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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. Carcinogenicity of azo dyes: Acid Black 52 and Yellow 3 in hamsters and rats. Volume 2. Technical report (Final)

    Energy Technology Data Exchange (ETDEWEB)

    Plankenhorn, L.J.

    1983-09-30

    This document is an appendix to a study concerning the carcinogenicity of the azo dyes acid-black-52 and yellow-3 in male and female hamsters and rats and contains individual histopathology studies of both dyes. Histopathological features were reported in tabular form for the skin, mammary gland, muscle, salivary gland, mandibular lymph node, sciatic nerve, thymus, larynx, thyroid, parathyroid, trachea, bronchus, esophagus, adrenal, stomach, duodenum, jejunem, ileum, cecum, colon, rectum, mesenteric lymph node, lung, liver, gallbladder, spleen, pancreas, kidney, heart, urinary bladder, seminal vesicle, prostate, testis, cerebrum, cerebellum, pituitary, sternabrae, femur, bone marrow, and nasal cavity.

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

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    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.

  4. The effect of vitamin C on the hamster cheek pouch treated with the water soluble carcinogen 4-nitroquinoline-1-oxide (4NQO).

    Science.gov (United States)

    Kandarkar, S V; Sawant, S S

    1996-07-01

    Vitamin C is an essential nutrient whose protective influence is carcinogenesis has been reported frequently, suggesting that vitamin C inhibits the formation of some carcinogens and decreases the incidence and delays of the neoplastic lesions. However, the mechanisms by which this occurs are unknown. In this study, the water soluble carcinogen 4-nitroquinoline-1-oxide (4NQO) has been used to induce a high yield of tumours in the oral cavity either singly or in combination with tobacco. Since the mucosa of rats is less susceptible to carcinogens than the hamster cheek pouch, the hamster cheek pouch has been used to study the influence of vitamin C on 4NQO-induced oral malignancy. The aim of this study was to determine whether topically applied vitamin C had an effect on the oral carcinogenesis induced by application of 4NQO. Similarly, an attempt was made to study the modulating effect of vitamin C on the histopathological and ultrastructural changes during the neoplastic process in the hamster. Vitamin C appeared to delay tumour induction and had other protective effects against neoplasia. PMID:8776418

  5. N-nitrosodiethanolamine: analysis, formation in tobacco products and carcinogenicity in Syrian golden hamsters

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    Hoffmann, D.; Brunnemann, K.D.; Rivenson, A.; Hecht, S.S.

    1982-01-01

    An analytical GC-TEA method has been developed for the quantitative determination of N-nitrosodiethanolamine (NDELA) in tobacco and tobacco smoke. US smoking and chewing tobaccos and experimental cigarette tobaccos contained between 80 and 420 micrograms/kg of NDELA. Two snuff samples contained 3200 and 6800 micrograms/kg of NDELA. NDELA in mainstream smoke of US cigarettes amounted to 10 - 68 ng per cigarette. Evidence was presented which incriminates diethanolamine as a major precursor for NDELA in tobacco and tobacco smoke. Diethanolamine is used as a solubilizing agent for maleic hydrazide, the major sucker-growth inhibitor for US tobacco crops. NDELA was bioassayed in Syrian golden hamsters by skin painting, swabbing of the oral cavity and by subcutaneous injection. Independently of the form of application, NDELA at the higher dose (500 mg/kg) induced carcinomas of the nasal cavity, papillomas of the trachea and tumours of the larynx in some animals. NDELA uptake through the oral cavity in hamsters is presumably greater than through the skin, judging by the higher tumour yield induced by painting of the oral cavity, compared to skin painting. Studies with 14C-labeled NDELA are currently underway to document this observation quantitiatively. The present analytical data for NDELA in tobacco and tobacco smoke, together with the carcinogenicity data reported here and elsewhere, strongly suggest a review of the use of maleic hydrazide-diethanolamine as sucker-growth inhibitor in the cultivation of tobacco and other crops.

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

    Science.gov (United States)

    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 compounds to identify processes that occur in common between alachlor- and butachlor-treated rats. Because we have previously shown that matrix metalloproteinase-2 (MMP2) is activated in OM by alachlor, in the present studies we evaluated both MMP2 activation and changes in OM gene expression in response to carcinogenic and non-carcinogenic chloracetanilide treatments. All three chloracetanilides activated MMP2, and > 300 genes were significantly up- or downregulated between control and alachlor-treated rats. The most significantly regulated gene was vomeromodulin, which was dramatically upregulated by alachlor and butachlor treatment (>60-fold), but not by propachlor treatment. Except for similar gene responses in alachlor- and butachlor-treated rats, we did not identify clear-cut differences that would predict OM carcinogenicity in this study. PMID:19425180

  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. Bioavailability and disposition of solanine in rats and hamsters

    NARCIS (Netherlands)

    Groen K; Pereboom-de Fauw DPKH; Besamusca P; Beekhof PK; Speijers GJA; Derks HJGM

    1992-01-01

    The toxicokinetics of [3H]-alpha-solanine after oral (po) and intravenous (iv) administration in rats and hamsters were studied, in order to decide which is the most appropriate model in risk assessment studies. The iv dose was 54 mug/kg; the oral dose was 170 mug/kg. After iv administration, the

  9. Carcinogenic risk of copper gluconate evaluated by a rat medium-term liver carcinogenicity bioassay protocol

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    Abe, Masayoshi; Usuda, Koji; Hayashi, Seigo; Ogawa, Izumi; Furukawa, Satoshi [Nissan Chemical Industries Limited, Toxicology and Environmental Science Department, Biological Research Laboratories, Saitama (Japan); Igarashi, Maki [Tokyo University of Agriculture, Laboratory of Protection of Body Function, Department of Food and Nutritional Science, Graduate School of Agriculture, Tokyo (Japan); Nakae, Dai [Tokyo University of Agriculture, Laboratory of Protection of Body Function, Department of Food and Nutritional Science, Graduate School of Agriculture, Tokyo (Japan); Tokyo Metropolitan Institute of Public Health, Tokyo (Japan)

    2008-08-15

    Carcinogenic risk and molecular mechanisms underlying the liver tumor-promoting activity of copper gluconate, an additive of functional foods, were investigated using a rat medium-term liver carcinogenicity bioassay protocol (Ito test) and a 2-week short-term administration experiment. In the medium-term liver bioassay, Fischer 344 male rats were given a single i.p. injection of N-nitrosodiethylamine at a dose of 200 mg/kg b.w. as a carcinogenic initiator. Starting 2 weeks thereafter, rats received 0, 10, 300 or 6,000 ppm of copper gluconate in diet for 6 weeks. All rats underwent 2/3 partial hepatectomy at the end of week 3, and all surviving rats were killed at the end of week 8. In the short-term experiment, rats were given 0, 10, 300 or 6,000 ppm of copper gluconate for 2 weeks. Numbers of glutathione S-transferase placental form (GST-P) positive lesions, single GST-P-positive hepatocytes and 8-oxoguanine-positive hepatocytes, and levels of cell proliferation and apoptosis in the liver were significantly increased by 6,000 ppm of copper gluconate in the medium-term liver bioassay. Furthermore, hepatic mRNA expression of genes relating to the metal metabolism, inflammation and apoptosis were elevated by 6,000 ppm of copper gluconate both in the medium-term liver bioassay and the short-term experiments. These results indicate that copper gluconate possesses carcinogenic risk toward the liver at the high dose level, and that oxidative stress and inflammatory and pro-apoptotic signaling statuses may participate in its underlying mechanisms. (orig.)

  10. Toxicology and metabolism of nickel compounds. Progress report, December 1, 1978-November 30, 1979. [Hamsters and rats

    Energy Technology Data Exchange (ETDEWEB)

    Sunderman, F.W. Jr.

    1979-08-15

    The toxicology and metabolism of nickel compounds were investigated in rats and hamsters. The new knowledge includes; demonstration that nickel carbonyl is teratogenic for hamsters; elucidation of physiological factors which influence ..cap alpha..Ni/sub 3/S/sub 2/-induced erythrocytosis in rats; development of a sensitive assay for heme oxygenase activity in renal microsomes for use in studies of renal effects of nickel compounds; demonstration that administration of Ni(CO)/sub 4/ to rats inhibits incorporation of /sup 3/H-thymidine into DNA during hepatic regeneration; demonstration that clones of Syrian hamster fetal cells which have been transformed by in vitro exposure to ..cap alpha..Ni/sub 3/S/sub 2/ consistently cause sarcomas following sc injection into nude mice; demonstration that nickel carbonyl-cyclopentadiene dimer induces rhabdomyosarcomas following im injection in rats; observation of differences in carcinogenic activities of several insoluble nickel compounds; discovery that intraocular injection of ..cap alpha..Ni/sub 3/S/sub 2/ induces amelanotic melanomas in rats; and refinement of analytical methods for nickel in biological materials.

  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. Carboxylesterases in the respiratory tracts of rabbits, rats and Syrian hamsters.

    Science.gov (United States)

    Dahl, A R; Miller, S C; Petridou-Fischer, J

    1987-04-01

    Esters are a widespread class of organic compounds found both in industry and the environment. Because esters are often volatile and, therefore, readily inhaled, the capacity of respiratory tract tissues as well as liver S-9 homogenates from rats, rabbits, and Syrian hamsters to hydrolyze a variety of esters was investigated. A new technique to determine hydrolysis rates by measuring carboxylic acid residues using ion chromatography was proven effective. The results indicated that esters, including potentially carcinogenic beta-lactones, are readily hydrolyzed by respiratory tract enzymes. Species and tissue differences were apparent. The nasal ethmoturbinates had especially high levels of esterase activity with tissue weight-normalized activities from rabbits and hamsters for most substrates exceeding all other tissues tested, including liver. Phenyl acetate was the most rapidly hydrolyzed by ethmoturbinate tissue of the esters tested. Among straight chain aliphatic alcohol acetates, hydrolysis rates increased with carbon number up to pentyl alcohol and then decreased. Branched 4-carbon alcohol acetates were less rapidly hydrolyzed than n-butyl acetate. Correlation of hydrophobicity constants with hydrolysis rates indicated that, for the straight chain aliphatic acetates, a bilinear model best fit the data. PMID:3576643

  14. Bioavailability and disposition of 3H-solanine in rat and hamster.

    Science.gov (United States)

    Groen, K; Pereboom-de Fauw, D P; Besamusca, P; Beekhof, P K; Speijers, G J; Derks, H J

    1993-09-01

    1. The toxicokinetics of [3H]-alpha-solanine after oral (p.o.) and intravenous (i.v.) administration in rat and hamster were studied, in order to decide which is the most appropriate model in risk assessment studies. The i.v. dose was 54 micrograms/kg; the oral dose was 170 micrograms/kg. 2. After i.v. administration, the toxicokinetics of total radioactivity in blood were comparable in rat and hamster. However, the clearance of total radioactivity from plasma was more effective in rat than in hamster. The half-lives of distribution and of the terminal phase of unchanged alpha-solanine were not different between rat and hamster, whereas the systemic and metabolic clearance were, respectively, about 1.6 and 2.7 times higher in rat than in hamster. The clearance of unchanged alpha-solanine is more effective than of total radioactivity. 3. After p.o. administration in rat and hamster, the mean bioavailability of total radioactivity is about 29 and 57%, respectively. The bioavailability of unchanged alpha-solanine is only 1.6 and 3.2%, respectively, when compared with i.v. administration. 4. T1/2el of alpha-solanine after p.o. administration was in rats a factor of four and in hamsters a factor of two shorter than after i.v. administration. A strong retention of radioactivity was seen in the hamsters after p.o. administration; only 40% of the dose was excreted within 7 days versus 90% in rat. 5. Based on these and toxicological data from literature, it was decided that the hamster is a more appropriate model in (sub)-chronic toxicity studies with alpha-solanine than the rat.

  15. 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,...

  16. In vitro metabolism of cannabinol in rat, mouse, rabbit, guinea pig, hamster, gerbil and cat.

    Science.gov (United States)

    Brown, N K; Harvey, D J

    1990-01-01

    Metabolism of cannabinol (CBN) was studied in hepatic microsomal incubates from mouse, rat, rabbit, guinea pig, cat, hamster and gerbil. Metabolites were extracted with ethyl acetate, concentrated by chromatography on Sephadex LH-20 and identified by GC/MS as TMS derivatives. Six monohydroxy metabolites were identified. These had hydroxy groups at C-11 and at all positions of the pentyl side-chain. Metabolism varied considerably between the species. 11-Hydroxylation was the most prominent route in the majority of species, but in the hamster and cat the major metabolic pathway was 4'-hydroxylation. Metabolites hydroxylated in the pentyl chain were generally more abundant in guinea pig, hamster and cat. PMID:2253656

  17. Comparison of Pavlovian serial conditional discrimination in rats and hamsters in the same experimental situation

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    J.L.O. Bueno

    2001-12-01

    Full Text Available The present study compares behavioral changes between two distinct rodent groups, hamsters (Mesocricetus auratus and Wistar rats, when submitted in the same homogeneous experimental situations to a serial conditional discrimination procedure which involves water deprivation and the processing of temporal variables. Both hamsters and rats acquired serial positive conditional discrimination as indicated by higher frequencies of magazine-oriented behavior during the tone followed by reinforcement (T+ and preceded by the feature stimulus light (L and during the empty interval, than during the tone alone not followed by reinforcement (T-. Rats' frequencies of magazine-oriented behavior were high during T+ and T-, initially during training, and decreased during T- as the training progressed. However, the hamsters' frequencies of magazine-oriented behavior started very low and increased only during T+ as the training progressed. Comparison of the frequencies of magazine-oriented behavior during the empty interval in relation to the frequencies during the preceding L period showed that rats' frequencies remained very high and hamsters' frequencies increased during training. These results suggest that rats and hamsters have different behavioral strategies for the acquisition of a conditional discrimination. The results of the comparisons made in these experiments support the view of the importance of an ecological psychology approach to the understanding of complex learning in animals.

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

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    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

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    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. 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

  4. 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

  5. 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.

  6. 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.

  7. Two-year carcinogenicity study of acrylamide in Wistar Han rats with in utero exposure.

    Science.gov (United States)

    Maronpot, R R; Thoolen, R J M M; Hansen, B

    2015-02-01

    Acrylamide is an important chemical with widespread industrial and other uses in addition to generalized population exposure from certain cooked foods. Previous rat studies to assess the carcinogenic potential of acrylamide have been carried out exclusively in the Fischer 344 rat with identification of a number of tumors amongst which mesotheliomas of the tunica vaginalis is an important tumor endpoint in the classification of acrylamide as a 'probably human carcinogen. In a rat carcinogenicity study to determine the human relevance of mesotheliomas Wistar Han rats were exposed to 0, 0.5, 1.5, or 3.0mg acrylamide/kg body weight/day in drinking water starting at gestation day 6. At the end of two years, mammary gland fibroadenomas in females and thyroid follicular cell tumors in both sexes were the only tumors increased in acrylamide treated rats. These tumor endpoints have rat-specific modes of action suggesting less likelihood of human cancer risk than previously estimated. This study demonstrates that tunica vaginalis mesotheliomas are strain specific and not likely of genotoxic origin.

  8. 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

  9. 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.)

  10. INHIBITION OF IN VITRO FERTILIZATION IN THE HAMSTER BY ANTIBODIES RAISED AGAINST THE RAT SPERM PROTEIN SP22

    Science.gov (United States)

    INHIBITION OF IN VITRO FERTILIZATION IN THE HAMSTER BY ANTIBODIES RAISED AGAINST THE RAT SPERM PROTEIN SP22. SC Jeffay*, SD Perreault, KL Bobseine*, JE Welch*, GR Klinefelter, US EPA, Research Triangle Park, NC. SP22, a rat sperm membrane protein that is highly-correlated w...

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

    Science.gov (United States)

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

    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.

  12. 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...

  13. 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...

  14. 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

  15. The carcinogenicity of certain derivatives of p-dimethylaminozobenz in the rat.

    Science.gov (United States)

    MILLER, J A; MILLER, E C

    1948-02-01

    1. Eighteen known or possible metabolites of the hepatic carcinogen 4- (or p-) dimethylaminoazobenzene were tested for carcinogenic activity in the rat. Of these compounds only 4-monomethylaminoazobenzene, a known metabolite, proved to be active. Eight compounds, which appear to be metabolites of the dye, were inactive; these included 4-aminoazobenzene, 4'-hydroxy-4-monomethylaminoazobenzene, 4'-hydroxy-4-aminoazobenzene, N-methyl-p-phenylenediamine, p-phenylenediamine, aniline, p-aminophenol, and o-aminophenol. Nine compounds which may possibly be metabolites also were inactive; these compounds were 4'-hydroxy-, 3'-hydroxy-, and 2'-hydroxy-4-dimethylaminoazobenzene, 4-formylaminoazobenzene, 4-hydroxyazobenzene, 2, 4'-diamino-5-dimethylaminodiphenyl, 3-dimethylaminocarbazole, N,N-dimethyl-p-phenylenediamine, and p-hydroquinone. A mixture of 9 known and possible metabolites was also found to be inactive. These data indicate that the primary carcinogen operative in tumor formation by 4-dimethylaminoazobenzene is probably an azo dye closely related to the parent carcinogen. This conclusion is supported by recent work from this laboratory which indicates that the primary carcinogen consists of either or both of the protein-bound dyes found in the liver, i.e. 4-monomethylaminoazobenzene and an unidentified polar aminoazo dye, and that the formation of bound dye constitutes one of the first steps in this carcinogenic process. 2. The carcinogenic activities of 19 other compounds related to 4-dimethyl-aminoazobenzene were tested to obtain more information on the structural features needed for a 4-aminoazo dye to possess strong activity in the rat. 3'-Methyl-4-monomethylaminoazobenzene and the corresponding dimethylamino derivative were nearly twice as active and 4-ethylmethylaminoazobenzene had the same activity as 4-dimethylaminoazobenzene. As tested 3'-nitro- and 3'-chloro-4-dimethylaminoazobenzene both had about the same activity as 4-dimethylaminoazobenzene; however

  16. 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

  17. 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

  18. 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

    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...

  19. 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

  20. Investigation on the carcinogenic effects of coal tar pitch in rat respiratory tract by intratracheal instillations.

    Science.gov (United States)

    Chang, F; Wang, L; Zhao, Q; Zhu, Q; Wu, Y; Chen, C; Syrjänen, S; Syrjänen, K

    1992-02-01

    The effects of coal tar pitch (CTP) on the tracheobronchial mucosa of Wistar rats were studied. Three groups of animals received 10 weekly intratracheal instillations of CTP at the cumulative doses of 6.48, 136.56 and 200 mg respectively. The control group of rats received 10 weekly intratracheal instillations of charcoal powder at a cumulative dose of 20 mg. The study in which the animals were killed serially revealed that CTP had conspicuous damage on the respiratory system of rats, especially on the bronchiolo-alveolar areas. The lesions induced by CTP ranged from hyperplastic, metaplastic and dysplastic changes to extensive cancers. These lesions were usually multifocal, and were more severe in the rats receiving higher dosages of CTP. The deposition of CTP particles within or adjacent to these lesions could be readily identified. Lung cancers occurred in 12.5% (4/32) and 25% (10/40) of the rats treated with 136.56 and 200 mg of CTP, whereas no tumors were found in control rats and the rats that received 6.48 mg of CTP. The overall cancer incidence significantly related to the cumulative dose of CTP. The histological types of lung cancers consisted of squamous cell carcinomas (10 out of the 14 lung cancers), adenocarcinoma (1/14), and combined squamous and adenocarcinomas (3/14). The development of CTP-induced rat lung cancers appears to derive from the hyperplasias of bronchiolo-alveolar epithelium, and processing stages of squamous metaplasias and/or dysplasias to carcinomas. The present results confirmed the carcinogenic effects of CTP on the respiratory system of rats, and provided experimental evidence for human lung carcinogenesis, particularly in those occupationally exposed to coal tars or tar products.

  1. 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.

  2. 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 ... opening, which marks puberty onset, by 2.5 days (p milk before puberty exhibited reduced carcinogen-induced mammary carcinogenesis; that is, their tumor latency was longer (p

  3. Absence of carcinogenic and anticarcinogenic effects of annatto in the rat liver medium-term assay.

    Science.gov (United States)

    Agner, A R; Barbisan, L F; Scolastici, C; Salvadori, D M F

    2004-10-01

    Annatto (Bixa orellana L.) is a natural food colorant extensively used in many processed foods, especially dairy products. The lower cost of production and the low toxicity, make annatto a very attractive and convenient pigment in substitution to the many synthetic colorants. In the present study we investigate the carcinogenic and anticarcinogenic effects of dietary annatto in Wistar rat liver using the preneoplastic glutathione S-transferase (GST-P) foci and DNA damage biomarkers. Annatto, containing 5% bixin, was administered in the diet at concentrations of 20, 200, and 1000 ppm (0.07; 0.80 and 4.23 bixin/kg body wt/day, respectively), continuously during 2 weeks before, or 8 weeks after DEN treatment (200 mg/kg body wt, i.p.), to evaluate its effect on the liver-carcinogenesis medium-term bioassay. The comet assay was used to investigate the modifying potential of annatto on DEN (20 mg/kg body wt)-induced DNA damage. The results showed that annatto was neither genotoxic nor carcinogenic at the highest concentration tested (1000 ppm). No protective effects were also observed in both GST-P foci development and comet assays. In conclusion, in such experimental conditions, annatto shows no hepatocarcinogenic effect or modifying potential against DEN-induced DNA damage and preneoplastic foci in the rat liver. PMID:15354320

  4. Azoreductase activity of Sprague Dawley and Wistar-derived rats towards both carcinogenic and non-carcinogenic analogues of 4-dimethylaminophenylazobenzene (DAB).

    Science.gov (United States)

    Elliott, B M

    1984-08-01

    Azoreductase activity towards the hepatocarcinogen p-dimethylaminophenylazobenzene (DAB) and four analogues has been measured in vitro in the liver and caecum of Sprague Dawley (Alpk/SD) and Alderley Park (Alpk/AP Wistar-derived) rats. Two carcinogenic DAB analogues, 3'-methyl-p-dimethylaminophenylazobenzene (3M) and 6-p-dimethylaminophenylazobenzothiazole (6BT) and two non-carcinogenic analogues, 4-N-pyrrolidinylazobenzene (4N) and 5-p-dimethylaminophenylazoindazole (5I) have been examined. The azoreductase activity towards DAB of a 9000 g supernatant of liver homogenate was greater in the SD than the AP strain between 6 and 13 weeks of age, but comparable to that of AP rats at 4 weeks of age. The activity towards DAB fell in both strains with increasing age. Animals of both strains fed a riboflavin-low diet (2-3 mg kg-1) had reduced azoreductase activity with DAB when compared to a standard diet at all ages studied, although the difference was less marked in the AP rats. 3M and 4N were azoreduced by the livers of both strains of rat fed a standard diet at a rate of approximately 50% of that of DAB, whereas 5I and 6BT were cleaved at a much lower rate (5-20%). All the chemicals were reduced by an oxygen-insensitive enzyme in the liver preparation, as has previously been reported for DAB. DAB, 3M and 6BT were reduced at a similar rate to each other by a fraction containing caecal contents, both in and between the two strains of rat. Similarly, 4N and 5I were reduced by a caecal preparation at a similar rate to each other in and between both strains of rat, but at a rate of only 30-50% that shown by DAB, 3M and 6BT. In contrast to the conditions required by the liver azoreductase enzyme, anaerobic conditions were required for maximal activity of the caecal preparation. Liver azoreductase activity towards all the DAB analogues was reduced in both strains of rat maintained on a riboflavin-low diet, while the caecal azoreductase activity was unaffected. Neither the

  5. 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.)

  6. Carcinogenicities in mice and rats of IQ, MeIQ, and MeIQx.

    Science.gov (United States)

    Ohgaki, H; Hasegawa, H; Kato, T; Suenaga, M; Sato, S; Takayama, S; Sugimura, T

    1985-01-01

    The mutagenic heterocyclic amines, 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) are present in broiled fish, fried beef, and beef extract. Their carcinogenicities in CDF1 mice and F344 rats were tested by their oral administration in the diet. In mice given diet containing 0.03% IQ, tumors developed in the liver (hepatocellular carcinomas or hepatocellular adenomas), forestomach (squamous cell carcinomas or papillomas), and lung (adenocarcinomas or adenomas) at high incidences. In mice given diet containing 0.04% or 0.01% MeIQ, squamous cell carcinomas and papillomas of the forestomach developed at high incidences. About 40% of the squamous cell carcinomas induced in the forestomach by 0.04% MeIQ metastasized to the liver. Clear dose-response relations were seen in the incidences of tumors in the groups given 0.04% and 0.01% MeIQ. The squamous cell carcinoma-papilloma ratios were higher in 0.04% groups than in 0.01% groups. Female mice treated with 0.04% and 0.01% MeIQ showed significantly higher incidences of liver tumors than controls. The experiment on the carcinogenicity of MeIQx at a dose of 0.06% in mice is still in progress but by experimental week 74, 4 of 16 males and 7 of 18 females autopsied were found to have liver tumors. Rats given diet containing 0.03% IQ showed high incidences of hepatocellular carcinomas, adenocarcinomas of the small and large intestines, and squamous cell carcinomas of the Zymbal gand, clitoral gland, and skin. Except for the liver, the target organs of IQ in CDF1 mice and F344 rats were different. PMID:3842704

  7. Development of a Medium-term Animal Model Using gpt Delta Rats to Evaluate Chemical Carcinogenicity and Genotoxicity

    Science.gov (United States)

    Matsushita, Kohei; Kijima, Aki; Ishii, Yuji; Takasu, Shinji; Jin, Meilan; Kuroda, Ken; Kawaguchi, Hiroaki; Miyoshi, Noriaki; Nohmi, Takehiko; Ogawa, Kumiko; Umemura, Takashi

    2013-01-01

    In this study, the potential for development of an animal model (GPG46) capable of rapidly detecting chemical carcinogenicity and the underlying mechanisms of action were examined in gpt delta rats using a reporter gene assay to detect mutations and a medium-term rat liver bioassay to detect tumor promotion. The tentative protocol for the GPG46 model was developed based on the results of dose-response exposure to diethylnitrosamine (DEN) and treatment with phenobarbital over time following DEN administration. Briefly, gpt delta rats were exposed to various chemicals for 4 weeks, followed by a partial hepatectomy (PH) to collect samples for an in vivo mutation assay. The mutant frequencies (MFs) of the reporter genes were examined as an indication of tumor initiation. A single intraperitoneal (ip) injection of 10 mg/kg DEN was administered to rats 18 h after the PH to initiate hepatocytes. Tumor-promoting activity was evaluated based on the development of glutathione S-transferase placental form (GST-P)-positive foci at week 10. The genotoxic carcinogens 2-acetylaminofluorene (2-AAF), 2-amino-3-methylimidazo [4,5-f] quinolone (IQ) and safrole (SF), the non-genotoxic carcinogens piperonyl butoxide (PBO) and phenytoin (PHE), the non-carcinogen acetaminophen (APAP) and the genotoxic non-hepatocarcinogen aristolochic acid (AA) were tested to validate the GPG46 model. The validation results indicate that the GPG46 model could be a powerful tool in understanding chemical carcinogenesis and provide valuable information regarding human risk hazards. PMID:23723564

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

    NARCIS (Netherlands)

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

    2004-01-01

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

  9. 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

  10. Immunologic role of nitric oxide in acute rejection of golden hamster to rat liver xenotransplantation

    Institute of Scientific and Technical Information of China (English)

    Tong-Jin Diao; Tong-Ye Yuan; You-Lin Li

    2002-01-01

    AIM: To evaluate the immunologic role and expressionsignificances of nitric oxide(NO), nitric oxide synthase(NOS),and its isoenzyme in acute rejection to liverxenografts from golden hamster in rat.METHODS: Liver transplantations were randomlydivided into five groups(n=6-9):isografts (group I );xenografts (groupⅡ); xenografts plus cyclosporinetreatment (group Ⅲ), xenografts pluscyclophosphamide treatment combined withsplenectomy (group Ⅳ), and xenografts usingcyclophosphamide in combination with splenectomy(group Ⅳ) and xenografts using splenectomy inaddition to cyclophosphamide and cyclosporinetreatments(group V) .The levels of ALT, TNF- α, andnitric oxide production(NOx) in serum of reciprentswere examined,and expressions of type Ⅱ (iNOS) andtypeⅢ (cNOS) nitric oxide synthase(NOS)-inducibleNOS(iNOS) and constitutive NOS(cNOS) wereobserved by NADPH diaphorase histochemical andimmunohistochemical staining.RESULTS: The level of serum ALT, activity of serumTNF-α and systemic levels of NO metabolite in groupsⅡand Ⅳ were higher than those of groups Ⅰ andy(serum ALT, 2416±475, 2540±82.5) nkat. L-1 vs(556.8±43.5, 677.30±38.2 ) nkat. L-1, P<0.01;(serum TNF-α, 353.5±16.1,444.6±28.1) ng.L-1 vs38.5±5.2, 52.0±5.7) ng.L-1, P<0.01; (serum NOx514.6 ± 18.1, 336.0 ± 43.0 )nmol.g-1, vs 26.1 ± 5.7, 27.7±6.0) nmol.g-1, P<0.01.Cyclosporine in group Ⅲcan repress the cellular immune response and thesynthesis of nitric oxide and the expression of NOsynthase,but not prolong the liver xenograftsurvival.The over-expression of NOS, iNOS and cNOSin liver xenograft rejection in groups Ⅱand Ⅳ weredetected by NADPH diaphorase histochemical andimmunohistochemical staining.CONCLUSION: The degrees of acute rejection can beeffectively repressed in golden hamster to rat liverxenografts with splenectomy and cyclosporine. Nitricoxide metabolites, and nitric oxide synthase and itsisoenzymes,above all inducible NOS (iNOS) can beused as potential diagnostic

  11. Hepatic gene mutations induced in Big Blue rats by both the potent rat liver azo-carcinogen 6BT and its reported noncarcinogenic analogue 5BT.

    Science.gov (United States)

    Fletcher, K; Soames, A R; Tinwell, H; Lefevre, P A; Ashby, J

    1999-01-01

    The potent rat liver carcinogen 6-p-dimethylaminophenylazobenzthiazole (6BT) and its reported noncarcinogenic analogue 5-p-dimethylaminophenylazobenzthiazole (5BT; evaluated for carcinogenicity under the similar limited bioassay conditions used for 6BT) have been studied in order to seek an explanation for their different carcinogenic activities. Both compounds act as DNA-damaging agents to the rat liver, and both have now been shown to induce lacI (-) gene mutations in the liver of Big Blue(trade mark) transgenic rats. Both compounds were mutagenic following ten daily gavage doses or following administration in diet for 10 days. Neither chemical induced cell proliferation in the liver following repeat gavage administrations. In contrast, dietary administration of 6BT, and to a lesser extent of 5BT, induced hepatic cell proliferation. The carcinogen 6BT, but not the noncarcinogen 5BT, caused proliferation of oval stem cells in the livers by both routes of administration. It is possible that mutations induced in oval cells by 6BT are responsible for its potent carcinogenicity, and that the comparative absence of these cells in 5BT-treated livers may account for the carcinogenic inactivity of 5BT. Equally, the proliferation of the oval cells may reflect changes in liver homeostasis associated with the liver toxicity observed at the dose level of 6BT used (which was, nonetheless, the dose level used in the positive cancer bioassays). It is concluded that the new data presented cannot explain the differing carcinogenic activities of 5BT and 6BT, and that the reported noncarcinogen 5BT may also be carcinogenic when adequately assessed for this activity.

  12. Cytokine production during the inhibition of acute vascular rejection in a concordant hamster-to-rat cardiac xenotransplantation model

    Institute of Scientific and Technical Information of China (English)

    ZHANG Xiao-gang; L(U) Yi; WANG Bo; LI Hui; YU Liang; LIU Chang; WU Zheng; LIU Xue-min

    2007-01-01

    Background The aim of the current study was to investigate the role of interleukin (IL)-2, interferon (IFN)-γ, IL-4 and IL-10 in a concordant hamster-to-rat cardiac xenotransplantation model. Methods A hamster-to-rat cardiac transplantation was performed using SD rats as recipients of Golden Syrian hamster hearts. A total of 60 SD rats were divided into four groups and treated as follows: control group (n=15); splenectomy group (n=15); CsA group (n=15); CsA + splenectomy group (n=15). Levels of IL-2, IFN-γ, IL-4 and IL-10 were measured by enzyme linked immunosorbent assay (ELISA). Sera were harvested at different time points in each group: day 1, and 3 as well as the day the xenograft stopped beating in the control group and CsA group; day 1, 3, 7, 14 and 30 in the splenectomy group and CsA+splenectomy group. The expression of P-selectin and intercellular adhesion molecule-1 (ICAM-1) was examined by immunohistochemical analysis of the xenograft after cardiac xenotransplantation. Results Serum levels of IL-2 and IFN-γ were upregulated in untreated (day 3) and splenectomy-treated animals (day 7) compared to CsA + splenectomy treated animals (day 7). IL-10 was upregulated in long-term survival recipients following splenectomy + CsA. Neither P-selectin nor ICAM-1 expression was detected in long-term survival xenografts. Conclusions Serum IL-2 and IFN-γ were elevated following acute vascular rejection. Serum IL-10 was correlated to immunosuppression and protective effects in long-term survival rats following concordant cardiac xenotransplantation.

  13. 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.

  14. Liver fatty acid binding protein is the mitosis-associated polypeptide target of a carcinogen in rat hepatocytes

    Energy Technology Data Exchange (ETDEWEB)

    Bassuk, J.A.; Tsichlis, P.N.; Sorof, S.

    1987-11-01

    Hepatocytes in normal rat liver were found previously to contain a cytoplasmic 14,000-dalton polypeptide (p14) that is associated with mitosis and is the principal early covalent target of activated metabolites of the carcinogen N-2-fluorenylacetamide (2-acetylaminofluorene). The level of immunohistochemically detected p14 was low when growth activity of hepatocytes was low, was markedly elevated during mitosis in normal and regenerating livers, but was very high throughout interphase during proliferation of hyperplastic and malignant hepatocytes induced in rat liver by a carcinogen (N-2-fluorenylacetamide or 3'-methyl-4-dimethylaminoazobenzene). The authors report here that p14 is the liver fatty acid binding protein. The nucleotide sequence of p14 cDNA clones, isolated by screening a rat liver cDNA library in bacteriophage lambdagt11 using p14 antiserum, was completely identical to part of the sequence reported for liver fatty acid binding protein. Furthermore, the two proteins shared the following properties: size of mRNA, amino acid composition, molecular size according to NaDodSO/sub 4/ gel electrophoresis, and electrophoretic mobilities in a Triton X-100/acetic acid/urea gel. The two polypeptides bound oleic acid similarly. Finally, identical elevations of cytoplasmic immunostain were detected specifically in mitotic hepatocytes with either antiserum. The collected findings are suggestive that liver fatty acid binding protein may carry ligands that promote hepatocyte division and may transport certain activated chemical carcinogens.

  15. 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.)

  16. 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 ...

  17. 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.

  18. Inhibitory effects of freeze-dried milk fermented by selected Lactobacillus bulgaricus strains on carcinogenesis induced by 1,2-dimethylhydrazine in rats and by diethylnitrosamine in hamsters.

    Science.gov (United States)

    Balansky, R; Gyosheva, B; Ganchev, G; Mircheva, Z; Minkova, S; Georgiev, G

    1999-12-01

    Fermented milk products might be used for cancer chemoprevention due to their putative anticarcinogenic and antitumor activities. The diet was supplemented with freeze-dried milk fermented by Lactobacillus bulgaricus strain LBB.B 144 (product FFM.B 144) added throughout the experiment at doses of 1.3 g and 2.5 g per rat, 5 times a week starting 3 weeks before the first carcinogen injection. This treatment significantly inhibited, by 26.2-28.6% and by 34.2%, the total intestinal carcinogenesis induced by 1,2-dimethylhydrazine (DMH, 21 mg/kg, s.c., once per week for 20 weeks) in male and female BD6 rats, respectively. FFM.B144 decreased the tumor incidence and multiplicity in large bowel, caecum, and duodenum. Protective effects were better expressed in female animals, with exception of that observed in duodenum. Supplementation of diet with freeze-dried milk fermented by Lactobacillus bulgaricus strain LBB.B5 (product FFM.B5) inhibited DMH-induced carcinogenesis only in the large bowel, but had no significant protective effect when all intestinal tumors were taken into account. However, both freeze-dried products favorably shifted the differentiation of large bowel tumors by increasing the proportion of benign and highly differentiated malignant tumors and decreasing in parallel the number of poorly differentiated carcinomas without influencing the tumor size. A lower number of cases with visible mesenterial metastasis was also observed in FFM-treated rats. In addition, both FFM.B 144 and FFM.B5 significantly inhibited, by 26-33%, the induction in the same rats of ear-duct tumors. FFM.B144 but not FFM.B5 was also effective in inhibiting the tracheal carcinogenesis induced in Syrian golden hamsters by diethylnitrosamine (DEN, 100 mg/kg, two s.c. injections), the protective effect being better expressed in female animals. The anticarcinogenic potential of some fermented milk products might be exploited in chemoprevention of cancer in humans.

  19. Cellular distribution of cell cycle-related molecules in the renal tubules of rats treated with renal carcinogens for 28 days: relationship between cell cycle aberration and carcinogenesis.

    Science.gov (United States)

    Taniai, Eriko; Hayashi, Hitomi; Yafune, Atsunori; Watanabe, Maiko; Akane, Hirotoshi; Suzuki, Kazuhiko; Mitsumori, Kunitoshi; Shibutani, Makoto

    2012-09-01

    Some renal carcinogens can induce karyomegaly, which reflects aberrant cell division in the renal tubules, from the early stages of exposure. To clarify the cell cycle-related changes during the early stages of renal carcinogenesis, we performed immunohistochemical analysis of tubular cells in male F344 rats treated with carcinogenic doses of representative renal carcinogens for 28 days. For this purpose, the karyomegaly-inducing carcinogens ochratoxin A (OTA), ferric nitrilotriacetic acid, and monuron, and the non-karyomegaly-inducing carcinogens tris(2-chloroethyl) phosphate and potassium bromate were examined. For comparison, a karyomegaly-inducing non-carcinogen, p-nitrobenzoic acid, and a non-carcinogenic non-karyomegaly-inducing renal toxicant, acetaminophen, were also examined. The outer stripe of the outer medulla (OSOM) and the cortex + OSOM were subjected to morphometric analysis of immunoreactive proximal tubular cells. Renal carcinogens, irrespective of their karyomegaly-inducing potential, increased proximal tubular cell proliferation accompanied by an increase in topoisomerase IIα-immunoreactive cells, suggesting a reflection of cell proliferation. Karyomegaly-inducing carcinogens increased nuclear Cdc2-, γH2AX-, and phosphorylated Chk2-immunoreactive cells in both areas, the former two acting in response to DNA damage and the latter one suggestive of sustained G₂. OTA, an OSOM-targeting carcinogen, could easily be distinguished from untreated controls and non-carcinogens by evaluation of molecules responding to DNA damage and G₂/M transition in the OSOM. Thus, all renal carcinogens examined facilitated proximal tubular proliferation by repeated short-term treatment. Among these, karyomegaly-inducing carcinogens may cause DNA damage and G₂ arrest in the target tubular cells.

  20. 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

  1. CARCINOGENICITY OF INDIVIDUAL AND A MIXTURE OF DRINKING WATER DISINFECTION BY-PRODUCTS IN A RAT MODEL OF HEREDITARY RENAL CELL CARCINOMA

    Science.gov (United States)

    Carcinogenicity of Individual and a Mixture of Drinking Water Disinfection By-Products in a Rat Model of Hereditary Renal Cell Carcinoma Eker rats develop hereditary renal cell carcinoma secondary to a germline mutation in the tuberous sclerosis 2 (Tsc2) gene and are ligh...

  2. [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

  3. 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

  4. 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

  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. 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.

  8. 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.

  9. 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

  10. 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

  11. 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 ...

  12. The urinary bladder carcinogen propoxur does not produce genotoxic effects in the urinary bladder of Wistar male rats.

    Science.gov (United States)

    Iatropoulos, M J; Duan, J-D; Schmuck, G; Williams, G M

    2015-09-01

    Propoxur (PPX) is a carbamate insecticide which induced urinary bladder cancer in Wistar rats when fed at 5000ppm in Altromin 1321 diet (1321). In the present investigation, PPX was studied for induction of several key events related to modes of action (MOA) of carcinogenicity in urinary bladders (UBs). Wistar rats were administered the compound for 28 days at 8000ppm in Provini Liba SA 3883 diet, which is similar to the 1321 diet. o-Anisidine HCl (AH) was used as a genotoxic UB carcinogenic comparator, and trisodium nitrilotriacetate (NTA) as an epigenetic UB carcinogen comparator. Along with the non-dosed control and three test substance groups (PPX, AH, NTA), four more groups were additionally fed 2% ammonium chloride (AC) in the diet to acidify the urine, since 1321 was reported to increase urinary pH. AC did acidify the urine, as expected, although the 3883 diet itself did not increase pH values above 8. In the alkaline comet assay, AH produced DNA single strand breaks (SSBs) in the UB urothelium (UBU) irrespective of AC administration, whereas PPX and NTA did not. In the nucleotide (32)P-postlabeling assay (NPL), AH produced DNA adducts irrespective of AC administration, whereas PPX and NTA did not. Routine (H&E) histopathology evaluation of the UBU did not reveal any hyperplasia or evidence of luminal microprecipitates or calculi in any of the groups. Assessment of UBU proliferation as measured by immunohistochemistry of proliferating cell nuclear antigen, revealed that NTA and NTA plus AC increased the replicating fraction (RF). Also AH plus AC, but not AH alone, increased the RF of UBU, whereas PPX groups were not significantly different from controls. Thus, the results reveal no evidence for DNA SSBs, binding, or alteration of DNA synthesis in the UBU by PPX, while demonstrating UBU DNA damage by AH and showing that NTA does not damage DNA, but causes increased UBU proliferation. The findings are in accord with a genotoxic MOA for AH, and an epigenetic

  13. The urinary bladder carcinogen propoxur does not produce genotoxic effects in the urinary bladder of Wistar male rats.

    Science.gov (United States)

    Iatropoulos, M J; Duan, J-D; Schmuck, G; Williams, G M

    2015-09-01

    Propoxur (PPX) is a carbamate insecticide which induced urinary bladder cancer in Wistar rats when fed at 5000ppm in Altromin 1321 diet (1321). In the present investigation, PPX was studied for induction of several key events related to modes of action (MOA) of carcinogenicity in urinary bladders (UBs). Wistar rats were administered the compound for 28 days at 8000ppm in Provini Liba SA 3883 diet, which is similar to the 1321 diet. o-Anisidine HCl (AH) was used as a genotoxic UB carcinogenic comparator, and trisodium nitrilotriacetate (NTA) as an epigenetic UB carcinogen comparator. Along with the non-dosed control and three test substance groups (PPX, AH, NTA), four more groups were additionally fed 2% ammonium chloride (AC) in the diet to acidify the urine, since 1321 was reported to increase urinary pH. AC did acidify the urine, as expected, although the 3883 diet itself did not increase pH values above 8. In the alkaline comet assay, AH produced DNA single strand breaks (SSBs) in the UB urothelium (UBU) irrespective of AC administration, whereas PPX and NTA did not. In the nucleotide (32)P-postlabeling assay (NPL), AH produced DNA adducts irrespective of AC administration, whereas PPX and NTA did not. Routine (H&E) histopathology evaluation of the UBU did not reveal any hyperplasia or evidence of luminal microprecipitates or calculi in any of the groups. Assessment of UBU proliferation as measured by immunohistochemistry of proliferating cell nuclear antigen, revealed that NTA and NTA plus AC increased the replicating fraction (RF). Also AH plus AC, but not AH alone, increased the RF of UBU, whereas PPX groups were not significantly different from controls. Thus, the results reveal no evidence for DNA SSBs, binding, or alteration of DNA synthesis in the UBU by PPX, while demonstrating UBU DNA damage by AH and showing that NTA does not damage DNA, but causes increased UBU proliferation. The findings are in accord with a genotoxic MOA for AH, and an epigenetic

  14. 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

    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...... detected when the F1 rats were more than 2 yr old. Tumours were found in many other organs of some of the treated rats, but their incidence was not significantly different from that in controls. The role of BHT in the development of hepatocellular tumours requires further elucidation....

  15. 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...

  16. Carcinogenicity of the antineoplastic agent, 5-(3,3-dimethyl-1-triazeno)-imidazole-4-carboxamide, and its metabolites in rats.

    Science.gov (United States)

    Beal, D D; Skibba, J L; Croft, W A; Cohen, S M; Bryan, G T

    1975-04-01

    Chronic oral administration of the antineoplastic agent, 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide (NSC-45388, DTIC), induced predominantly thymic and mammary tumors as demonstrated previously. Male and female Sprague-Dawley and female Buffalo rats were susceptible to the carcinogenicity of DTIC. A 50% incidence of mammary adenocarcinomas was induced in males within 18 weeks. Type of tumor and tumor incidence were dose dependent. Single and multiple intraperitoneal injections of DTIC did not alter organ specificity. DTIC-induced thymic lymphosarcomas and mammary adenocarcinomas were transplantable. Tissue distribution studies revealed no correlation between uptake of DTIC by a given tissue and its susceptibility to carcinogenicity. Metabolites of DTIC were tested for carcinogenic activity. Animals administered 5-diazoimidazole-4-carboxamide orally, intraperitoneally, or intragastrically developed low incidences of thymic, stomach, bladder, or mammary tumors. A low incidence of mammary tumors developed in rats fed 2-azahypoxanthine. A variety of tumors, including several ependymoblastomas, were induced in rats that received 5-aminoimidazole-4-carboxamide orally. 5-(3-Methyl-1-triazeno)imidazole-4-carboxamide (MTIC), when fed or given in single or multiple intraperitoneal injections, induced a high incidence of mammary adenofibromas and a low incidence of uterine leiomyosarcomas. Control rats had low incidences of mammary adenocarcinomas and adenofibromas after 52 weeks. These data show that the carcinogenic properties of DTIC resemble those of carcinogenic N-nitroso compounds, hydrazine, azo, and azoxy-alkanes and aryltriazenes and thus suggest similar mechanism(s) of action. These data also indicate that MTIC is involved in the induction of mammary adenofibromas and uterine leiomyosarcomas by DTIC.

  17. 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.

  18. The carcinogenic effect of localized fission fragment irradiation of rat lung.

    Science.gov (United States)

    Batchelor, A L; Buckley, P; Gore, D J; Jenner, T J; Major, I R; Bailey, M R

    1980-03-01

    In a preliminary investigation of 'hot particle' carcinogenesis uranium oxide particles were introduced into the lungs of rats either by intubation of a liquid suspension of the particles or by inhalation of an aerosol. Subsequently the animals were briefly exposed to slow neutrons in a nuclear reactor, resulting in localized irradiation of the lung by fission fragments emitted from 235U atoms in the oxide particles. The uranium used in the intubation experiments was either enriched or depleted in 235U. Squamous cell carcinomas developed at the site of deposition of the enriched uranium oxide in many cases but no lung tumours occurred in the rats with the depleted uranium oxide, in which the lung tissue was exposed to very few fission fragments. Only enriched uranium oxide was used in the inhalation experiments. Pulmonary squamous cell carcinomas occurred after the fission fragment irradiation but were fewer than in the intubation experiments. Adenocarcinomas of the lung were seen in rats exposed to uranium oxide without subsequent irradiation by neutrons in the reactor and in rats irradiated with neutrons but not previously exposed to uranium oxide. It is concluded that (i) fission fragments were possibly implicated in the genesis of the squamous cell carcinomas, which only developed in those animals exposed to enriched uranium oxide and neutrons and (ii) the adenocarcinomas in the rats inhaling enriched uranium oxide only were likely to have been caused by protracted irradiation of the lung with alpha-rays emitted from the enriched uranium.

  19. 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.

  20. 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.;

    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...... groups were isocaloric. Clinical appearance, food consumption, body weight and weight gain, survival, haematology, and clinical chemistry parameters were examined. Gross and histopathological examinations, including neoplastic and non-neoplastic lesions, were performed on all groups. Time to occurrence...

  1. Equivocal colonic carcinogenicity of Aloe arborescens Miller var. natalensis berger at high-dose level in a Wistar Hannover rat 2-y study.

    Science.gov (United States)

    Yokohira, M; Matsuda, Y; Suzuki, S; Hosokawa, K; Yamakawa, K; Hashimoto, N; Saoo, K; Nabae, K; Doi, Y; Kuno, T; Imaida, K

    2009-03-01

    A 2-y carcinogenicity study of Aloe, Aloe arborescens Miller var. natalensis Berger, a food additive, was conducted for assessment of toxicity and carcinogenic potential in the diet at doses of 4% or 0.8% in groups of male and female Wistar Hannover rats. Both sexes receiving 4% showed diarrhea, with loss of body weight gain. The survival rate in the 4% female group was significantly increased compared with control females after 2 y. Hematological and biochemical examination showed increase of RBC, Hb, and Alb in the 4% males. The cause of these increases could conceivably have been dehydration through diarrhea. AST and Na were significantly decreased in the males receiving 4%, and Cl was significantly decreased in both 4% and 0.8% males. A/G was significantly increased in the 4% females, and Cl was significantly decreased (0.8%) in the female group. Histopathologically, both sexes receiving 4% showed severe sinus dilatation of ileocecal lymph nodes, and yellowish pigmentation of ileocecal lymph nodes and renal tubules. Adenomas or adenocarcinomas in the cecum, colon, and rectum were observed in 4% males but not in the 0.8% and control male groups. Similarly, in females, adenomas in the colon were also observed in the 4% but not 0.8% and control groups. In conclusion, Aloe, used as a food additive, exerted equivocal carcinogenic potential at 4% high-dose level on colon in the 2-y carcinogenicity study in rats. Aloe is not carcinogenic at nontoxic-dose levels and that carcinogenic potential in at 4% high-dose level on colon is probably due to irritation of the intestinal tract by diarrhea. PMID:19323775

  2. 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 2.5% bo......,12-dimethylbenz[alpha]anthracene, aflatoxin B1, dimethylnitrosamine, 1,2-dimethylhydrazine, and methylazoxymethanol acetate into chemical species that bind to cellular DNA and protein....

  3. Site-specific in vivo mutagenicity in the kidney of gpt delta rats given a carcinogenic dose of ochratoxin A.

    Science.gov (United States)

    Hibi, Daisuke; Suzuki, Yuta; Ishii, Yuji; Jin, Meilan; Watanabe, Maiko; Sugita-Konishi, Yoshiko; Yanai, Tokuma; Nohmi, Takehiko; Nishikawa, Akiyoshi; Umemura, Takashi

    2011-08-01

    Ochratoxin A (OTA) can induce renal tumors that originate from the S3 segment of the proximal tubules in rodents, but the results of conventional mutagenicity tests have caused controversy regarding the role of genotoxic mechanisms in the carcinogenesis. Human exposure to OTA from various foods is unavoidable. Therefore, an understanding of OTA-induced renal carcinogenesis is necessary for accurate estimates of the human risk hazard. In the present study, a 13-week exposure of gpt delta rats to OTA at a carcinogenic dose induced karyomegaly and apoptosis at the outer stripe of the outer medulla (OM) of the kidney but failed to affect the reporter gene mutations in DNA extracted from whole kidneys. This site specificity resulting from the kinetics of specific transporters might be responsible for the negative outcome of in vivo mutagenicity. The kidney was then macroscopically divided, based on anatomical characteristics, into the cortex, the OM, and the inner medulla, each of which was histopathologically confirmed. Spi⁻ mutant frequencies (MFs) but not gpt MFs in the OM after a 4-week exposure to OTA were significantly higher than in controls despite the absence of cortical changes. There were also no changes in 8-hydroxydeoxyguanosine levels in kidney DNA. These results strongly suggest the involvement of a genotoxic mechanism, with the exception of oxidative DNA damage in OTA-induced renal carcinogenesis. In addition, the reporter gene mutation assay using DNA from target sites could be a more powerful tool to investigate in vivo genotoxicities.

  4. Carcinogenicity and co-carcinogenicity studies on propoxur in mouse skin.

    Science.gov (United States)

    Shukla, Y; Baqar, S M; Mehrotra, N K

    1998-12-01

    Propoxur (2-isopropoxyphenyl methylcarbamate) is a widely used broad spectrum carbamate insecticide mainly used to control household pests. Propoxur exposure is reported to inhibit cholinesterase activity in rodents. Apart from other toxic effects, propoxur was found to possess tumorigenic activity in rats after oral administration. Propoxur does not produce tumours in mice or hamsters, or bladder hyperplasia in dogs and monkeys following oral feeding. In this set of investigations the complete carcinogenic, tumour initiating and promoting potential of propoxur was evaluated in male and female Swiss albino mice, since no information was available following dermal exposure of propoxur. The animals were exposed to propoxur through topical painting on the interscapular region at a dose of 100 mg/kg body weight. The results revealed that propoxur has tumour promoting potential on mouse skin following a two-stage initiation-promotion protocol, but it failed to induce the tumour(s) at a significant level, when tested for tumour initiating and complete carcinogenic property.

  5. The Anatomic Pathology Evaluation of Liver with Diethylinitrosamine Treated via Intraperitoneal Injection Singly and Peros for 90 Days Carcinogenicity Study in F344 Rats

    Institute of Scientific and Technical Information of China (English)

    LI Shan-shan; KANEKO Toyozo; XING Rui-chang; WANG Xiu-wen; LI Bo; ZHANG Lin; LI Bao-wen; LANG Shu-hui; YANG Yan-wei; ZHANG Di; ZHANG Yang; NARAMA Isao; KAWAYI Zeshow

    2008-01-01

    Objective:To establish the integrity experiment method of short(medium)-term carcinogenicity test pursuant to GLP, make into relative SOP and improve the safeguard in the center.Methods:Diethylinitrosamine(DEN) is known as carcinogenic agent,whose target organ is liver. Using the two-stage carcinogenesis test method, DEN was treated to F344 rats via intraperitoneal injection singly(200 mg/kg), and peros administrated for 90 days(10 ppm). The liver in any group rat will be examined by light microscopy.Results:In pathologic examination, no liver cell tumor was shown in the livers of the rats that were singly treated with a carcinogenic chemical-DEN.Foci of cellular alteration were observed in the livers of these rats. The proliferation lesions of liver from slight to seveity(foci of cellular alteration-hepatocelluar adenoma-hepatocellular carcinoma)were observed in the livers of the rats which exposed peros to a low dose of DEN for 90 days after initiation by a single intraperitoneal injection. The incidence of hepatocelluar tumor was 35% in male animal,which was not shown in the liver of female rat.Conclusion:For current results, it may be possible that low-dose DEN acts as a promotor of hepatocelluar tumor if it was exposed in a population for a long time. It is considered that male hormone has a synergistic effect on hepatocelluar tumor development of DEN. This two-stage carcinogenesis test might be a new model for the study of drug induced and promoted carcinogenesis,which could be used to evaluate the carcinogenesis of chemical compound fast.

  6. 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.

  7. 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].

  8. Clear evidence of carcinogenic activity by a whole-leaf extract of Aloe barbadensis miller (aloe vera) in F344/N rats.

    Science.gov (United States)

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

    2013-01-01

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

  9. 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

  10. 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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1979-06-01

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

  12. Expression of recombinant rat Neurotrophin-3 in Chinese hamster ovary cells

    Institute of Scientific and Technical Information of China (English)

    季爱民; 舒斯云; 包新民; 邹恒琴; 张忠义; 李明

    1999-01-01

    The CHO cell line stably producing recombinant rat NT-3 was established. The insertion of rNT-3 cDNA into transferred cell gonome was analyzed with Southern blot. The expressed protein was identified by Dot ELISA (enzyme-linked immunosorbent assay) and Western blot. Western blot showed a clear specifie band of about 14 ku for NT-3. The mean level of rNT-3 in four NT-3eDNA/CHO cell lines was about 2 100 ng/10~6 cells/48 h determined by EIA. The conditioned-medium (CM) of NT-3cDNA/CHO cells could promote the fiber outgrowth of the dissociated dorsal root ganglion of 8-day-old chick embryos, which shows a dose-response relationship. A half-maximal concentration of the biological activity (EC50) of the recombinant protein was approximately 16.7 ng/mL. The MoAb 3W3 of NT-3 could neutralize the biological activity of the rNT-3.

  13. 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 ...

  14. 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

  15. Chemoprevention of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine-induced carcinogen-DNA adducts by Chinese cabbage in rats

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    AIM The food-borne carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) induces colon and mammary gland tumors in rats and has been implicated in the etiology of human colorectal cancer. This study was conducted to examine the potentially preventive effect of Chinese cabbage (Brassica chinensis), a brassica vegetable most commonly consumed in China, against this carcinogen-induced DNA adduct formation in rats and its possible mechanisms.METHODS Sprague-Dawley rats were maintained for 10 days on basal diet or diet containing 20% (w/ w) freeze-dried cabbage powder prior to administration of a single dose of PhIP (10 mg/ kg) by oral gavage. Rats were sacrificed at 20 h after PhIP treatment and PhIP-DNA adducts in the colon, heart, lung and liver were analyzed using 32P-postlabeling technique. Levels of hepatic cytochrome P450 (CYP) 1A1 and 1A2, as indicated by 7-ethoxyresorufin O-deethylase and 7-methlxyresorufin O-demethylase activity, and cytosolic glutathione S-transferases (GSTs) towards 1-chloro-2, 4-dinitrobenzene (CDNB) in the liver, lung and colon were measured.RESULTS Rats pre-treated with Chinese cabbage and given a single dose of PhIP had reduced levels of PhIP-DNA adducts in the colon, heart, lung and liver, with inhibition rates of 82.3%, 60.6%, 48.4% and 48.9%, respectively (P<0.01). The enzyme assays revealed that Chinese cabbage induced both CYP1A1 and 1A2 activity, but the induction was preferential for CYP1A1 over 1A2 (81% vs 51%). GST activity towards CDNB in the liver and lung, but not colon, was also significantly increased by cabbage treatment.CONCLUSION The results indicate that Chinese cabbage has a preventive effect on PhIP-initiated carcinogenesis in rats and the mechanism is likely to involve the induction of detoxification enzymes.

  16. 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

  17. 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)

  18. Carcinogenicity of azo colorants: influence of solubility and bioavailability.

    Science.gov (United States)

    Golka, Klaus; Kopps, Silke; Myslak, Zdislaw W

    2004-06-15

    In the past, azo colorants based on benzidine, 3,3'-dichlorobenzidine, 3,3'-dimethylbenzidine (o-tolidine), and 3,3'-dimethoxybenzidine (o-dianisidine) have been synthesized in large amounts and numbers. Studies in exposed workers have demonstrated that the azoreduction of benzidine-based dyes occurs in man. The metabolic conversion of benzidine-, 3,3'-dimethylbenzidine- and 3,3'-dimethoxybenzidine-based dyes to their (carcinogenic) amine precursors in vivo is a general phenomenon that must be considered for each member of this class of chemicals. Several epidemiological studies have demonstrated that the use of the benzidine-based dyes has caused bladder cancer in humans. However, in contrast to water-soluble dyes, the question of biological azoreduction of (practically insoluble) pigments has been a matter of discussion. As a majority of azo pigments are based on 3,3'-dichlorobenzidine, much of the available experimental data are focused on this group. Long-term animal carcinogenicity studies performed with pigments based on 3,3'-dichlorobenzidine did not show a carcinogenic effect. The absence of a genotoxic effect has been supported by mutagenicity studies with the 3,3'-dichlorobenzidine-based Pigment Yellow 12. Studies in which azo pigments based on 3,3'-dichlorobenzidine had been orally administered to rats, hamsters, rabbits and monkeys could generally not detect significant amounts of 3,3'-dichlorobenzidine in the urine. It, therefore, appears well established that the aromatic amine components from azo pigments based on 3,3'-dichlorobenzidine are practically not bioavailable. Hence, it is very unlikely that occupational exposure to insoluble azo pigments would be associated with a substantial risk of (bladder) cancer in man. According to current EU regulations, azo dyes based on benzidine, 3,3'-dimethoxybenzidine and 3,3'-dimethylbenzidine have been classified as carcinogens of category 2 as "substances which should be regarded as if they are carcinogenic

  19. [Carcinogenic and promoting effects of fish juice, preserved rice and salted dry fish on the forestomach epithelium of mice and esophageal epithelium of rats].

    Science.gov (United States)

    Lin, P Z; Zhang, J S; Ding, Z W; Cai, H Y

    1986-09-01

    The carcinogenic and promoting effects of fish juice, preserved rice and salted dry fish from Nanau county, Guangdong province, a high incidence area of esophageal cancer, were studied in mice and rats. The homemade fish juice as well as fish juice in market, whether or not added with NaNO2, did not cause tumor in the forestomach of mice and the esophagus of rats. When the mice were intubated with an initiator, nitrososarcosinethylester (NSEE) twice, no carcinoma was found at the end of the experiment (D 120). Only papilloma appeared in the forestomach epithelium. The incidence was only 37.5%. However, when the mice were intubated with NSEE for 2 times followed by gastric doses of homemade fish juice, the tumor incidence in the forestomach was increased to 89.7%, in which 20.5% was carcinoma. The tumor and carcinoma incidences of initiator (NSEE and NMBzA) group and initiator + market fish juice group in mice and rats were without significant difference. The experimental results show that the homemade fish juice proved distinct promoting effect on the process of cocarcinogenesis initiated by NSEE in the forestomach of mice, while the market fish juice has no significant promoting effect on the forestomach epithelium of mice and the esophageal epithelium of rats. NSEE induced 31.6% carcinoma in the forestomach epithelium of mice on standard diet. While in mice fed with preserved rice and salted dry fish, the carcinoma incidence was increased to 63.6%. It appears that preserved rice and salted dry fish have promoting effect on the process of cocarcinogenesis initiated by NSEE in the forestomach of mice.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3568985

  20. 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...

  1. Differences in the Rate of in Situ Mammary Gland Development and Other Developmental Endpoints in Three Strains of Female Rat Commonly Used in Mammary Carcinogenesis Studies: Implications for Timing of Carcinogen Exposure.

    Science.gov (United States)

    Stanko, Jason P; Kissling, Grace E; Chappell, Vesna A; Fenton, Suzanne E

    2016-10-01

    The potential of chemicals to alter susceptibility to mammary tumor formation is often assessed using a carcinogen-induced study design in various rat strains. The rate of mammary gland (MG) development must be considered so that the timing of carcinogen administration is impactful. In this study, in situ MG development was assessed in females of the Harlan Sprague-Dawley (Hsd:SD), Charles River Sprague-Dawley (Crl:SD), and Charles River Long-Evans (Crl:LE) rat strains at postnatal days 25, 33, and 45. Development was evaluated by physical assessment of growth parameters, developmental scoring, and quantitative morphometric analysis. Although body weight (BW) was consistently lower and day of vaginal opening (VO) occurred latest in female Hsd:SD rats, they exhibited accelerated pre- and peripubertal MG development compared to other strains. Glands of Crl:SD and Crl:LE rats exhibited significantly more terminal end buds (TEBs) and TEB/mm than Hsd:SD rats around the time of VO. These data suggest a considerable difference in the rate of MG development across commonly used strains, which is independent of BW and timing of VO. In mammary tumor induction studies employing these strains, administration of the carcinogen should be timed appropriately, based on strain, to specifically target the peak of TEB occurrence. PMID:27613105

  2. 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.

  3. 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.

  4. Part 1. Assessment of carcinogenicity and biologic responses in rats after lifetime inhalation of new-technology diesel exhaust in the ACES bioassay.

    Science.gov (United States)

    McDonald, Jacob D; Doyle-Eisele, Melanie; Seagrave, JeanClare; Gigliotti, Andrew P; Chow, Judith; Zielinska, Barbara; Mauderly, Joe L; Seilkop, Steven K; Miller, Rodney A

    2015-01-01

    The Health Effects Institute and its partners conceived and funded a program to characterize the emissions from heavy-duty diesel engines compliant with the 2007 and 2010 on-road emissions standards in the United States and to evaluate indicators of lung toxicity in rats and mice exposed repeatedly to 2007-compliant new-technology diesel exhaust (NTDE*). The a priori hypothesis of this Advanced Collaborative Emissions Study (ACES) was that 2007-compliant on-road diesel emissions "... will not cause an increase in tumor formation or substantial toxic effects in rats and mice at the highest concentration of exhaust that can be used ... although some biological effects may occur." This hypothesis was tested at the Lovelace Respiratory Research Institute (LRRI) by exposing rats by chronic inhalation as a carcinogenicity bioassay. Indicators of pulmonary toxicity in rats were measured after 1, 3, 12, 24, and 28-30 months of exposure. Similar indicators of pulmonary toxicity were measured in mice, as an interspecies comparison of the effects of subchronic exposure, after 1 and 3 months of exposure. A previous HEI report (Mauderly and McDonald 2012) described the operation of the engine and exposure systems and the characteristics of the exposure atmospheres during system commissioning. Another HEI report described the biologic responses in mice and rats after subchronic exposure to NTDE (McDonald et al. 2012). The primary motivation for the present chronic study was to evaluate the effects of NTDE in rats in the context of previous studies that had shown neoplastic lung lesions in rats exposed chronically to traditional technology diesel exhaust (TDE) (i.e., exhaust from diesel engines built before the 2007 U.S. requirements went into effect). The hypothesis was largely based on the marked reduction of diesel particulate matter (DPM) in NTDE compared with emissions from older diesel engine and fuel technologies, although other emissions were also reduced. The DPM

  5. 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)

  6. Inhalation toxicity studies with 1,3-butadiene 3 two year toxicity/carcinogenicity study in rats

    Energy Technology Data Exchange (ETDEWEB)

    Owen, P.E.; Glaister, J.R.; Gaunt, I.F.; Pullinger, D.H.

    1987-05-01

    Groups of 110 male and 110 female CD (Sprague-Dawley) rats were exposed to atmospheres containing 0 (control), 1000 or 8000 ppm v/v butadiene for 6 hr/day and 5 days/week. Ten of each sex from each group were killed at 52 weeks. The study was terminated when it was predicted that survival would drop to 20% to 25%. High dose rats had wet, ruffled fur and showed slight incoordination during the first exposure each week. During the second year, mortality in both treated female groups was increased because of humanitarian sacrifice of animals with large subcutaneous masses, while increased mortality in the high dose males was accompanied by an increase of the severity of nephropathy. Body weight was slightly lower than controls in both sexes at the high dose, but statistically significant only over the first 12 weeks. There were no effects in hematological analyses or tests of neuromuscular function that definitely could be associated with treatment. Liver weights at both doses were increased in both sexes with no associated pathological change. Kidney weight was increased in males at the high dose, together with an increase in the severity of nephrosis. There were increases in the incidences of pancreatic exocrine adenoma; uterine sarcoma; Zymbal gland carcinoma; mammary tumors; thyroid follicular cell tumors; and testis Leydig-cell tumors. These data suggest the butadiene is a weak oncogen to the rat under the conditions of exposure used in this study.

  7. 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...

  8. 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...

  9. 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

  10. Neuropeptide Y induces torpor-like hypothermia in Siberian hamsters.

    Science.gov (United States)

    Paul, Matthew J; Freeman, David A; Park, Jin Ho; Dark, John

    2005-09-01

    Intracerebroventricular (ICV) injections of neuropeptide Y (NPY) are known to decrease body temperature (Tb) of laboratory rats by 1-3 degrees C. Several NPY pathways in the brain terminate in hypothalamic structures involved in energy balance and thermoregulation. Laboratory rats are homeothermic, maintaining Tb within a narrow range. We examined the effect of ICV injected NPY on Tb in the heterothermic Siberian hamster (Phodopus sungorus), a species that naturally undergoes daily torpor in which Tb decreases by as much as 15-20 degrees C. Minimum effective dose was determined in preliminary testing then various doses of NPY were tested in cold-acclimated Siberian hamsters while food was withheld. NPY markedly reduced Tb in the heterothermic Siberian hamster. In addition, the reduction in Tb in 63% of the observations was sufficient to reach the criterion for daily torpor (Tb Siberian hamster. NPY treatment may be activating hypothalamic systems that normally integrate endogenous torpor-producing signals and initiate torpor.

  11. 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

  12. 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

  13. 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.

  14. [Carcinogenic activity of the pesticide propoxur].

    Science.gov (United States)

    Pylev, L N; Vasil'eva, L A; Smirnova, O V; Khrustalev, S A; Trukhina, G M

    2010-01-01

    Wistar rats were fed propoxur in their diet at 0, 500, 3000, and 8000 ppm during throughout their life. The number of tumors was equal in the control and experimental groups. These were hemoblastoses and breast and uterine tumors. All tumors occurred spontaneously in the rats. A few experimental animals were found to have bladder epithelial hyperplasia that might be pretumorous; however, no bladder tumors were detected. It is concluded that the investigations revealed no carcinogenic activity of propoxur.

  15. Carcinogenic effects of benzene: Cesare Maltoni's contributions.

    Science.gov (United States)

    Mehlman, Myron A

    2002-12-01

    Cesare Maltoni's contributions to understanding, identifying, and characterizing widely used commercial chemicals in experimental animals are among the most important methods developed in the history of toxicology and serve to protect working men and women, the general population, and our environment from hazardous substances. Maltoni developed experimental methods that have reached the "platinum standard" for protection of public health. Benzene was among the 400 or more chemicals that Maltoni and his associates tested for carcinogenicity. In 1976, Maltoni reported that benzene is a potent experimental carcinogen. Maltoni's experiments clearly demonstrated that benzene is carcinogenic in Sprague-Dawley rats, Wistar rats, Swiss mice, and RF/J mice when administered by inhalation or ingestion. Benzene caused carcinomas of the Zymbal gland, oral cavity, nasal cavities; cancers of the skin, forestomach, mammary glands, and lungs; angiosarcomas and hepatomas of the liver; and hemolymphoreticular cancers. Thus, benzene was shown to be a multipotential carcinogen that produced cancers in several species of animals by various routes of administration. On November 2, 1977, Chemical Week reported that Maltoni provided a "bombshell" when he demonstrated the "first direct link" between benzene and cancer. In this paper, I shall summarize early experiments and human studies and reports; Maltoni's experimental contribution to understanding the carcinogenicity of benzene in humans and animals; earlier knowledge concerning benzene toxicity; and benzene standards and permissible exposure levels.

  16. 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

  17. 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

  18. Renal histopathology in toxicity and carcinogenicity studies with tert-butyl alcohol administered in drinking water to F344 rats: a pathology working group review and re-evaluation.

    Science.gov (United States)

    Hard, Gordon C; Bruner, Richard H; Cohen, Samuel M; Pletcher, John M; Regan, Karen S

    2011-04-01

    An independent Pathology Working Group (PWG) re-evaluated the kidney changes in National Toxicology Program (NTP) toxicology/carcinogenicity studies of tert-butyl alcohol (TBA) in F344/N rats to determine possible mode(s) of action underlying renal tubule tumors in male rats at 2-years. In the 13-week study, the PWG confirmed that the normal pattern of round hyaline droplets in proximal convoluted tubules was replaced by angular droplet accumulation, and identified precursors of granular casts in the outer medulla, changes typical of alpha(2u)-globulin (α(2u)-g) nephropathy. In the 2-year study, the PWG confirmed the NTP observation of increased renal tubule tumors in treated male groups. Linear papillary mineralization, another hallmark of the α(2u)-g pathway was present only in treated male rats. Chronic progressive nephropathy (CPN) was exacerbated in high-dose males and females, with a relationship between advanced grades of CPN and renal tumor occurrence. Hyperplasia of the papilla lining was a component of CPN in both sexes, but there was no pelvic urothelial hyperplasia. High-dose females showed no TBA-related nephrotoxicity. The PWG concluded that both α(2u)-g nephropathy and exacerbated CPN modes of action were operative in TBA renal tumorigenicity in male rats, neither of which has relevance for human cancer risk.

  19. 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.

  20. 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 we...... of the exocyclic amino group. Estimations of human cancer risk have indicated that ingestion of food containing aminoimidazoazaarenes are of importance....... found to be multiple organ carcinogens. The aminoimidazoazaarenes are metabolically activated by hydroxylation of the exocyclic aminogroup to the N-hydroxyamino derivative. The resultant proximate mutagens often need further activation by phase II transferases for formation of reactive species that form...

  1. 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

  2. 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.)

  3. 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).

  4. 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

    in female rat offspring. Pregnant Sprague-Dawley rats were given HIM, LIM or tap water (control) from gestational day (GD) 11 until birth; hereafter all rats received tap water. Mammary tumorigenesis was induced by administrating 7,12-dimethylbenz[a]anthracene (DMBA) on postnatal day (PND) 50....... No differences in maternal serum estradiol (P = 0.19) and IGF-1 levels (P = 0.15) at GD 19 or birth weight among the milk and water groups were seen, but estradiol, and IGF-1 levels and birth weight were numerically higher in the LIM than in the HIM group. Puberty onset occurred earlier in the LIM offspring than...

  5. 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

  6. 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...

  7. 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...

  8. 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).

  9. 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)

  10. 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.

  11. 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

  12. 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

  13. Re-evaluation of kidney histopathology from 13-week toxicity and two-year carcinogenicity studies of melamine in the F344 rat: morphologic evidence of retrograde nephropathy.

    Science.gov (United States)

    Hard, G C; Flake, G P; Sills, R C

    2009-11-01

    The histopathologic changes induced in F344 rat kidney by oral administration of melamine for 13-week and 2-year periods in studies conducted by the National Toxicology Program, NIH,(25) from 1976 to 1983 have been re-evaluated and described in detail. A constellation of tubule changes extending from papilla to cortex consistently included tubule dilatation and tubule basophilia as salient features at the subchronic time point. By 2 years, these lesions had usually resolved into fibrotic scars, in which tubule loss and collagen deposition were prominent, running from superficial cortex into the medulla. These fibrotic lesions required discrimination from chronic scars resulting from infarcts and foci of chronic progressive nephropathy (CPN). A case is presented here for interpreting the constellation of histologic changes induced in rats by melamine as representing an ascending form of nephropathy. The term retrograde nephropathy is considered to be the appropriate nomenclature for both the acute and chronic lesions. The cause for the reflux, emanating from the lower urinary tract, appeared not to be infection as an inflammatory response was not prominent. It can be speculated that melamine precipitation in the lower urinary tract created pressure effects through transient obstruction leading to the renal changes. These changes were different from those involved in a major US outbreak of renal disease and death in cats and dogs associated with triazine-contaminated pet food, in which crystalluria from insoluble melamine/cyanuric acid complexes occurred in the kidney. However, the rat findings may be relevant to melamine-associated kidney disease recently reported in infants in China.

  14. 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...

  15. 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.

  16. 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

  17. Effects of Black Raspberry Extract and Protocatechuic Acid on Carcinogen-DNA Adducts and Mutagenesis, and Oxidative Stress in Rat and Human Oral Cells.

    Science.gov (United States)

    Guttenplan, Joseph B; Chen, Kun-Ming; Sun, Yuan-Wan; Kosinska, Wieslawa; Zhou, Ying; Kim, Seungjin Agatha; Sung, Youngjae; Gowda, Krishne; Amin, Shantu; Stoner, Gary D; El-Bayoumy, Karam

    2016-08-01

    Effects of black raspberry (BRB) extract and protocatechuic acid (PCA) on DNA adduct formation and mutagenesis induced by metabolites of dibenzo[a,l]pyrene (DBP) were investigated in rat oral fibroblasts. The DBP metabolites, (±)-anti-11,12-dihydroxy-11,12,-dihydrodibenzo[a,l]pyrene (DBP-diol) and 11,12-dihydroxy-13,14-epoxy-11,12,13,14-tetrahydrodibenzo[a,l]pyrene (DBPDE) induced dose-dependent DNA adducts and mutations. DBPDE was considerably more potent, whereas the parent compound had no significant effect. Treatment with BRB extract (BRBE) and PCA resulted in reduced DBP-derived DNA adduct levels and reduced mutagenesis induced by DBP-diol, but only BRBE was similarly effective against (DBPDE). BRBE did not directly inactivate DBPDE, but rather induced a cellular response-enhanced DNA repair. When BRBE was added to cells 1 day after the DBP-diol, the BRBE greatly enhanced removal of DBP-derived DNA adducts. As oxidative stress can contribute to several stages of carcinogenesis, BRBE and PCA were investigated for their abilities to reduce oxidative stress in a human leukoplakia cell line by monitoring the redox indicator, 2',7'-dichlorodihydrofluorescein diacetate (H2DCF) in cellular and acellular systems. BRBE effectively inhibited the oxidation, but PCA was only minimally effective against H2DCF. These results taken together provide evidence that BRBE and PCA can inhibit initiation of carcinogenesis by polycyclic aromatic hydrocarbons; and in addition, BRBE reduces oxidative stress. Cancer Prev Res; 9(8); 704-12. ©2016 AACR. PMID:27267891

  18. 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.

  19. 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.

  20. Quantitative predictivity of the transformation in vitro assay compared with the Ames test. [Hamsters

    Energy Technology Data Exchange (ETDEWEB)

    Parodi, S.; Taningher, M.; Russo, P.; Pala, M.; Vecchio, D.; Fassina, G.; Santi, L.

    For 59 chemical compounds, homogeneous data on transformation in vitro, mutagenicity in the Ames test, and carcinogenicity was reviewed. The potency in inducing transformation in vitro in hamster fibroblast cells was compared with the carcinogenic potency and a modest correlation coefficient was found between the two parameters. For these same 59 compounds it was also possible to compare mutagenic potency in the Ames test with carcinogenic potency. The correlation level was very similar. The predictivity of transformation in vitro increased significantly when only compounds for which some kind of dose-response relationship was available were utilized. This result stresses the importance of the quantitative aspect of the response in predictivity studies. The present study is compared with previous studies on the quantitative predictivity of different short-term tests. The work is not definitive, but gives an idea of the possible type of approach to the problem of comparing quantitative predictivities.

  1. Carcinogenicity of hair dye components.

    Science.gov (United States)

    Van Duuren, B L

    1980-03-01

    The available animal carcinogenicity data on hair dye components was reviewed. From this review it became clear that certain hair dye components, some of which are still in hair dye formulations now on the market, are animal carcinogens. The compounds of concern that are still in use are: 3-amino-4-methoxyaniline, 2-nitro-4-aminoaniline and 3-nitro-4-hydroxyaniline. Certain azo dyes formerly used, and related compounds still in use, contain the benzidine moiety. Two of these compounds, Direct Blue 6 and Direct Black 38, have been shown to be metabolized in animals to the human carcinogen benzidine. Furthermore, skin absorption studies carried out with radiolabeled hair dye components applied to animal or human skin have conclusively shown that these compounds are systemically absorbed and excreted. Known cocarcinogens such as catechol and pyrogallol, which enhance benzo(a)pyrene carcinogenicity on mouse skin, are used as hair dye components. It is not known whether such compounds will enhance the carcinogenicity of substituted aniline hair dye chemicals. The available epidemiologic data are not sufficient to link hair dye use with an increased incidence in human cancer.

  2. 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.

  3. Aflatoxin B1 metabolism by 3-methylcholanthrene-induced hamster hepatic cytochrome P-450s.

    Science.gov (United States)

    Lai, T S; Chiang, J Y

    1990-01-01

    We have studied the activation of aflatoxin B1 by hamster liver microsomes and purified hamster cytochrome P-450 isozymes using a umu mutagen test. The hamster liver microsomes or S-9 fractions were much more active than rat liver microsomes or S-9 fractions in the activation of umu gene expression by aflatoxin B1 metabolites. 3-Methyl-cholanthrene treatment increased aflatoxin B1 activation by hamster liver microsomes. Two major 3-methylcholanthrene-inducible cytochrome P-450 isozymes, P-450 MC1 (IIA) and P-450 MC4 (IA2), were purified from 3-methylcholanthrene-treated hamster liver microsomes, and the metabolism of aflatoxin B1 by these two cytochromes was studied. In the reconstituted enzyme system, both P-450 MC1 and P-450 MC4 were highly active in the activation of aflatoxin B1, and antibodies against these P-450s specifically inhibited these activities. Antibody against P-450 MC1 inhibited the activation of aflatoxin B1 by 20% in the presence of 3-methyl-cholanthrene-treated hamster liver microsomes. In contrast, antibody against P-450 MC4 stimulated the activity by 175%. These results indicated that hamster P-450 MC1 might convert aflatoxin B1 to more toxic metabolite(s), whereas P-450 MC4 might convert aflatoxin B1 to less toxic metabolite(s), than aflatoxin B1 in liver microsomes. The metabolite(s) produced by both hamster cytochrome P-450 MC1 and MC4 were genotoxic in the umu mutagen test. PMID:2126562

  4. In vitro determination of carcinogenicity of sixty-four compounds using a bovine papillomavirus DNA-carrying C3H/10T(1/2) cell line.

    Science.gov (United States)

    Kowalski, L A; Laitinen, A M; Mortazavi-Asl, B; Wee, R K; Erb, H E; Assi, K P; Madden, Z

    2000-01-01

    A new in vitro test for predicting rodent carcinogenicity is evaluated against a testing database of 64 chemicals including both genotoxic and nongenotoxic carcinogens and carcinogens that normally require addition of an S-9 microsomal fraction for detection in the bacterial mutagenicity assay. The assay uses focus formation in a stable, bovine papillomavirus type 1 (BPV-1) DNA carrying C3H/10T(1/2) mouse embryo fibroblast cell line (T1) that does not require transfection, infection with virus, isolation of primary cells from animals, or addition of a microsomal fraction. Of a total database of 64 compounds, 92% of the carcinogens, promoters, or noncarcinogens were correctly predicted. Based on previously reported results, the test of bacterial mutagenicity would have correctly predicted 58% of carcinogens, promoters or noncarcinogens and the Syrian hamster embryo test would have correctly predicted 87% of carcinogens, promoters, or noncarcinogens of this database. Of carcinogens that normally require addition of an S-9 fraction, T1 cells correctly predicted rodent carcinogenicity of polyaromatic hydrocarbons, aflatoxins, azo-compounds, nitrosamines, and hydrazine without the addition of an S-9 fraction. Of nongenotoxic carcinogens, T1 cells correctly predicted diethylstilbestroel, diethylhexylphthalate, acetamides, alkyl halides, ethyl carbamate, and phorbol ester tumour promoters.

  5. 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.)

  6. 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....

  7. 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.

  8. 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.

  9. 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 "...

  10. Toxicologic evaluation of metronidazole with particular reference to carcinogenic, mutagenic, and teratogenic potential.

    Science.gov (United States)

    Roe, F J

    1983-01-01

    The gastrointestinal tract and nervous system are the main targets for metronidazole toxicity. With the possible exception of certain neurotoxic effects in a few heavily treated patients, all the toxic effects of metronidazole are transient and reversible on withdrawal of the drug. Properly designed tests for embryotoxicity and teratogenicity in rats, rabbits, and mice have produced convincingly negative results, and no adverse effects on the fetus have been observed in women given the drug for trichomoniasis during various stages of pregnancy. The antimicrobial activity of metronidazole is thought to depend on its nitroreduction to form short-lived cytotoxic metabolites capable of reacting with deoxyribonucleic acid. It is therefore perhaps not surprising that metronidazole has been reported to be mutagenic for certain strains of Salmonella typhimurium. Metronidazole gave negative results in the mouse micronucleus test and no increase in sister chromatid exchanges or chromosomal aberrations in cultured human lymphocytes. Prolonged exposure to metronidazole in the treatment of patients with Crohn's disease was not associated with any increase in the frequency of chromosomal aberrations. Prolonged high-dose exposure of mice to metronidazole led to an increased incidence of lung tumors in three separate studies and to a suggestive increase in lymphoreticular neoplasia in female animals in one of the studies. These effects are probably nonspecific, since major effects on the incidence of neoplasms of the same and other kinds have been produced by merely varying the amount of a standard diet that mice consume. A reported excess of liver tumors in rats exposed to metronidazole can be explained by the fact that the authors failed to age standardize their data despite a big and highly significant beneficial effect of the drug on survival. Two carcinogenicity studies in hamsters have given entirely negative results. The follow-up for 10 or more years of 771 women first

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

    Science.gov (United States)

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

    2013-09-01

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

  12. 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

  13. Rodent carcinogenicity with the thiazolidinedione antidiabetic agent troglitazone.

    Science.gov (United States)

    Herman, J R; Dethloff, L A; McGuire, E J; Parker, R F; Walsh, K M; Gough, A W; Masuda, H; de la Iglesia, F A

    2002-07-01

    Carcinogenic potential of the thiazolidinedione antidiabetic troglitazone was assessed in 104-week studies in mice and rats. Mice were given 50, 400, or 800 mg/kg, male rats 100, 400, or 800 mg/kg, and female rats 25, 50, or 200 mg/kg. Vehicle and placebo controls were included. Survival was significantly decreased in both sexes of both species at high doses, but was adequate for valid evaluation of carcinogenicity. Hypertrophy and hyperplasia of brown adipose tissue was observed in both species at all doses, and fatty change and hypocellularity of bone marrow was noted in mice at all doses and in female rats at 50 and 200 mg/kg. Hepatocellular vacuolation was observed in mice at 400 and 800 mg/kg, and centrilobular hepatocellular hypertrophy occurred in rats at > or = 200 mg/kg. Ventricular dilatation, myocardial fibrosis, and atrial myocyte karyomegaly in male rats at 400 and 800 mg/kg and female rats at all doses were morphologically similar to spontaneous lesions, but incidence and severity were increased compared with controls. In mice, the incidence of hemangiosarcoma was increased in females at 400 mg/kg and in both sexes at 800 mg/kg. The incidence of hepatocellular carcinoma was increased in female mice at 800 mg/kg. Troglitazone exposure [AUC((0-24))] at the lowest dose associated with increased tumor incidence in mice was 16 times human therapeutic exposure at 400 mg daily. No tumors of any type were increased in rats at exposures up to 47 times therapeutic exposure.

  14. 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

  15. 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.

  16. 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.

  17. 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

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

    Science.gov (United States)

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

    2014-04-01

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

  19. Strategies of reducing the carcinogenic risk of cytostatic agents on the basis of bioassay evaluation.

    Science.gov (United States)

    Berger, M R

    1991-01-01

    This article described strategies that can be used to reduce the carcinogenic risk of cytostatic chemotherapy and summarizes our recent experimental results. Reduction of neoplasms caused by the carcinogenic potency inherent in cytostatic agents can be obtained. (A) by chemical modifications such as: (1) exchanging a chlorine atom in N, N'-bis-(2-chloroethyl)-N-nitrosourea (BCNU) in the chloroethyl group at N'-position for a hydroxyl group to form the less carcinogenic analog N-(2-chloroethyl)-N'-(2-hydroxyethyl)-N-nitrosourea (HECNU); (2) linking chlorambucil to the steroid prednisolone to obtain a conjugate (prednimustine) with distinctly lower carcinogenic potential than chlorambucil; (3) progressive ring halogenation of phenyl-triazenes to generate agents with decreased long-term toxic risk; (B) by replacing cyclophosphamide within the carcinogenic drug combination of cyclophosphamide, methotrexate and 5-fluorouracil (CMF) by vincristine to form the combination VMF which has no detectable carcinogenic potential; (C) by coadministration of cyclophosphamide and mesna to achieve a dose-related reduction of cyclophosphamide-induced urinary bladder carcinomas; (D) by administration of dinaline, a compound which reduces the spontaneous incidence of malignant tumors in rats. These examples demonstrate that the carcinogenic risk of single agents and drug combinations used for antineoplastic chemotherapy has successfully been reduced, as assessed in long-term bioassays. Such strategies should be considered in the treatment of patients with long life expectancy following cytotoxic chemotherapy.

  20. 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.

  1. 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

  2. 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.

  3. 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...

  4. Cholecystokinin-33 acutely attenuates food foraging, hoarding and intake in Siberian hamsters.

    Science.gov (United States)

    Teubner, Brett J W; Bartness, Timothy J

    2010-04-01

    Neurochemicals that stimulate food foraging and hoarding in Siberian hamsters are becoming more apparent, but we do not know if cessation of these behaviors is due to waning of excitatory stimuli and/or the advent of inhibitory factors. Cholecystokinin (CCK) may be such an inhibitory factor as it is the prototypic gastrointestinal satiety peptide and is physiologically important in decreasing food intake in several species including Siberian hamsters. Systemic injection of CCK-33 in laboratory rats decreases food intake, doing so to a greater extent than CCK-8. We found minimal effects of CCK-8 on food foraging and hoarding previously in Siberian hamsters, but have not tested CCK-33. Therefore, we asked: Does CCK-33 decrease normal levels or food deprivation-induced increases in food foraging, hoarding and intake? Hamsters were housed in a wheel running-based foraging system with simulated burrows to test the effects of peripheral injections of CCK-33 (13.2, 26.4, or 52.8 microg/kg body mass), with or without a preceding 56 h food deprivation. The highest dose of CCK-33 caused large baseline reductions in all three behaviors for the 1st hour post-injection compared with saline; in addition, the intermediate CCK-33 dose was sufficient to curtail food intake and foraging during the 1st hour. In food-deprived hamsters, we used a 52.8 microg/kg body mass dose of CCK-33 which decreased food intake, hoarding, and foraging almost completely compared with saline controls for 1h. Therefore, CCK-33 appears to be a potent inhibitor of food intake, hoarding, and foraging in Siberian hamsters.

  5. Realignment of signal processing within a sensory brainstem nucleus as brain temperature declines in the Syrian hamster, a hibernating species

    Science.gov (United States)

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

    2014-01-01

    Crucial for survival, the central nervous system must reliably process sensory information over all stages of a hibernation bout to ensure homeostatic regulation is maintained and well-matched to dramatically altered behavioral states. Comparing neural responses in the nucleus tractus solitarius of rats and euthermic Syrian hamsters, we tested the hypothesis that hamster nucleus tractus solitarius neurons have adaptations sustaining signal processing while conserving energy. Using patch-clamp techniques, we classified second-order nucleus tractus solitarius neurons as rapid-onset or delayed-onset spiking phenotypes based on their spiking-onset to a depolarizing pulse (following a −80 mV prepulse). As temperature decreased from 33°C to 15°C, the excitability of all neurons decreased. However, hamster rapid-onset neurons had the highest spiking response and shortest action potential width at every temperature, while hamster delayed-onset neurons had the most negative resting membrane potential. Spontaneous excitatory post-synaptic current frequency in both phenotypes decreased as temperature decreased, yet tractus solitarius stimulation-evoked excitatory post-synaptic current amplitudes were greater in hamsters than in rats regardless of phenotype and temperature. Changes were significant (P<0.05), supporting our hypothesis by showing that, as temperature falls, rapid-onset neurons contribute more to signal processing but less to energy conservation than do delayed-onset neurons. PMID:22262373

  6. 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...

  7. 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

  8. The breast cancer resistance protein (Bcrp1/Abcg2) restricts exposure to the dietary carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine

    NARCIS (Netherlands)

    van Herwaarden, AE; Jonker, JW; Wagenaar, E; Brinkhuis, RF; Schellens, JHM; Beijnen, JH; Schinkel, AH

    2003-01-01

    The food carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is the most abundant heterocyclic amine found in various protein containing foods. PhIP is mutagenic and carcinogenic in rodents, inducing lymphomas in mice and colon, mammary and prostate carcinomas in rats. It has also been

  9. 17. Exposure and Metabolism of Heterocyclic Amine Food Mutagens/Carcinogens in Humans

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    @@Carcinogens produced from overcooked foods are extremely mutagenic in numerous in vitro and in vivo test systems. One of these mutagens, 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (PhIP) induces breast, colon and prostate tumors in rats and has been implicated in dietary epidemiology studies for raising the risk of

  10. 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

  11. 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

  12. Qualitative and quantitative approaches in the dose-response assessment of genotoxic carcinogens.

    Science.gov (United States)

    Fukushima, Shoji; Gi, Min; Kakehashi, Anna; Wanibuchi, Hideki; Matsumoto, Michiharu

    2016-05-01

    Qualitative and quantitative approaches are important issues in field of carcinogenic risk assessment of the genotoxic carcinogens. Herein, we provide quantitative data on low-dose hepatocarcinogenicity studies for three genotoxic hepatocarcinogens: 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and N-nitrosodiethylamine (DEN). Hepatocarcinogenicity was examined by quantitative analysis of glutathione S-transferase placental form (GST-P) positive foci, which are the preneoplastic lesions in rat hepatocarcinogenesis and the endpoint carcinogenic marker in the rat liver medium-term carcinogenicity bioassay. We also examined DNA damage and gene mutations which occurred through the initiation stage of carcinogenesis. For the establishment of points of departure (PoD) from which the cancer-related risk can be estimated, we analyzed the above events by quantitative no-observed-effect level and benchmark dose approaches. MeIQx at low doses induced formation of DNA-MeIQx adducts; somewhat higher doses caused elevation of 8-hydroxy-2'-deoxyquanosine levels; at still higher doses gene mutations occurred; and the highest dose induced formation of GST-P positive foci. These data indicate that early genotoxic events in the pathway to carcinogenesis showed the expected trend of lower PoDs for earlier events in the carcinogenic process. Similarly, only the highest dose of IQ caused an increase in the number of GST-P positive foci in the liver, while IQ-DNA adduct formation was observed with low doses. Moreover, treatment with DEN at low doses had no effect on development of GST-P positive foci in the liver. These data on PoDs for the markers contribute to understand whether genotoxic carcinogens have a threshold for their carcinogenicity. The most appropriate approach to use in low dose-response assessment must be approved on the basis of scientific judgment.

  13. 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

    . 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 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.......,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...

  14. 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.

  15. 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

  16. 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

  17. Contribution to the normal fecal flora of the hamster: Proteus mirabilis in normal feces of hamster

    Directory of Open Access Journals (Sweden)

    Genesio Pacheco

    1955-05-01

    Full Text Available Proteus mirabilis must be considered a normal inhabitant of the intestine of hamsters. It is also found in the vaginal secretion of females of this animal, when in oestrus.1 Os hamsters são parasitados pelos Proteus. 2 As amostras isoladas foram identificadas ao Pr. mirabilis de Hauser. 3 O Proteus isolado não revelou ação patogênica sôbre camundongos mas se mostrou patogênico para cobaias. 4 O germen era presente na secreção vaginal de hamsters, na época do cio.

  18. 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...

  19. Inhalation toxicity and carcinogenicity studies of cobalt sulfate.

    Science.gov (United States)

    Bucher, J R; Hailey, J R; Roycroft, J R; Haseman, J K; Sills, R C; Grumbein, S L; Mellick, P W; Chou, B J

    1999-05-01

    Cobalt sulfate is a water-soluble cobalt salt with a variety of industrial and agricultural uses. Several cobalt compounds have induced sarcomas at injection sites in animals, and reports have suggested that exposure to cobalt-containing materials may cause lung cancer in humans. The present studies were done because no adequate rodent carcinogenicity studies had been performed with a soluble cobalt salt using a route relevant to occupational exposures. Groups of 50 male and 50 female F344/N rats and B6C3F1 mice were exposed to aerosols containing 0, 0.3, 1.0, or 3.0 mg/m3 cobalt sulfate hexahydrate, 6 h/day, 5 days/week, for 104 weeks. Survival and body weights of exposed rats and mice were generally unaffected by the exposures. In rats, proteinosis, alveolar epithelial metaplasia, granulomatous alveolar inflammation, and interstitial fibrosis were observed in the lung in all exposed groups. Nonneoplastic lesions of the nose and larynx were also attributed to exposure to all concentrations of cobalt sulfate. In 3.0 mg/m3 male rats and in female rats exposed to 1.0 or 3.0 mg/m3, the incidences of alveolar/bronchiolar neoplasms were increased over those in the control groups. Lung tumors occurred with significant positive trends in both sexes. The incidences of adrenal pheochromocytoma in 1.0 mg/m3 male rats and in 3.0 mg/m3 female rats were increased. Nonneoplastic lesions of the respiratory tract were less severe in mice than in rats. In mice, alveolar/bronchiolar neoplasms in 3.0 mg/m3 males and females were greater than those in the controls, and lung tumors occurred with significantly positive trends. Male mice had liver lesions consistent with a Helicobacter hepaticus infection. Incidences of liver hemangiosarcomas were increased in exposed groups of male mice; however, because of the infection, no conclusion could be reached concerning an association between liver hemangiosarcomas and cobalt sulfate. In summary, exposure to cobalt sulfate by inhalation

  20. Procarbazine effects on spermatogenesis in golden hamster: a flow cytometric evaluation.

    Science.gov (United States)

    Weissenberg, R; Golan, R; Shochat, L; Lewin, L M

    2002-01-01

    The response of hamster testis to the administration of 450mg/kg procarbazine (PCB) over a period of 4 weeks was evaluated. Flow cytometry was used to investigate changes in cell populations in testicular single cell suspensions and to correlate these changes with those observed in histological sections. PCB caused significant decrease in testicular and epididymal weight and a drastic reduction in haploid cells and spermatogenic arrest, demonstrating variation among the test animals. The results obtained confirm previous observations concerning detrimental effects of PCB upon spermatogenesis in species such as the rat and mouse, though its effect on hamster testis is milder and does not include the germinal stem cells. The histological evaluation of the testis showed a good correlation with flow cytometric evaluation, emphasizing the usefulness of this method in providing quantitative and rapid results.

  1. 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)

  2. Nipah virus transmission in a hamster model.

    Directory of Open Access Journals (Sweden)

    Emmie de Wit

    2011-12-01

    Full Text Available Based on epidemiological data, it is believed that human-to-human transmission plays an important role in Nipah virus outbreaks. No experimental data are currently available on the potential routes of human-to-human transmission of Nipah virus. In a first dose-finding experiment in Syrian hamsters, it was shown that Nipah virus was predominantly shed via the respiratory tract within nasal and oropharyngeal secretions. Although Nipah viral RNA was detected in urogenital and rectal swabs, no infectious virus was recovered from these samples, suggesting no viable virus was shed via these routes. In addition, hamsters inoculated with high doses shed significantly higher amounts of viable Nipah virus particles in comparison with hamsters infected with lower inoculum doses. Using the highest inoculum dose, three potential routes of Nipah virus transmission were investigated in the hamster model: transmission via fomites, transmission via direct contact and transmission via aerosols. It was demonstrated that Nipah virus is transmitted efficiently via direct contact and inefficiently via fomites, but not via aerosols. These findings are in line with epidemiological data which suggest that direct contact with nasal and oropharyngeal secretions of Nipah virus infected individuals resulted in greater risk of Nipah virus infection. The data provide new and much-needed insights into the modes and efficiency of Nipah virus transmission and have important public health implications with regards to the risk assessment and management of future Nipah virus outbreaks.

  3. 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

  4. Proteomic Analysis of Chinese Hamster Ovary Cells

    DEFF Research Database (Denmark)

    Baycin-Hizal, Deniz; Tabb, David L.; Chaerkady, Raghothama;

    2012-01-01

    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, multidimens...

  5. 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

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

    Science.gov (United States)

    Papamokos, George; Silins, Ilona

    2016-01-01

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

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

    Science.gov (United States)

    Papamokos, George; Silins, Ilona

    2016-01-01

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

  8. Neonatal monosodium glutamate treatment counteracts circadian arrhythmicity induced by phase shifts of the light-dark cycle in female and male Siberian hamsters.

    Science.gov (United States)

    Prendergast, Brian J; Onishi, Kenneth G; Zucker, Irving

    2013-07-12

    Studies of rats and voles suggest that distinct pathways emanating from the anterior hypothalamic-retrochiasmatic area and the mediobasal hypothalamic arcuate nucleus independently generate ultradian rhythms (URs) in hormone secretion and behavior. We evaluated the hypothesis that destruction of arcuate nucleus (ARC) neurons, in concert with dampening of suprachiasmatic nucleus (SCN) circadian rhythmicity, would compromize the generation of ultradian rhythms (URs) of locomotor activity. Siberian hamsters retain-->of both sexes treated neonatally with monosodium glutamate (MSG) that destroys ARC neurons were subjected in adulthood to a circadian disrupting phase-shift protocol (DPS) that produces SCN arrhythmia. MSG treatments induced hypogonadism and obesity, retain-->and markedly reduced the size of the optic chiasm and optic nerves. MSG-treated hamsters exhibited normal entrainment to the light-dark cycle, but MSG treatretain-->ment counteracted the circadian arrhythmicity induced by the DPS protocol: only 6% of retain-->MSG-treated hamsters exhibited circadian arrhythmia, whereas 50% of control hamsters were circadian disrupted. In MSG-treated hamsters that retained circadian rhythmicity after DPS treatment, quantitative parameters of URs appeared normal, but in the two MSG-treated hamsters that became circadian arrhythmic after DPS, both dark-phase and light-phase URs were abolished. Although preliminary, these data are consistent with reports in voles suggesting that the combined disruption of SCN and ARC function impairs the expression of behavioral URs. The data also suggest that light thresholds for entrainment of circadian rhythms may be lower than those required to disrupt circadian organization.

  9. 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

  10. 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

  11. 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.

  12. 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

  13. [Leather azo dyes: mutagenic and carcinogenic risks].

    Science.gov (United States)

    Clonfero, E; Venier, P; Granella, M; Levis, A G

    1990-01-01

    The paper reviews the carcinogenicity and mutagenicity data on azo dyes used in the leather industry. Two water soluble benzidine-based dyes were classified as "probably carcinogenic to humans" by the International Agency for Research on Cancer (IARC). No other dyes have been evaluated by the IARC. Of the 48 azo dyes assayed in the Salmonella/microsome test, 20 gave positive results. Attention is drawn to the important role of the in vivo metabolism of azo compounds, which includes a preliminary reduction of the azo bonds and subsequent release of the aromatic amines of the dye. A useful assay (Prival test) for evaluating the mutagenic properties of azo dyes involves a reductive step that permits the release of any genotoxic agents present in the compounds. A list of leather azo dyes is furnished that are considered as potentially harmful due to the presence of a carcinogenic aromatic amine (benzidine, p-aminobenzene and derivatives) in their formulae.

  14. Mutagenicity, carcinogenicity and teratogenicity of beryllium.

    Science.gov (United States)

    Léonard, A; Lauwerys, R

    1987-07-01

    The carcinogenicity of a number of beryllium compounds has been confirmed in experiments on laboratory animals and this metal has to be treated as a possible carcinogenic threat to man. These carcinogenic properties are associated with mutagenic activity as shown by the results of short-term tests performed in vitro with beryllium chloride and beryllium sulfate. These soluble beryllium compounds can produce some infidelity of in vitro synthesis, forward gene mutations in microorganisms and in mammalian cells. They are also able to induce cell transformation. In addition to the positive results obtained in several short-term assays beryllium compounds have been found to bind to nucleoproteins, to inhibit certain enzymes needed for DNA synthesis, to bind nucleic acids to cell membranes and to inhibit microtubule polymerization. The teratogenicity of beryllium salts is relatively unknown and needs additional investigation.

  15. In Silico Methods for Carcinogenicity Assessment.

    Science.gov (United States)

    Golbamaki, Azadi; Benfenati, Emilio

    2016-01-01

    Screening compounds for potential carcinogenicity is of major importance for prevention of environmentally induced cancers. A large sequence of alternative predictive models, ranging from short-term biological assays (e.g. mutagenicity tests) to theoretical models, have been attempted in this field. Theoretical approaches such as (Q)SAR are highly desirable for identifying carcinogens, since they actively promote the replacement, reduction, and refinement of animal tests. This chapter reports and describes some of the most noted (Q)SAR models based on the human expert knowledge and statistically approach, aiming at predicting the carcinogenicity of chemicals. Additionally, the performance of the selected models has been evaluated and the results are interpreted in details by applying these prediction models to some pharmaceutical molecules.

  16. The ISS Carcinogens Data Bank (BDC).

    Science.gov (United States)

    Binetti, Roberto; Ceccarelli, Federica; Costamagna, Francesca Marina; D'Angiolini, Antonella; Fabri, Alessandra; Ferri, Maurizio; Riva, Giovanni; Roazzi, Paolo; Trucchi, Daniela; Marcello, Ida

    2008-01-01

    The Data Bank on Carcinogens (Banca Dati Cancerogeni, BDC) is a factual data bank, available on the Istituto Superiore di Sanità website, 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 website. 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. PMID:18469374

  17. 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.

  18. 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%.

  19. 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...

  20. 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.

  1. Quantitative comparison between in vivo DNA adduct formation from exposure to selected DNA-reactive carcinogens, natural background levels of DNA adduct formation and tumour incidende in rodent bioassays

    NARCIS (Netherlands)

    Paini, A.; Scholz, G.; Marin-Kuan, M.; Schilter, B.; O'Brien, J.; Bladeren, van P.J.; Rietjens, I.

    2011-01-01

    This study aimed at quantitatively comparing the occurrence/formation of DNA adducts with the carcinogenicity induced by a selection of DNA-reactive genotoxic carcinogens. Contrary to previous efforts, we used a very uniform set of data, limited to in vivo rat liver studies in order to investigate w

  2. Molecular and immunological characterization of the first allergenic lipocalin in hamster: the major allergen from Siberian hamster (Phodopus sungorus).

    Science.gov (United States)

    Torres, José Alberto; de Las Heras, Manuel; Maroto, Aroa Sanz; Vivanco, Fernando; Sastre, Joaquín; Pastor-Vargas, Carlos

    2014-08-22

    The most frequent pet allergy is to cat and dog, but in recent years, it has become increasingly popular to have other pets, and the risk of exposure to new allergens is more prevalent. The list of new pets includes hamsters, and one of the most popular hamsters is the Siberian hamster (Phodopus sungorus). The aim of this study was the characterization and cloning of the major allergen from this hamster. The study of its allergenicity and cross-reactivity could improve the specific diagnosis and treatment for hamster-allergic patients. Thirteen Siberian hamster-allergic patients were recruited at the outpatient clinic. Protein extracts were prepared from the hair, urine, and salivary glands of four hamster species (European, golden, Siberian, and Roborovski). IgE-binding proteins were detected by immunoblotting and identified by mass spectrometry. The recombinant protein was produced in Escherichia coli and then purified by metal chelate affinity chromatography. The allergenic properties of the recombinant protein were tested by ELISA and immunoblotting, and biological activity was tested according to capacity for basophil activation. Three IgE-binding proteins were identified in extracts obtained from Siberian hamster hair, urine, and salivary glands. All proteins corresponded to the same protein, which was identified as a lipocalin. This lipocalin had no cross-reactivity with common and golden hamsters. The recombinant allergen was cloned and purified, showing similar IgE reactivity in vitro to Siberian hamster protein extracts. Also, the recombinant allergen was capable of producing biological activation in vivo. The major Siberian hamster allergen was cloned, and allergenic properties were characterized, providing a new tool for specific diagnosis of allergy to Siberian hamster.

  3. Occupational exposures to carcinogens in developing countries.

    Science.gov (United States)

    Pearce, N; Matos, E; Boffetta, P; Kogevinas, M; Vainio, H

    1994-09-01

    There have been very few studies of exposure to occupational carcinogens in developing countries, and even fewer studies of the health consequences of such exposures. However, all industrial chemicals, occupations and industrial processes classified by the International Agency for Research on Cancer (IARC) as Group 1 or Group 2A (carcinogenic or possibly carcinogenic to humans) have been described in developing countries, and there is growing concern that the health impact of many chemicals used in the developing world has been underestimated. In all regions a very large workforce is employed in the construction industry, in which substantial exposure to asbestos may occur, and there has been a rapid increase in production in countries such as Brazil and India. There is, for instance, a similar pattern for tyre production with a large increase in production in developing countries in the 1980s. Thus, the number of workers in industries entailing a carcinogenic risk is increasing in developing countries, partly as a result of the transfer of hazardous industry from industrialized countries. There is much that could be achieved in the prevention of occupational cancer in developing countries, and there have been a number of successful initiatives. However, the greatest progress in the prevention of occupational cancer in developing countries is most likely to come from political and economic changes. PMID:7847748

  4. Carcinogenic compounds in alcoholic beverages: an update.

    Science.gov (United States)

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

    2016-10-01

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

  5. 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

  6. Roborovskin, a lipocalin in the urine of the Roborovski hamster, Phodopus roborovskii.

    Science.gov (United States)

    Turton, Michael J; Robertson, Duncan H L; Smith, Julia R; Hurst, Jane L; Beynon, Robert J

    2010-10-01

    Many rodents are now known to exhibit an obligate proteinuria that delivers urine-mediated chemosignals. In this paper, we explore the urinary proteins of the Roborovski hamster (Phodopus roborovskii). Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of urine from individual male and female Roborovski hamsters revealed 2 proteins, with approximate masses of 6 and 17 kDa, the expression pattern of which showed little variation between individuals or between sexes. Peptide mass fingerprints obtained from these 2 proteins revealed a number of features: 1) the proteins of a given mass were the same in all individuals regardless of sex, 2) the 6 kDa protein was not a fragment of the 21 kDa protein, and 3) neither protein was a fragment of a larger, conserved protein such as serum albumin. Electrospray mass spectrometry of purified protein preparations established the mass of the larger protein as invariant, at 17144 ± 2 Da in all samples. This protein has been termed roborovskin. The primary structure of roborovskin was determined by tandem mass spectrometry of peptides derived from independent and overlapping digestion with 3 proteases, supported by Edman degradation of the protein N-terminus. Roborovskin shared significant homology with olfactory-binding proteins from Myodes glareolus (bank vole) and with aphrodisin and submandibular protein from the golden hamster Mesocricetus auratus, all of which belong to the lipocalin superfamily. Lower levels of homology were also indicated between a variety of other lipocalins including the major urinary proteins from house mice and Norway rats. A model of the tertiary structure of roborovskin was constructed from the primary sequence by homology modeling. This model structure resembled other 8-stranded beta barrel lipocalins. Thus, the Roborovski hamster may demonstrate another variant of urinary lipocalin expression, as for the animals studied here, there appears to be no polymorphism in expression either

  7. 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.)

  8. 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...

  9. Emissions and air exposure of carcinogens and co-carcinogens in four Nordic countries

    DEFF Research Database (Denmark)

    Fauser, Patrik; Plejdrup, Marlene Schmidt; Ketzel, Matthias;

    . A list of carcinogenic andco-carcinogenic pollutants (particles, heavy metals and organic compounds) emittedfrom energy production, industrial activities, road transport, navigation, agriculture, residential heating and product use was compiled. Pollutant emissions levels for 2010and trends for 1990...... sources, traffic and residential wood combustion. An overview of local studies on exposure for cities or communities with emphasis on wood combustion and traffic and a discussion of existing epidemiological studies on cancer and environment were given...

  10. 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...

  11. 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.)

  12. 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.

  13. Circadian rhythms of photorefractory siberian hamsters remain responsive to melatonin.

    Science.gov (United States)

    Butler, Matthew P; Paul, Matthew J; Turner, Kevin W; Park, Jin Ho; Driscoll, Joseph R; Kriegsfeld, Lance J; Zucker, Irving

    2008-04-01

    Short day lengths increase the duration of nocturnal melatonin (Mel) secretion, which induces the winter phenotype in Siberian hamsters. After several months of continued exposure to short days, hamsters spontaneously revert to the spring-summer phenotype. This transition has been attributed to the development of refractoriness of Mel-binding tissues, including the suprachiasmatic nucleus (SCN), to long-duration Mel signals. The SCN of Siberian hamsters is required for the seasonal response to winter-like Mel signals, and becomes refractory to previously effective long-duration Mel signals restricted to this area. Acute Mel treatment phase shifts circadian locomotor rhythms of photosensitive Siberian hamsters, presumably by affecting circadian oscillators in the SCN. We tested whether seasonal refractoriness of the SCN to long-duration Mel signals also renders the circadian system of Siberian hamsters unresponsive to Mel. Males manifesting free-running circadian rhythms in constant dim red light were injected with Mel or vehicle for 5 days on a 23.5-h T-cycle beginning at circadian time 10. Mel injections caused significantly larger phase advances in activity onset than did the saline vehicle, but the magnitude of phase shifts to Mel did not differ between photorefractory and photosensitive hamsters. Similarly, when entrained to a 16-h light/8-h dark photocycle, photorefractory and photosensitive hamsters did not differ in their response to Mel injected 4 h before the onset of the dark phase. Activity onset in Mel-injected hamsters was masked by light but was revealed to be significantly earlier than in vehicle-injected hamsters upon transfer to constant dim red light. The acute effects of melatonin on circadian behavioral rhythms are preserved in photorefractory hamsters.

  14. 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.

  15. 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...

  16. Evidence for a direct effect of melatonin on mitochondrial genome expression of Siberian hamster brown adipocytes.

    Science.gov (United States)

    Prunet-Marcassus, B; Ambid, L; Viguerie-Bascands, N; Pénicaud, L; Casteilla, L

    2001-03-01

    Photoperiod variations are known to participate in the regulation of energy balance in different rodent species via melatonin, a neurosecretory product synthesized by the pineal gland during the night. A direct effect of melatonin on adipose tissue has been suggested since binding sites for the indole have been described on brown adipocytes. The aim of this study was to investigate a genetic effect of melatonin on isolated Siberian hamster brown adipocytes using differential display RT-PCR (DDRT-PCR). Brown adipose cells were isolated from brown adipose tissue and treated for 3 hr with 0.1 and 10 microM melatonin. Total RNA was extracted and DDRT-PCR experiments were performed. A differential band, which disappeared after melatonin treatment, was detected. After confirmation and cloning, the corresponding cDNA fragment B18 was sequenced. B18 had 85 and 81% similarity with a portion of rat and mouse cytochrome b mRNA, respectively, suggesting that B18 corresponds to hamster cytochrome b. This hypothesis was confirmed by the close parallel between the changes in mRNA content, detected by B18, and by cytochrome b mRNA content, detected by a rat probe. Cytochrome b mRNA is encoded by the mitochondrial genome, suggesting a similar effect of melatonin on the whole mitochondrial transcripts. Indeed, 3 hr of treatment with melatonin (10 nM and 0.1 microM) decreased by 44% mitochondrial transcript contents. This work constitutes the first evidence of a direct biological effect of melatonin on Siberian hamster brown adipocytes.

  17. The evolving definition of carcinogenic human papillomavirus

    Directory of Open Access Journals (Sweden)

    Castle Philip E

    2009-05-01

    Full Text Available Abstract Thirteen human papillomavirus (HPV genotypes have been judged to be carcinogenic or probably carcinogenic, and the cause of virtually all cervical cancer worldwide. Other HPV genotypes could possibly be involved. Although the inclusion of possibly carcinogenic HPV genotypes may hurt test specificity, it may indirectly increase the reassurance following a negative HPV test (i.e. the negative predictive value of an HPV test for cervical precancer and cancer. The future of cervical cancer screening in low-resource setting, however, may include once-in-a-lifetime, low-cost and rapid HPV testing. However, the tradeoff of more false positives for greater reassurance may not be acceptable if the local infrastructure cannot manage the screen positives. Now is the time for the community of scientists, doctors, and public health advocates to use the data presented at the 100th International Agency for Research on Cancer monograph meeting to rationally decide the target HPV genotypes for the next generation of HPV tests for use in high-resource and low-resource settings. The implications of including possibly HPV genotypes on HPV test performance, also for guidance on the use of these tests for cervical cancer prevention programs, are discussed.

  18. 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.

  19. Anatomical and functional characterisation of a dopaminergic system in the suprachiasmatic nucleus of the neonatal Siberian hamster.

    Science.gov (United States)

    Duffield, G E; McNulty, S; Ebling, F J

    1999-05-24

    In altricial rodents, maternal influences entrain the developing circadian system in the perinatal period before the capacity to respond directly to photic cues develops. The aim of these studies was to investigate the potential role of dopamine in this process in the Siberian hamster. An initial study investigated the ontogeny of retinal innervation of the suprachiasmatic nuclei (SCN) by using cholera toxin B subunit as a tracer. This revealed that retinal fibres first innervate the SCN on postnatal day 3 (PD3), and ingrowth of fibres is extensive by PD6. In situ hybridisation studies revealed the presence of D1-dopamine receptor (D1-R) mRNA in the SCN on PD2, and levels of expression were similar in PD6 pups and adult hamsters. Immunocytochemical staining for tyrosine hydroxylase revealed abundant catecholaminergic fibres within the ventromedial zone of the SCN from the day of birth through PD20; however, in contrast, few fibres were present in adult SCN. Dopamine-beta-hydroxylase-immunoreactive fibres were absent from the neonatal and adult SCN, suggesting that the fibres in the SCN are dopaminergic. The function of this dopaminergic system was investigated by determining the effects of D1-R agonists on the expression of the immediate-early gene c-fos in the SCN. This was assessed in pups ages PD1- PD5 by in situ hybridisation and immunocytochemical localisation of its protein product. No induction was seen in the SCN, in marked contrast to studies in the developing rat. A final series of studies investigated dopaminergic function by determining whether a D1-agonist could induce phosphorylation of Ca2+/cyclic AMP response element-binding protein (CREB) on Ser133. Hypothalamic slices containing SCN taken from PD1 and PD2 hamsters were treated with D1-R agonists, and levels of phosphorylated CREB were assayed by Western blots. Phosphorylation of CREB was stimulated by D1-R agonists in both Syrian and Siberian hamster hypothalamus, but the response was far greater

  20. Investigation of the uptake of drugs, carcinogens and mutagens by individual mammalian cells using a scanning proton microprobe

    Science.gov (United States)

    Cholewa, M.; Turnbull, I. F.; Legge, G. J. F.; Weigold, H.; Marcuccio, S. M.; Holan, G.; Tomlinson, E.; Wright, P. J.; Dillon, C. T.; Lay, P. A.; Bonin, A. M.

    1995-09-01

    The use of micro-PIXE [1] in measuring the quantitative uptake of drugs containing metal atoms by individual Vero cells (African green monkey kidney cell line) and V79 Chinese hamster lung cells is demonstrated. One class of drugs, heteropolytungstates, which are being assessed for activity against the HIV virus, were studied using Vero cells. The cellular uptake of a series of chromium compounds, including carcinogens and mutagens, in which the metal oxidation state was either (III), (V) or (VI), was measured using V79 cells. It was found that, unlike any other techniques, scanning proton microprobe (SPM) offers both the sensitivity and spatial resolution to carry out unicellular analysis. The use of cultured cell lines in these analyses was shown to have distinct advantages over cells such as peripheral blood lymphocytes (PBLs).

  1. Dietary fish oil blocks carcinogen-induced down-regulation of colonic protein kinase C isozymes.

    Science.gov (United States)

    Jiang, Y H; Lupton, J R; Chapkin, R S

    1997-02-01

    In order to elucidate the influence of dietary constituents on colonic intracellular signal transduction, the effect of different fats on rat colonic epithelial protein kinase C (PKC) alpha (classical), delta (novel) and lambda-zeta (atypical) expression was determined in carcinogen-treated animals. Sprague-Dawley rats were provided with one of two fats (corn oil and fish oil); plus or minus the carcinogen azoxymethane (AOM) and killed at two time points (15 and 37 weeks) in a 2x2x2 factorial design. At 5 and 6 weeks of age, animals were injected s.c. with either AOM at a dose of 15 mg/kg body weight or saline once a week for 2 weeks and continued on the same diet until termination of the study. At 15 and 37 weeks after the second injection, 10 rats from each treatment group were killed. Colonic PKC alpha, delta and lambda-zeta steady-state protein and mRNA levels were determined using immunoblotting and relative quantitative polymerase chain reaction, respectively. Colonic mucosa from rats injected with AOM had significantly suppressed membrane and cytosolic PKC alpha and cytosolic lambda-zeta protein levels (P fish oil diets had significantly higher (P protein levels relative to animals fed corn oil diets. However, the effect of diet and AOM on the steady-state expression of PKC alpha, delta and zeta mRNA was not consistent with changes in the respective isozyme protein levels, suggesting regulation at the post-transcriptional level. These data demonstrate that dietary fish oil blocks the carcinogen-induced decrease in the steady-state levels of colonic mucosal PKC delta and lambda-zeta, which may in part explain why this fat source protects against colon cancer development.

  2. 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

  3. Torpor shortens the period of Siberian hamster circadian rhythms.

    Science.gov (United States)

    Thomas, E M; Jewett, M E; Zucker, I

    1993-10-01

    We investigated the influence of ambient and body temperature (Ta and Tb) on circadian rhythms of gonadectomized male Siberian hamsters. Animals that entered torpor (Tb circadian periods (tau s) than did nontorpid hamsters at a Ta of 13 degrees C (24.17 +/- 0.05 vs. 24.33 +/- 0.04 h). The tau s of homeothermic hamsters were not affected by Ta change. Short-term decreases in Tb, rather than changes in Ta, appear to affect tau. Access to activity wheels inhibited expression of torpor in short daylengths and was associated with significant increases in body mass. Running wheel activity can mask or block specific short-day responses.

  4. 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.

  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. The comet assay with multiple mouse organs: comparison of comet assay results and carcinogenicity with 208 chemicals selected from the IARC monographs and U.S. NTP Carcinogenicity Database.

    Science.gov (United States)

    Sasaki, Y F; Sekihashi, K; Izumiyama, F; Nishidate, E; Saga, A; Ishida, K; Tsuda, S

    2000-11-01

    The comet assay is a microgel electrophoresis technique for detecting DNA damage at the level of the single cell. When this technique is applied to detect genotoxicity in experimental animals, the most important advantage is that DNA lesions can be measured in any organ, regardless of the extent of mitotic activity. The purpose of this article is to summarize the in vivo genotoxicity in eight organs of the mouse of 208 chemicals selected from International Agency for Research on Cancer (IARC) Groups 1, 2A, 2B, 3, and 4, and from the U.S. National Toxicology Program (NTP) Carcinogenicity Database, and to discuss the utility of the comet assay in genetic toxicology. Alkylating agents, amides, aromatic amines, azo compounds, cyclic nitro compounds, hydrazines, halides having reactive halogens, and polycyclic aromatic hydrocarbons were chemicals showing high positive effects in this assay. The responses detected reflected the ability of this assay to detect the fragmentation of DNA molecules produced by DNA single strand breaks induced chemically and those derived from alkali-labile sites developed from alkylated bases and bulky base adducts. The mouse or rat organs exhibiting increased levels of DNA damage were not necessarily the target organs for carcinogenicity. It was rare, in contrast, for the target organs not to show DNA damage. Therefore, organ-specific genotoxicity was necessary but not sufficient for the prediction of organ-specific carcinogenicity. It would be expected that DNA crosslinkers would be difficult to detect by this assay, because of the resulting inhibition of DNA unwinding. The proportion of 10 DNA crosslinkers that was positive, however, was high in the gastrointestinal mucosa, stomach, and colon, but less than 50% in the liver and lung. It was interesting that the genotoxicity of DNA crosslinkers could be detected in the gastrointestinal organs even though the agents were administered intraperitoneally. Chemical carcinogens can be classified

  7. DNA-damaging activity in vivo and bacterial mutagenicity of sixteen aromatic amines and azo-derivatives, as related quantitatively to their carcinogenicity.

    Science.gov (United States)

    Parodi, S; Taningher, M; Russo, P; Pala, M; Tamaro, M; Monti-Bragadin, C

    1981-01-01

    Sixteen aromatic amines and azo-derivatives were studied. They were: benzidine; 2-acetylaminofluorene; 3'-methyl-p-dimethylaminobenzene; o-aminoazo-toluene; p-dimethylaminoazobenzene; 2,4-diamino-toluene; 4,4'-oxydianiline; 2,4-diaminoanisole; 4,4'-methylenedianiline; 2-naphthylamine; Auramine O; Rhodamine B; Ponceau MX; 1-naphthylamine; p-aminoazobenzene and aniline. The compounds were examined for their capability to induce alkaline DNA fragmentation in rat liver after treatment in vivo, for their mutagenicity in the Salmonella strains TA 98 and TA 100, for their acute toxicity and for their carcinogenicity in mice and rats. For each parameter a quantitative potency index was established, and the correlation existing amongst the different parameters investigated. Only mutagenicity in the strain TA 98 was slightly correlated with carcinogenic potency (r = 0.408). DNA fragmentation and toxicity were not correlated with carcinogenicity. A significant correlation was found between DNA fragmentation and toxicity (r = 0.539). No correlation was found between DNA fragmentation and mutagenicity. The lack of correlation between DNA fragmentation and carcinogenicity is in contrast with previous results obtained with a family of hydrazine derivatives (12) and a group of nitrosocompounds (22). For these two groups of chemicals correlation between DNA fragmentation and carcinogenicity existed, but not between carcinogenicity and mutagenicity in the Ames' test. It is suggested that short term tests can perform very differently for different classes of chemicals.

  8. 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

  9. 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.

  10. Occurrence, uses, and carcinogenicity of arylamines.

    Science.gov (United States)

    Chung, King-Thom

    2015-01-01

    Arylamines are chemically synthesized and contained in oxidants, epoxy polymers, explosives, fungicides, pesticides, colorants, polyurethanes, and used in rubber, pharmacology, cosmetics, and other chemical industries. Many arylamines are ubiquitously present in cigarette smoke, cooking fume hoods, foods, automobile exhaust, industrial sites, etc. Some arylamines can be generated through azo reduction by intestinal, skin, and environmental microorganisms from azo dyes that are widely used. Arylamines can also be generated by reduction of the nitro-group containing polyhydrated hydrocarbons including muntions. Some arylamines are released by burning nitrogen containing organic materials at high temperatures. Some medical drugs are also arylamines. Furthermore, many arylamines are essential constituents of normal metabolism or the result of abnormal metabolism or dietary sources. Some arylamines are mutagenic, carcinogenic or the cause of other kinds of maladies. Some arylamine are considered the major etiological agents of bladder tumors in humans and animals but may also induce other types of cancers in various organs. The organ, tissue, and species specificity of the arylamine-inducing carcinogenesis may be determined by their availability, distribution, and the presence of metabolic activation/detoxicification enzymes of each organ or tissue of different species. The ubiquitous arylamines, therefore, pose serious hazards to human health and environment. This article will address the occurrence, uses, carcinogenicity, and other arylamines-induced diseases.

  11. 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...

  12. 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...

  13. 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

  14. 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.

  15. 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.

  16. 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

  17. 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...

  18. Use of inverted intestinal sacs to assess the effect of gastrointestinal insult on carcinogen absorption.

    Science.gov (United States)

    Capel, I D; Cosier, R S; Pinnock, M H; Williams, D C

    1981-01-01

    Rats were subjected to various forms of treatment in the manner likely to induce gastrointestinal insult. These and control animals were sacrificed and, using inverted sacs, the rate of absorption of either dimethylnitrosamine and benzo(a)pyrene determined. The gastrointestinal injury resulting from the differing treatments did not significantly affect the absorption of benzo(a)pyrene, whereas that of dimethylnitrosamine was significantly increased after each incubation time, most notably by alcohol pretreatment. The results demonstrate that intestinal damage increases the absorption of some carcinogens.

  19. 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)

  20. 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.

  1. 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)

  2. 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...

  3. Social thermoregulation and torpor in the Siberian hamster.

    Science.gov (United States)

    Jefimow, Małgorzata; Głabska, Marta; Wojciechowski, Michał S

    2011-04-01

    Social thermoregulation and huddling bring about energy benefits to animals sharing a nest because of the smaller surface-to-volume ratio of a huddle and the higher local temperature in the nest. We tested whether living in groups and huddling affect daily torpor, metabolic rate and seasonal changes in the body mass of a small heterothermic rodent, the Siberian hamster (Phodopus sungorus), housed under semi-natural conditions both singly and in groups of four litter-mates. We predicted that in hamsters housed in groups: (1) synchronized torpor bouts would be longer and deeper than non-synchronized ones but shallower than in solitary hamsters, (2) seasonal variations in metabolic rate would be lower than in solitary hamsters, and (3) the winter decrease in body mass would be smaller in grouped than in singly housed hamsters. We found that group housing led to a smaller decrease in body mass in winter, and affected the length and depth of daily torpor. In group-living hamsters more than 50% of all torpor episodes were synchronized and torpid animals were often found in huddles formed of all cage-mates. The longest and deepest torpor bouts in groups were recorded when all animals in a group entered torpor simultaneously. Although the minimum body temperature during torpor was higher, torpor duration was slightly longer than in solitary hamsters. We did not record significant differences in the body mass-adjusted rate of oxygen consumption between solitary and grouped animals, either in the cold or at the lower critical temperature. We conclude that social thermoregulation enables maintenance of a larger body mass, and thus a larger body fat content, which can ensure better body condition at the beginning of the reproductive season.

  4. 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).

  5. 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)

  6. 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

  7. 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

  8. Social context modulates food hoarding in Syrian hamsters

    Directory of Open Access Journals (Sweden)

    Bibiana Montoya

    2016-09-01

    Full Text Available The effect of the presence of a con-specific in the temporal organization of food hoarding was studied in two varieties of Syrian hamster (Mesocricetus auratus: golden and long-haired. Four male hamsters of each variety were used. Their foraging behavior was observed during four individual and four shared trials in which animals were not competing for the same food source or territory. During individual trials, long-haired hamsters consumed food items directly from the food source, transporting and hoarding only remaining pieces. During shared trials, the long-haired variety hoarded food items before consumption, and increased the duration of hoarding trips, food handling in the storage, and cache size. Golden hamsters maintained the same temporal organization of hoarding behavior (i.e., hoarding food items before consumption throughout both individual and shared trials. However, the golden variety increased handling time at the food source and decreased the duration of hoarding trips, the latency of hoarding and storing size throughout the shared trials. In Syrian hamsters, the presence of a con-specific may signal high probability of food source depletion suggesting that social pressures over food availability might facilitate hoarding behavior. Further studies are required to evaluate cost-benefit balance of food hoarding and the role of cache pilferage in this species.

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

    Science.gov (United States)

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

    2010-11-01

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

  11. 9 CFR 3.36 - Primary enclosures used to transport live guinea pigs and hamsters.

    Science.gov (United States)

    2010-01-01

    ... live guinea pigs and hamsters. 3.36 Section 3.36 Animals and Animal Products ANIMAL AND PLANT HEALTH..., Care, Treatment, and Transportation of Guinea Pigs and Hamsters Transportation Standards § 3.36 Primary enclosures used to transport live guinea pigs and hamsters. No person subject to the Animal...

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

    Energy Technology Data Exchange (ETDEWEB)

    Reddy, M.V.; Gupta, R.C.; Randerath, E.; Randerath, K.

    1984-02-01

    Carcinogen--DNA adducts were detected and determined by /sup 32/P-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'-/sup 32/P-labeled deoxyribonucleoside 3',5'-bisphosphates by T4 polynucleotide kinase-catalyzed (/sup 32/P)phosphate transfer from (gamma-/sup 32/P)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(/sup 8/) normal nucleotides, while the limit of detection of methylated adducts was 1 adduct in approximately 6 X 10(/sup 5/) nucleotides. The results show that a great number of carcinogen-DNA adducts of diverse structure are substrates for /sup 32/P-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, /sup 32/P-postlabeling analysis of carcinogen--DNA adducts in mammalian tissues may serve as a test for the screening of chemicals for potential carcinogenicity.

  13. 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

  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. Towards incorporating epigenetic mechanisms into carcinogen identification and evaluation.

    Science.gov (United States)

    Herceg, Zdenko; Lambert, Marie-Pierre; van Veldhoven, Karin; Demetriou, Christiana; Vineis, Paolo; Smith, Martyn T; Straif, Kurt; Wild, Christopher P

    2013-09-01

    Remarkable progress in the field of epigenetics has turned academic, medical and public attention to the potential applications of these new advances in medicine and various fields of biomedical research. The result is a broader appreciation of epigenetic phenomena in the a etiology of common human diseases, most notably cancer. These advances also represent an exciting opportunity to incorporate epigenetics and epigenomics into carcinogen identification and safety assessment. Current epigenetic studies, including major international sequencing projects, are expected to generate information for establishing the 'normal' epigenome of tissues and cell types as well as the physiological variability of the epigenome against which carcinogen exposure can be assessed. Recently, epigenetic events have emerged as key mechanisms in cancer development, and while our search of the Monograph Volume 100 revealed that epigenetics have played a modest role in evaluating human carcinogens by the International Agency for Research on Cancer (IARC) Monographs so far, epigenetic data might play a pivotal role in the future. Here, we review (i) the current status of incorporation of epigenetics in carcinogen evaluation in the IARC Monographs Programme, (ii) potential modes of action for epigenetic carcinogens, (iii) current in vivo and in vitro technologies to detect epigenetic carcinogens, (iv) genomic regions and epigenetic modifications and their biological consequences and (v) critical technological and biological issues in assessment of epigenetic carcinogens. We also discuss the issues related to opportunities and challenges in the application of epigenetic testing in carcinogen identification and evaluation. Although the application of epigenetic assays in carcinogen evaluation is still in its infancy, important data are being generated and valuable scientific resources are being established that should catalyse future applications of epigenetic testing.

  16. 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.

  17. cDNA sequence and Fab crystal structure of HL4E10, a hamster IgG lambda light chain antibody stimulatory for γδ T cells.

    Directory of Open Access Journals (Sweden)

    Petra Verdino

    Full Text Available Hamsters are widely used to generate monoclonal antibodies against mouse, rat, and human antigens, but sequence and structural information for hamster immunoglobulins is sparse. To our knowledge, only three hamster IgG sequences have been published, all of which use kappa light chains, and no three-dimensional structure of a hamster antibody has been reported. We generated antibody HL4E10 as a probe to identify novel costimulatory molecules on the surface of γδ T cells which lack the traditional αβ T cell co-receptors CD4, CD8, and the costimulatory molecule CD28. HL4E10 binding to γδ T cell, surface-expressed, Junctional Adhesion Molecule-Like (JAML protein leads to potent costimulation via activation of MAP kinase pathways and cytokine production, resulting in cell proliferation. The cDNA sequence of HL4E10 is the first example of a hamster lambda light chain and only the second known complete hamster heavy chain sequence. The crystal structure of the HL4E10 Fab at 2.95 Å resolution reveals a rigid combining site with pockets faceted by solvent-exposed tyrosine residues, which are structurally optimized for JAML binding. The characterization of HL4E10 thus comprises a valuable addition to the spartan database of hamster immunoglobulin genes and structures. As the HL4E10 antibody is uniquely costimulatory for γδ T cells, humanized versions thereof may be of clinical relevance in treating γδ T cell dysfunction-associated diseases, such as chronic non-healing wounds and cancer.

  18. 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.

  19. 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.

  20. 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

  1. Homeostatic regulation of sleep in arrhythmic Siberian hamsters.

    Science.gov (United States)

    Larkin, Jennie E; Yokogawa, Tohei; Heller, H Craig; Franken, Paul; Ruby, Norman F

    2004-07-01

    Sleep is regulated by independent yet interacting circadian and homeostatic processes. The present study used a novel approach to study sleep homeostasis in the absence of circadian influences by exposing Siberian hamsters to a simple phase delay of the photocycle to make them arrhythmic. Because these hamsters lacked any circadian organization, their sleep homeostasis could be studied in the absence of circadian interactions. Control animals retained circadian rhythmicity after the phase shift and re-entrained to the phase-shifted photocycle. These animals displayed robust daily sleep-wake rhythms with consolidated sleep during the light phase beginning about 1 h after light onset. This marked sleep-wake pattern was circadian in that it persisted in constant darkness. The distribution of sleep in the arrhythmic hamsters over 24 h was similar to that in the light phase of rhythmic animals. Therefore, daily sleep amounts were higher in arrhythmic animals compared with rhythmic ones. During 2- and 6-h sleep deprivations (SD), it was more difficult to keep arrhythmic hamsters awake than it was for rhythmic hamsters. Because the arrhythmic animals obtained more non-rapid eye movement sleep (NREMS) during the SD, they showed a diminished compensatory response in NREMS EEG slow-wave activity during recovery sleep. When amounts of sleep during the SD were taken into account, there were no differences in sleep homeostasis between experimental and control hamsters. Thus loss of circadian control did not alter the homeostatic response to SD. This supports the view that circadian and homeostatic influences on sleep regulation are independent processes.

  2. 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.

  3. 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.

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

    DEFF Research Database (Denmark)

    2015-01-01

    for identifying a CHO cell line having a desired genetic trait, as well as for generating a desired CHO cell line having a genetic basis for a desired phenotype. Additionally, described herein are methods for constructing and analyzing in silico models of biological networks for CHO cells.......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...

  5. 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

  6. 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...

  7. 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...

  8. Best practices for clinical pathology testing in carcinogenicity studies.

    Science.gov (United States)

    Young, Jamie K; Hall, Robert L; O'Brien, Peter; Strauss, Volker; Vahle, John L

    2011-02-01

    The Society of Toxicologic Pathology (STP) and American Society for Veterinary Clinical Pathology (ASCVP) convened a Clinical Pathology in Carcinogenicity Studies Working Group to recommend best practices for inclusion of clinical pathology testing in carcinogenicity studies. Regulatory guidance documents and literature were reviewed, and veterinary pathologists from North America, Japan, and Europe were surveyed regarding current practices, perceived value, and recommendations for clinical pathology testing in carcinogenicity studies. For two-year rodent carcinogenicity studies, the Working Group recommends that clinical pathology testing be limited to collection of blood smears at scheduled and unscheduled sacrifices to be examined only if indicated to aid in the diagnosis of possible hematopoietic neoplasia following histopathologic evaluation. Additional clinical pathology testing is most appropriately used to address specific issues from prior toxicity studies or known test article-related class effects. Inadequate data were available to make a recommendation concerning clinical pathology testing for alternative six-month carcinogenicity assays using genetically modified mice, although the Working Group suggests that it may be appropriate to use the same approach as for two-year carcinogenicity studies since the study goal is the same.

  9. 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

  10. Enhancement of 5-iododeoxyuridine-induced endogenous C-type virus activation by polycyclic hydrocarbons: apparent lack of parallelism between enhancement and carcinogenicity.

    Science.gov (United States)

    Yoshikura, H; Zajdela, F; Perin, F; Perin-Roussel, O; Jacquignon, P; Latarjet, R

    1977-04-01

    When mouse MLg cells were treated with 3-methylcholanthrene or 7,12-dimethylbenz[alpha]anthracene in the presence of microsomal enzymes and NADPH after 5-iododeoxyuridine (IUDR) treatment, the induction rate of the endogenous C-type virus was increased fivefold to sixfold in comparison with the culture treated with IUDR only. In this reaction, both the microsomal enzymes and NADPH were indispensable. 7,8-Benzoflavone, an inhibitor of the metabolism of hydrocarbons in hamster embryo cultures, inhibited the reaction. For detecting the enhancing activity, the concentration of IUDR for the pretreatment, the concentration of the test products, and the duration of the treatment with the products were important factors. In screening 30 polycyclic hydrocarbons, we were unable to detect a correlation between the in vivo carcinogenicity in the skin and the enhancing activity in the conditions tested.

  11. Melatonin production accompanies arousal from daily torpor in Siberian hamsters.

    Science.gov (United States)

    Larkin, Jennie E; Yellon, Steven M; Zucker, Irving

    2003-01-01

    Arousal from deep hibernation is accompanied by a transient rise of melatonin (Mel) in circulation; there are no comparable analyses of Mel concentrations in species that undergo much shallower, shorter duration episodes of daily torpor. Serum Mel concentrations were determined during arousal from both natural daily torpor and torpor induced by 2-deoxy-D-glucose (2-DG) treatment (2,500 mg/kg, intraperitoneal [IP]); blood samples were drawn from the retro-orbital sinus of anesthetized Siberian hamsters. For animals kept in darkness during torpor, Mel concentrations were highest during early arousal when thermogenesis is maximal, and they decreased as body temperature increased during arousal and returned to baseline once euthermia was reestablished. In hamsters kept in the light during the torpor bout, Mel concentrations were elevated above basal values during arousal, but the response was significantly blunted in comparison with values recorded in darkness. Increased Mel concentrations were detected in hamsters only during arousal from torpor (either natural or 2-DG induced) and were not simply a result of the drug treatment; hamsters that remained euthermic or manifested mild hypothermia after drug treatment maintained basal Mel concentrations. We propose that increased Mel production may reflect enhanced sympathetic activation associated with intense thermogenesis during arousal from torpor rather than an adjustment of the circadian rhythm of Mel secretion.

  12. 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.

  13. 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...

  14. 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

  15. 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

  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. 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

  18. 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.

  19. Prediction of Non-Genotoxic Carcinogenicity Based on Genetic Profiles of Short Term Exposure Assays

    Science.gov (United States)

    Pérez, Luis Orlando; González-José, Rolando; García, Pilar Peral

    2016-01-01

    Non-genotoxic carcinogens are substances that induce tumorigenesis by non-mutagenic mechanisms and long term rodent bioassays are required to identify them. Recent studies have shown that transcription profiling can be applied to develop early identifiers for long term phenotypes. In this study, we used rat liver expression profiles from the NTP (National Toxicology Program, Research Triangle Park, USA) DrugMatrix Database to construct a gene classifier that can distinguish between non-genotoxic carcinogens and other chemicals. The model was based on short term exposure assays (3 days) and the training was limited to oxidative stressors, peroxisome proliferators and hormone modulators. Validation of the predictor was performed on independent toxicogenomic data (TG-GATEs, Toxicogenomics Project-Genomics Assisted Toxicity Evaluation System, Osaka, Japan). To build our model we performed Random Forests together with a recursive elimination algorithm (VarSelRF). Gene set enrichment analysis was employed for functional interpretation. A total of 770 microarrays comprising 96 different compounds were analyzed and a predictor of 54 genes was built. Prediction accuracy was 0.85 in the training set, 0.87 in the test set and increased with increasing concentration in the validation set: 0.6 at low dose, 0.7 at medium doses and 0.81 at high doses. Pathway analysis revealed gene prominence of cellular respiration, energy production and lipoprotein metabolism. The biggest target of toxicogenomics is accurately predict the toxicity of unknown drugs. In this analysis, we presented a classifier that can predict non-genotoxic carcinogenicity by using short term exposure assays. In this approach, dose level is critical when evaluating chemicals at early time points.

  20. N,N-diethyl-4-aminoazobenzene (DEAB): acute actions with respect to possible carcinogenicity as well as the role of solvents. Morphological and pharmacological investigations.

    Science.gov (United States)

    Danz, M; Klinger, W; Müller, D; Kleeberg, U; Glöckner, R; Ziebarth, D; Urban, H

    1978-01-01

    The acute action of the azo dye DEAB was investigated in Sprague-Dawley (SD) and Wistar (Wi) rats. The substance was dissolved both in DMSO and sunflower oil and was administered once by stomach tube. Cytochrome P-450-DEPENDENT N-demethylation of ethylmorphine and dimethylnitrosamine are differentially altered depending on the solvent used. The excretion of DEAB as well as of N,N-dimethyl-4-amino-azobenzene (DAB) is delayed and diminished if the substances are dissolved in DMSO. Beside these effects the mitotic number in the adrenal cortex is significantly elevated in both strains of rats. But, in SD rats only DMSO-solution of DEAB is effective. In Wi rats both are effective, the oily solution more than that in DMSO. In this respect DEAB resembles DAB and various other carcinogens which are efficient in stimulating adrenocortical cell division. Considering the positive short-term assay after three other substances which revealed carcinogenic properties in long-term experiments we conclude that also DEAB may be carcinogenic in adequate long-term examination.

  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. 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.

  3. 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

  4. Central administration of thyrotropin releasing hormone (TRH) and related peptides inhibits feeding behavior in the Siberian hamster.

    Science.gov (United States)

    Steward, Carolyn A; Horan, Tracey L; Schuhler, Sandrine; Bennett, Geoffrey W; Ebling, Francis J P

    2003-04-15

    Centrally acting thyrotropin releasing hormone (TRH), independent of endocrine action, has been shown to regulate several metabolic and behavioral parameters in rats, including food intake and locomotor activity. The present study investigated and compared the effects of central TRH on feeding behavior in Siberian hamsters exposed to long (LP) or short (SP) photoperiods, which induce natural physiological states of obesity and leanness respectively. The effects of two TRH analogues, RX77368 (a metabolically stable TRH analogue) and TRH-Gly (an endogenous precursor to TRH with putative preferential action at the central TRH receptor, TRH-R2), were also investigated. All peptides were infused via the third ventricle (i.c.v.). Food intake was measured, and the proportion of time spent interacting with food, active or resting was scored. TRH (5 microg) significantly reduced food intake without producing associated changes in activity in hamsters maintained in both LP (p hamsters exposed to SP, indicating that there may be an underlying difference in sensitivity to TRH depending on metabolic state. RX77368 (1 microg) produced substantial hypophagia (p < 0.001) and decreased the proportion of time spent interacting with food, but, unlike TRH, may produce this via an increase in locomotor activity. TRH-Gly (5 microg) produced a small decrease in food intake (p < 0.05), lasting for 6 h. We conclude that TRH and TRH analogues possess anorexigenic capacities in this species, with a likely site of action in the hypothalamus. Increased sensitivity to the hypophagic effects of central TRH may contribute to the long-term catabolic state induced by short photoperiods.

  5. Studies in vitro to discern the structural requirements for carcinogenicity in analogues of the carcinogen 4-dimethylaminoazobenzene (butter yellow).

    Science.gov (United States)

    Ashby, J; Styles, J A; Paton, D

    1980-01-01

    4-Dimethylaminoazobenzene (butter yellow, DAB), is the parent member of a large family of 'azo-carcinogens'. Experiments have been conducted in vitro to determine the key structural requirements for carcinogenic activity in this chemical class, and it is suggested, based on the activity observed for 4-cyano-N,N-dimethylaniline, that the 4-phenylazo group of DAB is not an essential structural feature per se. The N-oxide derivative of DAB has been evaluated in vitro and the positive response observed related to its metabolic activation. It is concluded that cyclic amines, such as pyrrolidine, can replace the N-dimethyl group of DAB with a retention of biological activity. The confusion that exists in the literature concerning the chemical identity and carcinogenic status of 2-dimethylaminobenzo[c]cinnoline has been investigated, and it is concluded that it is a potential animal carcinogen. This observation also indicates that the phenylazo group of DAB can be incorporated within an aromatic ring system with a retention of biological activity. As observed earlier with a mixture of azobenzene and DAB, azobenzene also potentiates the cell transforming properties of the above cinnoline derivative in vitro. Two charts are presented. The first attempts to integrate DAB within a much larger family of carcinogens, and the second illustrates the usefulness of structure-activity studies in general.

  6. 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.

  7. 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.

  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. Cannabis and tobacco smoke are not equally carcinogenic

    Directory of Open Access Journals (Sweden)

    Melamede Robert

    2005-10-01

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

  10. 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

  11. 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.

  12. Cystolithiasis in a Syrian hamster: a different outcome.

    Science.gov (United States)

    Petrini, D; Di Giuseppe, M; Deli, G; De Caro Carella, C

    2016-01-01

    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. PMID:27540515

  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. 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...

  16. 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...

  17. Photoperiodic influences on ultradian rhythms of male Siberian hamsters.

    Science.gov (United States)

    Prendergast, Brian J; Zucker, Irving

    2012-01-01

    Seasonal changes in mammalian physiology and behavior are proximately controlled by the annual variation in day length. Long summer and short winter day lengths markedly alter the amplitude of endogenous circadian rhythms and may affect ultradian oscillations, but the threshold photoperiods for inducing these changes are not known. We assessed the effects of short and intermediate day lengths and changes in reproductive physiology on circadian and ultradian rhythms of locomotor activity in Siberian hamsters. Males were maintained in a long photoperiod from birth (15 h light/day; 15 L) and transferred in adulthood to 1 of 7 experimental photoperiods ranging from 14 L to 9 L. Decreases in circadian rhythm (CR) robustness, mesor and amplitude were evident in photoperiods ≤14 L, as were delays in the timing of CR acrophase and expansion of nocturnal activity duration. Nocturnal ultradian rhythms (URs) were comparably prevalent in all day lengths, but 15 L markedly inhibited the expression of light-phase URs. The period (τ'), amplitude and complexity of URs increased in day lengths ≤13 L. Among hamsters that failed to undergo gonadal regression in short day lengths (nonresponders), τ' of the dark-phase UR was longer than in photoresponsive hamsters; in 13 L the incidence and amplitude of light-phase URs were greater in hamsters that did not undergo testicular regression. Day lengths as long as 14 L were sufficient to trigger changes in the waveform of CRs without affecting UR waveform. The transition from a long- to a short-day ultradian phenotype occurred for most UR components at day lengths of 12 L-13 L, thereby establishing different thresholds for CR and UR responses to day length. At the UR-threshold photoperiod of 13 L, differences in gonadal status were largely without effect on most UR parameters.

  18. Circadian arrhythmia dysregulates emotional behaviors in aged Siberian hamsters.

    Science.gov (United States)

    Prendergast, Brian J; Onishi, Kenneth G; Patel, Priyesh N; Stevenson, Tyler J

    2014-03-15

    Emotional behaviors are influenced by the circadian timing system. Circadian disruptions are associated with depressive-like symptoms in clinical and preclinical populations. Circadian rhythm robustness declines markedly with aging and may contribute to susceptibility to emotional dysregulation in aged individuals. The present experiments used a model of chronic circadian arrhythmia generated noninvasively, via a series of circadian-disruptive light treatments, to investigate interactions between circadian desynchrony and aging on depressive- and anxiety-like behaviors, and on limbic neuroinflammatory gene expression that has been linked with emotionality. We also examined whether a social manipulation (group housing) would attenuate effects of arrhythmia on emotionality. In aged (14-18 months of age) male Siberian hamsters, circadian arrhythmia increased behavioral despair and decreased social motivation, but decreased exploratory anxiety. These effects were not evident in younger (5-9 months of age) hamsters. Social housing (3-5 hamsters/cage) abolished the effects of circadian arrhythmia on emotionality. Circadian arrhythmia alone was without effect on hippocampal or cortical interleukin-1β (IL-1β) and indoleamine 2,3-dioxygenase (Ido) mRNA expression in aged hamsters, but social housing decreased hippocampal IL-1β and Ido mRNAs. The data demonstrate that circadian disruption can negatively impact affective state, and that this effect is pronounced in older individuals. Although clear associations between circadian arrhythmia and constitutive limbic proinflammatory activity were not evident, the present data suggest that social housing markedly inhibits constitutive hippocampal IL-1β and Ido activity, which may contribute to the ameliorating effects of social housing on a number of emotional behaviors.

  19. Antibody Prophylaxis and Therapy against Nipah Virus Infection in Hamsters

    OpenAIRE

    Guillaume, V; Contamin, H.; Loth, P.; Grosjean, I.; Courbot, M. C. Georges; Deubel, V.; Buckland, R; Wild, T F

    2006-01-01

    Nipah virus (NiV), a member of the Paramyxoviridae family, causes a zoonotic infection in which the reservoir, the fruit bat, may pass the infection to pigs and eventually to humans. In humans, the infection leads to encephalitis with >40 to 70% mortality. We have previously shown that polyclonal antibody directed to either one of two glycoproteins, G (attachment protein) or F (fusion protein), can protect hamsters from a lethal infection. In the present study, we have developed monoclonal an...

  20. Cystic squamous cell carcinomas in the lungs of Syrian golden hamsters induced by coal oven flue exhaust mixed with pyrolized tar pitch in combination with benzo(a)pyrene.

    Science.gov (United States)

    Rittinghausen, S; Dungworth, D L; Dasenbrock, C; Ernst, H; Mohr, U

    1997-02-01

    Among a variety of induced pulmonary tumours, cystic squamous cell carcinomas were observed in five Syrian hamsters that inhaled a mixture of pyrolized tar pitch with coal oven flue exhaust (PCE) and additionally received intratracheal injections of benzo(a)pyrene. The histological appearance of these particular tumours is described, compared to similar tumour types in rats and the susceptibility of both species to inert particles is discussed.

  1. 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

  2. Female-biased anorexia and anxiety in the Syrian hamster.

    Science.gov (United States)

    Shannonhouse, John L; Fong, Li An; Clossen, Bryan L; Hairgrove, Ross E; York, Daniel C; Walker, Benjamin B; Hercules, Gregory W; Mertesdorf, Lauren M; Patel, Margi; Morgan, Caurnel

    2014-06-22

    Anorexia and anxiety cause significant mortality and disability with female biases and frequent comorbidity after puberty, but the scarcity of suitable animal models impedes understanding of their biological underpinnings. It is reported here that in adult or weanling Syrian hamsters, relative to social housing (SH), social separation (SS) induced anorexia characterized as hypophagia, weight loss, reduced adiposity, and hypermetabolism. Following anorexia, SS increased reluctance to feed, and thigmotaxis, in anxiogenic environments. Importantly, anorexia and anxiety were induced post-puberty with female biases. SS also reduced hypothalamic corticotrophin-releasing factor mRNA and serum corticosteroid levels assessed by RT-PCR and RIA, respectively. Consistent with the view that sex differences in adrenal suppression contributed to female biases in anorexia and anxiety by disinhibiting neuroimmune activity, SS elevated hypothalamic interleukin-6 and toll-like receptor 4 mRNA levels. Although corticosteroids were highest during SH, they were within the physiological range and associated with juvenile-like growth of white adipose, bone, and skeletal muscle. These results suggest that hamsters exhibit plasticity in bioenergetic and emotional phenotypes across puberty without an increase in stress responsiveness. Thus, social separation of hamsters provides a model of sex differences in anorexia and anxiety during adulthood and their pathogeneses during adolescence.

  3. Experience-independent development of the hamster circadian visual system.

    Directory of Open Access Journals (Sweden)

    August Kampf-Lassin

    Full Text Available 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 introduction of a light-dark cycle. In adulthood, previously-occluded eyes were challenged with visual stimuli. Whereas image-formation and motion-detection were markedly impaired by monocular occlusion, neither entrainment to a light-dark cycle, nor phase-resetting responses to shifts in the light-dark cycle were affected by prior monocular deprivation. Cholera toxin-b subunit fluorescent tract-tracing revealed that in monocularly-deprived hamsters the density of fibers projecting from the retina to the suprachiasmatic nucleus (SCN was comparable regardless of whether such fibers originated from occluded or exposed eyes. In addition, long-term monocular deprivation did not attenuate light-induced c-Fos expression in the SCN. Thus, in contrast to the thalamocortical projections of the primary visual system, retinohypothalamic projections terminating in the SCN develop into normal adult patterns and mediate circadian responses to light largely independent of light experience during development. The data identify a categorical difference in the requirement for light input during postnatal development between circadian and non-circadian visual systems.

  4. Learned magnetic compass orientation by the Siberian hamster, Phodopus sungorus

    Energy Technology Data Exchange (ETDEWEB)

    Deutschlander, Mark E.; Freake, Michael J.; Borland, Christopher; Phillips, John B.; Madden, R C.; Anderson, Larry E.; Wilson, B W.

    2003-04-01

    Magnetic orientation has been demonstrated in Siberian hamsters, Phodopus sungorus. The behavior, using a nest building assay, shows a directional preference in nest position and appears in this animal to be a learned behavior. Hamsters were housed prior to testing in rectangular cages aligned along perpendicular axes. When subsequently tested in a radially-symmetrical arena, the hamsters positioned their nests in a bimodal distribution that coincided with the magnetic direction of the long-axis of the holding cages. In addition, results are presented that illustrate some of the factors that can influence behavioral responses to the magnetic field. In particular for P. sungorus, holding conditions prior to testing and the presence of non-magnetic cues may influence the strength and expression of magnetic orientation. Failure to consider these and other factors may help to explain why previous attempts to demonstrate magnetic orientation in a number of rodent species have failed or, when positive results have been obtained, have been difficult to replicate in other laboratories.

  5. 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.

  6. 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

  7. 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

  8. Binding of chemical carcinogens to macromolecules in cultured human colon

    DEFF Research Database (Denmark)

    1977-01-01

    Metabolic activation of different chemical classes of carcinogens was studied in cultured human colon epithelia. Human colon epithelia were maintained in explant culture up to 4 days. Binding of benzo(a)pyrene, dimethylnitrosamine, and 1,2- dimethylhydrazine was found in both cell DNA and protein...

  9. 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...

  10. 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...

  11. 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

  12. 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

  13. 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.

  14. 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

  15. Androgen dependence in hamsters: overdose, tolerance, and potential opioidergic mechanisms.

    Science.gov (United States)

    Peters, K D; Wood, R I

    2005-01-01

    Anabolic steroids are drugs of abuse. However, the potential for steroid reward and addiction remains largely unexplored. This study used i.c.v. testosterone self-administration and controlled infusions of testosterone or vehicle in hamsters to explore central mechanisms of androgen overdose. Forty-two hamsters used nose-pokes to self-administer 1 microg/microl testosterone i.c.v. 4 h/day in an operant chamber. During 1-56 days of androgen self-administration, 10 (24%) hamsters died. Deaths correlated with peak daily intake of testosterone. Of the hamsters that self-administered a peak intake of testosterone intake peaked at 20-60 microg/day. Only 30% (three of 10) survived when daily testosterone intake exceeded 60 microg/day. Deaths are not due to volume or vehicle because i.c.v. infusions of 80 mul vehicle had no effect. Testosterone overdose resembles opiate intoxication. When male hamsters received infusions of 40 microg testosterone, locomotion (25.1+/-18.8 grid-crossings/10 min), respiration (72.7+/-5.4 breaths/min) and body temperature (33.5+/-0.4 degrees C) were significantly reduced, compared with males receiving vehicle infusions (186.1+/-8.1 crossings/10 min, 117.6+/-1.0 breaths/min, 35.9+/-0.1 degrees C, Ptestosterone infusion. After 15 days, locomotion (170.2+/-6.3 crossings), respiration (118.4+/-1.3 breaths/min), and body temperature (35.3+/-0.3 degrees C) in testosterone-infused males were equivalent to that in vehicle controls (P>0.05). The depressive effects of testosterone infusion are blocked by the opioid antagonist, naltrexone. With naltrexone pre-treatment (10 mg/kg s.c.), locomotion (183.7+/-1.8 crossings/10 min), respiration (116.9+/-0.3 breaths/min), and body temperature (36.1+/-0.4 degrees C) during testosterone infusion were equivalent to vehicle controls. Likewise, naltrexone prevents the reinforcing effects of i.c.v. testosterone self-administration. These results indicate that testosterone at high doses causes central autonomic

  16. 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...

  17. 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

  18. 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

  19. Tandem mass spectrometry analysis of N2-(trans-isoestragol-3'-yl)-2'-deoxyguanosine as a strategy to study species differences in sulfotransferase conversion of the proximate carcinogen 1'-hydroxyestragole

    NARCIS (Netherlands)

    Punt, A.; Delatour, T.; Scholz, G.; Schilter, B.; Bladeren, van P.J.; Rietjens, I.M.C.M.

    2007-01-01

    To get more insight into possible species differences in the bioactivation of estragole, the kinetics for sulfonation of the proximate carcinogen 1'-hydroxyestragole were compared for male rat, male mouse, and mixed gender human liver S9 homogenates. In order to quantify sulfonation, 2'-deoxyguanosi

  20. 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

  1. 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

  2. Lactoperoxidase-catalyzed activation of carcinogenic aromatic and heterocyclic amines.

    Science.gov (United States)

    Gorlewska-Roberts, Katarzyna M; Teitel, Candee H; Lay, Jackson O; Roberts, Dean W; Kadlubar, Fred F

    2004-12-01

    Lactoperoxidase, an enzyme secreted from the human mammary gland, plays a host defensive role through antimicrobial activity. It has been implicated in mutagenic and carcinogenic activation in the human mammary gland. The potential role of heterocyclic and aromatic amines in the etiology of breast cancer led us to examination of the lactoperoxidase-catalyzed activation of the most commonly studied arylamine carcinogens: 2-amino-1-methyl-6-phenylimidazo[4,5-b]-pyridine (PhIP), benzidine, 4-aminobiphenyl (ABP), 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx). In vitro activation was performed with lactoperoxidase (partially purified from bovine milk or human milk) in the presence of hydrogen peroxide and calf thymus DNA. Products formed during enzymatic activation were monitored by HPLC with ultraviolet and radiometric detection. Two of these products were characterized as hydrazo and azo derivatives by means of mass spectrometry. The DNA binding level of 3H- and 14C-radiolabeled amines after peroxidase-catalyzed activation was dependent on the hydrogen peroxide concentration, and the highest levels of carcinogen binding to DNA were observed at 100 microM H2O2. Carcinogen activation and the level of binding to DNA were in the order of benzidine > ABP > IQ > MeIQx > PhIP. One of the ABP adducts was identified, and the level at which it is formed was estimated to be six adducts/10(5) nucleotides. The susceptibility of aromatic and heterocyclic amines for lactoperoxidase-catalyzed activation and the binding levels of activated products to DNA suggest a potential role of lactoperoxidase-catalyzed activation of carcinogens in the etiology of breast cancer.

  3. 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.

  4. 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)...

  5. 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.

  6. 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.

  7. 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 ...

  8. 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

  9. DNA repair in human xeroderma pigmentosum and chinese hamster cells

    NARCIS (Netherlands)

    Zelle, B.

    1980-01-01

    An important feature of living cells is their capacity to maintain the integrity of their hereditary material, the DNA. DNA can be damaged by a variety of physical and chemical agents, among which ultraviolet radiation (UV), ion1z1ng radiation and chemical carcinogens as 4-nitroquinoline-1-oxide (4N

  10. DNA repair in human xeroderma pigmentosum and Chinese hamster cells

    NARCIS (Netherlands)

    B. Zelle (Bauke)

    1980-01-01

    textabstractAn important feature of living cells is their capacity to maintain the integrity of their hereditary material, the DNA. DNA can be damaged by a variety of physical and chemical agents, among which ultraviolet radiation (UV), ion1z1ng radiation and chemical carcinogens as 4-nitroquinoline

  11. 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

  12. 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....

  13. The Chemistry of Cold: Mechanisms of Torpor Regulation in the Siberian Hamster.

    Science.gov (United States)

    Cubuk, Ceyda; Bank, Jonathan H H; Herwig, Annika

    2016-01-01

    Siberian hamsters use spontaneous daily torpor, a state of hypometabolism and hypothermia, to save energy during winter. Multiple neuroendocrine signals set the scene for spontaneous torpor to occur, and several brain areas have been identified as potential sites for torpor regulation. Here, we summarize the known mechanisms of a fascinating physiological state in the Siberian hamster.

  14. Diet affects resting, but not basal metabolic rate of normothermic Siberian hamsters acclimated to winter.

    Science.gov (United States)

    Gutowski, Jakub P; Wojciechowski, Michał S; Jefimow, Małgorzata

    2011-12-01

    We examined the effect of different dietary supplements on seasonal changes in body mass (m(b)), metabolic rate (MR) and nonshivering thermogenesis (NST) capacity in normothermic Siberian hamsters housed under semi-natural conditions. Once a week standard hamster food was supplemented with either sunflower and flax seeds, rich in polyunsaturated fatty acids (FA), or mealworms, rich in saturated and monounsaturated FA. We found that neither of these dietary supplements affected the hamsters' normal winter decrease in m(b) and fat content nor their basal MR or NST capacity. NST capacity of summer-acclimated hamsters was lower than that of winter-acclimated ones. The composition of total body fat reflected the fat composition of the dietary supplements. Resting MR below the lower critical temperature of the hamsters, and their total serum cholesterol concentration were lower in hamsters fed a diet supplemented with mealworms than in hamsters fed a diet supplemented with seeds. These results indicate that in mealworm-fed hamsters energy expenditure in the cold is lower than in animals eating a seed-supplemented diet, and that the degree of FA unsaturation of diet affects energetics of heterotherms, not only during torpor, but also during normothermy.

  15. Carcinogenicity of oil shale tars, some of their components, and commercial products.

    Science.gov (United States)

    Bogovski, P A; Vinkmann, F

    1979-06-01

    Bioassays for carcinogenicity of various primary processing products (crude oils or tars) and commercial products obtained from Estorian oil shale have been carried out since 1951. The products (undiluted or diluted) were painted twice weekly 50 times on the interscapular area of the skin of random-bred or CC57Br mice. The products processed at high temperatures have a higher carcinogenic activity. Blends of products containing over 10% of high temperature crude oil (chamber furnace oil) have about the same carcinogenic activity as the latter. There is no strict correlation between the concentration of benzo(a)pyrene (BP) in oil shale products and their carcinogenic activity. Determination of BP in such products can serve as an approximate estimate of carcinogenic properties. The results of animal experiments with chromatographic fractions of the high temperature shale oil demonstrated the presence of compounds which lengthen the latency period of the carcinogenic effect of BP in the aromatic fraction of this oil as well as other carcinogens and compounds enhancing the activity of carcinogenic compounds. Under industrial conditions, contact of workers with carcinogenic shale oils can be reduced by means of coking the carcinogenic oils, which results in production of solid coke and of distillate which is recycled. Medical vaseline potentiates the carcinogenic action of BP and similar compounds. Dilution of shale oils with oils containing aliphatic hydrocarbons cannot be considered as diminution of the carcinogenic potency of these products. PMID:446447

  16. 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.

  17. Analysis of adrenergic regulation of melatonin synthesis in Siberian hamster pineal emphasizes the role of HIOMT.

    Science.gov (United States)

    Ceinos, R M; Chansard, M; Revel, F; Calgari, C; Míguez, J M; Simonneaux, V

    2004-01-01

    Seasonal variations of environmental factors are translated into annual fluctuations in synthesis and release of melatonin, which in turn acts as a neuroendocrine messenger for the synchronization of annual functions. So far, most studies performed to understand the regulation of melatonin synthesis have used the non seasonal laboratory rat. It was demonstrated that nocturnal melatonin synthesis depends on alpha- and beta-adrenergic activation of the enzyme arylalkylamine N-acetyltransferase (AA-NAT). In this study, we investigated the mechanisms of melatonin synthesis in the Siberian hamster, a seasonal species with marked photoperiodic variation in melatonin peak duration and amplitude. A beta-adrenergic receptor agonist alone markedly stimulated AA-NAT activity and melatonin synthesis and release. An alpha-adrenergic receptor agonist, while having no effect per se, potentiated the beta-adrenergic stimulation of AA-NAT activity both in vitro and in vivo. Strikingly, the potentiation of AA-NAT activity did not result in a potentiation of melatonin synthesis, suggesting that the rate of melatonin production is limited downstream in the metabolic pathway, most probably at the level of hydroxyindole-O-methyltransferase (HIOMT). HIOMT presented a constitutively high activity that was not acutely (within hours) stimulated by beta-adrenergic agonist, but was rather up-regulated by chronic application of the agonist. This long-term beta-adrenergic regulation may explain the reported large photoperiodic variation of HIOMT activity that drives the photoperiodic variation in melatonin peak.

  18. 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

  19. Chronic exposure to pulsed low-intensity microwaves is carcinogenic and tumorogenic

    Science.gov (United States)

    Lundquist, Marjorie

    2004-03-01

    To study health effects of lifetime exposure to low-intensity pulsed radiation >890 MHz, one controlled laboratory study of SPF* rats[1-3] and two of mice[4,5] were conducted, but only one[4] reported that its data showed an association between irradiation and cancer; reports of the other two studies minimized or denied such association. Critical review of these identified data evaluation errors; their correction enables a conclusion of microwave carcinogenicity from each study (the rat study also shows an association with endocrine-system primary malignancies and with a benign tumor of the adrenal medulla), enhancing the credibility of an epidemiological study[6] reporting a brain cancer risk for users of both analog and digital cellular phones. [1] J. Raloff. Science News 126(7):103(1984). [2] K. R. Foster & A. W. Guy. Sci Am 255(3):32-39(1986). [3] C.-K. Chou et al. Bioelectromagnetics 13:469-496(1992). [4] M. H. Repacholi et al. Radiat Res 147:631-640(1990)SPF\\. [5] T. D. Utteridge et al. Radiat Res 158:357-364(2002)non-SPF\\. [6] L. Hardell et al. Int J Oncol 22:399-407(2003). * SPF = specific-pathogen-free

  20. 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.

  1. 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

  2. Melatonin attenuates photic disruption of circadian rhythms in Siberian hamsters.

    Science.gov (United States)

    Ruby, N F; Kang, T; Heller, H C

    1997-10-01

    Body temperature (Tb) was recorded via a biotelemetry system from 28 adult male Siberian hamsters maintained in a light-dark (LD) cycle of 16 h light/day for several months. After Tb was recorded for 3 wk, the LD cycle was phase delayed by extending the light phase by 5 h for 1 day; animals remained on a 16:8 LD cycle for the remainder of the experiment. Hamsters were injected daily with melatonin or vehicle solution for several weeks, beginning either 2 mo after (experiment 1) or on the day of (experiment 2) the phase shift; injections occurred within 30 min of dark onset. In experiment 1, 75% of animals free ran with circadian periods >24 h, beginning on the day of the phase shift, and never reentrained to the LD cycle; no hamsters unambiguously entrained to daily injections. In contrast, 78% of animals in experiment 2 entrained to melatonin injections, and 71% of those animals subsequently reentrained to the photocycle when the injection regimen ended. No vehicle-treated animals entrained to the injection schedule. Melatonin had no effect on daily mean Tb and Tb rhythm amplitude in either experiment; however, melatonin doubled the duration of a hyperthermic response that occurred after each injection. Thus melatonin can prevent loss of entrainment induced by a phase shift of the LD cycle but cannot restore entrainment to free-running animals. Failure to reentrain in the presence of two appropriately coordinated entraining agents also suggests that a phase shift of the photocycle can diminish the sensitivity of the circadian system to both photic and nonphotic input.

  3. Photoperiodic regulation of FGF21 production in the Siberian hamster.

    Science.gov (United States)

    Samms, Ricardo J; Fowler, Maxine J; Cooper, Scott; Emmerson, Paul; Coskun, Tamer; Adams, Andrew C; Kharitonenkov, Alexei; Tsintzas, Kostas; Ebling, Francis J P

    2014-06-01

    This article is part of a Special Issue "Energy Balance". FGF21 is an endocrine member of the fibroblast growth factor superfamily that has been shown to play an important role in the physiological response to nutrient deprivation. Food restriction enhances hepatic FGF21 production, which serves to engage an integrated response to energy deficit. Specifically, elevated FGF21 levels lead to reduced gluconeogenesis and increased hepatic ketogenesis. However, circulating FGF21 concentrations also paradoxically rise in states of metabolic dysfunction such as obesity. Furthermore, multiple peripheral tissues also produce FGF21 in addition to the liver, raising questions as to its endocrine and paracrine roles in the control of energy metabolism. The objectives of this study were to measure plasma FGF21 concentrations in the Siberian hamster, a rodent which undergoes a seasonal cycle of fattening and body weight gain in the long days (LD) of summer, followed by reduction of appetite and fat catabolism in the short days (SD) of winter. Groups of adult male hamsters were raised in long days, and then exposed to SD for up to 12 weeks. Chronic exposure of LD animals to SD led to a significant increase in circulating FGF21 concentrations. This elevation of circulating FGF21 was preceded by an increase in liver FGF21 protein production evident as early as 4 weeks of exposure to SD. FGF21 protein abundance was also increased significantly in interscapular brown adipose tissue, with a positive correlation between plasma levels of FGF21 and BAT protein abundance throughout the experimental period. Epididymal white adipose tissue and skeletal muscle (gastrocnemius) also produced FGF21, but levels did not change in response to a change in photoperiod. In summary, a natural programmed state of fat catabolism was associated with increased FGF21 production in the liver and BAT, consistent with the view that FGF21 has a role in adapting hamsters to the hypophagic winter state.

  4. [Carcinogenic N-nitrosamines in the tire industry].

    Science.gov (United States)

    Sokol?kaia, N N; Krivosheeva, L V; Khesing, A Ia; Piven, V A; Kavun, S M

    1993-01-01

    The level of volatile carcinogenic N-nitrosamines (NA) was studied in the air of various technological sites of tyre production. Reported total levels of NA in air exceeded MACs set in certain countries for the same enterprises. For example, German total MAC for 12 carcinogenic NA is 1 g/m3. N-nitrosomorpholine appeared to have the highest level (91 g/m3), probably, because its derivatives are used as raw material for technological process. Relative rate of volatile NA release from rubber samples containing 4-nitrosodiphenylamine (modifier) was studied. The parameter was reported to have no influence on NA outlet in conditions simulating technological process. NA was detected by means of gas chromatography with thermal energy detector TEA 502A provided by Thermo Electron Corporation, USA. The article necessitates regulation of NA in tyre production and better rubber mixtures to control the pollution of atmosphere. PMID:8069502

  5. 4-Dimethylaminoazobenzenes: carcinogenicities and reductive cleavage by microsomal azo reductase.

    Science.gov (United States)

    Lambooy, J P; Koffman, B M

    1985-01-01

    Twenty-four 4-dimethylaminoazobenzenes (DABs) in which systematic structural modifications have been made in the prime ring have been studied for substrate specificity for microsomal azo reductase. The DABs were also evaluated for carcinogenicity and it was found that there was no correlation between carcinogenicity and extent of azo bond cleavage by azo reductase. While any substituent in the prime ring reduces the rate of cleavage of the azo bond relative to the unsubstituted dye, there is a correlation between substituent size and susceptibility to the enzyme. Substituent size was also found to be a significant factor in the induction of hepatomas by the dyes. Preliminary studies have shown that there appears to be a positive correlation between microsomal riboflavin content and the activity of the azo reductase.

  6. Aflatoxin is not a probably human carcinogen: the published evidence is sufficient.

    Science.gov (United States)

    Stoloff, L

    1989-12-01

    Since the early 1960s, when aflatoxin, the mold-produced contaminant of a number of important food commodities, was found to be a potent hepatocarcinogen for laboratory rats, there has been a sustained search for evidence to support the regulatory presumption that aflatoxin is a probable human carcinogen. The developing laboratory evidence of differences between species in metabolism of aflatoxin and susceptibility to its oncogenic effects indicated that humans were probably refractory to aflatoxin carcinogenesis, but the early epidemiological evidence indicated otherwise. That epidemiological evidence, however, contained flaws so that Working Groups of the International Agency for Research on Cancer (IARC) meeting in 1970, 1976, and 1982, although ignoring the biochemical evidence, did consider the available epidemiological evidence insufficient for a conclusion of human carcinogenicity. During the 1970s and 1980s, studies on the connection between chronic infection with hepatitis B virus (HBV) and primary liver cell cancer (PLC), the expected lesion from aflatoxin exposure, had established a very strong etiological relationship between HBV and PLC. Since all the epidemiological studies of aflatoxin and PLC conducted prior to 1982 had been of populations with endemic HBV infection, and, in addition to other flaws, had not been controlled for this confounding factor, there was a solid basis for their rejection. Most epidemiological studies in the 1980s of aflatoxin and PLC were either in the United States, where HBV-infected groups could be excluded from the study, or, when in areas of chronic HBV infection, attempts were made to include that factor. The study of U.S. populations showed no difference in mortality rates from PLC that could be attributed to aflatoxin exposure. The studies of populations with endemic HBV infection produced no convincing evidence to support a primary role for aflatoxin in the induction of human PLC, although an accessory role to HBV

  7. Some carcinogenic polycyclic aromatic hydrocarbons by photoacoustic spectroscopy

    Science.gov (United States)

    Garg, R. K.; Kumar, Pardeep; Ram, R. S.; Zaidi, Zahid H.

    1999-12-01

    Polycyclic aromatic hydrocarbons (PAHs) have attracted spectroscopists, astrophysicts and environmentalist because of their importance in our day to day life. It is well known that epoxides are produced during the metabolism of PAHs and have the requisite chemical reactivity to qualify them for the role as an ultimate carcinogenic form of PAHs. Several carcinogenic PAHs such as 3.4-benzopyrene, 1.2,3.4-dibenzopyrene, 3.4,9.10- dibenzopyrene etc. are found to be present in tobacco smoke and among air pollutants. Although PAH molecules are being studied for last several years by using conventional spectroscopy but no systematic attempt has been made to study non-radiative transitions. In our laboratory, we have studied many PAH molecules by a non-destructive technique with unique capability and sensitivity, known as Photoacoustic (PA) spectroscopy. PA spectroscopy is an analytical and research tool to get information about non-radiative transitions and singlet-triplet electronic transitions, where the conventional spectroscopic technique fails. The study of electronic transitions of some carcinogenic molecules are reported using PA and optical absorption spectra in boric acid glass in the region 250 - 400 nm. The electronic transitions of these molecules observed experimentally, have been interpreted using the optimized geometries and CNDO/S-CI method. A good agreement is found between the experimental and calculated results. Assignments of observed electronic transitions are made on the basis of singlet-triplet electronic transitions. Vibrations attached to these electronic transitions are attributed to the ground state vibrational modes.

  8. Linearity of dose-response relationships for human carcinogenic exposures

    Energy Technology Data Exchange (ETDEWEB)

    Smith, A.H. (Univ. of California, Berkeley (USA))

    The shape of dose-response relationships is a critical factor in considering cancer risks for the work place and environmental exposure to carcinogens. Markedly different risk estimates result from assumptions of linearity versus sublinear and threshold assumptions. This paper presents evidence that the relationship between the relative risk of development of cancer and the dose rate to carcinogenic exposures is frequently linear with no evidence for thresholds. Dose-response relationships from four studies of asbestos and lung cancer were examined, all of which were consistent with a linear relationship. Analysis of the relationship between the relative risk of lung cancer and exposure to nickel in a smelter study, selected because of relatively good exposure data, demonstrated a close agreement with a linear relationship. The relationship between the level of arsenic in drinking wter and the prevalence of skin cancer also was linear for males in the highest prevalence age group in Taiwan, although there was some evidence of sublinearity for females and younger persons. Also, the relationships between the number of cigarettes smoked per day and the relative risk of lung cancer was very close to linear in many studies. The analysis of these and other studies involving human exposure to carcinogens provides empirical evidence for linearity when the response variable is a rate ratio measure, rather than a risk difference measure. Linearity in dose-response is biologically plausible, without invoking a one-hit model. Except in special circumstances. the epidemiological evidence supports linear extrapolation of cancer relative risks.

  9. Sex differences in Siberian hamster ultradian locomotor rhythms.

    Science.gov (United States)

    Prendergast, Brian J; Stevenson, Tyler J; Zucker, Irving

    2013-02-17

    Sex differences in ultradian activity rhythms (URs) and circadian rhythms (CRs) were assessed in Siberian hamsters kept in long day (LD) or short day (SD) photoperiods for 40 weeks. For both sexes URs of locomotor activity were more prevalent, greater in amplitude and more robust in SDs. The UR period was longer in females than males in both day lengths. The reproductive system underwent regression and body mass declined during the initial 10 weeks of SD treatment, and in both sexes these traits spontaneously reverted to the LD phenotype at or before 40 weeks in SD, reflecting the development of neuroendocrine refractoriness to SD patterns of melatonin secretion. Hamsters of both sexes, however, continued to display SD-like URs at the 40 weeks time point. CRs were less prevalent and the waveform less robust and lower in amplitude in SDs than LDs; the SD circadian waveform also did not revert to the long-day phenotype after 40 weeks of SD treatment. Short day lengths enhanced ultradian and diminished circadian rhythms in both sexes. Day length controls several UR characteristics via gonadal steroid and melatonin-independent mechanisms. Sex differences in ultradian timing may contribute to sex diphenisms in rhythms of sleep, food intake and exercise.

  10. Constant darkness restores entrainment to phase-delayed Siberian hamsters.

    Science.gov (United States)

    Ruby, Norman F; Joshi, Nirav; Heller, H Craig

    2002-12-01

    Over 90% of Siberian hamsters (Phodopus sungorus) fail to reentrain to a 5-h phase delay of a 16:8-h photocycle. Because constant darkness (DD) restores rhythms disrupted by constant light, we tested whether DD could also restore entrainment. DD began 0, 5, or 14 days after a 5-h phase delay, and the light-dark cycle was reinstated 14 days later. All hamsters exposed to DD on day 0 reentrained, whereas 42% reentrained irrespective of whether DD began 5 or 14 days later. For these latter two groups, tau (tau) and alpha (alpha) in DD predicted reentrainment; animals that reentrained had a mean tau and alpha of 24.1 and 8.9 h, respectively, whereas those that failed to reentrain maintained a mean tau and alpha of 25.0 and of 7.1 h, respectively. Restoration of entrainment by DD is somewhat paradoxical because it suggests that reentrainment to the photocycle was prevented by continued exposure to that same photocycle. The dichotomy of circadian responses to DD suggests "entrainment" phenotypes that are similar to those of photoperiodic responders and nonresponders.

  11. Is Senna Laxative Use Associated to Cathartic Colon, Genotoxicity, or Carcinogenicity?

    Directory of Open Access Journals (Sweden)

    M. A. Morales

    2009-01-01

    Full Text Available Due to their natural origin, apparent low oral toxicity, effectiveness, and accessibility without a medical prescription, the anthranoid laxatives are a popular remedy for constipation and are frequently used abusively. Therefore, it is important to characterize its harmful and/or toxic effects. The sennosides, main active metabolites of senna, exhibit a very low toxicity in rats, and its genotoxic activity in bacterial strains as well as mammal cells was classified as weak in those cases where it was shown to be significant. The toxicological and mutagenic status of the crude extract of senna, however, is not as well characterized, and it is necessary to do so since it is frequently, and at the same time incorrectly, believed that the chronic use of anthranoid laxatives is a risk factor for the development of colorectal cancer. The objective of this article was to review the information that arises in various scientific medical databases using key words such as senna, sen, Senna alexandrina, Cassia angustifolia, sennosides, laxative toxicity, mainly ISI and non-ISI articles of journals with an editorial committee. Web pages of products or companies that publicize or commercialize this type of laxative were not included. This analysis establishes that (1 there is no convincing evidence that the chronic use of senna has, as a consequence, a structural and/or functional alteration of the enteric nerves or the smooth intestinal muscle, (2 there is no relation between long-term administration of a senna extract and the appearance of gastrointestinal tumors or any other type in rats, (3 senna is not carcinogenic in rats even after a two-year daily dose of up to 300 mg/kg/day, and (4 the current evidence does not show that there is a genotoxic risk for patients who take laxatives containing senna extracts or sennosides.

  12. Is senna laxative use associated to cathartic colon, genotoxicity, or carcinogenicity?

    Science.gov (United States)

    Morales, M A; Hernández, D; Bustamante, S; Bachiller, I; Rojas, A

    2009-01-01

    Due to their natural origin, apparent low oral toxicity, effectiveness, and accessibility without a medical prescription, the anthranoid laxatives are a popular remedy for constipation and are frequently used abusively. Therefore, it is important to characterize its harmful and/or toxic effects. The sennosides, main active metabolites of senna, exhibit a very low toxicity in rats, and its genotoxic activity in bacterial strains as well as mammal cells was classified as weak in those cases where it was shown to be significant. The toxicological and mutagenic status of the crude extract of senna, however, is not as well characterized, and it is necessary to do so since it is frequently, and at the same time incorrectly, believed that the chronic use of anthranoid laxatives is a risk factor for the development of colorectal cancer. The objective of this article was to review the information that arises in various scientific medical databases using key words such as senna, sen, Senna alexandrina, Cassia angustifolia, sennosides, laxative toxicity, mainly ISI and non-ISI articles of journals with an editorial committee. Web pages of products or companies that publicize or commercialize this type of laxative were not included. This analysis establishes that (1) there is no convincing evidence that the chronic use of senna has, as a consequence, a structural and/or functional alteration of the enteric nerves or the smooth intestinal muscle, (2) there is no relation between long-term administration of a senna extract and the appearance of gastrointestinal tumors or any other type in rats, (3) senna is not carcinogenic in rats even after a two-year daily dose of up to 300 mg/kg/day, and (4) the current evidence does not show that there is a genotoxic risk for patients who take laxatives containing senna extracts or sennosides.

  13. Is Senna Laxative Use Associated to Cathartic Colon, Genotoxicity, or Carcinogenicity?

    Science.gov (United States)

    Morales, M. A.; Hernández, D.; Bustamante, S.; Bachiller, I.; Rojas, A.

    2009-01-01

    Due to their natural origin, apparent low oral toxicity, effectiveness, and accessibility without a medical prescription, the anthranoid laxatives are a popular remedy for constipation and are frequently used abusively. Therefore, it is important to characterize its harmful and/or toxic effects. The sennosides, main active metabolites of senna, exhibit a very low toxicity in rats, and its genotoxic activity in bacterial strains as well as mammal cells was classified as weak in those cases where it was shown to be significant. The toxicological and mutagenic status of the crude extract of senna, however, is not as well characterized, and it is necessary to do so since it is frequently, and at the same time incorrectly, believed that the chronic use of anthranoid laxatives is a risk factor for the development of colorectal cancer. The objective of this article was to review the information that arises in various scientific medical databases using key words such as senna, sen, Senna alexandrina, Cassia angustifolia, sennosides, laxative toxicity, mainly ISI and non-ISI articles of journals with an editorial committee. Web pages of products or companies that publicize or commercialize this type of laxative were not included. This analysis establishes that (1) there is no convincing evidence that the chronic use of senna has, as a consequence, a structural and/or functional alteration of the enteric nerves or the smooth intestinal muscle, (2) there is no relation between long-term administration of a senna extract and the appearance of gastrointestinal tumors or any other type in rats, (3) senna is not carcinogenic in rats even after a two-year daily dose of up to 300 mg/kg/day, and (4) the current evidence does not show that there is a genotoxic risk for patients who take laxatives containing senna extracts or sennosides. PMID:20107583

  14. Evaluation of cytogenetic effects of a naturally occurring non-ice-nucleation Pseudomonas fluorescens strain in Chinese hamster ovary (CHO) cells.

    Science.gov (United States)

    Caruso, P; Andreozzi, L; Motta, S; Mosesso, P

    1995-01-01

    One of the main methods for eliminating ice-nucleation-active (INA+) bacteria the micro-organisms responsible for frost injuries to plants at mild freezing temperatures, is the use, as competitors, of other naturally occurring non-nucleating strains (non-INA). In the present article we investigated the cytogenetic effects of a naturally occurring non-INA strain of Pseudomonas fluorescens (MS 1640 R3), evaluating the induction of chromosomal aberrations and sister chromatid exchanges (SCEs) in Chinese hamster ovary (CHO) cells in the absence and presence of rat S9 metabolism. The results obtained did not show any increase in either chromosomal aberrations or SCEs, both in the absence and presence of rat S9 metabolism when used as i) intact bacteria cells, ii) sonicated bacteria (i.e., potential endotoxins), or iii) metabolic bacterial products (i.e., potential exotoxins) released in the growth medium. PMID:8584981

  15. 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 ...

  16. Pineal-independent regulation of photo-nonresponsiveness in the Siberian hamster (Phodopus sungorus).

    Science.gov (United States)

    Prendergast, B J; Freeman, D A

    1999-02-01

    The pineal hormone melatonin influences circadian rhythms and also mediates reproductive responses to photoperiod. The authors tested whether pinealectomy influences circadian oscillators responsible for induction of nonresponsiveness to short day lengths by preventing normal short-day patterns of circadian entrainment. Adult male Siberian hamsters were pinealectomized or sham operated, maintained in either 18 h light per day (18L) or 15L for 10 weeks, and then tested for responsiveness to 10L. Because pinealectomized hamsters do not show gonadal regression in short day lengths, responsiveness was assessed by measuring phase angle of entrainment and the length of the nightly activity period following transfer to 10L. The incidence of nonresponsiveness was significantly higher in 18L hamsters than in 15L hamsters but was unaffected by pineal status. Fully 88% of 18L hamsters failed to entrain to 10L in the normal short-day manner; the duration of nightly activity remained compressed, and the phase angle of entrainment was large and negative relative to lights off. The 15L hamsters entrained normally to 10L. Exposure to constant light after 10L treatment was equally effective in inducing arrhythmicity in pinealectomized and intact hamsters. Changes in the period of morning and evening circadian oscillators subsequent to 18L treatment did not predict circadian responsiveness to short photoperiod. Long-day induction of photo-nonresponsiveness, which prevents winter responses to short day lengths, occurs independently of pineal melatonin feedback on the circadian system.

  17. 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)

  18. NTP Toxicology and Carcinogenesis Studies of Salicylazosulfapyridine (CAS No. 599-79-1) in F344/N Rats and B6C3F1 Mice (Gavage Studies).

    Science.gov (United States)

    1997-05-01

    Salicylazosulfapyridine is widely used for the treatment of ulcerative colitis and Crohn's disease. It has been beneficial in the treatment of psoriasis and rheumatoid arthritis, and it has been used in veterinary medicine for the treatment of granulomatous colitis. Salicylazosulfapyridine was nominated for toxicity and carcinogenicity testing by the National Cancer Institute on the basis of its widespread use in humans and because it is a representative chemical from a class of aryl sulfonamides. Salicylazosulfapyridine is a suspect carcinogen because reductive cleavage of the azo linkage yields a p-amino aryl sulfonamide (sulfapyridine), and a related p-amino aryl sulfonamide (sulfamethoxazole) has been shown to produce thyroid neoplasms in rats. Toxicology and carcinogenicity studies were conducted in F344/N rats and B6C3F1 mice. Rats and mice were administered salicylazosulfapyridine (96% to 98% pure) in corn oil by gavage for 16 days, 13 weeks, or 2 years. The gavage route of administration was selected for these studies because it approximates the typical route of human exposure to the chemical. Genetic toxicology studies were conducted in vitro in Salmonella typhimurium and cultured Chinese hamster ovary cells and in vivo in rat and mouse bone marrow and mouse peripheral blood cells. 16-DAY STUDY IN RATS: Groups of five male and five female rats were administered 0, 675, 1,350, or 2,700 mg salicylazosulfapyridine/kg body weight in corn oil by gavage for 16 days excluding weekends. All rats survived to the end of the study. With the exception of the 675 mg/kg male group, the final mean body weights of all dosed groups of males and females were significantly lower than those of controls. Mean body weight gains of all dosed groups were less than those of controls. Clinical findings included ruffled fur and distended abdomens in male and female rats receiving 2,700 mg/kg. Hypothyroidism, evidenced by decreased serum triiodothyronine and thyroxine concentrations

  19. Activity of quinfamide against natural infections of Entamoeba criceti in hamsters: a new potent agent for intestinal amoebiasis.

    Science.gov (United States)

    Slighter, R G; Yarinsky, A; Drobeck, H P; Bailey, D M

    1980-08-01

    A novel tetrahydroquinolinyl ester, quinfamide, administered orally in multiple doses for 3 days had an ED50 of 0.25 mg/kg/day (total dose 0.75 mg/kg) for eradicating Entamoeba criceti in hamsters in several tests. It was significantly more active by direct comparison than 3 commercially available amoebicides and at least as active as 2 other esters of the parent compound, 1-(dichloroacety)-1,2,3,4-tetrahydro-6-quinolinol. After administration of a single dose, ED50 calculations for quinfamide averaged 0.9 mg/kg. Quinfamide was considerably more active than the other tetrahydroquinolinols, diloxanide furoate and teclozan, and it was approximately 1.5 times more active than etofamide; a statistical significance between the latter 2 drugs could be demonstrated in one of 4 tests. Administered prophylactically, quinfamide was shown to protect hamsters from re-infection with E. criceti. It also inhibited propagation of E. histolytica in vitro at a concentration of 20 microgram/ml. No adverse effects were noted in rodents after a single dose as high as 10 g/kg. Daily administration to monkeys of doses up to 500 mg/kg for as long as 37 days produced no pharmacological aberrations during or after medication; haematological studies and urine analyses were normal and no gross or microscopical tissue changes attributable to quinfamide were observed. No toxicity was revealed following acute (2 g/kg) and chronic (500 mg/kg/day x 31 days) administration of the drug to dogs and rats, respectively.

  20. 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...

  1. 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

  2. AMAP, the alleged non-toxic isomer of acetaminophen, is toxic in rat and human liver

    NARCIS (Netherlands)

    Hadi, Mackenzie; Dragovic, Sanja; van Swelm, Rachel; Herpers, Bram; van de Water, Bob; Russel, Frans G. M.; Commandeur, Jan N. M.; Groothuis, Geny M. M.

    2013-01-01

    N-acetyl-meta-aminophenol (AMAP) is generally considered as a non-toxic regioisomer of the well-known hepatotoxicant acetaminophen (APAP). However, so far, AMAP has only been shown to be non-toxic in mice and hamsters. To investigate whether AMAP could also be used as non-toxic analog of APAP in rat

  3. 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...

  4. Uptake of indocyanine green by hamster sebaceous glands

    Science.gov (United States)

    McMillan, Kathleen; Lo, Kai-Ming; Wang, Zhi

    2001-05-01

    Photothermal injury to the sebaceous glands is a potential curative treatment for the common skin disease acne vulgaris. Accumulation of the exogenous chromophore indocyanine green in the sebaceous glands may be accomplished using an emulsion or liposomal formulation applied to the skin surface. An emulsion containing 0.09% by weight indocyanine green (ICG) was applied to the epidermis of hamster ears ex vivo and the flank organ in vivo. Fluorescence microscopy demonstrated selective accumulation of ICG in the underlying sebaceous glands. The concentration of ICG that may be expected to accumulate in sebaceous glands of humans was then estimated on the basis of the gland size and orifice area, for the case of topical application of a more concentrated 1% ICG liposomal formulation. Monte Carlo modeling and heat transfer calculations showed that the sebaceous glands containing the exogenous chromophore may be selectively damaged by pulsed 810 nm laser radiation in conjunction with cryogen spray cooling.

  5. 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)

  6. 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

  7. 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

  8. 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

  9. Photoperiod Regulates vgf-Derived Peptide Processing in Siberian Hamsters.

    Science.gov (United States)

    Noli, Barbara; Brancia, Carla; Pilleri, Roberta; D'Amato, Filomena; Messana, Irene; Manconi, Barbara; Ebling, Francis J P; Ferri, Gian-Luca; Cocco, Cristina

    2015-01-01

    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.

  10. 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.

  11. 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...

  12. Seasonal adaptation of dwarf hamsters (Genus Phodopus): differences between species and their geographic origin.

    Science.gov (United States)

    Müller, D; Hauer, J; Schöttner, K; Fritzsche, P; Weinert, D

    2015-12-01

    The genus Phodopus consists of three species--P. campbelli (Pc), P. sungorus (Ps), and P. roborovskii (Pr). They inhabit steppes, semi-deserts, and deserts in continental Asia with a climate changing from a moderate to a hard Continental one with extreme daily and seasonal variations. These different environmental challenges are likely to have consequences for hamsters' morphology, physiology, and behavior. Hamsters of all three species were investigated during the course of the year in the laboratory though using natural lighting and temperature conditions. Motor activity and body temperature were measured continuously, and body mass, testes size, and fur coloration every 1-2 weeks. With regard to the pattern of activity, nearly twice as many Pc as Ps hamsters (25 vs. 14%) failed to respond to changes of photoperiod, whereas all Pr hamsters did. Body mass and testes size were high in summer and low in winter, with the biggest relative change in Ps and the lowest in Pr hamsters. Changes of fur coloration were found in Ps hamsters only. All responding animals (that is excluding Pr), exhibited regular torpor bouts during the short winter days. In autumn, seasonal changes started considerably earlier in Ps hamsters. To investigate the putative causes of these different time courses, a further experiment was performed, to identify the critical photoperiod. Hamsters were kept for 10 weeks under different photoperiods, changing from 16 to 8 h light per day. Motor activity was recorded continuously, to identify responding and non-responding animals. Body mass was measured at the beginning and the end of the experiment, testes mass only at the end. The critical photoperiod was found to be similar in all three species. Though in a further experiment, Pc and Pr hamsters showed a delayed response, whereas the changes in Ps hamsters started immediately following transfer to short-day conditions. The results show that interspecific differences in seasonal adaptation exist, even

  13. KEYNOTE LECTURES-KL1 New development in risk assessment of genotoxic carcinogens in foods

    Institute of Scientific and Technical Information of China (English)

    CHEN Jun-Shi

    2006-01-01

    @@ The no-observed-effect level (NOEL) in a study of carcinogenicity for compounds that are both genotoxic and carcinogenic represents the limit of detection in that bioassay, rather than an estimate of a possible threshold. Therefore, for those genotoxic and carcinogenic contaminants (e.g. acrylamides, PAHs, etc.) in foods it is not possible to develop health-based guidance values (e.g. ADI or PTWI) using the traditional NOEL and safety/uncertainty factors.

  14. Carcinogenic effects of circadian disruption: an epigenetic viewpoint.

    Science.gov (United States)

    Salavaty, Abbas

    2015-08-08

    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 modifications and the formation of circadian epigenomes. Aberrant epigenetic modifications, 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 first discuss some of the circadian genes and regulatory proteins. Then, I summarize the current evidence related to the epigenetic modifications 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 viewpoint. Finally, the importance of chronotherapy in cancer treatment is highlighted.

  15. 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.

  16. The liver fluke Opisthorchis felineus: biology, epidemiology and carcinogenic potential.

    Science.gov (United States)

    Pakharukova, Mariya Y; Mordvinov, Viatcheslav A

    2016-01-01

    The liver fluke Opisthorchis felineus is a member of the triad of epidemiologically important liver fluke species belonging to the family Opisthorchiidae and the major agent causing opisthorchiasis over a vast territory, covering Russia, Kazakhstan and several European countries. The similarity between the diseases caused by O. felineus and other liver flukes, O. viverrini and Clonorchis sinensis, in clinical manifestations and course suggests that the scenarios of their development and, possibly, complications have much in common. The International Agency for Research on Cancer classified O. viverrini and C. sinensis as group 1 agents and the major factors inducing cholangiocarcinoma in endemic regions. However, a carcinogenic potential of O. felineus is poorly studied. This review characterizes O. felineus, briefs the epidemiological situation in Western Siberia, the world's largest opisthorchiasis focus, and assesses the carcinogenic potential of this liver fluke. The review is based on a comprehensive analysis of the published medical data on opisthorchiasis and its complications in Western Siberia. Results of performed analysis reflect the actual epidemiological situation in opisthorchiasis focus and suggest an association of this disease with bile duct cancer. PMID:26740360

  17. 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.

  18. 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...

  19. 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.

  20. 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...

  1. 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...

  2. 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...

  3. Leptin mediates seasonal variation in some but not all symptoms of sickness in Siberian hamsters.

    Science.gov (United States)

    Carlton, Elizabeth D; Demas, Gregory E

    2014-11-01

    Many seasonally breeding species, including Siberian hamsters (Phodopus sungorus), exhibit seasonal variation in sickness responses. One hypothesis regarding the mechanism of this variation is that sickness intensity tracks an animal's energetic state, such that sickness is attenuated in the season that an animal has the lowest fat stores. Energetic state may be signaled via leptin, an adipose hormone that provides a signal of fat stores. Siberian hamsters respond to extended housing in short, winter-like days by reducing fat stores and leptin levels, relative to those housed in long, summer-like days. Sickness responses are also attenuated in short-day hamsters as compared to long-day hamsters. We hypothesized that leptin provides a physiological signal by which seasonally breeding animals modulate sickness responses, such that animals with higher leptin levels show increased sickness intensity. To test this, we provided short-day hamsters with a long-day-like leptin signal and assessed their responses to lipopolysaccharide (LPS), a sickness-inducing antigen. We compared these responses to short-day vehicle-, long-day vehicle-, and long-day leptin-treated hamsters. Unexpectedly, LPS induced a hypothermic response (rather than fever) in all groups. Short-day vehicle-treated hamsters exhibited the greatest LPS-induced hypothermia, and leptin treatment attenuated this response, making hypothermia more long-day-like. Contrary to our hypothesis, short-day leptin-treated hamsters showed the least pronounced LPS-induced anorexia among all groups. These results suggest that leptin may mediate some but not all aspects of seasonal sickness variation in this species. Future studies should be targeted at determining roles of other energetic hormones in regulating seasonal sickness response variation.

  4. 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...

  5. 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.

  6. 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

  7. 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.

  8. 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

  9. 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

  10. Individual differences in circadian waveform of Siberian hamsters under multiple lighting conditions.

    Science.gov (United States)

    Evans, Jennifer A; Elliott, Jeffrey A; Gorman, Michael R

    2012-10-01

    Because the circadian clock in the mammalian brain derives from a network of interacting cellular oscillators, characterizing the nature and bases of circadian coupling is fundamental to understanding how the pacemaker operates. Various phenomena involving plasticity in circadian waveform have been theorized to reflect changes in oscillator coupling; however, it remains unclear whether these different behavioral paradigms reference a unitary underlying process. To test whether disparate coupling assays index a common mechanism, we examined whether there is covariation among behavioral responses to various lighting conditions that produce changes in circadian waveform. Siberian hamsters, Phodopus sungorus, were transferred from long to short photoperiods to distinguish short photoperiod responders (SP-R) from nonresponders (SP-NR). Short photoperiod chronotyped hamsters were subsequently transferred, along with unselected controls, to 24-h light:dark:light: dark cycles (LDLD) with dim nighttime illumination, a procedure that induces bifurcated entrainment. Under LDLD, SP-R hamsters were more likely to bifurcate their rhythms than were SP-NR hamsters or unselected controls. After transfer from LDLD to constant dim light, SP-R hamsters were also more likely to become arrhythmic compared to SP-NR hamsters and unselected controls. In contrast, short photoperiod chronotype did not influence more transient changes in circadian waveform. The present data reveal a clear relationship in the plasticity of circadian waveform across 3 distinct lighting conditions, suggesting a common mechanism wherein individual differences reflect variation in circadian coupling.

  11. 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.

  12. Genomic organization and expression of immunoglobulin genes in the Chinese hamster (Cricetulus griseus).

    Science.gov (United States)

    Qin, T; Zhu, H; Wang, D; Hao, H; Du, W

    2015-01-01

    In science, the hamsters are widely used as a model for studying the human diseases because they display many features like humans. The utility of the Chinese hamster as a biology model can be further enhanced by further characterization of the genes encoding components of the immune system. Here, we report the genomic organization and expression of the Chinese hamster immunoglobulin heavy and light chain genes. The Chinese hamster IgH locus contains 268 VH segments (132 potentially functional genes, 12 ORFs and 124 pseudogenes), 4 DH segments, 6 JH segments, four constant region genes (μ, γ, ε and α) and one reverse δ remnant fragment. The Igκ locus contains only a single Cκ gene, 4 Jκ segments and 48 Vκ segments (15 potentially functional genes and 33 pseudogenes), whereas the Igλ locus contains 4 Cλ genes, but only Cλ 3 and Cλ 4 each preceded by a Jλ gene segment. A total of 49 Vλ segments (39 potentially functional genes, 3 ORFs and 7 pseudogenes) were identified. Analysis of junctions of the recombined V(D)J transcripts reveals complex diversity in both expressed H and κ sequences, but the microhomology-directed VJ recombination obviously results in very limited diversity in the Chinese hamster λ gene despite more potential germline-encoded combinatorial diversity. This is the first study to make a comprehensive analysis of the Ig genes in the Chinese hamster, which provides insights into the Ig genes in placental mammals.

  13. Enzymes oxidizing the azo dye 1-phenylazo-2-naphthol (Sudan I) and their contribution to its genotoxicity and carcinogenicity.

    Science.gov (United States)

    Stiborova, Marie; Schmeiser, Heinz H; Frei, Eva; Hodek, Petr; Martinek, Vaclav

    2014-01-01

    Sudan I [1-(phenylazo)-2-naphthol, C.I. Solvent Yellow 14] is an industrial dye, which was found as a contaminant in numerous foods in several European countries. Because Sudan I has been assigned by the IARC as a Category 3 carcinogen, the European Union decreed that it cannot be utilized as food colorant in any European country. Sudan I induces the malignancies in liver and urinary bladder of rats and mice. This carcinogen has also been found to be a potent mutagen, contact allergen and sensitizer, and exhibits clastogenic properties. The oxidation of Sudan I increases its toxic effects and leads to covalent adducts in DNA. Identification of enzymatic systems that contribute to Sudan I oxidative metabolism to reactive intermediates generating such covalent DNA adducts on the one hand, and to the detoxification of this carcinogen on the other, is necessary to evaluate susceptibility to this toxicant. This review summarizes the identification of such enzymes and the molecular mechanisms of oxidation reactions elucidated to date. Human and animal cytochrome P450 (CYP) and peroxidases are capable of oxidizing Sudan I. Of the CYP enzymes, CYP1A1 is most important both in Sudan I detoxification and its bio-activation. Ring-hydroxylated metabolites and a dimer of this carcinogen were found as detoxification products of Sudan I generated with CYPs and peroxidases, respectively. Oxidative bio-activation of this azo dye catalyzed by CYPs and peroxidases leads to generation of proximate genotoxic metabolites (the CYP-catalyzed formation of the benzenediazonium cation and the peroxidase-mediated generation of one-electron oxidation products), which covalently modify DNA both in vitro and in vivo. The predominant DNA adduct generated with the benzenediazonium cation was characterized to be 8-(phenylazo)guanine. The Sudan I radical species mediated by peroxidases reacts with the -NH2 group in (deoxy)guanosine, generating the 4-[(deoxy)guanosin-N(2)-yl]Sudan I product. Sudan I

  14. 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...

  15. Toxicology and Carcinogenesis Studies of Furfuryl Alcohol (CAS No. 98-00-0) in F344/N Rats and B6C3F1 Mice (Inhalation Studies).

    Science.gov (United States)

    1999-02-01

    Furfuryl alcohol-based resins are used as binding agents in foundry sand and as corrosion inhibitors in mortar, grout, and cement. Because of their heat resistance, furan resins are used in the manufacture of fiberglass-reinforced plastic equipment. Furfuryl alcohol was selected for evaluation because of the absence of data on its carcinogenic potential and its large production volume, widespread use in manufacturing, and ubiquitous presence in consumer goods. Male and female F344/N rats and B6C3F1 mice were exposed to furfuryl alcohol (greater than 98% pure) by inhalation for 16 days, 14 weeks, or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, cultured Chinese hamster ovary cells, and mouse bone marrow cells. 16-DAY STUDY IN RATS: Groups of five male and five female rats were exposed to concentrations of 0, 16, 31, 63, 125, or 250 ppm furfuryl alcohol by inhalation, 6 hours per day, 5 days per week for 16 days. All male and female rats exposed to 250 ppm died by day 2 of the study, and one male rat exposed to 125 ppm died on day 5. Final mean body weights of male and female rats exposed to 125 ppm were significantly less than those of the chamber control groups. Male rats exposed to 31, 63, or 125 ppm and female rats exposed to 125 ppm gained less weight than the chamber control groups. Clinical findings included dyspnea, hypoactivity, and nasal and ocular discharge in males and females exposed to 63, 125, or 250 ppm. All exposed animals developed lesions in the nasal respiratory epithelium and olfactory epithelium, and the severities of these lesions generally increased with increasing exposure concentration. 16-DAY STUDY IN MICE: Groups of five male and five female mice were exposed to concentrations of 0, 16, 31, 63, 125, or 250 ppm furfuryl alcohol by inhalation, 6 hours per day, 5 days per week for 16 days. All male and female mice exposed to 250 ppm died by day 4 of the study, and one female mouse exposed to 125 ppm died on day

  16. 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)

  17. Carcinogenicity, allergenicity, and lupus-inducibility of arylamines.

    Science.gov (United States)

    Chung, King-Thom

    2016-01-01

    Arylamines are widely used in food, drugs, and cosmetics as well as other industries. These chemicals are present ubiquitously in cigarette smoke, smoke emitted from cooking fume hoods as well as are generated by diverse industries. Arylamines can be generated by cleavage of azo dyes by intestinal and skin microbiota. Some arylamines are used as drugs while others are constituents of human metabolism. Many of the arylamines are mutagenic and carcinogenic. They are generally recognized as the major cause of human bladder cancer, but arylamines can induce cancers of other organs in humans and animals. Some arylamines are allergenic, causing lupus like syndrome, or other maladies. In view of their unbiquitious nature and the diseases they cause, arylamines are probably the most important chemicals causing health problems.

  18. 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.

  19. Carcinogenic risks associated with radiation pollution. [UV radiation, sunlight

    Energy Technology Data Exchange (ETDEWEB)

    Latarjet, R.

    1976-01-01

    The cancerogenic pollution by non-ionizing radiations is limited to the case of solar ultraviolet, whose activity at ground level may be increased as a consequence of the stratospheric depletion of ozone, produced by certain chemical pollutants: nitrogen oxides from supersonic aircrafts, freon. As regards ionizing radiations, the discussion is focused on the fundamental problem of the threshold, and on the means by which one may obtain some quantitative data related to carcinogenesis by small radiation doses in man. A new concept, that of a practical threshold, is proposed. A theory which links radiocancerogenesis, as well as chemical cancerogenesis, to errors produced in the repair of lesions in the DNA is discussed. The rads-equivalent project for chemical mutagens and carcinogens is described.

  20. 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

  1. Retraction: Evaluation of carcinogenic effects of electromagnetic fields (EMF).

    Science.gov (United States)

    Mehic, Bakir

    2010-11-01

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

  2. [Thoughts on carcinogenic pollution caused by ionizing radiation].

    Science.gov (United States)

    Latarjet, R

    1976-01-01

    The pollution phenomenon groups the effects of small doses of radiation on large populations. These effects on Man are not directly accessible. One must: a) consider some epidemiological statistics (cosmic radiation at high altitudes; radioactivity from granitic surroundings); b) extrapolate from datas obtained with high doses; c) extrapolate from datas obtained with low doses in micro-organisms or mammalian cells in vitro. The interpolation scheme of Abrahamson et al. is so available for mutagenicity. The question of a threshold remains theoretical, although radiation-induced carcinogenesis often displays a dose-effects curve with a well market threshold. A new concept, that of a "practical threshold" is developped, which may be of great usefulness. The main genetic considerations are listed upon which the present international admissible doses are based. Finally, in order to establish quantitative comparisons between chemical and radiation carcinogenic pollution, the concept of "rad equivalents" for the main chemical mutagens is stressed.

  3. 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

  4. 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,...

  5. 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

  6. OVERVIEW OF DRINKING WATER MUTAGENICITY AND CARCINOGENICITY AND RISK FOR BLADDER CANCER

    Science.gov (United States)

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

  7. 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

  8. 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.

  9. 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

  10. Transmission of chronic wasting disease identifies a prion strain causing cachexia and heart infection in hamsters.

    Directory of Open Access Journals (Sweden)

    Richard A Bessen

    Full Text Available Chronic wasting disease (CWD is an emerging prion disease of free-ranging and captive cervids in North America. In this study we established a rodent model for CWD in Syrian golden hamsters that resemble key features of the disease in cervids including cachexia and infection of cardiac muscle. Following one to three serial passages of CWD from white-tailed deer into transgenic mice expressing the hamster prion protein gene, CWD was subsequently passaged into Syrian golden hamsters. In one passage line there were preclinical changes in locomotor activity and a loss of body mass prior to onset of subtle neurological symptoms around 340 days. The clinical symptoms included a prominent wasting disease, similar to cachexia, with a prolonged duration. Other features of CWD in hamsters that were similar to cervid CWD included the brain distribution of the disease-specific isoform of the prion protein, PrP(Sc, prion infection of the central and peripheral neuroendocrine system, and PrP(Sc deposition in cardiac muscle. There was also prominent PrP(Sc deposition in the nasal mucosa on the edge of the olfactory sensory epithelium with the lumen of the nasal airway that could have implications for CWD shedding into nasal secretions and disease transmission. Since the mechanism of wasting disease in prion diseases is unknown this hamster CWD model could provide a means to investigate the physiological basis of cachexia, which we propose is due to a prion-induced endocrinopathy. This prion disease phenotype has not been described in hamsters and we designate it as the 'wasting' or WST strain of hamster CWD.

  11. Identification, expression, and physiological functions of Siberian hamster gonadotropin-inhibitory hormone.

    Science.gov (United States)

    Ubuka, Takayoshi; Inoue, Kazuhiko; Fukuda, Yujiro; Mizuno, Takanobu; Ukena, Kazuyoshi; Kriegsfeld, Lance J; Tsutsui, Kazuyoshi

    2012-01-01

    Gonadotropin-inhibitory hormone (GnIH) is a hypothalamic neuropeptide that inhibits gonadotropin secretion in birds and mammals. To further understand its physiological roles in mammalian reproduction, we identified its precursor cDNA and endogenous mature peptides in the Siberian hamster brain. The Siberian hamster GnIH precursor cDNA encoded two RFamide-related peptide (RFRP) sequences. SPAPANKVPHSAANLPLRF-NH(2) (Siberian hamster RFRP-1) and TLSRVPSLPQRF-NH(2) (Siberian hamster RFRP-3) were confirmed as mature endogenous peptides by mass spectrometry from brain samples purified by immunoaffinity chromatography. GnIH mRNA expression was higher in long days (LD) compared with short days (SD). GnIH mRNA was also highly expressed in SD plus pinealectomized animals, whereas expression was suppressed by melatonin, a nocturnal pineal hormone, administration. GnIH-immunoreactive (-ir) neurons were localized to the dorsomedial region of the hypothalamus, and GnIH-ir fibers projected to hypothalamic and limbic structures. The density of GnIH-ir perikarya and fibers were higher in LD and SD plus pinealectomized hamsters than in LD plus melatonin or SD animals. The percentage of GnRH neurons receiving close appositions from GnIH-ir fiber terminals was also higher in LD than SD, and GnIH receptor was expressed in GnRH-ir neurons. Finally, central administration of hamster RFRP-1 or RFRP-3 inhibited LH release 5 and 30 min after administration in LD. In sharp contrast, both peptides stimulated LH release 30 min after administration in SD. These results suggest that GnIH peptides fine tune LH levels via its receptor expressed in GnRH-ir neurons in an opposing fashion across the seasons in Siberian hamsters.

  12. 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.

  13. 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

  14. 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

  15. Chlorpromazine distribution in hamsters and mice bearing transplantable melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Fairchild, R.G. (Brookhaven National Lab., Upton, NY); Greenberg, D.; Watts, K.P.; Packer, S.; Atkins, H.L.; Som, P.; Hannon, S.J.; Brill, A.B.; Fand, I.; McNally, W.P.

    1982-02-01

    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 ..mu..g 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 /sup 10/B(n,..cap alpha..)/sup 7/Li reaction.

  16. 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

  17. 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.

  18. Propranolol induced chromosomal aberrations in Chinese hamster ovary cell line

    Directory of Open Access Journals (Sweden)

    Mozhgan Sedigh-Ardekani

    2013-03-01

    Full Text Available Propranolol (PL, a non-selective beta-blocker, is a cardiovascular drug widely used to treat hypertension. The present study was concerned with assessing the cytogenetic effects of this drug on Chinese hamster ovary (CHO cell line. MTT assay was then carried out to determine the cytotoxicity index (IC50 of the drug. The IC50 value of PL was 0.43±0.02 mM. To investigate the clastogenic effects of the drug, chromatid and chromosome breaks and polyploidy in metaphases were analyzed. CHO cells were exposed to different concentrations of the drug (0.1, 0.2, 0.3, 0.4 mM for 24 hours. Considering that PL has liver metabolism, experiments were carried out in the presence and absence of the metabolic activation system (S9 mix. Mitomycin-C and sodium arsenite were used as positive controls. It was observed that in cells treated with different PL concentrations as 0.1, 0.2 and 0.3 mM, the frequency of chromatid and chromosome breaks as well as polyploidy increased when compared with untreated CHO cells. The addition of S9 mix significantly decreased the chromatid breaks, chromosome breaks and polyploidy compared to the treatment of PL alone. It is concluded that, PL causes chromatid and chromosome aberrations in CHO cell line and the metabolic activation system (S9 mix, playing an important role in drug cytotoxicity reduction.

  19. Teratogenic effects of mescaline, epinephrine, and norepinephrine in the hamster.

    Science.gov (United States)

    Hirsch, K S; Fritz, H I

    1981-06-01

    Mescaline was administered orally at doses of 16 and 32 mg/kg on the seventh through tenth days of gestation to pregnant cream-strain hamsters. This treatment resulted in a dose-dependent effect on reproductive success and skeletal ossification. The effect of mescaline on reproductive success included an increased number of resorptions resulting in a decreased litter size. The 32 mg/kg dose of mescaline caused 48.8% resorptions, while 16 mg/kg and control animals had 12.0% and 6.4% resorptions, respectively. Litter size was decreased from 12.0 pups in controls to 10.3 (16 mg/kg) and 6.5 (32 mg/kg) pups per litter in treated groups. No gross abnormalities were observed at necropsy; there was, however, a dose-dependent increased delay in the ossification of the skull, sternum, and metatarsals. Both epinephrine and norepinephrine caused a decrease in reproductive success when administered at 500 micrograms/kg. Epinephrine appeared to cause a trend toward preimplantation wastage as indicated by an increased corpora lutea to implantation site ratio (from 1.3-1.9). Norepinephrine, however, caused an increased number of resorptions (29.1% in controls). Both norepinephrine and epinephrine produced similar delays in ossification.

  20. 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 ...

  1. 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

  2. Dim nocturnal illumination alters coupling of circadian pacemakers in Siberian hamsters, Phodopus sungorus.

    Science.gov (United States)

    Gorman, M R; Elliott, J A

    2004-08-01

    The circadian pacemaker of mammals comprises multiple oscillators that may adopt different phase relationships to determine properties of the coupled system. The effect of nocturnal illumination comparable to dim moonlight was assessed in male Siberian hamsters exposed to two re-entrainment paradigms believed to require changes in the phase relationship of underlying component oscillators. In experiment 1, hamsters were exposed to a 24-h light-dark-light-dark cycle previously shown to split circadian rhythms into two components such that activity is divided between the two daily dark periods. Hamsters exposed to dim illumination (rhythms compared to hamsters exposed to completely dark scotophases. In experiment 2, hamsters were transferred to winter photoperiods (10 h light, 14 h dark) from two different longer daylengths (14 h or 18 h light daily) in the presence or absence of dim nighttime lighting. Dim nocturnal illumination markedly accelerated adoption of the winter phenotype as reflected in the expansion of activity duration, gonadal regression and weight loss. The two experiments demonstrate substantial efficacy of light intensities generally viewed as below the threshold of circadian systems. Light may act on oscillator coupling through rod-dependent mechanisms.

  3. 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.

  4. Effect of dietary fatty acids on metabolic rate and nonshivering thermogenesis in golden hamsters.

    Science.gov (United States)

    Jefimow, Małgorzata; Wojciechowski, Michał S

    2014-02-01

    Hibernating rodents prior to winter tend to select food rich in polyunsaturated fatty acids (PUFA). Several studies found that such diet may positively affect their winter energy budget by enhancing torpor episodes. However, the effect of composition of dietary fatty acids (FA) on metabolism of normothermic heterotherms is poorly understood. Thus we tested whether diets different in FA composition affect metabolic rate (MR) and the capacity for nonshivering thermogenesis (NST) in normothermic golden hamsters (Mesocricetus auratus). Animals were housed in outdoor enclosures from May 2010 to April 2011 and fed a diet enriched with PUFA (i.e., standard food supplemented weekly with sunflower and flax seeds) or with saturated and monounsaturated fatty acids (SFA/MUFA, standard food supplemented with mealworms). Since diet rich in PUFA results in lower MR in hibernating animals, we predicted that PUFA-rich diet would have similar effect on MR of normothermic hamsters, that is, normothermic hamsters on the PUFA diet would have lower metabolic rate in cold and higher NST capacity than hamsters supplemented with SFA/MUFA. Indeed, in winter resting metabolic rate (RMR) below the lower critical temperature was higher and NST capacity was lower in SFA/MUFA-supplemented animals than in PUFA-supplemented ones. These results suggest that the increased capacity for NST in PUFA-supplemented hamsters enables them lower RMR below the lower critical temperature of the thermoneural zone.

  5. 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.

  6. Hematologic, serologic, and histologic profile of aged Siberian hamsters (Phodopus sungorus).

    Science.gov (United States)

    McKeon, Gabriel P; Nagamine, Claude M; Ruby, Norman F; Luong, Richard H

    2011-05-01

    Biologic samples from 18 (12 female, 6 male) Siberian hamsters (Phodopus sungorus) representing an aged colony (17 to 27 mo) were examined. Values for CBC and serum biochemical parameters were determined, and macroscopic and microscopic pathologic evaluations were performed. Blood urea nitrogen levels were significantly higher in male (54.2 ± 14 mg/dL) compared with female (35.3 ± 22 mg/dL) hamsters and correlated histologically with a higher incidence of chronic glomerulonephropathy in males (5 of 6 males; 0 of 12 females). All 18 hamsters had histologic evidence of follicular mite infestation. Half (6 of 12) of the female hamsters showed cystic rete ovarii. Other histologic findings included thymic or thyroid branchial cysts (3 of 18), focal enteritis (2 of 18), and single cases of hepatic hemangiosarcoma, renal adenoma, subcutaneous mast cell tumor, cutaneous sebaceous adenoma, cutaneous trichofolliculoma, squamous papilloma of the nonglandular stomach, epididymal cholesteatoma, pyometra, and pituitary craniopharyngeal cyst. This study is the first published report of hematologic and serum chemical values for any population of Siberian hamsters and the first published report showing a potential male predisposition for chronic progressive glomerulonephropathy and a potential female predisposition for cystic rete ovarii.

  7. Hepatoprotective activity of bacoside A against N-nitrosodiethylamine-induced liver toxicity in adult rats.

    Science.gov (United States)

    Janani, Panneerselvam; Sivakumari, Kanakarajan; Parthasarathy, Chandrakesan

    2009-10-01

    N-Nitrosodiethylamine (DEN) is a notorious carcinogen, present in many environmental factors. DEN induces oxidative stress and cellular injury due to enhanced generation of reactive oxygen species; free radical scavengers protect the membranes from DEN-induced damage. The present study was designed to evaluate the protective effect of bacoside A (the active principle isolated from Bacopa monniera Linn.) on carcinogen-induced damage in rat liver. Adult male albino rats were pretreated with 15 mg/kg body weight/day of bacoside A orally (for 14 days) and then intoxicated with single necrogenic dose of N-nitrosodiethylamine (200 mg/kg bodyweight, intraperitonially) and maintained for 7 days. The liver weight, lipid peroxidation (LPO), and activity of serum marker enzymes (aspartate transaminases, alanine transaminases, lactate dehydrogenase, alkaline phosphatase, and gamma-glutamyl transpeptidase) were markedly increased in carcinogen-administered rats, whereas the activities of marker enzymes were near normal in bacoside A-pretreated rats. Activities of antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutatione-S-transferase, and reduced glutathione) in liver also decreased in carcinogen-administered rats, which were significantly elevated in bacoside A-pretreated rats. It is concluded that pretreatment of bacoside A prevents the elevation of LPO and activity of serum marker enzymes and maintains the antioxidant system and thus protects the rats from DEN-induced hepatotoxicity.

  8. Human carcinogens: an evaluation study via the COMPACT and HazardExpert procedures.

    Science.gov (United States)

    Lewi, D F V; Bird, M G; Jacobs, M N

    2002-03-01

    The results of computer-optimized molecular parametric analysis of chemical toxicity (COMPACT) and HazardExpert evaluations on 14 established human carcinogens are reported. The concordances between COMPACT and carcinogenicity (71%) and between HazardExpert and carcinogenicity (57%) are significantly improved when taken in combination, where all 14 carcinogens are correctly identified by the two systems used in conjunction. However, if a negative energy of the highest occupied molecular orbital (E(HOMO)) value is regarded as evidence of electrophilic reactivity likely to give rise to mutagenicity and carcinogenicity, then 13/14 (93%) of the carcinogens are correctly identified by combination with the COMPACT procedure alone. It is possible, therefore, to establish likely carcinogenicity arising from either P450 mediation (CYP1 and CYP2E) or compound electrophilicity via the employment of a straightforward approach to molecular and electronic structure calculation, a process that can be performed in a relatively short time frame (i.e., less than 1 hour per chemical) and at a low cost. PMID:12102536

  9. Feeding schedule controls circadian timing of daily torpor in SCN-ablated Siberian hamsters.

    Science.gov (United States)

    Paul, Matthew J; Kauffman, Alexander S; Zucker, Irving

    2004-06-01

    Timing of daily torpor was assessed in suprachiasmatic nucleus-ablated (SCNx) and sham-ablated Siberian hamsters fed restricted amounts of food each day either in the light or dark phase of a 14:10 light-dark cycle. Eighty-five percent of sham-ablated and 45% of SCNx hamsters displayed a preferred hour for torpor onset. In each group, time of torpor onset was not random but occurred at a mean hour that differed significantly from chance. Time of food presentation almost completely accounted for the timing of torpor onset in SCNx animals and significantly affected timing of this behavior in intact hamsters. These results suggest that the circadian pacemaker in the SCN controls the time of torpor onset indirectly by affecting timing of food intake, rather than by, or in addition to, direct neural and humoral outputs to relevant target tissues.

  10. A brief view of known landmarks reorientates path integration in hamsters

    Science.gov (United States)

    Etienne, A. S.; Boulens, V.; Maurer, R.; Rowe, T.; Siegrist, C.

    In darkness, hamsters commute between their nest and a feeding site through path integration only, and therefore show cumulative errors in the return direction to the nest. We examined whether a brief presentation of familiar room cues could reset the path integrator. The hamsters could see the room cues either during, or at the end of, the outward journey to the food place, in a conflict situation where motion cues and visual information were set at variance. In both conditions, the animals used mainly visual information to return home. Thus, hamsters can determine their azimuth, and possibly their location, through a visual fix, and can reset their path integrator through the fix. This allows them to update their position during further locomotion in the dark and thus to compute a correct homing vector with respect to a visually induced reference frame. Taking episodic positional fixes may greatly enhance the functional value of path integration.

  11. Neuropeptides and anticipatory changes in behaviour and physiology: seasonal body weight regulation in the Siberian hamster.

    Science.gov (United States)

    Mercer, Julian G; Tups, Alexander

    2003-11-01

    The Siberian hamster, Phodopus sungorus, is a powerful model of physiological body weight regulation. This seasonal model offers the potential to distinguish between the compensatory neuroendocrine systems that defend body weight against imposed negative energy balance, and those that are involved in the programming of the level of body weight that will be defended-a seasonally appropriate body weight. Of the known, studied, components of the hypothalamic energy balance system, the anorexogenic peptide, cocaine- and amphetamine-regulated transcript (CART), is the only candidate where gene expression changes in a manner consistent with a role in initiating or sustaining photoperiod-induced differences in body weight trajectory. Siberian hamsters effect a reversible biannual switch in leptin sensitivity in which only short day (SD)-acclimated hamsters that have undergone a reduction in body weight, adiposity and plasma leptin are sensitive to peripheral exogenous leptin. The suppressor of cytokine signalling protein, SOCS3, appears to be the molecular correlate of this seasonal sensitivity.

  12. 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

  13. 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.

  14. Peripheral kisspeptin reverses short photoperiod-induced gonadal regression in Syrian hamsters by promoting GNRH release

    DEFF Research Database (Denmark)

    Ansel, L; Bentsen, A H; Ancel, C;

    2011-01-01

    In seasonal breeders, reproduction is synchronised by day length via the pineal hormone melatonin. In short winter days (short day, SD), the Syrian hamster displays a complete gonadal atrophy together with a marked reduction in expression of kisspeptins (Kp), a family of potent hypothalamic...... stimulators of GNRH neurons. Both central and peripheral acute injections of Kp have been reported to activate the gonadotropic axis in mammals. The aim of this study was to determine if and how peripheral administration of Kp54 could restore gonadal function in photo-inhibited hamsters. Testicular activity...... of hamsters kept in SD was reactivated by two daily i.p. injections of Kp54 but not by chronic subcutaneous delivery of the same peptide via mini-pumps. Acute i.p. injection of Kp54-induced FOS (c-Fos) expression in a large number of GNRH neurons and pituitary gonadotrophs together with a strong increase...

  15. 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.

  16. [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

  17. 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.

  18. Pubertal growth of the medial amygdala delayed by short photoperiods in the Siberian hamster, Phodopus sungorus.

    Science.gov (United States)

    Cooke, Bradley M; Jordan, Cynthia L; Breedlove, S Marc

    2007-09-01

    We investigated whether puberty influences the morphology of the medial nucleus of the amygdala (MeA) by comparing Siberian hamsters (Phodopus sungorus) that had been raised from birth in either long day (LD; 16:8 h light:dark) or short day (SD; 8:16) photoperiods. Hamsters were sacrificed at 42-49 days of age, at which point all LD hamsters were reproductively mature, as evidenced by adult-like testes weights (mean: 657 mg). In contrast, the testes weights of the SD hamsters were low (mean: 31 mg), indicating that the SD photoperiod had delayed puberty. The regional volume and mean soma size of the four MeA subnuclei was estimated bilaterally by stereological procedures. In the posterior dorsal and ventral MeA subnuclei, regional volume was 22-25% larger, and mean soma size 18% larger, in LD males than SD males. Unbiased cell counts in the posterior dorsal MeA showed that LD and SD hamsters have equivalent neuron numbers. In the anterior MeA subnuclei, regional volumes and soma sizes from LD and SD hamsters were equivalent. Additionally, the regional volume of the posteroventral subnucleus was larger in the right hemisphere than the left, but this laterality did not respond to photoperiod manipulation. These results suggest that the extant neurons within the posterior MeA, a steroid-sensitive nucleus implicated in socio-sexual behavior, grow in response to the elevated levels of circulating androgen accompanying puberty, and that photoperiodic regulation of puberty affects morphological maturation of this nucleus.

  19. Reversal of acetaminophen toxicity in isolated hamster hepatocytes by dithiothreitol

    Energy Technology Data Exchange (ETDEWEB)

    Tee, L.B.; Boobis, A.R.; Huggett, A.C.; Davies, D.S.

    1986-04-01

    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 (/sup 14/C)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.

  20. 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.

  1. 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)

  2. 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...

  3. 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

  4. 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...

  5. A variable embryotoxic response to lead in different strains of hamsters

    Energy Technology Data Exchange (ETDEWEB)

    Gale, T.F. (Medical College of Georgia, Augusta (USA))

    1978-12-01

    Lead nitrate was administered intravenously at 50 mg/kg to five inbred strains (MHA, LSH, LHC, CB, and P 4) and the non-inbred LVG strain of pregnant hamsters early on the 8th gestation day. All fetuses from treated and control hamsters were collected on the 15th gestation day and examined for the frequency and kinds of external, internal, and skeletal abnormalities. The major embryotoxic effects included resorptions, tail bud abnormalities, hydrocephalus, and skeletal defects. It is concluded that the LSH, LHC, LVG, and PD4 strains are susceptible while the MHA and CB strains are relatively resistant to the lead exposure.

  6. 1,3-Propane sultone as an extremely potent human carcinogen: description of an exposed cohort in Germany.

    Science.gov (United States)

    Bolt, Hermann M; Golka, Klaus

    2012-01-01

    1,3-Propane sultone (1,3-PS) is a directly alkylating, genotoxic and carcinogenic substance. In rats, 1,3-PS induces local and systemic tumors at multiple sites, including the mammary gland, intestine, hematopoietic system, kidneys, and the central nervous system (CNS), especially in the form of gliomas. In one particular company, 1,3-PS had been manufactured in limited amounts in the 1950s and 1960s, and for a few purposes until the 1970s. The number of individuals having been in contact with the compound occupationally comprised 55 in total. Data were obtained from this group with an open question of legal compensation regarding an occupational disease. Particular emphasis was placed on malignancies occurring among the occupationally exposed persons. As cerebral gliomas are a major type of tumor induced by 1,3-PS experimentally, the occurrence of two glioblastomas among the previously exposed persons was significant. Three intestinal malignancies were recorded within the cases observed. It is also noteworthy that there was one case of a duodenal carcinoma, which is normally a rare human malignancy. Two hematopoietic/lymphatic malignancies were observed, and there was one case of a renal cell carcinoma. The types of malignancies within a group of only 55 exposed persons are surprisingly consistent with the results from rodent studies. Data clearly indicate that 1,3-PS is carcinogenic in humans. Evidence indicates that 12 cases with various neoplasms were legally compensated within the period of 1985-2010 as an occupational disease, based on the "opening clause" of § 9 (2) SGB VII of legislation in Germany.

  7. 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

  8. 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.

  9. 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 ...

  10. 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...

  11. 29 CFR 1990.131 - Priority lists for regulating potential occupational carcinogens.

    Science.gov (United States)

    2010-07-01

    ... List. The inclusion or exclusion of any substance on these lists shall not be subject to judicial... carcinogen which has not been placed on these lists. The inclusion of a substance on either of these...

  12. 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...

  13. Carcinogenicity evaluation for the application of carbon nanotubes as biomaterials in rasH2 mice

    Science.gov (United States)

    Takanashi, Seiji; Hara, Kazuo; Aoki, Kaoru; Usui, Yuki; Shimizu, Masayuki; Haniu, Hisao; Ogihara, Nobuhide; Ishigaki, Norio; Nakamura, Koichi; Okamoto, Masanori; Kobayashi, Shinsuke; Kato, Hiroyuki; Sano, Kenji; Nishimura, Naoyuki; Tsutsumi, Hideki; Machida, Kazuhiko; Saito, Naoto

    2012-07-01

    The application of carbon nanotubes (CNTs) as biomaterials is of wide interest, and studies examining their application in medicine have had considerable significance. Biological safety is the most important factor when considering the clinical application of CNTs as biomaterials, and various toxicity evaluations are required. Among these evaluations, carcinogenicity should be examined with the highest priority; however, no report using transgenic mice to evaluate the carcinogenicity of CNTs has been published to date. Here, we performed a carcinogenicity test by implanting multi-walled CNTs (MWCNTs) into the subcutaneous tissue of rasH2 mice, using the carbon black present in black tattoo ink as a reference material for safety. The rasH2 mice did not develop neoplasms after being injected with MWCNTs; instead, MWCNTs showed lower carcinogenicity than carbon black. Such evaluations should facilitate the clinical application and development of CNTs for use in important medical fields.

  14. 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

  15. 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):...

  16. Correlation of levels of volatile versus carcinogenic particulate polycyclic aromatic hydrocarbons in air samples from smokehouses

    DEFF Research Database (Denmark)

    Hansen, Åse Marie; Poulsen, O M; Christensen, J M

    1991-01-01

    In the present study, data on the concentration of polycyclic aromatic hydrocarbons (PAH) in air samples from fish smokehouses (Nordholm et al. 1986) and meat smokehouses (Hansen et al. submitted for publication) were used to analyze the extent to which six different volatile PAH compounds could...... carcinogenic PAH compounds in air samples from smokehouses, whereas fluoranthene and pyrene displayed the highest specificity. However, when the applicability of the six markers was tested on air samples from iron foundries, only naphthalene and pyrene were useful as markers for the carcinogenic compounds...... function as markers for the total concentration of six different carcinogenic particulate PAH compounds. Although a significant positive correlation was observed between the concentration of each of six volatile compounds and the total concentration of carcinogenic PAH compounds, a particularly good...

  17. 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...

  18. Carcinogenicity of sublimed urethane in mice through the respiratory tract.

    Science.gov (United States)

    Nomura, T; Hayashi, T; Masuyama, T; Tanaka, S; Nakajima, H; Kurokawa, N; Isa, Y

    1990-08-01

    The carcinogenicity of sublimed urethane (ethyl carbamate) in air was examined with mice. JCL:ICR mice were nursed in a plastic cage inside a vinyl chamber which was ventilated 4 times per hour. The mice were exposed to urethane gas for various periods by passing air which contained a high concentration of sublimed urethane (1.29 micrograms/ml) into the vinyl chamber, or by placing a vessel containing crystalline urethane inside the vinyl chamber so that it was filled with spontaneously-sublimed urethane gas at a low concentration (0.25 microgram/ml). When female mice were killed 5 months after exposure, lung tumor frequency increased almost linearly with the number of days of exposure in the low concentration experiment, but increased in a non-linear manner in the high concentration experiment. In terms of nearly the same total dose, i.e., (concentration of urethane gas in air) X (days of inhalation), one day of exposure to urethane gas at the low concentration induced lung tumors at a significantly higher frequency than 1/4 day of exposure to urethane gas at the high concentration. When male mice were killed at 12 months after exposure to examine the progressive change of induced tumors, malignant, invasive and metastatic tumors were found to have been induced more frequently in the lung after exposure to urethane gas at the low concentration (0.25 microgram/ml for 10 days) than at the high concentration (1.29 microgram/ml for 4 days), although the total dose in the former group was about half of that in the latter. Continuous exposure to urethane gas for a longer period at the low concentration seems to be more efficient for the induction, promotion and/or progression of lung tumors than the exposure for a shorter period at the high concentration.

  19. Assignment of genes encoding metallothioneins I and II to Chinese hamster chromosomes 3. Evidence for the role of chromosome rearrangement in gene amplification

    Energy Technology Data Exchange (ETDEWEB)

    Stallings, R.L.; Munk, A.C.; Longmire, J.L.; Hildebrand, C.E.; Crawford, B.D.

    1984-12-01

    Cadmium resistant (Cd/sup r/) variants with coordinately amplified metallothionein I and II (MTI and MTII) genes have been derived from both Chinese hamster ovary and near-euploid Chinese hamster cell lines. Cytogenetic analyses of Cd/sup r/ variants consistently revealed breakage and rearrangement involving chromosome 3p. In situ hybridization with Chinese hamster MT-encoding cDNA probe localized amplified MT gene sequences near the translocation breakpoint involving chromosome 3p. These observations suggested that both functionally related, isometallothionein loci are linked on Chinese hamster chromosome 3. Southern blot analyses of DNAs isolated from a panel of Chinese hamster x mouse somatic cell hybrids which segregate hamster chromosomes confirmed that both MTI and MTII are located on chromosome 3. The authors speculate that rearrangement of chromosome 3p could be causally involved with the amplification of MT genes in Cd/sup r/ hamster cell lines. 34 references, 3 figures, 1 table.

  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...

  1. 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 ...

  2. 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...

  3. Mutagenic and carcinogenic potential of a textile azo dye processing plant effluent that impacts a drinking water source.

    Science.gov (United States)

    Alves de Lima, Rodrigo Otávio; Bazo, Ana Paula; Salvadori, Daisy Maria Fávero; Rech, Célia Maria; de Palma Oliveira, Danielle; de Aragão Umbuzeiro, Gisela

    2007-01-10

    river, Chemosphere 60 (2005) 55-64]. Therefore, it is important to evaluate the possible risks involved in the human consumption of this contaminated water. With that objective, one sample of the cited industrial effluent was tested for carcinogenicity in the aberrant crypt foci medium-term assay in colon of Wistar rats. The rats received the effluent in natura through drinking water at concentrations of 0.1%, 1%, and 10%. The effluent mutagenicity was also confirmed in the Salmonella/microsome assay with the strains TA98 and YG1041. There was an increased number of preneoplastic lesions in the colon of rats exposed to concentrations of 1% and 10% of the effluent, and a positive response for both Salmonella strains tested. These results indicate that the discharge of the effluent should be avoided in waters used for human consumption and show the sensitivity of the ACF crypt foci assay as an important tool to evaluate the carcinogenic potential of environmental complex mixtures.

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

    Science.gov (United States)

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

    2013-11-01

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

  5. A comprehensive review of the carcinogenic and anticarcinogenic potential of capsaicin.

    Science.gov (United States)

    Bley, Keith; Boorman, Gary; Mohammad, Bashir; McKenzie, Donald; Babbar, Sunita

    2012-08-01

    Human exposure to capsaicin, the most abundant pungent chili pepper component, is ubiquitous. Evaluation of capsaicin's carcinogenic potential has produced variable results in in vitro and in vivo genotoxicity and carcinogenicity assays. The capsaicin tested in older studies was often from pepper plant extracts and included other capsaicinoids and diverse impurities. Recent studies utilizing high-purity capsaicin and standardized protocols provide evidence that the genotoxic and carcinogenic potential of capsaicin is quite low and that the purity of capsaicin is important. Several small epidemiological studies suggest a link between capsaicin consumption and stomach or gall bladder cancer, but contamination of capsaicin-containing foods with known carcinogens renders their interpretation problematic. The postulated ability of capsaicin metabolites to damage DNA and promote carcinogenesis remains unsupported. Anticancer activities of capsaicin have been widely reported, as it inhibits the activity of carcinogens and induces apoptosis in numerous cancer cell lines in vitro and explanted into rodents. Diverse mechanisms have been postulated for capsaicin's anticancer properties. One hypothesis is that inhibition of cytochrome P450 enzymes-particularly CYP2E1-retards carcinogen activation but is contradicted by the low potency of capsaicin for CYP inhibition. The potential for dietary capsaicin to act as a chemopreventative is now widely postulated. PMID:22563012

  6. α-Tocopherol Improves Microcirculatory Dysfunction on Fructose Fed Hamsters.

    Directory of Open Access Journals (Sweden)

    Beatriz C S Boa

    Full Text Available Fructose, an everyday component of western diet associated to chronic hyperglycemia and enhanced free radical production, impairs endothelial function and supplementation with antioxidants might improve it. In this study we investigated if vitamin E could reverse the microvascular damage elicited by fructose. Male Syrian golden hamsters drank either 10% fructose solution (F or filtered water (C, combined with three concentrations of vitamin E in their chows [zero, normal (VE or 5X (5XVE] during 60 days. Microvascular reactivity in response to topical application of acetylcholine (Ach; endothelium-dependent vasodilator or sodium nitroprusside (SNP; endothelium-independent vasodilator and macromolecular permeability increase induced by either 30 min ischemia followed by reperfusion (I/R or topical application of histamine (5 μM were assessed using the cheek pouch preparation. Compared to controls (drinking filtered water, fructose-drinking animals showed decreased vasodilatation to acetylcholine in all concentrations tested (-56.2% for 10-9M, -53.9% for 10-7M and -43.7% for 10-5M. On the other hand, vitamin E supplementation resulted in increased responses for both water and fructose drinking groups (177.4% for F vs. F/5XVE and 241.6% for C vs. C/5XVE for 10-5M Ach. Endothelial-independent vasodilatation explored by topical application of SNP was restored and even enhanced with the supplementation of 5X vitamin E in both groups (80.1% for F vs. F/5XVE; 144.2% for C vs. C/5XVE; 3.4% of difference for C/5XVE vs. F/5XVE on 10-5M SNP. The number of leaky sites after I/R and histamine stimuli in vitamin E supplemented animals decreased (-25.1% and -15.3% for F vs. F/5XVE; and -21.7% and -16% of leaky sites comparing C vs. C/5XVE, respectively for I/R and histamine stimuli pointing to tightening of the endothelial barrier for macromolecular permeability. Our results strongly suggest that vitamin E could improve the endothelial function and permeability

  7. Thermal acclimation and nutritional history affect the oxidation of different classes of exogenous nutrients in Siberian hamsters, Phodopus sungorus.

    Science.gov (United States)

    McCue, Marshall D; Voigt, Christian C; Jefimow, Małgorzata; Wojciechowski, Michał S

    2014-11-01

    During acclimatization to winter, changes in morphology and physiology combined with changes in diet may affect how animals use the nutrients they ingest. To study (a) how thermal acclimation and (b) nutritional history affect the rates at which Siberian hamsters (Phodopus sungorus) oxidize different classes of dietary nutrients, we conducted two trials in which we fed hamsters one of three (13) C-labeled compounds, that is, glucose, leucine, or palmitic acid. We predicted that under acute cold stress (3 hr at 2°C) hamsters previously acclimated to cold temperatures (10°C) for 3 weeks would have higher resting metabolic rate (RMR) and would oxidize a greater proportion of dietary fatty acids than animals acclimated to 21°C. We also investigated how chronic nutritional stress affects how hamsters use dietary nutrients. To examine this, hamsters were fed four different diets (control, low protein, low lipid, and low-glycemic index) for 2 weeks. During cold challenges, hamsters previously acclimated to cold exhibited higher thermal conductance and RMR, and also oxidized more exogenous palmitic acid during the postprandial phase than animals acclimated to 21°C. In the nutritional stress trial, hamsters fed the low protein diet oxidized more exogenous glucose, but not more exogenous palmitic acid than the control group. The use of (13) C-labeled metabolic tracers combined with breath testing demonstrated that both thermal and nutritional history results in significant changes in the extent to which animals oxidize dietary nutrients during the postprandial period.

  8. Effects of sex and scotorefractory state on obesity induced by photostimulation and serum leptin in Siberian hamsters (Phodopus sungorus).

    Science.gov (United States)

    Cudney, Sarah E; Place, Ned J

    2012-12-01

    The rising prevalence of obesity is associated with an increasing incidence of heart disease, diabetes and other health risks. In addition, severe cases of obesity are associated with an even greater risk of morbidity and mortality. Therefore, animal models of morbid obesity are required to better elucidate the underlying mechanisms. Our investigations in the Siberian hamster (Phodopus sungorus) suggest that pronounced obesity can be reliably induced in this species without relying on genetic manipulation or overly fatty and palatable foods. In a prior study on reproductive aging in female Siberian hamsters, we incidentally observed marked obesity in a group of hamsters that were exposed to a particular photoperiodic regime. In short day (SD) lengths, Siberian hamsters inhibit their reproductive physiology and reduce food intake and body mass. However, hamsters become refractory to SD after 15-20weeks and revert to the long day (LD) phenotype. In the previous study, refractory animals appeared to be particularly sensitive to photostimulation (transfer to LD), in terms of increasing body mass. To test the hypothesis that refractoriness to SD predisposes hamsters to severe obesity, we photostimulated females and males in different states of SD responsiveness (inhibited or refractory). We determined that photostimulation during the SD-refractory state is particularly effective in inducing pronounced obesity and high serum leptin concentration in female hamsters. We propose that this experimental framework is a useful model to investigate the factors and signals that create a predisposition to excessive food intake and body mass, without having to rely on genetic or dietary manipulations.

  9. 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.

  10. Benefit of multiple trait selection to increase reproductive traits; experimental evidence from Golden hamsters.

    NARCIS (Netherlands)

    Satoh, M.; Nishida, A.; Arendonk, van J.A.M.; Lende, van der T.

    1997-01-01

    Fifteen generations of selection were conducted to study responses for litter size at birth (LSB), weight at weaning of standardized litter (LWW), and individual body weight at 8 wk of age (BW8) using golden hamsters as an experimental model for pigs. The experiment involved three lines: selection o

  11. Differential cytokine gene expression according to outcome in a hamster model of leptospirosis.

    Directory of Open Access Journals (Sweden)

    Frédérique Vernel-Pauillac

    Full Text Available BACKGROUND: Parameters predicting the evolution of leptospirosis would be useful for clinicians, as well as to better understand severe leptospirosis, but are scarce and rarely validated. Because severe leptospirosis includes septic shock, similarities with predictors evidenced for sepsis and septic shock were studied in a hamster model. METHODOLOGY/PRINCIPAL FINDINGS: Using an LD50 model of leptospirosis in hamsters, we first determined that 3 days post-infection was a time-point that allowed studying the regulation of immune gene expression and represented the onset of the clinical signs of the disease. In the absence of tools to assess serum concentrations of immune effectors in hamsters, we determined mRNA levels of various immune genes, especially cytokines, together with leptospiraemia at this particular time-point. We found differential expression of both pro- and anti-inflammatory mediators, with significantly higher expression levels of tumor necrosis factor alpha, interleukin 1alpha, cyclo-oxygenase 2 and interleukin 10 genes in nonsurvivors compared to survivors. Higher leptospiraemia was also observed in nonsurvivors. Lastly, we demonstrated the relevance of these results by comparing their respective expression levels using a LD100 model or an isogenic high-passage nonvirulent variant. CONCLUSIONS/SIGNIFICANCE: Up-regulated gene expression of both pro- and anti-inflammatory immune effectors in hamsters with fatal outcome in an LD50 model of leptospirosis, together with a higher Leptospira burden, suggest that these gene expression levels could be predictors of adverse outcome in leptospirosis.

  12. The genomic sequence of the Chinese hamster ovary (CHO)-K1 cell line

    DEFF Research Database (Denmark)

    Xu, Xun; Pan, Shengkai; Liu, Xin;

    2011-01-01

    Chinese hamster ovary (CHO)-derived cell lines are the preferred host cells for the production of therapeutic proteins. Here we present a draft genomic sequence of the CHO-K1 ancestral cell line. The assembly comprises 2.45 Gb of genomic sequence, with 24,383 predicted genes. We associate most of...

  13. Metabolic rate changes proportionally to circadian frequency in tau mutant Syrian hamsters

    NARCIS (Netherlands)

    Oklejewicz, M; Hut, RA; Daan, S; Loudon, ASI; Stirland, AJ; Loudon, Andrew S.I.; Stirland, Anne J.

    1997-01-01

    The tau mutation in Syrian hamsters (Mesocricetus auratus) is phenotypically expressed in a period of the circadian rhythm of about 20 h in homozygotes (SS) and about 22 h in heterozygotes (S+). The authors investigate whether this well-defined model for variation in circadian period exhibits associ

  14. Characterization of Chinese Hamster Ovary Cells Producing Coagulation Factor VIII Using Multi-omics Tools

    DEFF Research Database (Denmark)

    Kaas, Christian Schrøder

    The first public draft of a genome from Chinese hamster ovary (CHO) cells was published in 2011, an entire decade after the first draft of the human genome. This publication of a relevant CHO reference genome, in combination with the fact that the cost for DNA sequencing has dropped more than 10,...

  15. Toward genome-scale models of the Chinese hamster ovary cells: incentives, status and perspectives

    DEFF Research Database (Denmark)

    Kaas, Christian Schrøder; Fan, Yuzhou; Weilguny, Dietmar;

    2014-01-01

    Bioprocessing of the important Chinese hamster ovary (CHO) cell lines used for the production of biopharmaceuticals stands at the brink of several redefining events. In 2011, the field entered the genomics era, which has accelerated omics-based phenotyping of the cell lines. In this review we des...

  16. Simulated natural day lengths synchronize seasonal rhythms of asynchronously born male Siberian hamsters.

    Science.gov (United States)

    Butler, Matthew P; Turner, Kevin W; Park, Jin Ho; Butler, James P; Trumbull, Justin J; Dunn, Sean P; Villa, Philip; Zucker, Irving

    2007-07-01

    Photoperiodism research has relied on static day lengths and abrupt transitions between long and short days to characterize the signals that drive seasonal rhythms. To identify ecologically relevant critical day lengths and to test the extent to which naturally changing day lengths synchronize important developmental events, we monitored nine cohorts of male Siberian hamsters (Phodopus sungorus) born every 2 wk from 4 wk before to 12 wk after the summer solstice in a simulated natural photoperiod (SNP). SNP hamsters born from 4 wk before to 2 wk after the solstice underwent rapid somatic and gonadal growth; among those born 4-6 wk after the solstice, some delayed puberty by many weeks, whereas others manifested early puberty. Hamsters born eight or more weeks after the solstice failed to undergo early testicular development. The transition to delayed development occurred at long day lengths, which induce early puberty when presented as static photoperiods. The first animals to delay puberty may do so predominantly on the basis of postnatal decreases in day length, whereas in later cohorts, a comparison of postnatal day length to gestational day length may contribute to arrested development. Despite differences in timing of birth and timing of puberty, autumn gonadal regression and spring gonadal and somatic growth occurred at similar calendar dates in all cohorts. Incrementally changing photoperiods exert a strong organizing effect on seasonal rhythms by providing hamsters with a richer source of environmental timing cues than are available in simple static day lengths.

  17. Timing of puberty and synchronization of seasonal rhythms by simulated natural photoperiods in female Siberian hamsters.

    Science.gov (United States)

    Butler, Matthew P; Trumbull, Justin J; Turner, Kevin W; Zucker, Irving

    2007-07-01

    The timing of puberty is a critical life history trait of short-lived species; spring-born individuals mature rapidly and breed in the season of birth, whereas young born in mid- to late summer delay puberty until the next spring. The cues that govern the transition from rapid to delayed maturation in natural populations remain unknown. To identify ecologically relevant photoperiod cues that control timing of puberty, we monitored nine cohorts of female Siberian hamsters (Phodopus sungorus) born every 2 wk from 4 wk before to 12 wk after the summer solstice in a simulated natural photoperiod (SNP). Hamsters born by the summer solstice underwent rapid somatic growth and achieved puberty that summer; among females born 2-4 wk after the solstice, some delayed puberty by many weeks, whereas others manifested early puberty. Hamsters born 6 or more weeks after the solstice generally delayed puberty until the following spring. The transition from accelerated to delayed pubertal development in the SNP occurred at day lengths that induce early puberty when presented as static photoperiods. Despite differences in timing of birth and timing of puberty, fall and subsequent spring seasonal events occurred at similar calendar dates in all cohorts. We found no evidence that prenatal photoperiod history influenced postnatal development of female hamsters. Considered together with a parallel study on males, the present findings point to sex differences in responsiveness to natural photoperiod variations. In both sexes, incrementally changing photoperiods exert a strong organizing effect on seasonal rhythms.

  18. Dissociation of ultradian and circadian phenotypes in female and male Siberian hamsters.

    Science.gov (United States)

    Prendergast, Brian J; Cisse, Yasmine M; Cable, Erin J; Zucker, Irving

    2012-08-01

    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 arrhythmic (ARR). The period of the ultradian locomotor rhythm (UR) did not differ among the 3 circadian phenotypes; neuroendocrine generation of URs remains viable in the absence of coherent circadian organization and appears to be mediated by substrates functionally and anatomically distinct from those that generate CRs. Pronounced light-dark differences in several UR characteristics in ENTR hamsters were completely absent in circadian arrhythmic hamsters. The disruptive phase-shifting protocol may compromise direct visual input to ultradian oscillators but more likely indirectly affects URs by interrupting visual afference to the circadian system. Additional experiments documented that deuterium oxide and constant light, each of which substantially lengthened the period of free-running CRs, failed to change the period of concurrently monitored URs. The resistance of URs to deuteration contrasts with the slowing of virtually all other biological timing processes, including CRs. Considered together, the present results point to the existence of separable control mechanisms for generation of circadian and ultradian rhythms.

  19. Secretion and regulatory mechanism of leptin during pregnancy in the golden hamster (Mesocricetus auratus)

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    The aim of this study is to investigate the secretion pattern and regulatory mechanism of leptin during pregnancy in the golden hamster (Mesocricetus auratus). 100 pregnant golden hamsters were separated into 16 groups and the serum was sampled daily throughout gestation for the leptin assay. Results indicated that a gestational leptin profile existed during pregnancy in the golden hamster. To investigate if endocrine conditions during pregnancy contribute to this gestational leptin profile, serums collected during different reproductive stages were added to the adipocyte culture medium. Results showed that sera collected from all reproductive stages have significant stimulating effect on the secretion of leptin as compared with the control (P 0.05). However, sera from mid and late pregnancy significantly stimulate leptin secretion as compared with the cycling sera (P < 0.01). Serum collected on day 15 of pregnancy have the strongest stimulating effect on leptin secretion compared with sera collected on day 8 (P < 0.0001) and day 12 (P < 0.001) of the pregnancy. But after the extraction of steroid hormones, sera collected during different reproductive stages have the same effect on leptin secretion in vitro. Further study showed that dexamethason, progesterone and insulin stimulated while estradiol suppressed leptin secretion in vitro. Our results suggested that steroid hormones (or other steroid factors) have significant regulating effect on the leptin secretion during pregnancy and they may be the most important contributors of the gestational leptin profile in the golden hamster.

  20. Induction of chromosome aberrations in Chinese hamster cells after heavy ion irradiation

    International Nuclear Information System (INIS)

    The induction of structural chromosome changes in V 79-Chinese hamster cells following heavy ion irradiation is studied. Asynchronous exponentially growing cells are exposed to the heavy ion beams at the Unilac, Darmstadt and the Ganil, Caen. The induction of chromosome aberrations was measured as a function of time after exposure. (orig./MG)

  1. Cytokinetics and histogenesis of cultured hamster tracheal epithelium. Effects of vitamin A and cigarette smoke condensate.

    NARCIS (Netherlands)

    Rutten, A.A.J.J.L.

    1988-01-01

    The studies reported in this thesis primarily deal with the influence of vitamin A (all-trans retinol) and cigarette smoke condensate on cellular proliferation, and differentiation and intercellular communication in tracheal epithelium. The experiments were carried out with Syrian Golden hamster tra

  2. 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;

    2013-01-01

    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...

  3. Altered cytokeratin expression during chemoprevention of hamster buccal pouch carcinogenesis by S-allylcysteine.

    Science.gov (United States)

    Balasenthil, Seetharaman; Rao, Kunchala S; Nagini, Siddavaram

    2003-01-01

    We examined the effect of S-allylcysteine (SAC), a water-soluble garlic constituent, on cytokeratin expression, a sensitive and specific marker for differentiation status during 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis in male Syrian hamsters. Hamsters were divided into four groups of six animals each. Animals in group 1 were painted with a 0.5% solution of DMBA in liquid paraffin on the right buccal pouches three times a week for 14 weeks. Group 2 animals were painted with DMBA as in group I, and in addition they received orally 200 mg/kg of SAC on days alternate to DMBA application. Group 3 animals received SAC as in group 2. Group 4 animals received neither DMBA nor SAC and served as the control. The hamsters were killed after an experimental period of 14 weeks. Cytokeratin expression was detected by Western blot analysis using monoclonal antibodies AE1 and AE3. In DMBA-induced HBP tumors, the decreased expression of high molecular weight cytokeratins of molecular mass between 55-70 kDa was observed. Administration of SAC (200 mg/kg) to animals painted with DMBA suppressed the incidence of DMBA-induced carcinomas and was associated with restoration of normal cytokeratin expression. The results of the present study suggest that inhibition of HBP tumorigenesis by SAC may be due to its regulatory effects on differentiation, tumor invasiveness, and its ability to migrate and form metastases. PMID:14704476

  4. Histiocytic Sarcoma and Bilateral Facial Vein Thrombosis in a Siberian Hamster (Phodopus sungorus).

    Science.gov (United States)

    Coble, Dondrae J; Shoemaker, Margaret; Harrington, Bonnie; Dardenne, Adrienne D; Bolon, Brad

    2015-04-01

    A 21-mo-old, male Siberian hamster (Phodopus sungorus) presented with left-sided facial swelling, proptosis of the left eye, and blepharospasm of the right eye. The hamster had been used only for breeding. Because of the poor prognosis, the hamster was euthanized without additional diagnostic assays or treatments. Routine gross pathologic evaluation demonstrated exophthalmos and presumptive hyphema of the left eye, bilateral facial edema, freely movable nodules within the mesentery, white foci within the liver, and a large mass effacing the cranial pole of the right kidney. On histologic evaluation, the mesenteric nodules and liver foci expressed histiocytic marker CD163 and thus were diagnosed as sites of histiocytic sarcoma, whereas the kidney mass was a well-differentiated renal cell carcinoma. The facial swelling resulted from bilateral, chronic, severe, branching thrombi in many facial veins. Additional age-related histopathologic findings were observed in other organs, including diffuse glomerulopathy, nesidioblastosis (pancreatic islet neoformation), and multiple foci of severe cartilage degeneration in the axial skeleton. To our knowledge, this report provides the first description of histiocytic sarcoma in a Siberian hamster.

  5. Contractile and morphological properties of hamster retractor muscle following 16 h of cold preservation

    NARCIS (Netherlands)

    de With, Miriam C. J.; van der Heijden, E. P. A. Brigitte; van Oosterhout, Matthijs F.; Kon, M.; Kroese, Alfons B. A.

    2009-01-01

    Introduction: Cold hypoxia is a common factor in cold tissue preservation and mammalian hibernation. The purpose of this study was to determine the effects of cold preservation on the function of the retractor (RET) muscle of the hamster in the non-hibernating state and compare these with previously

  6. Central amygdalar nucleus treated with orexin neuropeptides evoke differing feeding and grooming responses in the hamster.

    Science.gov (United States)

    Alò, Raffaella; Avolio, Ennio; Mele, Maria; Di Vito, Anna; Canonaco, Marcello

    2015-04-15

    Interaction of the orexinergic (ORXergic) neuronal system with the excitatory (glutamate, l-Glu) or the inhibitory (GABA) neurosignaling complexes evokes major homeostatic physiological events. In this study, effects of the two ORXergic neuropeptides (ORX-A/B) on their receptor (ORX-2R) expression changes were correlated to feeding and grooming actions of the hibernating hamster (Mesocricetus auratus). Infusion of the central amygdala nucleus (CeA) with ORX-A caused hamsters to consume notable quantities of food, while ORX-B accounted for a moderate increase. Interestingly the latter neuropeptide was responsible for greater frequencies of grooming with respect to both controls and the hamsters treated with ORX-A. These distinct behavioral changes turned out to be even greater in the presence of l-Glu agonist (NMDA) while the α1 GABAA receptor agonist (zolpidem, Zol) greatly reduced ORX-A-dependent feeding bouts. Moreover, ORX-A+NMDA mainly promoted greater ORX-2R expression levels with respect to ORX-A-treated hamsters while ORX-B+Zol was instead largely responsible for a down-regulatory trend. Overall, these features point to CeA ORX-2R sites as key sensory limbic elements capable of regulating eating and grooming responses, which may provide useful insights regarding the type of molecular mechanism(s) operating during feeding bouts.

  7. Persistence of experimental Rocio virus infection in the golden hamster (Mesocricetus auratus

    Directory of Open Access Journals (Sweden)

    Daniele Freitas Henriques

    2012-08-01

    Full Text Available Rocio virus (ROCV is an encephalitic flavivirus endemic to Brazil. Experimental flavivirus infections have previously demonstrated a persistent infection and, in this study, we investigated the persistence of ROCV infection in golden hamsters (Mesocricetus auratus. The hamsters were infected intraperitoneally with 9.8 LD50/0.02 mL of ROCV and later anaesthetised and sacrificed at various time points over a 120-day period to collect of blood, urine and organ samples. The viral titres were quantified by real-time-polymerase chain reaction (qRT-PCR. The specimens were used to infect Vero cells and ROCV antigens in the cells were detected by immunefluorescence assay. The levels of antibodies were determined by the haemagglutination inhibition technique. A histopathological examination was performed on the tissues by staining with haematoxylin-eosin and detecting viral antigens by immunohistochemistry (IHC. ROCV induced a strong immune response and was pathogenic in hamsters through neuroinvasion. ROCV was recovered from Vero cells exposed to samples from the viscera, brain, blood, serum and urine and was detected by qRT-PCR in the brain, liver and blood for three months after infection. ROCV induced histopathological changes and the expression of viral antigens, which were detected by IHC in the liver, kidney, lung and brain up to four months after infection. These findings show that ROCV is pathogenic to golden hamsters and has the capacity to cause persistent infection in animals after intraperitoneal infection.

  8. Persistence of experimental Rocio virus infection in the golden hamster (Mesocricetus auratus).

    Science.gov (United States)

    Henriques, Daniele Freitas; Quaresma, Juarez Antonio Simões; Fuzii, Helen Thais; Nunes, Márcio Roberto Teixeira; Silva, Eliana Vieira Pinto da; Carvalho, Valéria Lima; Martins, Lívia Carício; Casseb, Samir Mansour Moraes; Chiang, Jannifer Oliveira; Vasconcelos, Pedro Fernando da Costa

    2012-08-01

    Rocio virus (ROCV) is an encephalitic flavivirus endemic to Brazil. Experimental flavivirus infections have previously demonstrated a persistent infection and, in this study, we investigated the persistence of ROCV infection in golden hamsters (Mesocricetus auratus). The hamsters were infected intraperitoneally with 9.8 LD50/0.02 mL of ROCV and later anaesthetised and sacrificed at various time points over a 120-day period to collect of blood, urine and organ samples. The viral titres were quantified by real-time-polymerase chain reaction (qRT-PCR). The specimens were used to infect Vero cells and ROCV antigens in the cells were detected by immunefluorescence assay. The levels of antibodies were determined by the haemagglutination inhibition technique. A histopathological examination was performed on the tissues by staining with haematoxylin-eosin and detecting viral antigens by immunohistochemistry (IHC). ROCV induced a strong immune response and was pathogenic in hamsters through neuroinvasion. ROCV was recovered from Vero cells exposed to samples from the viscera, brain, blood, serum and urine and was detected by qRT-PCR in the brain, liver and blood for three months after infection. ROCV induced histopathological changes and the expression of viral antigens, which were detected by IHC in the liver, kidney, lung and brain up to four months after infection. These findings show that ROCV is pathogenic to golden hamsters and has the capacity to cause persistent infection in animals after intraperitoneal infection.

  9. Stimulatory effect of RFRP-3 on the gonadotrophic axis in the male Syrian hamster

    DEFF Research Database (Denmark)

    Ancel, Caroline; Bentsen, Agnete H; Sébert, Marie-Emilie;

    2012-01-01

    In seasonal mammals, a distinct photoneuroendocrine circuit that involves the pineal hormone melatonin tightly synchronizes reproduction with seasons. In the Syrian hamster, a seasonal model in which sexual activity is inhibited by short days, we have previously shown that the potent GnRH stimula...

  10. Appropriateness of the hamster as a model to study diet-induced atherosclerosis

    Science.gov (United States)

    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 apo...

  11. Melatonin and schistosomal antigens ameliorate the anti-oxidative and biochemical response to Schistosoma mansoni infection in hamster

    Institute of Scientific and Technical Information of China (English)

    Nahla S.El-SHENAWY; Maha F.M.SOLIMAN; Shimaa E.Abel-RAHMAN

    2009-01-01

    The present study was designed to investigate the potential protective effect of melatonin as an antioxidant separately or in combination with antigens (cercarial; CAP or soluble worm; SWAP) against Schistosoma mansoni infection in hamsters. Each hamster was sensitized with an initial immunization of 0.6 ml of the extracted antigen (30 μg protein/mL). After four days, a second injection of 0.4 mL was given (20 μg protein/mL). Then, each hamster was exposed to 260±20 S.mansoni cercariae followed with melatonin treatment (3.5 mg/kg) for thirty days from the 1st day of post infection. Levels of lipid peroxidation (LPO) products, catalase (CAT) activity, hepatic glutathione (GSH) and biochemical changes in the liver and kidneys functions were investigated. The results revealed a high significant increasing of LPO and decreasing of CAT and GSH in liver of infected hamsters. Biochemical observations showed severe damage in the liver enzyme activities and increasing cholesterol level in infected animals. Melatonin co-treatment with antigen to the infected-hamster attenuated the increase of LPO and restored the activity of CAT and levels of hepatic GSH. Also, the biochemical damages in the liver and kidneys functions were reduced. The present study suggests that melatonin may be useful in combating free radical-induced damage due to infection toxicity. The immunization with previous antigens resulted in a remarkable improvement on the liver enzyme activities, which were increased after infection. Thus, vaccination of hamsters with antigens (both CAP and SWAP) and melatonin treatment has more potent effect on the enhancement of antioxidant and biochemical of S.mansoni infected-hamster than each treatment separately. Immunization of the hamster with SWAP followed by melatonin was the best way among the other regime treatments to improve the biochemical and antioxidant parameters of the infected-hamsters[Current Zoology 55(2):165-172,2009].

  12. Evaluation of human health risks posed by carcinogenic and non-carcinogenic multiple contaminants associated with consumption of fish from Taihu Lake, China.

    Science.gov (United States)

    Yu, Yingxin; Wang, Xinxin; Yang, Dan; Lei, Bingli; Zhang, Xiaolan; Zhang, Xinyu

    2014-07-01

    The present study estimated the human daily intake and uptake of organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), polycyclic aromatic hydrocarbons (PAHs), and toxic trace elements [mercury (Hg), chromium (Cr), cadmium (Cd), and arsenic (As)] due to consumption of fish from Taihu Lake, China, and the associated potential health risks posed by these contaminants. The health risks posed by the contaminants were assessed using a risk quotient of the fish consumption rate to the maximum allowable fish consumption rate considering the contaminants for carcinogenic and non-carcinogenic effect endpoints. The results showed that fish consumption would not pose non-cancer risks. However, some species would cause a cancer risk. Relative risks of the contaminants were calculated to investigate the contaminant which posed the highest risk to humans. As a result, in view of the contaminants for carcinogenic effects, As was the contaminant which posed the highest risk to humans. However, when non-carcinogenic effects of the contaminants were considered, Hg posed the highest risk. The risk caused by PBDEs was negligible. The results demonstrated that traditional contaminants, such as As, Hg, DDTs (dichlorodiphenyltrichloroethane and its metabolites), and PCBs, require more attention in Taihu Lake than the other target contaminants. PMID:24727049

  13. Evaluation of human health risks posed by carcinogenic and non-carcinogenic multiple contaminants associated with consumption of fish from Taihu Lake, China.

    Science.gov (United States)

    Yu, Yingxin; Wang, Xinxin; Yang, Dan; Lei, Bingli; Zhang, Xiaolan; Zhang, Xinyu

    2014-07-01

    The present study estimated the human daily intake and uptake of organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), polycyclic aromatic hydrocarbons (PAHs), and toxic trace elements [mercury (Hg), chromium (Cr), cadmium (Cd), and arsenic (As)] due to consumption of fish from Taihu Lake, China, and the associated potential health risks posed by these contaminants. The health risks posed by the contaminants were assessed using a risk quotient of the fish consumption rate to the maximum allowable fish consumption rate considering the contaminants for carcinogenic and non-carcinogenic effect endpoints. The results showed that fish consumption would not pose non-cancer risks. However, some species would cause a cancer risk. Relative risks of the contaminants were calculated to investigate the contaminant which posed the highest risk to humans. As a result, in view of the contaminants for carcinogenic effects, As was the contaminant which posed the highest risk to humans. However, when non-carcinogenic effects of the contaminants were considered, Hg posed the highest risk. The risk caused by PBDEs was negligible. The results demonstrated that traditional contaminants, such as As, Hg, DDTs (dichlorodiphenyltrichloroethane and its metabolites), and PCBs, require more attention in Taihu Lake than the other target contaminants.

  14. Clinical laboratory, virologic, and pathologic changes in hamsters experimentally infected with Pirital virus (Arenaviridae): a rodent model of Lassa fever.

    Science.gov (United States)

    Sbrana, Elena; Mateo, Rosa I; Xiao, Shu-Yuan; Popov, Vsevolod L; Newman, Patrick C; Tesh, Robert B

    2006-06-01

    The clinical laboratory, virologic, and pathologic changes occurring in hamsters after infection with Pirital virus (Arenaviridae) are described. Pirital virus infection in the hamsters was characterized by high titered viremia, leukocytosis, coagulopathy, pulmonary hemorrhage and edema, hepatocellular and splenic necrosis, and marked elevation of serum transaminase levels. All of the animals died within 9 days. The clinical and histopathological findings in the Pirital virus-infected hamsters were very similar to those reported in severe human cases of Lassa fever, suggesting that this new animal model could serve as a low-cost and relatively safe alternative for studying the pathogenesis and therapy of Lassa fever. PMID:16760527

  15. Age-associated metabolic and morphologic changes in mitochondria of individual mouse and hamster oocytes.

    Directory of Open Access Journals (Sweden)

    Fatma Simsek-Duran

    Full Text Available BACKGROUND: In human oocytes, as in other mammalian ova, there is a significant variation in the pregnancy potential, with approximately 20% of oocyte-sperm meetings resulting in pregnancies. This frequency of successful fertilization decreases as the oocytes age. This low proportion of fruitful couplings appears to be influenced by changes in mitochondrial structure and function. In this study, we have examined mitochondrial biogenesis in both hamster (Mesocricetus auratus and mouse (Mus musculus ova as models for understanding the effects of aging on mitochondrial structure and energy production within the mammalian oocyte. METHODOLOGY/PRINCIPAL FINDINGS: Individual metaphase II oocytes from a total of 25 young and old mice and hamsters were collected from ovarian follicles after hormone stimulation and prepared for biochemical or structural analysis. Adenosine triphosphate levels and mitochondrial DNA number were determined within individual oocytes from young and old animals. In aged hamsters, oocyte adenosine triphosphate levels and mitochondrial DNA molecules were reduced 35.4% and 51.8%, respectively. Reductions of 38.4% and 44% in adenosine triphosphate and mitochondrial genomes, respectively, were also seen in aged mouse oocytes. Transmission electron microscopic (TEM analysis showed that aged rodent oocytes had significant alterations in mitochondrial and cytoplasmic lamellae structure. CONCLUSIONS/SIGNIFICANCE: In both mice and hamsters, decreased adenosine triphosphate in aged oocytes is correlated with a similar decrease in mtDNA molecules and number of mitochondria. Mitochondria in mice and hamsters undergo significant morphological change with aging including mitochondrial vacuolization, cristae alterations, and changes in cytoplasmic lamellae.

  16. Hypothalamic gene expression rapidly changes in response to photoperiod in juvenile Siberian hamsters (Phodopus sungorus).

    Science.gov (United States)

    Herwig, A; Petri, I; Barrett, P

    2012-07-01

    Siberian hamsters are seasonal mammals that survive a winter climate by making adaptations in physiology and behaviour. This includes gonadal atrophy, reduced food intake and body weight. The underlying central mechanisms responsible for the physiological adaptations are not fully established but involve reducing hypothalamic tri-iodthyronine (T3) levels. Juvenile Siberian hamsters born or raised in short days (SD) respond in a similar manner, although with an inhibition of gonadal development and growth instead of reversing an established long day (LD) phenotype. Using juvenile male hamsters, the present study aimed to investigate whether the central mechanisms are similar before the establishment of the mature LD phenotype. By in situ hybridisation, we examined the response of genes involved in thyroid hormone (Dio2 and Dio3, which determine hypothalamic T3 levels) and glucose/glutamate metabolism in the ependymal layer, histamine H3 receptor and VGF as representatives of the highly responsive dorsomedial posterior arcuate nucleus (dmpARC), and somatostatin, a hypothalamic neuropeptide involved in regulating the growth axis. Differential gene expression of type 2 and type 3 deiodinase in the ependymal layer, histamine H3 receptor in the dmpARC and somatostatin in the ARC was established by the eighth day in SD. These changes are followed by alterations in glucose metabolism related genes in the ependymal layer by day 16 and increased secretogranin expression in the dmpARC by day 32. In conclusion, our data demonstrate similar but rapid and highly responsive changes in gene expression in the brain of juvenile Siberian hamsters in response to a switch from LD to SD. The data also provide a temporal definition of gene expression changes relative to physiological adaptations of body weight and testicular development and highlight the likely importance of thyroid hormone availability as an early event in the adaptation of physiology to a winter climate in juvenile

  17. Possible relationship between intestinal barrier function and formation of pigment gallstones in hamsters

    Institute of Scientific and Technical Information of China (English)

    Ying Fan; Shuo-Dong Wu; Lei Sun; Bei-Bei Fu; Yang Su

    2008-01-01

    BACKGROUND: The presence of bacteria in bile is an important factor in the formation of pigment gallstones. The bile of healthy people is sterile and bacteria in the biliary system come from endogenous infection from the gut. Yet, the route of bacterial translocation into the bile duct is still unclear. Theoretically, two routes exist:one is through the intestinal barrier and the other is by direct relfux from the sphincter of Oddi. This study was undertaken to explore the relationship between the effectiveness of intestinal barrier and the formation of pigment gallstones in hamsters. METHODS: Thirty-two hamsters were divided into an experimental and a control group, with 16 hamsters in each group. A low protein and high cellulose diet was given for 6 weeks to induce the formation of pigment gallstones in the experimental group (PS) and a normal diet was given to the control group (CON). Morphological changes, changes in the levels of serum endotoxin and diamine oxidase, and changes in the numbers of B lymphocytes, plasma cells and secretory immunoglobin A (sIgA) in the intestinal mucosa were assessed after 6 weeks. RESULTS:Four hamsters died during lithogenesis and body weight decreased in the PS group. Pigment gallstones were found in 11 hamsters at the end of the experiment, giving a lithogenesis rate of 91.67%. The serum endotoxin level before and after gallstone formation in the PS group was 0.2960±0.1734 U/ml and 8.2964±4.6268 U/ml, respectively (P CONCLUSIONS:A low protein and high cellulose diet can markedly reduce intestinal barrier function and facilitate the formation of pigment gallstones. The decrease of intestinal barrier function may take part in the formation of pigment gallstones.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-01-15

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

  19. Persistent and heritable structural damage induced in heterochromatic DNA from rat liver by N-nitrosodimethylamine

    International Nuclear Information System (INIS)

    Analysis, by benzoylated DEAE-cellulose chromatography, has been made of structural change in eu- and heterochromatic DNA from rat liver following administration of the carcinogen N-nitrosodimethylamine. Either hepatic DNA was prelabeled with [3H]thymidine administered 2-3 weeks before injection of the carcinogen or the labeled precursor was given during regenerative hyperplasia in rats treated earlier with N-nitrosodimethylamine. Following phenol extraction of either whole liver homogenate or nuclease-fractionated eu- and heterochromatin, carcinogen-modified DNA was examined by stepwise or caffeine gradient elution from benzoylated DEAE-cellulose. In whole DNA, nitrosamine-induced single-stranded character was maximal 4-24 h after treatment, declining rapidly thereafter; gradient elution of these DNA preparations also provided short-term evidence of structural change. Caffeine gradient chromatography suggested short-term nitrosamine-induced structural change in euchromatic DNA, while increased binding of heterochromatic DNA was evident for up to 3 months after carcinogen treatment. Preparations of newly synthesized heterochromatic DNA from animals subjected to hepatectomy up to 2 months after carcinogen treatment provided evidence of heritable structural damage. Carcinogen-induced binding of heterochromatic DNA to benzoylated DEAE-cellulose was indicative of specific structural lesions whose affinity equalled that of single-stranded DNA up to 1.0 kilobase in length. The data suggest that structural lesions in heterochromatin, which may be a consequence of incomplete repair, are preferentially degraded by endogenous nuclease(s)

  20. Investigations into the carcinogenicity of man-made mineral fibers

    Energy Technology Data Exchange (ETDEWEB)

    Muhle, H.

    1988-01-01

    With the aim of assessing a possible increase in tumour rates due to damage to the respiratory tissues of the upper respiratory tract the study, based on the inhalation effects found in rats, investigated into the cancerogenic effects of very thin glass fibers and crocidolite as well as into the combined effects of glass fibers and sulfur dioxide. Although there were no significantly higher tumour rates found with any of the fibers applied, high rates of bronchio-alveolar hyperplasies (74%), plate epithel metaplasy in one case, and adenoidal cancer after crocidolite treatments were found to be indicative of the tendency of crocidolite to induce neoplasms. After i.p. injections of 0.5 mg tumour rates were 17% in the case of JM 104/475 glass fibers and 55% in the case of crocidolite of South African origin. The parallelism of the diagnoses of humans exposed to crocidolite and of i.p. injections in rats shows the validity of the i.p. model. Valuable results were obtained with regard to the persistence of glass fibers in lungs after inhalation.