06-01

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

  11. Childhood cancer: Overview of incidence trends and environmental carcinogens

    Energy Technology Data Exchange (ETDEWEB)

    Zahm, S.H.; Devesa, S.S. [National Cancer Inst., Rockville, MD (United States)

    1995-09-01

    An estimated 8000 children 0 to 14 years of age are diagnosed annually with cancer in the United States. Leukemia and brain tumors are the most common childhood malignancies, accounting for 30 and 20% of newly diagnosed cases, respectively. From 1975 to 1978 to 1987 to 1990, cancer among white children increased slightly from 12.8 to 14.1/100,000. Increases are suggested for leukemia, gliomas, and, to a much lesser extent, Wilms` tumor. There are a few well-established environmental causes of childhood cancer such as radiation, chemotherapeutic agents, and diethylstilbestrol. Many other agents such as electromagnetic fields, pesticides, and some parental occupational exposures are suspected of playing roles, but the evidence is not conclusive at this time. Some childhood exposures such as secondhand cigarette smoke may contribute to cancers that develop many years after childhood. For some exposures such as radiation and pesticides data suggest that children may be more susceptible to the carcinogenic effects than similarly exposed adults. 143 refs., 1 fig., 3 tabs.

  12. Urban air carcinogens and their effects on health

    Energy Technology Data Exchange (ETDEWEB)

    Lechner, J.F.

    1994-11-01

    Airborne carcinogens may be relevant especially in metropolitan regions with extreme smog as a primary cause of lung cancer. Lung cancer is most common in urban environs and the incidence directly correlates with the size of the city. In addition, several, but not all formal epidemiological studies also suggest a positive correlation between lung cancer incidence and the intensity of air pollution exposure. There is further support for a role of air pollution; as of 1993, 4.4% of all of the bronchogenic adenocarcinoma cancer cases among Mexicans living in industrialized cities are under 40 years of age. It is plausible that chronic inhalation of automobile combustion products, factory emissions, and/or radon is at least partially responsible for the higher incidence of lung cancer exemplified by the never-smoking urban residents. The exceptionally high incidence of lung cancer cases among never-smokers living in highly industrialized Mexican cities offers a unique opportunity to use molecular epidemiology to test whether chronic inhalation of atmospheric pollutants increases the risk for this disease. Overall, the analysis of the genetic alterations in two cancer genes, and possibly the hprt locus should give new insight as to whether the urban never-smokers developed their cancers because of exposure to environmental pollutants.

  13. [Urban air pollution by carcinogenic N-nitrosamines].

    Science.gov (United States)

    Khesina, A Ia; Krivosheeva, L V; Sokol'skaia, N N; Koliadich, M N

    1996-01-01

    Moscow is used as an example to discuss the problem of urban atmospheric pollution by carcinogenic N-nitrosamines. An analytical method is proposed, which is based on the use of a Russian gas chromatograph compatible with a chemiluminescence detector, that is a TEA thermal energy analyzer (USA) having some modifications to reduce the time of analysis and loss during sample pretreatment. The minimal detected concentration is 3 ng/m3 for 2-hour sampling. The method identifies and quantifies 7 volatile N-nitrosamines: N-nitrosodimethylamine (NDMA), N-nitrosodiethylamine, N-nitrosodibutylamine, N-nitrosodipropylamine, N-nitrosopiperidine, N-nitrosopyrrolidine, N-nitrosomorpholine. The pollution of the Moscow air was evaluated in the center of Moscow (30-60 ng/m3 for NDMA), in the industrial emission area (as high as several hundred ng/m3, and in the heavy traffic area (100 ng/m3 or more). It is proposed to study the working area for rubber and tire industries, to establish nitrosamine tolerances for these industries and maximum allowable discharge concentrations in the urban air and to monitor these parameters. PMID:8672956

  14. Propagation of Asian isolates of canine distemper virus (CDV) in hamster cell lines

    OpenAIRE

    Yamaguchi Ryoji; Ueda Toshiki; Lan Nguyen; Sultan Serageldeen; Maeda Ken; Kai Kazushige

    2009-01-01

    Abstract Backgrounds The aim of this study was to confirm the propagation of various canine distemper viruses (CDV) in hamster cell lines of HmLu and BHK, since only a little is known about the possibility of propagation of CDV in rodent cells irrespective of their epidemiological importance. Methods The growth of CDV in hamster cell lines was monitored by titration using Vero.dogSLAMtag (Vero-DST) cells that had been proven to be susceptible to almost all field isolates of CDV, with the prep...

  15. Effect of trimetazidine and verapamil on the cardiomyopathic hamster myosin phenotype

    OpenAIRE

    D'hahan, Nathalie; Taouil, Karima; Janmot, Chantal; Morel, Jean-Emile

    1998-01-01

    In this study we investigated whether long-term trimetazidine (anti-ischaemic drug) therapy alters the ventricular myosin heavy chain (MHC) isoform composition in a model of cardiomyopathy.MHC isoforms were analysed in the native state by electrophoresis in a pyrophosphate buffer. Myosin isoform patterns were studied in cardiac muscle from cardiomyopathic hamsters (CMH) of the BIO 14 : 6 strain during the time course of the disease and compared with those of healthy golden hamsters (F1B). The...

  16. Use of vital dyes to assess embryonic viability in the hamster, Mesocricetus auratus

    International Nuclear Information System (INIS)

    Experiments were designed to assess the use of the vital dyes trypan blue and fluorescein diacetate as indicators of the viability of hamster ova and embryos. Exclusion of trypan blue and fluorescence with fluorescein diacetate showed high correlations with uptake of [3H]uridine by ova and further development of embryos in vitro. Ova killed by freezing and thawing incorporated [3H]uridine at background levels. Trypan blue exclusion and fluorescein diacetate uptake were highly correlated with each other (r = 0.99). Trypan blue and fluorescein diacetate serve as excellent indices of viability in ova and early embryos of hamsters

  17. Boron neutron capture therapy for the treatment of oral cancer in the hamster cheek pouch model

    International Nuclear Information System (INIS)

    We have proposed and validated the hamster cheek pouch model of oral cancer for BNCT studies separately. We herein report the first evidence of the usefulness of BNCT for the treatment of oral cancer in an experimental model. We assessed the response of hamster cheek pouch tumors, precancerous tissue and normal oral tissue to BPA-mediated BNCT employing the thermalized epithermal beam of the RA-6 Reactor at the Bariloche Atomic Center. BNCT leads to complete remission by 15 days post-treatment in 78% of tumors and partial remission in a further 13% of tumors with virtually no damage to normal tissue. (author)

  18. Elk3 from hamster-a ternary complex factor with strong transcriptional repressor activity

    DEFF Research Database (Denmark)

    Hjortoe, G.M.; Weilguny, D.; Willumsen, Berthe Marie

    2005-01-01

    transcription of genes that are activated during entry into G1. We have isolated the Cricetulus griseus Elk3 gene from the Chinese hamster ovary (CHO) cell line and investigated the transcriptional potential of this factor. Transient transfections revealed that, in addition to its regulation of the c......-fos promoter, Elk3 from CHO cells seems to inhibit other promoters controlling expression of proteins involved in G1/S phase progression; Cyclin D1 and DHFR. As has been described for the Elk3 homologs Net (Mouse) and Sap-2 (Human), the results of the present study further indicate that hamster Elk3 is a...

  19. Central vasopressin infusion prevents hibernation in the European hamster (Cricetus cricetus)

    OpenAIRE

    Hermes, M.L.H.J.; Buijs, R M; Masson-Pévet, M.; Woude, T.P. van der; PÉVET, P.; Brenkle, R.; Kirsch, R.

    1989-01-01

    The amount of immunocytochemically detectable vasopressin in the brain of the European hamster (Cricetus cricetus) shows a seasonal variation; i.e., dense vasopressin immunoreactivity is present in the lateral septum during summer but is absent in autumn and winter [Buijs, R. M., Pévet, P., Masson-Pévet, M., Pool, C. W., De Vries, G. J., Canguilhem, B. & Vivien-Roels, B. (1986) Brain Res. 371, 193-196]. In the winter period the European hamster hibernates. Since vasopressin in the lateral sep...

  20. Inhibition of cholesterol ester transfer protein CGS 25159 and changes in lipoproteins in hamsters.

    Science.gov (United States)

    Kothari, H V; Poirier, K J; Lee, W H; Satoh, Y

    1997-01-01

    As a result of screening, several isoflavans were identified to be antagonists of cholesterol ester transfer protein (CETP) activity. The present study evaluates CGS 25159, a synthetic isoflavan, as a putative inhibitor of CETP activity of human and hamster plasma. Determined by [3]CE transfer from HDL to VLDL + LDL fraction or by fluorescent-CE transfer assay, CGS 25159 inhibited CETP in both human plasma bottom fraction (d = 1.21 g/ml) and in plasma from Golden Syrian Hamsters with an IC50 contention that pharmacological down regulation of CETP activity could result in favorable changes in lipoprotein profile. PMID:9051198

  1. Histochemical study of brown-fat cells in the golden hamster (Mesocricetus auratus) in cultures

    International Nuclear Information System (INIS)

    The authors undertake the task of studying the synthesis of certain hormones by brown-fat cells. The authors used brown-fat cells from the golden hamster. The metabolism of brown-fat cells was studied on precultured cells, which made it possible to detect the synthesis of the studied substances rather than their accumulation in the organ. The authors conducted three experiments. First, fragments of brown fat were cultivated in diffusion chambers in vivo. Pieces of brown fat were cultivated in parallel in vitro on agar (organotypic cultures) and on plasma (histotypic cultures). During cultivation in diffusion chambers, the chambers were implanted in the abdominal cavity of young white rats. For in vitro cultivation, TCM 199 plus 15-20% calf serum was used. A total of 36 cultures with 12 cultures in each series of experiments were performed. The auto-radiographic studies of brown-fat cells were conducted on 24-hour cultures and on brown-fat fragments taken from the intact animal. The cultures were incubated with isotopes for 1 h. Either [3H]lysine (87.3 Ci/mM specific activity), [3H]arginine (16.7 Ci/mM), [3H]glycerol (43 Ci/mM), or [3H]cholesterol (43 Ci/mM) were added to the medium. After incubation, the cultures were washed three times in pure medium, fixed in Sierra fluid, and embedded in paraffin. The paraffin sections were covered with Ilford K2 emulsion, and the preparations were exposed for 20 days at 40C temperature. Radio-immunological methods were used to study the accumulation of estradiol-17-beta in the culture medium by the Dobson method and that of testerone. The culture medium was taken on cultivation days 2,4,6,8, and 10. The medium was changed during cultivation every third day, which made it possible to judge the rates of accumulation of material with increase in the cultivation times

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

    Science.gov (United States)

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

    2012-08-01

    Oxyfluorfen is a herbicide that is not genotoxic and produces liver toxicity in rodents, following repeated administration at high dose levels. Lifetime rodent feeding studies reported in 1977 with low-purity oxyfluorfen (85%) showed no increase in any tumor type in rats (800 ppm, high dose) and only a marginally increased incidence of hepatocellular tumors in male CD-1 mice at the highest dose (200 ppm). To evaluate the potential carcinogenicity of the currently registered oxyfluorfen (> 98% purity), we conducted a series of short-term liver mode of action (MOA) toxicology studies in male CD-1 mice administered dietary doses of 0, 40, 200, 800, and 1600 ppm for durations of 3, 7, 10, or 28 days. MOA endpoints examined included liver weight, histopathology, cell proliferation, nuclear receptor-mediated gene expression, and other peroxisome proliferator-specific endpoints and their reversibility. Minimal liver effects were observed in mice administered doses at or below 200 ppm for up to 28 days. Increased liver weight, single-cell necrosis, cell proliferation, and peroxisomal acyl-CoA oxidase (ACO) were observed at 800 ppm after 28 days, but there was no increase in peroxisomes. Expression of Cyp2b10 and Cyp4a10 transcripts, markers of constitutive androstane receptor and peroxisome proliferator activated receptor α nuclear receptor activation, respectively, were increased at 800 and 1600 ppm after 3 or 10 days. Collectively, these data along with the negative genotoxicity demonstrate that oxyfluorfen (> 98% purity) has the potential to induce mouse liver tumors through a nongenotoxic, mitogenic MOA with a clear threshold and is not predicted to be carcinogenic in humans at relevant exposure levels. PMID:22539621

  3. Post-initiation chlorophyllin exposure does not modulate aflatoxin-induced foci in the liver and colon of rats

    Directory of Open Access Journals (Sweden)

    Orner Gayle A

    2006-02-01

    Full Text Available Abstract Chlorophyllin (CHL is a promising chemopreventive agent believed to block cancer primarily by inhibiting carcinogen uptake through the formation of molecular complexes with the carcinogens. However, recent studies suggest that CHL may have additional biological effects particularly when given after the period of carcinogen treatment. This study examines the post-initiation effects of CHL towards aflatoxin B1 (AFB1-induced preneoplastic foci of the liver and colon. The single concentration of CHL tested in this study (0.1% in the drinking water had no significant effects on AFB1-induced foci of the liver and colons of rats.

  4. Genotoxic and non-genotoxic effects in rat liver epithelial cells exposed to carcinogenic PAHs

    Czech Academy of Sciences Publication Activity Database

    Topinka, Jan; Sevastyanova, Oksana; Marvanová, S.; Vondráček, Jan; Nováková, Zuzana; Milcová, Alena; Krčmář, P.; Pěnčíková, K.; Machala, M.

    Basel, 2007. s. 157. [European Environmental Mutagen Society, 37th Annual Meeting - 2007. 09.09.2007-13.09.2007, Basel] R&D Projects: GA AV ČR(CZ) KJB6004407 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702; CEZ:AV0Z50390512; CEZ:AV0Z50390703 Keywords : DNA adducts * cell proliferation * apoptosis Subject RIV: BO - Biophysics

  5. Mutagens and carcinogens - Occurrence and role during chemical and biological evolution

    Science.gov (United States)

    Giner-Sorolla, A.; Oro, J.

    1981-01-01

    The roles of mutagenic and carcinogenic substances in early biologic evolution is examined, along with terrestrial and extraterrestrial sources of mutagens and carcinogens. UV solar radiation is noted to have served to stimulate prebiotic life while also causing harmful effects in plants and animals. Aromatic compounds have been found in meteorites, and comprise leukemogens, polycyclic hydrocarbons, and nitrasamine precursors. Other mutagenic sources are volcanoes, and the beginning of evolution with mutagenic substances is complicated by the appearance of malignancies due to the presence of carcinogens. The atmosphere of the Precambrian period contained both mutagens and early carcinogens and, combined with volcanic activity discharges, formed an atmospheric chemical background analogous to the background ionizing radiation. Carcinogenesis is concluded to be intrinsic to nature, having initiated evolution and, eventually, cancer cells.

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

    NARCIS (Netherlands)

    Lierop, van J.B.H.

    1979-01-01

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

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

    Science.gov (United States)

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

  8. An investigation of carcinogenic agents at the Mississippi Sandhill Crane National Wildlife Refuge

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This report summarizes a study with the following results: 1. Three of the metals reported as carcinogens, arsenic, chromium, and nickel, were found within the...

  9. 78 FR 15020 - Report on Carcinogens Webinar on Pentachlorophenol; Notice of Public Webinar and Registration...

    Science.gov (United States)

    2013-03-08

    ... HUMAN SERVICES National Institutes of Health Report on Carcinogens Webinar on Pentachlorophenol; Notice of Public Webinar and Registration Information SUMMARY: The National Toxicology Program (NTP) announces a public webinar, ``Human cancer studies on exposure to pentachlorophenol (PCP):...

  10. Carcinogenicity prediction of noncongeneric chemicals by augmented top priority fragment classification.

    Science.gov (United States)

    Casalegno, Mosè; Sello, Guido

    2016-04-01

    Carcinogenicity prediction is an important process that can be performed to cut down experimental costs and save animal lives. The current reliability of the results is however disputed. Here, a blind exercise in carcinogenicity category assessment is performed using augmented top priority fragment classification. The procedure analyses the applicability domain of the dataset, allocates in clusters the compounds using a leading molecular fragment, and a similarity measure. The exercise is applied to three compound datasets derived from the Lois Gold Carcinogenic Database. The results, showing good agreement with experimental data, are compared with published ones. A final discussion on our viewpoint on the possibilities that the carcinogenicity modelling of chemical compounds offers is presented. PMID:26878128

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

    Science.gov (United States)

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

    2015-04-01

    Carcinogen contaminations in the food chain, for example heavy metal ions, pesticides, acrylamide, and mycotoxins, have caused serious health problems. A major objective of food-safety research is the identification and prevention of exposure to these carcinogens, because of their impossible-to-reverse tumorigenic effects. However, carcinogen detection is difficult because of their trace-level presence in food. Thus, reliable and accurate separation and determination methods are essential to protect food safety and human health. This paper summarizes the state of the art in separation and determination methods for analyzing carcinogen contamination, especially the advances in biosensing methods. Furthermore, the application of promising technology including nanomaterials, imprinted polymers, and microdevices is detailed. Challenges and perspectives are also discussed. PMID:25694149

  12. 78 FR 57868 - Nominations to the Report on Carcinogens; Request for Information

    Science.gov (United States)

    2013-09-20

    ... RoC. 20 Substances Nominated to the RoC* Aloe vera whole leaf extract (Aloe barbadensis Miller) 2..., ongoing, or planned studies related to evaluating carcinogenicity; (3) scientific issues important...

  13. Occupational toxicants. Critical data evaluation for MAK values and classification of carcinogens. Vol. 4

    International Nuclear Information System (INIS)

    33 occupational toxicants are reviewed. Data are presented according to toxic effects in animals and man, mode of action, carcinogenicity, genotoxicity, reproductive and development toxicity, and MAK value. (MG)

  14. Biomarkers for assessing potential carcinogenic effects of chronic arsenic exposure in Inner Mongolia, CHINA

    Science.gov (United States)

    Arsenic is ubiquitous in the environment. Chronic arsenic exposure via drinking water has been associated. with carcinogenic, cardiovascular, neurological and diabetic effects in humans and has been of great public health concern worldwide. In 2001, U.S. Environmental Protection ...

  15. An Analysis of the Role of Tobacco-Specific Nitrosamines in the Carcinogenicity of Tobacco Smoke

    OpenAIRE

    Brown, Buddy G.; Borschke, August J.; Doolittle, David J.

    2003-01-01

    Cigarette smoke is a complex mixture consisting of more than 4500 chemicals, including several tobacco-specific nitrosamines (TSNA). TSNA typically form in tobacco during the post-harvest period, with some fraction being transferred into mainstream smoke when a cigarette is burned during use. The most studied of the TSNA is 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). NNK has been shown to be carcinogenic in laboratory animals. Studies examining the carcinogenicity of NNK frequently ...

  16. Perturbation of Mitosis through Inhibition of Histone Acetyltransferases: The Key to Ochratoxin A Toxicity and Carcinogenicity?

    OpenAIRE

    Czakai, Kristin; Müller, Katja; Mosesso, Pasquale; Pepe, Gaetano; Schulze, Markus; Gohla, Antje; Patnaik, Debasis; Dekant, Wolfgang; Higgins, Jonathan M.G.; Mally, Angela

    2011-01-01

    Ochratoxin A (OTA) is one of the most potent rodent renal carcinogens studied to date. Although controversial results regarding OTA genotoxicity have been published, it is now widely accepted that OTA is not a mutagenic, DNA-reactive carcinogen. Instead, increasing evidence from both in vivo and in vitro studies suggests that OTA may promote genomic instability and tumorigenesis through interference with cell division. The aim of the present study was to provide further support for disruption...

  17. Recent developments in the multistage modeling of cohort data for carcinogenic risk assessment.

    OpenAIRE

    Mazumdar, S; Redmond, C K; Costantino, J P; Patwardhan, R N; Zhou, S. Y.

    1991-01-01

    The modeling of cohort data based on the Armitage-Doll multistage model of the carcinogenic process has gained popular acceptance as a methodology for quantitative risk assessment for estimating the dose-related relationships between different occupational and environmental carcinogenic exposures and cancer mortality. The multistage model can be used for extrapolation to low doses relevant for setting environmental standards and also provides information regarding whether more than one stage ...

  18. A review of the genotoxic and carcinogenic effects of aspartame: does it safe or not?

    OpenAIRE

    Yılmaz, Serkan; Uçar, Aslı

    2014-01-01

    The objective of this article is to review genotoxicologic and carcinogenic profile of the artificial sweetener aspartame. Aspartame is a synthetic dipeptide, nearly 180–200 times sweeter than sucrose. It is the most widely used artificial sweetener especially in carbonated and powdered soft drinks, beverages, drugs and hygiene products. There is a discussion ongoing for many years whether aspartame posses genotoxic and carcinogenic risk for humans. This question led to many studies to specif...

  19. In vivo transgenic bioassays and assessment of the carcinogenic potential of pharmaceuticals.

    OpenAIRE

    Contrera, J F; DeGeorge, J J

    1998-01-01

    There is general agreement in the scientific community on the need to improve carcinogenicity testing and the assessment of human carcinogenic risk and to incorporate more information on mechanisms and modes of action into the risk assessment process. Advances in molecular biology have identified a growing number of genes such as protooncogenes and tumor-suppressor genes that are highly conserved across species and are associated with a wide variety of human and animal cancers. In vivo transg...

  20. Analysis of carcinogenicity testing for regulatory purposes in the European Union

    OpenAIRE

    MADIA FEDERICA; Worth, Andrew; Corvi, Raffaella

    2016-01-01

    The approaches for evaluating the carcinogenic potential of substances, including whether carcinogenicity studies should be conducted, differ substantially across sectors. Despite variations in testing schemes, the two-year bioassay study in rodents represents the standard element across all sectors. The validity of the two-year bioassay though has been questioned in the last decade. Uncertainty is associated with the extrapolation of data from rodents to humans. Furthermore, these stud...