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

International Nuclear Information System (INIS)

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

2014-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2014-11-01

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

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

Science.gov (United States)

Singh, Vishal; Jain, Manish; Misra, Ankita; Khanna, Vivek; Prakash, Prem; Malasoni, Richa; Dwivedi, Anil Kumar; Dikshit, Madhu; Barthwal, Manoj Kumar

2015-06-01

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. 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. 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-1)α and PGC-1β genes known to be involved in lipid and glucose metabolism. High fructose feeding to rats and hamsters led to the development of insulin

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

Comparative toxicity in rats vs hamsters of inhaled radon daughters with and without uranium ore dust

International Nuclear Information System (INIS)

Gaven, J.C.; Palmer, R.F.; McDonald, K.E.; Lund, J.E.; Stuart, B.O.

1977-01-01

Simultaneous exposures of rats and hamsters to inhaled radon daughters, with and without uranium ore dust, were performed daily for five months. Pulmonary pathology developing in 6 to 13 mo after cessation of daily exposures included interstitial fibrosis, emphysema, epithelial hyperplasia, squamous metaplasia, and malignant neoplasia. Rats showed a greater variety and more severe response to these uranium mine inhalation exposures than did hamsters. Inhalation of radon daughters with uranium ore dust displayed the site of greatest damage, including squamous carcinoma, from the nasopharynx to the lungs. Sixty percent of the rats exposed to radon daughters with ore dust developed primary pulmonary carcinomas, providing an appropriate short-term experimental animal model for investigation of respiratory tract carcinogenesis in uranium miners

Oral carcinogenicity study with nickel sulfate hexahydrate in Fischer 344 rats

International Nuclear Information System (INIS)

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

2007-01-01

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

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

Science.gov (United States)

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

2011-06-01

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

Association of 239Pu with lysosomes in rat, Syrian hamster, and Chinese hamster liver as studied by carrier-free electrophoresis and electron microscopic autoradiography with 241Pu

International Nuclear Information System (INIS)

Seidel, A.; Krueger, E.W.; Wiener, M.; Hotz, G.; Balani, M.; Thies, W.G.

1985-01-01

The binding of injected monomeric plutonium in the liver of rats, Syrian hamsters, and Chinese hamsters (species which show profound differences in their ability to eliminate 239 Pu from the liver) was investigated by carrier-free electrophoresis using 239 Pu and electron microscopic autoradiography with 241 Pu. These studies are part of a program designed to obtain a better understanding of the mechanisms of the clearance of transuranium elements from liver of different mammals and man. Between 4 and 9 days after nuclide injection, a clear correlation between the majority of the 239 Pu and lysosomal enzymes was observed when the mitochondrial-lysosomal (ML) fraction of the livers was analyzed by carrier-free electrophoresis. In the two hamster species, a second 239 Pu peak exists from the beginning and increases with time to comprise 50% of the total radioactivity at later times. During electron microscopic examination 4 days after 241 Pu injection, beta tracks were frequently observed over globular structures resembling dense bodies in Chinese hamster liver. They were also observed frequently over chromatin-rich portions of the cell nuclei. These results, together with those from previous density gradient studies, show that lysosomes are the primary deposition site for 239 Pu in the liver cytoplasm of these three rodent species. The hypothesis of a morphologic transformation of these lysosomes with time in hamster liver and of rapid bulk exocytosis of the lysosomes in rats are still possible explanations for the extreme differences in the elimination among the three species

Molecular biomarkers of oxidative stress associated with bromate carcinogenicity

International Nuclear Information System (INIS)

Delker, Don; Hatch, Gary; Allen, James; Crissman, Bobby; George, Michael; Geter, David; Kilburn, Steve; Moore, Tanya; Nelson, Gail; Roop, Barbara; Slade, Ralph; Swank, Adam; Ward, William; DeAngelo, Anthony

2006-01-01

Potassium bromate (KBrO 3 ) is a chemical oxidizing agent found in drinking water as a disinfection byproduct of surface water ozonation. Chronic exposures to KBrO 3 cause renal cell tumors in rats, hamsters and mice and thyroid and testicular mesothelial tumors in rats. Experimental evidence indicates that bromate mediates toxicological effects via the induction of oxidative stress. To investigate the contribution of oxidative stress in KBrO 3 -induced cancer, male F344 rats were administered KBrO 3 in their drinking water at multiple concentrations for 2-100 weeks. Gene expression analyses were performed on kidney, thyroid and mesothelial cell RNA. Families of mRNA transcripts differentially expressed with respect to bromate treatment included multiple cancer, cell death, ion transport and oxidative stress genes. Multiple glutathione metabolism genes were up-regulated in kidney following carcinogenic (400 mg/L) but not non-carcinogenic (20 mg/L) bromate exposures. 8-Oxodeoxyguanosine glycosylase (Ogg1) mRNA was up-regulated in response to bromate treatment in kidney but not thyroid. A dramatic decrease in global gene expression changes was observed following 1 mg/L compared to 20 mg/L bromate exposures. In a separate study oxygen-18 ( 18 O) labeled KBrO 3 was administered to male rats by oral gavage and tissues were analyzed for 18 O deposition. Tissue enrichment of 18 O was observed at 5 and 24 h post-KBr 18 O 3 exposure with the highest enrichment occurring in the liver followed by the kidney, thyroid and testes. The kidney dose response observed was biphasic showing similar statistical increases in 18 O deposition between 0.25 and 50 mg/L (equivalent dose) KBr 18 O 3 followed by a much greater increase above 50 mg/L. These results suggest that carcinogenic doses of potassium bromate require attainment of a threshold at which oxidation of tissues occurs and that gene expression profiles may be predictive of these physiological changes in renal homeostasis

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

Science.gov (United States)

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

2018-01-01

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

In vitro transformation: interactions of chemical carcinogens and radiation

International Nuclear Information System (INIS)

DiPaolo, J.A.

1976-01-01

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

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

International Nuclear Information System (INIS)

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

1979-06-01

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

Label-free vascular imaging in a spontaneous hamster cheek pouch carcinogen model for pre-cancer detection (Conference Presentation)

Science.gov (United States)

Hu, Fangyao; Morhard, Robert; Liu, Heather; Murphy, Helen; Farsiu, Sina; Ramanujam, Nimmi

2016-03-01

Inducing angiogenesis is one hallmark of cancer. Tumor induced neovasculature is often characterized as leaky, tortuous and chaotic, unlike a highly organized normal vasculature. Additionally, in the course of carcinogenesis, angiogenesis precedes a visible lesion. Tumor cannot grow beyond 1-2 mm in diameter without inducing angiogenesis. Therefore, capturing the event of angiogenesis may aid early detection of pre-cancer -important for better treatment prognoses in regions that lack the resources to manage invasive cancer. In this study, we imaged the neovascularization in vivo in a spontaneous hamster cheek pouch carcinogen model using a, non-invasive, label-free, high resolution, reflected-light spectral darkfield microscope. Hamsters' cheek pouches were painted with 7,12-Dimethylbenz[a]anthracene (DMBA) to induce pre-cancerous to cancerous changes, or mineral oil as control. High resolution spectral darkfield images were obtained over the course of pre-cancer development and in control cheek pouches. The vasculature was segmented with a multi-scale Gabor filter with an 85% accuracy compared with manually traced masks. Highly tortuous vasculature was observed only in the DMBA treated cheek pouches as early as 6 weeks of treatment. In addition, the highly tortuous vessels could be identified before a visible lesion occurred later during the treatment. The vessel patterns as determined by the tortuosity index were significantly different from that of the control cheek pouch. This preliminary study suggests that high-resolution darkfield microscopy is promising tool for pre-cancer and early cancer detection in low resource settings.

Disruption of spindle checkpoint function in rats following 28 days of repeated administration of renal carcinogens.

Science.gov (United States)

Kimura, Masayuki; Mizukami, Sayaka; Watanabe, Yousuke; Hasegawa-Baba, Yasuko; Onda, Nobuhiko; Yoshida, Toshinori; Shibutani, Makoto

2016-02-01

We previously reported that 28-day exposure to hepatocarcinogens that facilitate cell proliferation specifically alters the expression of G1/S checkpoint-related genes and proteins, induces aberrant early expression of ubiquitin D (UBD) at the G2 phase, and increases apoptosis in the rat liver, indicating G1/S and spindle checkpoint dysfunction. The present study aimed to determine the time of onset of carcinogen-specific cell-cycle disruption after repeated administration of renal carcinogens for up to 28 days. Rats were orally administered the renal carcinogens nitrofurantoin (NFT), 1-amino-2,4-dibromoantraquinone (ADAQ), and 1,2,3-trichloropropane (TCP) or the non-carcinogenic renal toxicants 1-chloro-2-propanol, triamterene, and carboxin for 3, 7 or 28 days. Both immunohistochemical single-molecule analysis and real-time RT-PCR analysis revealed that carcinogen-specific expression changes were not observed after 28 days of administration. However, the renal carcinogens ADAQ and TCP specifically reduced the number of cells expressing phosphorylated-histone H3 at Ser10 in both UBD(+) cells and proliferating cells, suggestive of insufficient UBD expression at the M phase and early transition of proliferating cells from the M phase, without increasing apoptosis, after 28 days of administration. In contrast, NFT, which has marginal carcinogenic potential, did not induce such cellular responses. These results suggest that it may take 28 days to induce spindle checkpoint dysfunction by renal carcinogens; however, induction of apoptosis may not be essential. Thus, induction of spindle checkpoint dysfunction may be dependent on carcinogenic potential of carcinogen examined, and marginal carcinogens may not exert sufficient responses even after 28 days of administration.

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

International Nuclear Information System (INIS)

Winter, R.; Seidel, A.

1980-01-01

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 239 Pu administration. The animals were sacrificed 4 days later. In order to study the possible association with ferritin, 59 Fe 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 239 Pu 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.)

Keishibukuryogan is not carcinogenic in Sprague-Dawley rats

OpenAIRE

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

2016-01-01

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

The intrarenal distribution of 125I-albumin in the syrian hamster

International Nuclear Information System (INIS)

Moeller, P.

1977-01-01

The intrarenal distribution of radioiodinated human serum albumin ( 125 RISA) after intravenous injection was studied in Syrian hamsters by scintillation counting and frozen section autoradiogrpahy. After 15, 30, and 60 min the virtual plasma albumin space in the renal cortex of the hamster represented 6.49, 7.13, and 8.06% respectively of the kidney tissue volume. From the cortex to the renal papilla the albumin space increased to about 30% of the tissue volume. In comparison to this the albumin space in the renal cortex of the rat was about 20%, and in the renal papilla about 33% (11). Frozen section autoradiography indicated that the distribution of radioalbumin in the renal cortex if the Syrian hamster is limited mainly to the kidney vessels, being especially noticeable in the glomerular capillaries. Toward the papilla increasingly greater (mainly extratubular) activity could be observed not only intravascularly but also interstitially. In the cortex of the rat kidney, on the other hand, radioactive albumin was accumulated (probably by filtration and reabsorption) predominantly in the proximal tubular epithelium. Within 30 min the kidneys of the rat excreted more than 10 times as much 125 I than the hamster kidneys. These results (substantially less cortical accumulation and urinary excretion of radioalbumin in the Syrian hamster) indicate that, in contrast to the rat, obviously much less albumin is filtered (and then accumulated by proximal reabsorption) by the Syrian hamster glomeruli. This suggests that the Syrian hamster kidney is more suitable than the rat kidney for determining the interstitial, cortical, albumin space. (orig./AJ) [de

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

Science.gov (United States)

Zhang, Yu; Niewiesk, Stefan; Li, Jianrong

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 was found that BALB/c mice are not permissive for hMPV infection despite the use of a high dose (6.5 log10 PFU) of virus for intranasal inoculation. In hamsters, hMPV replicated efficiently in nasal turbinates but demonstrated only limited replication in lungs. In cotton rats, hMPV replicated efficiently in both nasal turbinate and lung when intranasally administered with three different doses (4, 5, and 6 log10 PFU) of hMPV. Lungs of cotton rats infected by hMPV developed interstitial pneumonia with mononuclear cells infiltrates and increased lumen exudation. By immunohistochemistry, viral antigens were detected at the luminal surfaces of the bronchial epithelial cells in lungs. Vaccination of cotton rats with hMPV completely protected upper and lower respiratory tract from wildtype challenge. The immunization also elicited elevated serum neutralizing antibody. Collectively, these results demonstrated that cotton rat is a robust small animal model for hMPV infection. PMID:25438015

Partial synchronization of spermatogenesis in the immature Djungarian hamster, but not in the immature Wistar rat

NARCIS (Netherlands)

van Haaster, L. H.; de rooij, D. G.

1994-01-01

The frequencies of the cellular associations of the seminiferous epithelium were determined at various ages after birth in immature Djungarian hamsters and Wistar rats. The frequencies of the cellular associations present in immature animals were then compared with the frequencies of the

Significant prolongation of hamster liver transplant survival in Lewis rats by total-lymphoid irradiation, cyclosporine, and splenectomy

International Nuclear Information System (INIS)

Yamaguchi, Y.; Halperin, E.C.; Harland, R.C.; Wyble, C.; Bollinger, R.R.

1990-01-01

The effects of total lymphoid irradiation, cyclosporine and splenectomy alone and in combination have been studied in liver transplants from the LVG hamster to the LEW rat. Neither CsA alone, splenectomy alone, nor TLI alone prolonged graft survival. CsA/splenectomy and TLI/CsA produced significant prolongation of graft survival. TLI/CsA/splenectomy prolonged graft survival by over sixfold compared with controls. While CsA alone was ineffective in reducing lymphocytotoxic antidonor antibody, splenectomy alone or CsA/splenectomy did significantly suppress production of antibody. Only very low levels of antibody could be detected in animals treated with TLI/CsA/splenectomy. TLI/CsA/splenectomy has an immunosuppressive effect sufficient to significantly prolong liver graft survival in the LVG hamster to LEW rat combination and may represent a promising treatment protocol in experimental cross-species transplantation

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

Science.gov (United States)

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

1983-01-01

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

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

International Nuclear Information System (INIS)

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

2006-01-01

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

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.

Comparison of the subcellular distribution of monomeric 239Pu and 59Fe in the liver of rat, mouse, and Syrian and Chinese hamsters

International Nuclear Information System (INIS)

Winter, R.; Seidel, A.

1982-01-01

The subcellular distribution of 239 Pu and 59 Fe 10 days after intravenous injection as a citrate complex was investigated by sucrose density gradient centrifugation in the liver of rat, mouse, and Syrian and Chinese hamsters. Lysosomes were separated from other cell constituents by injection of the nonionic detergent Triton WR 1339 4 days before sacrifice. The Triton-induced decrease in the density of the lysosomes was very similar in all four animal species and was followed closely by a corresponding decrease of the median density of the 239 Pu profiles in rat, mouse, and, to a smaller extent, Syrian hamster. However, in Chinese hamster a clear correspondence between lysosomes and 239 Pu was not found 10 days after nuclide injection. It was concluded that lysosomes are the main storage organelles fo 239 Pu in the liver of rat and mouse and that in all four animal species mitochondria and endoplasmic reticulum do not play any significant role in binding the radionuclide. The relevance of pericellular membranes has to be checked. The distribution patterns of 59 Fe and 239 Pu were quite different

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...

Autoradiographic demonstration of unscheduled DNA synthesis in oral tissues treated with chemical carcinogens in short-term organ culture

International Nuclear Information System (INIS)

Ide, F.; Umemura, S.; Ishikawa, T.; Takayama, S.

1981-01-01

A system in which oral tissues of inbred F344 adult rats and Syrian golden hamster embryos were used in combination with autoradiography was developed for measurement of unscheduled DNA synthesis (UDS). For this, oral mucosa, submandibular gland, tooth germ and mandible in short-term organ cultures were treated with 4-nitroquinoline l-oxide or N-methyl-N-nitrosourea plus (methyl- 3 H)thymidine. Significant numbers of silver grains, indicating UDS, were detected over the nuclei of cells of all these tissues except rat salivary gland after treatment with carcinogens. This autoradiographic method is suitable for detection of UDS in oral tissues in conditions mimicking those in vivo. Results obtained in this study indicated a potential use of this system for studies on the mechanism of carcinogenesis at a cellular level comparable to in vivo carcinogenesis studies on oral tissues. (author)

Individual recognition and odor in rat-like hamsters: behavioral responses and chemical properties.

Science.gov (United States)

Liu, Dingzhen; Huang, Ke-Jian; Zhang, Jian-Xu

2011-11-01

Individual recognition has been studied across a number of taxa and modalities; however, few attempts have been made to combine chemical and biological approaches and arrive at a more complete understanding of the use of secretions as signals. We combined behavioral habituation experiments with gas chromatography-mass spectrometry of glandular secretions from the left and right flank gland and midventral gland of the rat-like hamster, Tscheskia triton. We found that females became habituated to one scent and then could discriminate individuals via another scent source from the same individual only when familiar with the scent donor. However, this prior social interaction was not required for females to discriminate different individuals in single-stimulus habituation-dishabituation tests. Chemical analyses revealed a similarity in volatile compounds between the left and right flank gland and midventral gland scents. It appears that individually distinctive cues are integratively coded by a combination of both flank gland and midventral gland secretions, instead of a single scent, albeit animals show different preferences to the novel scent. Our results suggest that odors from the flank and midventral glands may provide information related to individuality and aid individual recognition in this species and confirm that prior interaction between individuals is a prerequisite for rat-like hamsters to form multi-odor memory of a particular conspecific.

Understanding arsenic carcinogenicity by the use of animal models

International Nuclear Information System (INIS)

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

2004-01-01

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

Secondary effects induced by the colon carcinogen azoxymethane in BDIX rats

DEFF Research Database (Denmark)

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

2004-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2015-12-01

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

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

International Nuclear Information System (INIS)

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

2015-01-01

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

Uptake of elemental mercury and activity of catalase in rat, hamster, guinea-pig, normal and acatalasemic mice

International Nuclear Information System (INIS)

Eide, I.; Syversen, T.L.M.

1982-01-01

Uptake of elemental mercury after inhalation (3.5 mg/m 3 ) and the activity of catalase in brain, liver, kidney and blood were investigated in rat, hamster, guinea-pig, and normal and acatalasemic mice. The uptake of mercury in the species investigated varied considerably, being highest in the two strains of mice, followed by rat and hamster, and lowest in the guinea-pig. The uptake seemed to be more dependent on pulmonary ventilation than on the activity of catalase. The two strains of mice were exposed to a wide range of mercury concentrations in air (0.002-3.5 mg/m 3 ). The content of mercury in brain, liver and kidney was linearly dependent on the mercury concentration in the air, whereas in blood this relationship was exponential. At the lower concentraions of mercury in the inhaled air, the mercury level in blood was significantly lower, and in kidney higher in the acatalasemic mice compared to the normal ones. In acatalasemic mice the mercury content in the liver has higher at all concentrations investigated, whereas in brain no difference between the two strains was found. (author)

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

International Nuclear Information System (INIS)

Mally, Angela; Chipman, James Kevin

2002-01-01

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

A 13-week toxicity study of acrylamide administered in drinking water to hamsters.

Science.gov (United States)

Imai, Toshio; Kitahashi, Tsukasa

2014-01-01

Acrylamide (AA) is known to induce tumors in various organs/tissues in rats and mice. Epidemiological studies of oral exposure have generated controversial results but mortality studies of people who work with AA have indicated increased rates of pancreatic cancer. In the present study, for dose selection for chronic toxicity/carcinogenicity studies, 13-week toxicity of AA was evaluated in Syrian hamsters, which are sensitive to induction of pancreatic ductal carcinogenesis, at concentrations required to provide doses of 0 (control), 20, 30 and 50 mg kg(-1) body weight in drinking water. Treatment with AA caused abnormal gait advancing to hind limb paralysis in all males and females at 50 mg kg(-1). Body weights in 30 and 50 mg kg(-1) males and 50 mg kg(-1) females were lower than in the controls. At termination of the study, red blood cells (RBC) and hemoglobin (Hb) were decreased or showed a tendency for a decrease at 20 and 30 mg kg(-1) in females. Microscopically, axonal/myelin degeneration of sciatic nerves was observed in all AA-treated groups with dose dependence. No obvious changes were found in pancreatic ducts/ductules in any groups of animal. These results indicated the maximum tolerated dose for long-term studies of AA to be 20 mg kg(-1) or less in both male and female Syrian hamsters. Copyright © 2012 John Wiley & Sons, Ltd.

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

International Nuclear Information System (INIS)

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

1987-01-01

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 λgt11 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 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

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

International Nuclear Information System (INIS)

Novicki, D.L.; Rosenberg, M.R.; Michalopoulos, G.

1985-01-01

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

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

Science.gov (United States)

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

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

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

International Nuclear Information System (INIS)

Allaben, W.T.; Weis, C.C.; Fullerton, N.F.; Beland, F.A.

1983-01-01

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

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

Science.gov (United States)

Borzelleca, J F; Hallagan, J B

1988-03-01

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

Molecular analysis of peroxisome proliferation in the hamster.

Science.gov (United States)

Choudhury, Agharul I; Sims, Helen M; Horley, Neill J; Roberts, Ruth A; Tomlinson, Simon R; Salter, Andrew M; Bruce, Mary; Shaw, P Nicholas; Kendall, David; Barrett, David A; Bell, David R

2004-05-15

Three novel P450 members of the cytochrome P450 4A family were cloned as partial cDNAs from hamster liver, characterised as novel members of the CYP4A subfamily, and designated CYP4A17, 18, and 19. Hamsters were treated with the peroxisome proliferator-activated receptor alpha (PPARalpha) agonists, methylclofenapate (MCP) or Wy-14,643, and shown to develop hepatomegaly and induction of CYP4A17 RNA, and concomitant induction of lauric acid 12- hydroxylase. This treatment also resulted in hypolipidaemia, which was most pronounced in the VLDL fraction, with up to 50% reduction in VLDL-triglycerides; by contrast, blood cholesterol concentration was unaffected by this treatment. These data show that hamster is highly responsive to induction of CYP4A by peroxisome proliferators. To characterise the molecular basis of peroxisome proliferation, the hamster PPARalpha was cloned and shown to encode a 468-amino-acid protein, which is highly similar to rat and mouse PPARalpha proteins. The level of expression of hamster PPARalpha in liver is intermediate between mouse and guinea pig. These results fail to support the hypothesis that the level of PPARalpha in liver is directly responsible for species differences in peroxisome proliferation.

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

Science.gov (United States)

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

1995-05-01

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

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

International Nuclear Information System (INIS)

Popescu, N.C.; Amsbaugh, S.C.; Larramendy, M.L.; DiPaolo

1982-01-01

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

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

International Nuclear Information System (INIS)

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

1984-01-01

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

Development of lesions in Syrian golden hamsters following exposure to radon daughters and uranium ore dust

International Nuclear Information System (INIS)

Cross, F.T.; Palmer, R.F.; Busch, R.H.; Filipy, R.E.; Stuart, B.O.

1981-01-01

The development of lesions in Syrian Golden hamsters was studied following life-span inhalation exposures to radon, radon daughters and uranium ore dust. Clinical measurements revealed that life-span exposures to radon daughters and uranium ore dust, singly or in combination, caused no significant changes in mortality patterns, body weights or hematological parameters compared with controls. Pulmonary and nonpulmonary lesions are presented. Exposure to uranium ore dust provoked inflammatory and proliferative responses in the lungs consisting of macrophage accumulation, alveolar cell hyperplasia, and adenomatous alteration of alveolar epithelium. The adenomatous lesions did not undergo further morphologic change. Exposure to radon and radon daughters was associated with increased occurrence of bronchiolar epithelial hyperplasia and with metaplastic changes of alveolar epithelium. Squamous carcinoma developed in only a few hamsters and only in those animals receiving radon daughter exposures exceeding 8000 WLM. It is concluded that an animal model other than the hamster would be more appropriate for study of the pulmonary carcinogenic potential of uranium ore alone. (author)

Nuclear ploidy of neonatal rat livers: effects of two hepatic carcinogens (mirex and dimethylnitrosamine)

International Nuclear Information System (INIS)

Carlson, J.; Abraham, R.

1985-01-01

The effect of two hepatic carcinogens, dimethylnitrosamine (DMN) (genotoxic) and mirex (epigenetic), on polyploidization in 12-d-old neonatal rats was investigated by Coulter counteranalysis and [ 3 H] thymidine uptake in isolated hepatic nuclear classes. DMN disturbed the normal ploidy development in the neonatal liver and the proportion of nuclei in the ploidy classes by inducing the premature formation of a significant population of tetraploids with a concommitant reduction in diploids. A great proportion of the replicative activity was present in tetraploid nuclei as measured by the incorporation of [ 3 H] thymidine. The labeling index and number of mitoses were also increased. In contrast to DMN, mirex had no influence on polyploidization. The neonatal rats used in these studies thus offer an opportunity to investigate in vivo the mode of action of genotoxic versus epigenetic compounds with reference to their effect on DNA

Effects of the PPARα Agonist and Widely Used Antihyperlipidemic Drug Gemfibrozil on Hepatic Toxicity and Lipid Metabolism

Directory of Open Access Journals (Sweden)

Michael L. Cunningham

2010-01-01

Full Text Available Gemfibrozil is a widely prescribed hypolipidemic agent in humans and a peroxisome proliferator and liver carcinogen in rats. Three-month feed studies of gemfibrozil were conducted by the National Toxicology Program (NTP in male Harlan Sprague-Dawley rats, B6C3F1 mice, and Syrian hamsters, primarily to examine mechanisms of hepatocarcinogenicity. There was morphologic evidence of peroxisome proliferation in rats and mice. Increased hepatocyte proliferation was observed in rats, primarily at the earliest time point. Increases in peroxisomal enzyme activities were greatest in rats, intermediate in mice, and least in hamsters. These studies demonstrate that rats are most responsive while hamsters are least responsive. These events are causally related to hepatotoxicity and hepatocarcinogenicity of gemfibrozil in rodents via peroxisome proliferator activated receptor-α (PPARα activation; however, there is widespread evidence that activation of PPARα in humans results in expression of genes involved in lipid metabolism, but not in hepatocellular proliferation.

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

International Nuclear Information System (INIS)

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

1986-01-01

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

Dotriacontane-16,17-14C distribution pattern in the respiratory system of two hamster species after passive exposure to radioactive labelled smoke

International Nuclear Information System (INIS)

Kmoch, N.; Mohr, U.

1974-01-01

The quantitative and qualitative distribution of 14 C labeled dotriacontane (DOT- 14 C) determined by liquid scintillation counting and autoradiography in the respiratory system, the digestive tract, liver and kidneys of Syrian golden and European hamsters, males and females, is described after they had been exposed to radioactive labeled cigarette smoke. The different DOT- 14 C distributions are discussed in detail with special attention given to the respiratory tract, related species differences and the topographic subdivisions of apex nasi, fundus nasi, pharynx, larynx, trachea, and lungs. It is apparent that the absolute amount of activity in the respiratory tract related to body size of the Syrian golden hamster is greater than in the European hamster but that the percentual distribution exhibits a greater filtering action of the upper respiratory tract of Syrian golden hamster than of the European hamster so that a larger percentual amount of total inhaled particulate matter reaches the lungs. The European hamster might be a more useful model for the investigation of respiratory tract carcinogenesis due to the possibility of a longer life time exposure and a higher sensitivity to respiratory tract carcinogens

Late effects of in utero exposure to carcinogens in rats, with special reference to postnatal growth and tumorigenesis

Energy Technology Data Exchange (ETDEWEB)

Naito, Y; Takizawa, S; Watanabe, H; Hirose, F [Hiroshima Univ. (Japan). Research Inst. for Nuclear Medicine and Biology

1976-11-01

Fifteen-day pregnant Wistar/Furth rats were irradiated with 100 rads of x ray of fast neutron (14.1 MeV). Fast neutron was found to be more effective than x rays in reducing the number of live-births and in retarding the postnatal growth of the offspring. Among the various organs examined, the brain, uterus, spleen and gonads were highly radiosensitive in terms of organ weight. Microscopic examination revealed a marked dysplasia of the ovary in the fast neutron-irradiated rats. Pre-conception irradiation did not cause any deleterious effects on the offspring. No substantial difference was noted in the peripheral blood pictures or on the tumor incidence in rats born from the irradiated female rats. On the other hand, it was noteworthy that N-butylnitrosourea given transplacentally induced 3 cases of brain tumor. The incidence of leukemia and mammary tumor was significantly higher in the irradiated or carcinogen-treated pregnant rats.

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

Directory of Open Access Journals (Sweden)

Natalja Fjodorova

2012-07-01

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

Induction of biotransformation enzymes by the carcinogenic air-pollutant 3-nitrobenzanthrone in liver, kidney and lung, after intra-tracheal instillation in rats.

Science.gov (United States)

Mizerovská, Jana; Dračínská, Helena; Frei, Eva; Schmeiser, Heinz H; Arlt, Volker M; Stiborová, Marie

2011-02-28

3-Nitrobenzanthrone (3-NBA), a carcinogenic air pollutant, was investigated for its ability to induce cytochrome P450 (CYP) 1A1/2 and NAD(P)H:quinone oxidoreductase (NQO1) in liver, kidney and lung of rats treated by intra-tracheal instillation. The organs used were from a previous study performed to determine the persistence of 3-NBA-derived DNA adducts in target and non-target tissues (Bieler et al., Carcinogenesis 28 (2007) 1117-1121, [22]). NQO1 is the enzyme reducing 3-NBA to N-hydroxy-3-aminobenzanthrone (N-OH-3-ABA) and CYP1A enzymes oxidize a human metabolite of 3-NBA, 3-aminobenzanthrone (3-ABA), to yield the same reactive intermediate. 3-NBA and 3-ABA are both activated to species forming DNA adducts by cytosols and/or microsomes isolated from rat lung, the target organ for 3-NBA carcinogenicity, and from liver and kidney. Each compound generated the same five DNA adducts detectable by (32)P-postlabelling. When hepatic cytosols from rats treated with 0.2 or 2mg/kg body weight of 3-NBA were incubated with 3-NBA, DNA adduct formation was 3.2- and 8.6-fold higher, respectively, than in incubations with cytosols from control animals. Likewise, cytosols isolated from lungs and kidneys of rats exposed to 3-NBA more efficiently activated 3-NBA than those of control rats. This increase corresponded to an increase in protein levels and enzymatic activities of NQO1. Incubations of hepatic, pulmonary or renal microsomes of 3-NBA-treated rats with 3-ABA led to an 9.6-fold increase in DNA-adduct formation relative to controls. The highest induction in DNA-adduct levels was found in lung. The stimulation of DNA-adduct formation correlated with expression of CYP1A1/2 induced by the intra-tracheal instillation of 3-NBA. The results demonstrate that 3-NBA induces NQO1 and CYP1A1/2 in livers, lungs and kidneys of rats after intra-tracheal instillation, thereby enhancing its own genotoxic and carcinogenic potential. Copyright © 2010 Elsevier B.V. All rights reserved.

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

Science.gov (United States)

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

2018-01-25

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

The biochemical mechanisms responsible for differences in the half-life of monomeric 239Pu in rat and Syrian hamster liver

International Nuclear Information System (INIS)

Seidel, A.; Winter, R.; Jentzsch, C.; Gruner, R.; Heumann, H.G.; Hanke, S.

1979-01-01

The subcellular distribution of 239 Pu citrate in rat and Syrian hamster liver was studied with the help of the non-ionic detergent Triton WR1339, used as method for separating lysosomes from other cell organelles. Triton WR1339 was injected six days after 239 Pu and the animals were sacrificed after Day 10. Liver homogenates were subjected to differential and isopycnic centrifugation in sucrose gradients. In both animal species 90% of 239 Pu of the post-nuclear supernatant was found in the fraction containing mitochondria, lysosomes, endoplasmatic reticulum and ferritin. Triton WR1339 injection caused a concomitant shift of the lysosomal marker acid phosphatase and of 239 Pu from high densities to rho approximately 1.10 in both animal species. According to our results, binding of 239 Pu to mitochondria and peroxisomes can be excluded, and association to endoplasmatic reticulum and plasma membranes is not very probable. We must consider the possibility that a part of the radioactivity occurring at rho approximately 1.10 can also be bound to ferritin. According to these findings, lysosomes could be one of the main storage sites for 239 Pu in both species. From studies on the pharmacokinetics of 3 H-labelled Triton WR1339 and on the behaviour of Triton-filled rat liver lysosomes, which are also presented in the paper, it is tentatively concluded that the rapid excretion of 239 Pu from rat liver is due to the normally rapid elimination of lysosomal material from hepatocytes into the bile in this species. In Syrian hamsters the fate of lysosomal material in liver may be different or redistribution of 239 Pu occurs at a later time. (author)

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

Science.gov (United States)

Boudreau, Mary D.

2013-01-01

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

Exhaustive physical exercise increases the number of colonic preneoplastic lesions in untrained rats treated with a chemical carcinogen.

Science.gov (United States)

Demarzo, Marcelo Marcos Piva; Garcia, Sérgio Britto

2004-12-08

Aberrant crypt foci (ACF) have been used for early detection of factors that influence colorectal carcinogenesis in rats. It has been observed that exhaustive exercise increases free radical DNA oxidative damage and depresses immune function, events also related to the increased risk for cancer development. Fifteen days after a single exhaustive swimming bout in untrained rats treated with a colon carcinogen, we observed a statistically significant increased number of ACF when compared to the non-exercised group. Thus, we concluded that exhaustive exercise increased the susceptibility for colon cancer in rats. From our finding and literature data, we hypothesize that, similarly to the suggested relationship between exercise and infections, exercise could be protective against cancer or it could increase the risk for this disease depending on its type, dose and duration.

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

Carcinogenicity tests of certain environmental and industrial chemicals

International Nuclear Information System (INIS)

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

1981-01-01

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

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

International Nuclear Information System (INIS)

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

2007-01-01

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

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.

Glyphosate rodent carcinogenicity bioassay expert panel review.

Science.gov (United States)

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

2016-09-01

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

Carcinogenicity of 1-methyl-3(p-chlorophenyl)-1-nitrosourea and its 1-methyl trideuterated derivative in rats.

Science.gov (United States)

Schreiber, D; Martin, J; Mendel, J

1986-01-01

The carcinogenic activity of 1-methyl-3(p-chlorophenyl)-1-nitrosourea (Cl-MPNU) and its 1-methyl trideuterated analog (Cl-MPNU-d3) was compared by intragastric administration to hooded rats of equimolar doses of both compounds. A 100% frequency of forestomach tumors was observed in both groups. However, the mean latency period of the animals treated with Cl-MPNU-d3 was significantly longer (P less than 0.01). The results suggest the occurrence of a deuterium isotope effect in nitrosoureas but not as distinct as in nitrosamines.

Metabolism and excretion of 1-hydroxymethylpyrene, the proximate metabolite of the carcinogen 1-methylpyrene, in rats

International Nuclear Information System (INIS)

Bendadani, Carolin; Steinhauser, Lisa; Albert, Klaus; Glatt, Hansruedi; Monien, Bernhard H.

2016-01-01

1-Methylpyrene, an alkylated polycyclic aromatic hydrocarbon and environmental carcinogen, is activated by side-chain hydroxylation to 1-hydroxymethylpyrene (1-HMP) and subsequent sulfo conjugation to the DNA-reactive 1-sulfooxymethylpyrene. In addition to the bioactivation, processes of metabolic detoxification and transport greatly influence the genotoxicity of 1-methylpyrene. For a better understanding of 1-HMP detoxification in vivo we studied urinary and fecal metabolites in rats following intraperitoneal doses of 19.3 mg 1-HMP/kg body weight (5 rats) or the same dose containing 200 μCi [ 14 C]1-HMP/kg body weight (2 rats). After 48 h, 48.0% (rat 1) and 29.1% (rat 2) of the radioactivity was recovered as 1-HMP in the feces. Six major metabolites were observed by UV and on-line radioactivity detection in urine samples and feces after HPLC separation. The compounds were characterized by mass spectrometry, 1 H NMR and 1 H- 1 H COSY NMR spectroscopy, which allowed assigning tentative molecular structures. Two prominent metabolites, 1-pyrene carboxylic acid (M-6) and the acyl glucuronide of 1-pyrene carboxylic acid (M-5) accounted for 17.7% (rat 1) and 25.2% (rat 2) of the overall radioactive dose. Further, we detected the acyl glucuronide of 6-hydroxy-1-pyrene carboxylic acid (M-1) and 8-sulfooxy-1-pyrene carboxylic acid (M-3) together with two regioisomers of M-3 (M-2 and M-4) differing in position of the sulfate group at the pyrene ring. In urine samples, the radioactivity of 1-pyrene carboxylic acid and its five derivatives amounted to 32.4% (rat 1) or 45.5% (rat 2) of the total [ 14 C]1-HMP dose.

The in vivo rodent test systems for assessment of carcinogenic potential

DEFF Research Database (Denmark)

van der Laan, Jan-Willem; Spindler, Per

2002-01-01

A Drug Information Association (DIA) workshop was held in May 2001 to discuss the outcome of the International Life Sciences Institute-Health and Environmental Sciences Institute (ILSI-HESI) project on alternative models for carcinogenicity assessment such as the P53(+/-) and XPA(+/-) knockout...... mouse models, the RasH2 and Tg.AC transgenic mouse models, and the neonatal mouse model. The "ICH Guideline S1B on Testing for Carcinogenicity of Pharmaceuticals" advocates that carcinogenicity testing of pharmaceuticals, when needed, might be carried out choosing one 2-year rodent carcinogenicity study...... (rat) plus one other study that supplements the 2-year study and providing additional information that is not readily available from the 2-year study: either (1) a short- or medium-term in vivo rodent test system or (2) a 2-year carcinogenicity study in a second rodent species (mouse). Another topic...

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

Beschermingsplan hamster 2005-2010

NARCIS (Netherlands)

Haye, la M.J.J.; Jansman, H.A.H.

2005-01-01

Alterra-Concept van het beschermingsplan hamster 2005-2010. De hamster is in het meest westelijke deel van het Europese verspreidingsgebied bedreigd. De kennis die in de afgelopen periode is opgedaan van de hamster en de maatregelen die in het veld zijn uitgevoerd vormen de basis voor dit tweede

Chronic Carcinogenicity Study of Gasoline Vapor Condensate (GVC) and GVC Containing Methyl Tertiary-Butyl Ether in F344 Rats

OpenAIRE

Benson, Janet M.; Gigliotti, Andrew P.; March, Thomas H.; Barr, Edward B.; Tibbetts, Brad M.; Skipper, Betty J.; Clark, Charles R.; Twerdok, Lorraine

2011-01-01

Chronic inhalation studies were conducted to compare the toxicity and potential carcinogenicity of evaporative emissions from unleaded gasoline (GVC) and gasoline containing the oxygenate methyl tertiary-butyl ether (MTBE; GMVC). The test materials were manufactured to mimic vapors people would be exposed to during refueling at gas stations. Fifty F344 rats per gender per exposure level per test article were exposed 6 h/d, 5 d/wk for 104 wk in whole body chambers. Target total vapor concentra...

Effects of light deprivation on prolactin regulation in the Golden Syrian hamster

International Nuclear Information System (INIS)

Massa, J.S.

1986-01-01

Pineal-mediated depressions in prolactin cell activity after light deprivation were studied in the male and female Golden Syrian hamster. Prolactin cell activity was determined by measuring radioimmunoassayable prolactin, newly synthesized prolactin, newly synthesized prolactin and prolactin mRNA levels in the pituitary. Serum prolactin was also measured by radioimmunoassay. Use of the recombinant DNA plasmid, pPRL-1, which contains the rat prolactin complimentary DNA sequence, was validated in this dissertation for measuring prolactin mRNA in the hamster. Male Hamsters blinded for 11, 21, or 42 days showed significant and progressively greater declines in prolactin mRNA levels which were completely prevented by pinealectomy. Female hamsters blinded for 28 days, however, showed no such decreases in prolactin cell activity if they continued to display estrous cyclicity. After 12 weeks of blinding, females were acyclic and had dramatically depressed levels of prolactin cell activity. However, pinealectomy did not completely prevent this decline due to blinding unless the females continue to display estrous cyclicity. In ovariectomized females, blinding caused a decline in prolactin cell activity. In a separate study, significant changes in prolactin cell activity during the estrous cycle were seen in untreated normally cycling female hamsters. These changes in prolactin mRNA, prolactin synthesis, and radioimmunoassayable prolactin in the pituitary were measured in the morning, when, consistent with other reports, no differences in serum prolactin were observed

Specificity of interaction between carcinogenic polynuclear aromatic hydrocarbons and nuclear proteins: widespread occurrence of a restricted pattern of histone-binding in intact cells

International Nuclear Information System (INIS)

MacLeod, M.C.; Pelling, J.C.; Slaga, T.J.; Nikbakht-Noghrei, P.A.; Mansfield, B.K.; Selkirk, J.K.

1982-01-01

Metabolic activation of benzo(a)pyrene [B(a)P] produces a number of potentially reactive metabolites. The endproducts of one metabolic pathway, 7,8-dihydroxy-9,10-oxy-7,8,9,10-tetrahydro-B(a)P (BPDE) are responsible for essentially all DNA adduct formation in animal cells treated with B(a)P, and a particular stereoisomer, designated (+)-anti-BPDE is thought to be the ultimate carcinogenic derivative of B(a)P. In hamster embryo cell nuclei treated with (+)-anti-BPDE, two of the histones of the nucleosomal core, H3 and H2A, are covalently modified, while the remaining core histones, H4 and H2B, are essentially unmodified. All four purified core histones, however, serve as targets. 7,12-dimethylbenz(a)anthracene and 3-methylcholanthrene show the same pattern of histone binding in hamster embryo cells. Treatment of mouse embryo cells with [ 3 H]-BPDE results in covalent binding of the hydrocarbon to histones H3 and H2A among the many cellular targets, while histones H2B and H4 are not bound. Similar binding patterns are seen in mouse embryo cells, a permanent murine, fibroblastic cell line, and a human mammary epithelial cell line, T47D, treated with [ 3 H]B(a)P. Again, the histones are unevenly labeled, displaying the H3 and H2A pattern. Histone-binding in the human cells may also be mediated by BPDE. Similar BPDE binding patterns were observed in other murine and human cell lines and in primary cultures of murine epidermal epithelial cells. The restriction of histone H2B and H4 binding appears to be general when intact cultured cells are studied. This specificity was not observed in a mixed reconstituted system in which rat liver microsomes were used to activate B(a)P. This finding reinforces reservations concerning the use of microsomal systems to probe the interactions of carcinogens with macromolecules and the relationships of adduct formation with the processes of carcinogenesis

Red Wine and Pomegranate Extracts Suppress Cured Meat Promotion of Colonic Mucin-Depleted Foci in Carcinogen-Induced Rats.

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Bastide, Nadia M; Naud, Nathalie; Nassy, Gilles; Vendeuvre, Jean-Luc; Taché, Sylviane; Guéraud, Françoise; Hobbs, Ditte A; Kuhnle, Gunter G; Corpet, Denis E; Pierre, Fabrice H F

2017-01-01

Processed meat intake is carcinogenic to humans. We have shown that intake of a workshop-made cured meat with erythorbate promotes colon carcinogenesis in rats. We speculated that polyphenols could inhibit this effect by limitation of endogenous lipid peroxidation and nitrosation. Polyphenol-rich plant extracts were added to the workshop-made cured meat and given for 14 days to rats and 100 days to azoxymethane-induced rats to evaluate the inhibition of preneoplastic lesions. Colons of 100-d study were scored for precancerous lesions (mucin-depleted foci, MDF), and biochemical end points of peroxidation and nitrosation were measured in urinary and fecal samples. In comparison with cured meat-fed rats, dried red wine, pomegranate extract, α-tocopherol added at one dose to cured meat and withdrawal of erythorbate significantly decreased the number of MDF per colon (but white grape and rosemary extracts did not). This protection was associated with the full suppression of fecal excretion of nitrosyl iron, suggesting that this nitroso compound might be a promoter of carcinogenesis. At optimized concentrations, the incorporation of these plant extracts in cured meat might reduce the risk of colorectal cancer associated with processed meat consumption.

Effect of total lymphoid irradiation on pancreatic islet xenograft survival in rats

International Nuclear Information System (INIS)

Nakajima, Y.; Lie, T.S.; Nakauo, H.; Nakagawa, K.; Segawa, M.

1984-01-01

Before transplantation of Syrian hamster pancreatic islet xenografts to diabetic rats the recipients received total lymphatic system irradiation and cyclosporin A treatment after transplantation for immunosuppression. The xenograft survival times were measured and the rat anti-hamster lymphocytotoxic titers were determined by 51 Cr release assay

Effect of total lymphoid irradiation on pancreatic islet xenograft survival in rats

Energy Technology Data Exchange (ETDEWEB)

Nakajima, Y; Lie, T S [Bonn Univ. (Germany, F.R.). Chirurgische Klinik und Poliklinik; Nakauo, H; Nakagawa, K; Segawa, M [Nara Women' s Univ. (Japan). Dept. of Physics

1984-01-01

Before transplantation of Syrian hamster pancreatic islet xenografts to diabetic rats the recipients received total lymphatic system irradiation and cyclosporin A treatment after transplantation for immunosuppression. The xenograft survival times were measured and the rat anti-hamster lymphocytotoxic titers were determined by /sup 51/Cr release assay.

Report on carcinogens monograph on 1-bromopropane.

Science.gov (United States)

2013-09-01

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

Two-year drinking water carcinogenicity study of methyl tertiary-butyl ether (MTBE) in Wistar rats.

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Dodd, Darol; Willson, Gabrielle; Parkinson, Horace; Bermudez, Edilberto

2013-07-01

Methyl tertiary-butyl ether (MTBE) has been used as a gasoline additive to reduce tailpipe emissions and its use has been discontinued. There remains a concern that drinking water sources have been contaminated with MTBE. A two-year drinking water carcinogenicity study of MTBE was conducted in Wistar rats (males, 0, 0.5, 3, 7.5 mg ml(-1); and females, 0, 0.5, 3, and 15 mg ml(-1)). Body weights were unaffected and water consumption was reduced in MTBE-exposed males and females. Wet weights of male kidneys were increased at the end of two years of exposure to 7.5 mg ml(-1) MTBE. Chronic progressive nephropathy was observed in males and females, was more severe in males, and was exacerbated in the high MTBE exposure groups. Brain was the only tissue with a statistically significant finding of neoplasms. One astrocytoma (1/50) was found in a female rat (15 mg ml(-1)). The incidence of brain astrocytomas in male rats was 1/50, 1/50, 1/50 and 4/50 for the 0, 0.5, 3 and 7.5 mg ml(-1) exposure groups, respectively. This was a marginally significant statistical trend, but not statistically significant when pairwise comparisons were made or when multiple comparisons were taken into account. The incidence of astrocytoma fell within historical control ranges for Wistar rats, and the brain has not been identified as a target organ following chronic administration of MTBE, ethyl tert-butyl ether, or tertiary butyl alcohol (in drinking water) to mice and rats. We conclude that the astrocytomas observed in this study are not associated with exposure to MTBE. Copyright © 2011 John Wiley & Sons, Ltd.

Genotoxicity induced by Taenia solium and its reduction by immunization with calreticulin in a hamster model of taeniosis.

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Salazar, Ana María; Mendlovic, Fela; Cruz-Rivera, Mayra; Chávez-Talavera, Oscar; Sordo, Monserrat; Avila, Guillermina; Flisser, Ana; Ostrosky-Wegman, Patricia

2013-06-01

Genotoxicity induced by neurocysticercosis has been demonstrated in vitro and in vivo in humans. The adult stage of Taenia solium lodges in the small intestine and is the main risk factor to acquire neurocysticercosis, nevertheless its carcinogenic potential has not been evaluated. In this study, we determined the genotoxic effect of T. solium infection in the hamster model of taeniosis. In addition, we assessed the effect of oral immunization with recombinant T. solium calreticulin (rTsCRT) plus cholera toxin as adjuvant on micronuclei induction, as this protein has been shown to induce 33-44% protection in the hamster model of taeniosis. Blood samples were collected from the orbital venous plexus of noninfected and infected hamsters at different days postinfection, as well as from orally immunized animals, to evaluate the frequency of micronucleated reticulocytes as a measure of genotoxicity induced by parasite exposure and rTsCRT vaccination. Our results indicate that infection with T. solium caused time-dependent DNA damage in vivo and that rTsCRT immunization reduced the genotoxic damage induced by the presence of the tapeworms. Copyright © 2013 Wiley Periodicals, Inc.

Evaluation of carcinogenic potential of diuron in a rat mammary two-stage carcinogenesis model.

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Grassi, Tony Fernando; Rodrigues, Maria Aparecida Marchesan; de Camargo, João Lauro Viana; Barbisan, Luís Fernando

2011-04-01

This study aimed to evaluate the carcinogenic potential of the herbicide Diuron in a two-stage rat medium-term mammary carcinogenesis model initiated by 7,12-dimethylbenz(a)anthracene (DMBA). Female seven-week-old Sprague-Dawley (SD) rats were allocated to six groups: groups G1 to G4 received intragastrically (i.g.) a single 50 mg/kg dose of DMBA; groups G5 and G6 received single administration of canola oil (vehicle of DMBA). Groups G1 and G5 received a basal diet, and groups G2, G3, G4, and G6 were fed the basal diet with the addition of Diuron at 250, 1250, 2500, and 2500 ppm, respectively. After twenty-five weeks, the animals were euthanized and mammary tumors were histologically confirmed and quantified. Tumor samples were also processed for immunohistochemical evaluation of the expressions of proliferating cell nuclear antigen (PCNA), cleaved caspase-3, estrogen receptor-α (ER-α), p63, bcl-2, and bak. Diuron treatment did not increase the incidence or multiplicity of mammary tumors (groups G2 to G4 versus Group G1). Also, exposure to Diuron did not alter tumor growth (cell proliferation and apoptosis indexes) or immunoreactivity to ER-α, p63 (myoephitelial marker), or bcl-2 and bak (apoptosis regulatory proteins). These findings indicate that Diuron does not have a promoting potential on mammary carcinogenesis in female SD rats initiated with DMBA.

Aspects of inhaled DTPA toxicity in the rat, hamster and beagle dog and treatment effectiveness for excorporation of plutonium from the rat

International Nuclear Information System (INIS)

Smith, V.H.; Ballou, J.E.; Lund, J.E.; Dagle, G.E.; Ragan, H.A.; Busch, R.H.; Hackett, P.L.; Willard, D.W.

1976-01-01

After inhaling 1 to 4 HD (human dose equivalents, i.e. 1g of calcium trisodium N,N-bis(2-bis (carboxymethyl) amino ethyl)glycinate per 70kg of body weight) of Ca-DTPA, rats and hamsters developed a transitory vesicular emphysema. This was not found in animals sacrified later than 3 weeks after the last exposure. Dogs were anesthetized and administered Ca-DTPA aerosols via an intratracheal catheter for 30min/day for 5 days. The average dose/exposure was 4 HD. One week after the last exposure, 3/4 treated dogs and 0/2 dogs exposed to saline aerosols showed enlargement and submucosal lymphoid follicles in the pyloric region of the stomach; this was not present in dogs sacrificed at 4, 8 or 18 weeks post-exposure. Ephitheleal atypia in the alveolar lining was noted in 5/16 dogs inhaling Ca-DTPA and in 1/8 dogs exposed to saline aerosols, and may or may not be treatment-related. In long-term studies, rats were administered a lung burden of about 78 nCi 239 Pu(NO 3 ) 4 by inhalation and 20 days later were given six inhalation treatments of about 1 HD Ca-DTPA. Over their lifetime these animals showed no difference in survival or bone or lung tumour incidence from rats receiving Pu alone. Rats receiving 1.2 μCi 238 Pu(NO 3 ) 4 intramuscularly were treated promptly with 1.2 HD inhaled or intraperitoneally injected Ca-DTPA. The two methods of Ca-DTPA administration gave statistically identical Pu excorporation. Similar treatments initiated 8 months after the Pu injection also showed no effect of administration route. These experiments and implications for the safety and efficacy of inhaled Ca-DTPA as treatment for transuranic incorporations in man are discussed. (author)

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

Directory of Open Access Journals (Sweden)

Lya G Hernández

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

Histochemical, light and electron microscopic study of polonium-210 induced peripheral tumours in hamster lungs -evidence implicating the Clara Cell as the cell of origin

International Nuclear Information System (INIS)

Kennedy, A.R.; McGandy, R.B.; Little, J.B.

1977-01-01

Peripheral lung tumors induced in Syrian golden hamsters by intratracheally administered polonium-210 ( 210 Po) are similar to the peripheral lung tumours induced in many species by a variety of carcinogens. In addition, they show many of the histopathological features observed in human bronchiolar-alveolar carcinomas. Serial sacrifice studies of hamsters exposed to multiple instillations of 210 Po have been carried our to identify the cell of origin of these tumors. By means of thin, plastic (glycol methacrylate) sections, electron microscopy, and histochemistry, it is concluded that the bronchiolar Clara cell is the probable cell of origin, and that this view is generally compatible with many of the reported cytological characteristics of the human tumor. (author)

Carcinogenic 3-nitrobenzanthrone but not 2-nitrobenzanthrone is metabolised to an unusual mercapturic acid in rats.

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Linhart, Igor; Mráz, Jaroslav; Hanzlíková, Iveta; Silhánková, Alexandra; Frantík, Emil; Himl, Michal

2012-02-05

3-Nitrobenzanthrone (3-NBA) is an extremely potent mutagen and suspect human carcinogen found in diesel exhaust. Its isomer 2-nitrobenzanthrone (2-NBA) has also been found in ambient air. These isomers differ in mutagenicity in Salmonella by 2-3 orders of magnitude. To identify their urinary metabolites and also to assess the assumed differences in their excretion, rats were dosed orally with 2mg/kg b.w. of either 2-NBA or 3-NBA. Their urine was collected for two consecutive days after dosage. Both LC-ESI-MS and GC-MS confirmed formation of the corresponding aminobenzanthrones (ABA). Excretion of these metabolites within the first day after dosing with 2- and 3-ABA amounted to 0.32±0.06 and 0.83±0.40% of the doses, respectively, while the excretion within the second day was by one order of magnitude lower. A novel mercapturic acid metabolite of 3-NBA was identified in urine by LC-ESI-MS as N-acetyl-S-(3-aminobenzanthron-2-yl)cysteine (3-ABA-MA) by comparison with the authentic standard. Its excretion amounted to 0.49±0.15 and 0.02±0.01% of dose within the first and second day after dosing, respectively. In contrast, no mercapturic acid was detected in the urine of rats dosed with 2-NBA. Observed difference in the mercapturic acid formation between 2- and 3-NBA is a new distinctive feature reflecting differences in the critical step of their metabolism, i.e., benzanthronylnitrenium ion formation that is intrinsically associated with biological activities of these two isomers. Moreover, 3-ABA-MA is a promising candidate biomarker of exposure to the carcinogenic 3-NBA. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

MicroRNAs and their predicted target messenger RNAs are deregulated by exposure to a carcinogenic dose of comfrey in rat liver.

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Li, Zhiguang; Fuscoe, James C; Chen, Tao

2011-07-01

MicroRNAs (MiRNAs) are small noncoding RNAs that function as regulators of gene expression to control cell growth and differentiation. In this study, we analyzed miRNA and mRNA expression in the livers of rats treated with a carcinogenic dose of comfrey (Symphytum officinale) for 12 weeks. Groups of six rats were fed a normal diet or a diet containing 8% comfrey root. The animals were sacrificed 1 day after the last treatment and the livers were isolated for miRNA expression analysis using LC Sciences miRNA microarrays and for mRNA expression analysis using Affymetrix rat genome microarrays. MiRNA expression levels were significantly changed by comfrey treatment. The treated samples were separated clearly from the control samples in both principal component analysis (PCA) and hierarchical clustering analysis (HCA). Quantitative measurements of seven miRNAs using TaqMan real-time PCR were consistent with the microarray results in terms of fold-change and the direction of the change in expression. Forty-five miRNAs (P comfrey treatment. Using a target prediction algorithm, 434 differentially expressed genes (DEGs) were predicted to be targeted by the differentially expressed miRNAs (DEMs). The DEM-targeted DEGs were more likely to be involved in carcinogenesis than the DEGs that were not targeted by the DEMs. The nontargeted DEGs were enriched in noncancer-related biological processes. Our data suggest that comfrey may exert its carcinogenic effects by disturbing miRNA expression resulting in altered mRNA levels of the DEM-targeted genes that are functionally associated with carcinogenesis. Copyright © 2011 Wiley-Liss, Inc.

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

Science.gov (United States)

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

2002-01-01

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

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

Science.gov (United States)

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

2006-07-01

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

Cytotoxicity and regenerative proliferation as the mode of action for diuron-induced urothelial carcinogenesis in the rat.

Science.gov (United States)

da Rocha, Mitscheli S; Nascimento, Merielen G; Cardoso, Ana Paula F; de Lima, Patrícia L A; Zelandi, Edneia A; de Camargo, João Lauro V; de Oliveira, Maria Luiza C S

2010-01-01

Diuron, a substituted urea herbicide, is carcinogenic to the urinary bladder of rats at high dietary levels. Its proposed carcinogenic mode of action (MOA) includes urothelial cytotoxicity and necrosis followed by regenerative cell proliferation and sustained urothelial hyperplasia. Cytotoxicity could be induced either by urinary solids or by chemical toxicity by diuron and/or metabolites excreted in the urine. Diuron was not genotoxic in a previous single-cell gel (comet) assay, but possible cross-linking activity remained to be evaluated. The present study explored the MOA of diuron and the effect of urinary acidification on the development of urothelial lesions. Male Wistar rats were fed diuron (2500 ppm, about 130 mg/kg of body weight) either with or without NH(4)Cl 10,000 ppm to acidify the urine. Reversibility of urothelial changes was also examined. The animals were euthanized after 15, 25, or 30 weeks. Diuron-fed rats had urinary amorphous precipitate and magnesium ammonium phosphate crystals similar to control animals. Groups treated with diuron + NH(4)Cl showed decreased urinary pH and reduced amounts of urinary crystals and precipitate. Urothelial necrosis and simple hyperplasia were observed by light microscopy and scanning electron microscopy both in diuron- and in diuron + NH(4)Cl-treated groups. Cytotoxicity and proliferative changes were mostly reversible. A modified comet assay developed in vitro with Chinese hamster ovary cells showed that diuron did not induce DNA cross-links. These data suggest that cytotoxicity with consequent regenerative cell proliferation is the predominant MOA for diuron rat urothelial carcinogenesis, the cytotoxicity being chemically induced and not due to urinary solids.

DNA repair synthesis in rat retinal ganglion cells treated with chemical carcinogens or ultraviolet light in vitro, with special reference to aging and repair level

International Nuclear Information System (INIS)

Ishikawa, T.; Takayama, S.; Kitagawa, T.

1978-01-01

A system in which the retinal tissues of noninbred Wistar rats were used in combination with autoradiography was developed for measurement of DNA repair synthesis in ganglion cells of the central nervous system. Retinal tissues in short-term organ culture were treated with various carcinogens plus tritiated thymidine ([methyl -3 H]dThd) or were irradiated with uv light and then treated with [methyl -3 H]dThd. Preliminary study with retinal tissues from rats at various ages revealed no age-associated changes in the levels of unscheduled DNA synthesis in ganglion cells

The Effect of VPA on Increasing Radiosensitivity in Osteosarcoma Cells and Primary-Culture Cells from Chemical Carcinogen-Induced Breast Cancer in Rats.

Science.gov (United States)

Liu, Guochao; Wang, Hui; Zhang, Fengmei; Tian, Youjia; Tian, Zhujun; Cai, Zuchao; Lim, David; Feng, Zhihui

2017-05-10

This study explored whether valproic acid (VPA, a histone deacetylase inhibitor) could radiosensitize osteosarcoma and primary-culture tumor cells, and determined the mechanism of VPA-induced radiosensitization. The working system included osteosarcoma cells (U2OS) and primary-culture cells from chemical carcinogen (DMBA)-induced breast cancer in rats; and clonogenic survival, immunofluorescence, fluorescent in situ hybridization (FISH) for chromosome aberrations, and comet assays were used in this study. It was found that VPA at the safe or critical safe concentration of 0.5 or 1.0 mM VPA could result in the accumulation of more ionizing radiation (IR)-induced DNA double strand breaks, and increase the cell radiosensitivity. VPA-induced radiosensitivity was associated with the inhibition of DNA repair activity in the working systems. In addition, the chromosome aberrations including chromosome breaks, chromatid breaks, and radial structures significantly increased after the combination treatment of VPA and IR. Importantly, the results obtained by primary-culture cells from the tissue of chemical carcinogen-induced breast cancer in rats further confirmed our findings. The data in this study demonstrated that VPA at a safe dose was a radiosensitizer for osteosarcoma and primary-culture tumor cells through suppressing DNA-double strand breaks repair function.

Oxidative Stress in the Carcinogenicity of Chemical Carcinogens

International Nuclear Information System (INIS)

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

2013-01-01

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

Oxidative Stress in the Carcinogenicity of Chemical Carcinogens

Energy Technology Data Exchange (ETDEWEB)

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

2013-10-28

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

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

Science.gov (United States)

Papamokos, George; Silins, Ilona

2016-01-01

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

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

Science.gov (United States)

Papamokos, George; Silins, Ilona

2016-01-01

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

Effects of dietary carbohydrates on glucose and lipid metabolism in golden Syrian hamsters.

Science.gov (United States)

Kasim-Karakas, S E; Vriend, H; Almario, R; Chow, L C; Goodman, M N

1996-08-01

Frequent coexistence of insulin resistance, central obesity, and hypertriglyceridemia in the same individual suggests an underlying common pathogenesis. Insulin resistance and hypertriglyceridemia can be induced by carbohydrate feeding in rats. Golden Syrian hamsters are believed to be resistant to the metabolic effects of dietary carbohydrates. We investigated the effects of diets containing 60% fructose or sucrose on glucose and lipid metabolism in hamsters, both in the fasting state and during an intravenous glucose tolerance test. Fructose caused obesity (weight after treatment: 131 +/- 7 gm in the control group, 155 +/- 5 gm in the fructose group, 136 +/- 7 gm in sucrose group, p < 0.04). Fructose also reduced glucose disappearance rate (KG: 2.69% +/- 0.39% in the control group, 1.45% +/- 0.18% in the fructose group, p < 0.02). Sucrose caused a marginal decrease in glucose disappearance (KG: 1.93% +/- 0.21%, p = 0.08 vs the control group). Only fructose feeding increased fasting plasma nonesterified fatty acids (0.645 +/- 0.087 mEq/L in the control group, 1.035 +/- 0.083 mEq/L in the fructose group, 0.606 +/- 0.061 mEq/L in the sucrose group, p < 0.002), plasma triglycerides (84 +/- 6 mg/dl in the control group, 270 +/- 65 mg/dl in the fructose group, 94 +/- 16 mg/dl in the sucrose group, p < 0.0002), and liver triglycerides (1.88 +/- 0.38 mg/gm liver weight in the control group, 2.35 =/- 0.24 mg/gm in the fructose group, 1.41 +/- 0.13 mg/gm in the sucrose group, p < 0.04). Previous studies in the rat have suggested that dietary carbohydrates induce insulin resistance by increasing plasma nonesterified fatty acids and triglycerides, which are preferentially used by the muscles. The present report shows that sucrose also can cause some decrease in glucose disappearance in the hamster without causing hypertriglyceridemia or increasing plasma nonesterified fatty acids. Thus other mechanisms may also contribute to the insulin resistance in the hamster. These

Oxidative Stress in the Carcinogenicity of Chemical Carcinogens

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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.

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

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

2013-09-01

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

Diet-induced metabolic hamster model of nonalcoholic fatty liver disease

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Bhathena J

2011-06-01

Full Text Available Jasmine Bhathena, Arun Kulamarva, Christopher Martoni, Aleksandra Malgorzata Urbanska, Meenakshi Malhotra, Arghya Paul, Satya PrakashBiomedical Technology and Cell Therapy Research Laboratory, Department of Biomedical Engineering, Artificial Cells and Organs Research Centre, Faculty of Medicine, McGill University, Montreal, Québec, CanadaBackground: Obesity, hypercholesterolemia, elevated triglycerides, and type 2 diabetes are major risk factors for metabolic syndrome. Hamsters, unlike rats or mice, respond well to diet-induced obesity, increase body mass and adiposity on group housing, and increase food intake due to social confrontation-induced stress. They have a cardiovascular and hepatic system similar to that of humans, and can thus be a useful model for human pathophysiology.Methods: Experiments were planned to develop a diet-induced Bio F1B Golden Syrian hamster model of dyslipidemia and associated nonalcoholic fatty liver disease in the metabolic syndrome. Hamsters were fed a normal control diet, a high-fat/high-cholesterol diet, a high-fat/high-cholesterol/methionine-deficient/choline-devoid diet, and a high-fat/high-cholesterol/choline-deficient diet. Serum total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, glucose, atherogenic index, and body weight were quantified biweekly. Fat deposition in the liver was observed and assessed following lipid staining with hematoxylin and eosin and with oil red O.Results: In this study, we established a diet-induced Bio F1B Golden Syrian hamster model for studying dyslipidemia and associated nonalcoholic fatty liver disease in the metabolic syndrome. Hyperlipidemia and elevated serum glucose concentrations were induced using this diet. Atherogenic index was elevated, increasing the risk for a cardiovascular event. Histological analysis of liver specimens at the end of four weeks showed increased fat deposition in the liver of animals fed

Aspects of inhaled DTPA toxicity in the rat, hamster and beagle dog and treatment effectiveness for excorporation of Pu from the rat

International Nuclear Information System (INIS)

Smith, V.H.; Ballou, J.E.; Lund, J.E.; Dagle, G.E.; Ragan, H.A.; Busch, R.H.; Hackett, P.L.; Willard, D.W.

1975-01-01

After inhaling 1 to 4 HD (human dose equivalents, i.e., 1 g calcium trisodium N,N-bis (2-bis(carboxymethyl)amino) ethyl) glycinate/70 kg body weight) of Ca-DTPA rats and hamsters developed a transitory vesicular emphysema. This was not found in animals sacrificed later than 3 weeks after the last exposure. Dogs were anesthetised and administered Ca-DTPA aerosols via an intratracheal catheter for 30 min/day for 5 days. The average dose/exposure was 4 HD. One week following the last exposure, 3/4 treated dogs and 0/2 dogs exposed to saline aerosols showed enlargement and submucosal lymphoid follicles in the pyloric region of the stomach; this was not present in dogs sacrificed at 4, 8 or 18 weeks postexposure. Epithelial atypia in the alveolar lining was noted in 5/16 dogs inhaling Ca-DTPA and in 1/8 dogs exposed to saline aerosols, and may or may not be treatment-related. Rats receiving 1.2 μCi 238 Pu(NO 3 ) 4 intramuscularly were treated promptly with 1.2 HD inhaled or intraperitoneally injected Ca-DTPA. The two methods of Ca-DTPA administration gave statistically identical Pu excorporation. Similar treatments initiated 8 months following the Pu injection also showed no effect of administration route. These experiments and implications for the safety and efficacy of inhaled Ca-DTPA as treatment for transuranic incorporations in man are discussed

The environmental pollutant and carcinogen 3-nitrobenzanthrone induces cytochrome P450 1A1 and NAD(P)H:quinone oxidoreductase in rat lung and kidney, thereby enhancing its own genotoxicity

International Nuclear Information System (INIS)

Stiborova, Marie; Dracinska, Helena; Mizerovska, Jana; Frei, Eva; Schmeiser, Heinz H.; Hudecek, Jiri; Hodek, Petr; Phillips, David H.; Arlt, Volker M.

2008-01-01

3-Nitrobenzanthrone (3-NBA) is a carcinogen occurring in diesel exhaust and air pollution. Using the 32 P-postlabelling method, we found that 3-NBA and its human metabolite, 3-aminobenzanthrone (3-ABA), are activated to species forming DNA adducts by cytosols and/or microsomes isolated from rat lung, the target organ for 3-NBA carcinogenicity, and kidney. Each compound generated identical five DNA adducts. We have demonstrated the importance of pulmonary and renal NAD(P)H:quinone oxidoreductase (NQO1) to reduce 3-NBA to species that are further activated by N,O-acetyltransferases and sulfotransferases. Cytochrome P450 (CYP) 1A1 is the essential enzyme for oxidative activation of 3-ABA in microsomes of both organs, while cyclooxygenase plays a minor role. 3-NBA was also investigated for its ability to induce NQO1 and CYP1A1 in lungs and kidneys, and for the influence of such induction on DNA adduct formation by 3-NBA and 3-ABA. When cytosols from rats treated i.p. with 40 mg/kg bw of 3-NBA were incubated with 3-NBA, DNA adduct formation was up to 2.1-fold higher than in incubations with cytosols from control animals. This increase corresponded to an increase in protein level and enzymatic activity of NQO1. Incubations of 3-ABA with microsomes of 3-NBA-treated rats led to up to a fivefold increase in DNA adduct formation relative to controls. The stimulation of DNA adduct formation correlated with the potential of 3-NBA to induce protein expression and activity of CYP1A1. These results demonstrate that 3-NBA is capable to induce NQO1 and CYP1A1 in lungs and kidney of rats thereby enhancing its own genotoxic and carcinogenic potential

Genetic effectiveness of gamma-irradiation with different emissive power in Syrian hamsters

International Nuclear Information System (INIS)

Vyglenov, A.

1990-01-01

The effectiveness of gamma-irradiation with dose rate8 X 10 -2 and 7 X 10 -3 Gy/min was determined. The translocation yield in Syrian hamster spermatogonia was used as index of genetic injury. The results obtained allowed to determine the RBE of the tested dose rate of photon radiation ti 0.8 and 0.4, respectively for 8 x 10 -2 and 7 x 10 -3 Gy/min. In contrast to mice and rats, under the same exposure conditions the mutation rate in Syrian hamsters showed a gradual decline with reducing the emissive power, without sharp changes. The reduction of the extent of genetic injury was also less abrupt. These results once more point to the importance of the mammalian species being used, regarding the manifestation of the effect of the dose rate. 1 fig., 2 tabs., 25 refs

Rapid promotion and progression of fibrovascular polyps by inflammation and/or hyperplasia in hamster check pouch: implications for carcinogenesis assay.

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McGaughey, C; Jensen, J L

1983-03-01

Tumor initiation by topical application of 7,12-dimethylbenz[a]anthracene (DMBA) in dimethyl sulfoxide (DMSO) followed by topical application of retinyl acetate (RA), ethylphenylpropiolate, or acetic acid in DMSO at inflammatory and hyperplasiogenic dose regimens caused the rapid promotion of fibrovascular polyps with dysplastic epithelium in hamster cheek pouch. Such lesions did not occur in control animals initiated with DMBA followed by application of DMSO only, where inflammation was also minimal. At the dose regimen employed, RA caused obvious cytotoxicity and tissue destruction. With EPP and AA, there was no histological evidence of tissue destruction. At dose regimens resulting in minimal inflammation and no apparent cytotoxicity, RA promoted almost no polyps, but a higher yield of other tumor types. Thus, inflammation and/or hyperplasia apparently exerted a strong polyp-promoting and progressive influence. This and other differences between the tumorigenic responses of hamster-pouch mucosa and mouse skin suggest that the former supplement the latter in carcinogenic risk assessment.

Electronegative LDL is linked to high-fat, high-cholesterol diet-induced nonalcoholic steatohepatitis in hamsters.

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Lai, Yu-Sheng; Yang, Tzu-Ching; Chang, Po-Yuan; Chang, Shwu-Fen; Ho, Shu-Li; Chen, Hui-Ling; Lu, Shao-Chun

2016-04-01

The pathogenesis of nonalcoholic steatohepatitis (NASH), like that of atherosclerosis, involves lipid accumulation, inflammation and fibrosis. Recent studies suggest that oxidized LDL (oxLDL) may be a risk factor for NASH, but oxLDL levels were not directly measured in these studies. The aim of this study was to examine whether there was an association between electronegative LDL [LDL(-)], a mildly oxLDL found in the blood, and the development of NASH using two animal models. Golden Syrian hamsters and C57BL/6 mice were fed a high-fat, high-cholesterol (HFC) diet for 6 or 12weeks, then liver lipid and histopathology, plasma lipoprotein profile and LDL(-) levels were examined. The HFC-diet-fed hamsters and mice had similar levels of hepatic lipid but different histopathological changes, with microvesicular steatosis, hepatocellular hypertrophy, inflammation and bridging fibrosis in the hamsters, but only in mild steatohepatitis with low inflammatory cell infiltration in the mice. It also resulted in a significant increase in plasma levels of LDL cholesterol and LDL(-) in hamsters, but only a slight increase in mice. Moreover, enlarged Kupffer cells, LDL(-) and accumulation of unesterified cholesterol were detected in the portal area of HFC-diet-fed hamsters, but not HFC-diet-fed mice. An in vitro study showed that LDL(-) from HFC-diet-fed hamsters induced TNF-α secretion in rat Kupffer cell through a LOX-1-dependent pathway. Our results strongly suggest that LDL(-) is one of the underlying causes of hepatic inflammation and plays a critical role in the development of NASH. Copyright © 2015 Elsevier Inc. All rights reserved.

Carcinogenicity of methyl-tertiary butyl ether in gasoline.

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Mehlman, Myron A

2002-12-01

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

Structure-Activity Relationship Models for Rat Carcinogenesis and Assessing the Role Mutagens Play in Model Predictivity

Science.gov (United States)

Carrasquer, C. Alex; Batey, Kaylind; Qamar, Shahid; Cunningham, Albert R.; Cunningham, Suzanne L.

2016-01-01

We previously demonstrated that fragment based cat-SAR carcinogenesis models consisting solely of mutagenic or non-mutagenic carcinogens varied greatly in terms of their predictive accuracy. This led us to investigate how well the rat cancer cat-SAR model predicted mutagens and non-mutagens in their learning set. Four rat cancer cat-SAR models were developed: Complete Rat, Transgender Rat, Male Rat, and Female Rat, with leave-one-out (LOO) validation concordance values of 69%, 74%, 67%, and 73%, respectively. The mutagenic carcinogens produced concordance values in the range of 69–76% as compared to only 47–53% for non-mutagenic carcinogens. As a surrogate for mutagenicity comparisons between single site and multiple site carcinogen SAR models was analyzed. The LOO concordance values for models consisting of 1-site, 2-site, and 4+-site carcinogens were 66%, 71%, and 79%, respectively. As expected, the proportion of mutagens to non-mutagens also increased, rising from 54% for 1-site to 80% for 4+-site carcinogens. This study demonstrates that mutagenic chemicals, in both SAR learning sets and test sets, are influential in assessing model accuracy. This suggests that SAR models for carcinogens may require a two-step process in which mutagenicity is first determined before carcinogenicity can be accurately predicted. PMID:24697549

Comparative Biochemistry and Metabolism. Part 1. Carcinogenesis

Science.gov (United States)

1982-08-01

1968), Nitrosamine-induced carcino- genesis. The alkylation of nucleic acids of the rat by N-methvl- N- nitrosourea , dimethylnitrosamine...inorganic reducing agent , hydrazine, is toxic and weakly carcinogenic. In earlier studies it was found that oral administration of a toxic dose of...metabolically activated to a methylatinj agent . Liver DNA from mice and hamsters contained considerably more 7-methyl- guanine and 0 6-methylguanine

Critical review of animal carcinogenesis by cadmium and its inorganic compounds

International Nuclear Information System (INIS)

Maximilien, R.; Dero, B.

1990-01-01

Animal carcinogenic biassays relative to 6 inorganic cadmium substances (cadmium metal, cadmium oxide, cadmium sulfide, cadmium sulfate, cadmium chloride and cadmium acetate) are reviewed (speciation). Critical evaluation of literature data on carcinogenicity has been performed by making reference to E.C. guidelines of good laboratory practice. There are few data on routes relevant for human risk assessment: experiments on inhalation demonstrate lung carcinogenicity of cadmium oxide, cadmium sulfide, cadmium sulfate and cadmium chloride in rats but not in mice nor in hamsters; no carcinogenic effects of cadmium compounds are observed following oral administration. For routes of less or no relevance for human risk assessment, some results are clearly positive: subcutaneous injection induces cancers in situ (various cadmium compounds), testicular tumours (cadmium sulfate and cadmium chloride) and prostatic tumours (cadmium chloride) but such effects are not observed using relevant malignancies in rats. With respect to other no relevant routes (intraperitoneal, intrarenal...) tumours are incidentally produced in situ, but not in remote organs. Numerous studies fail to demonstrate cadmium carcinogenicity, but methodologically acceptable negative ones are very limited in number. Accordingly strain dependent effects and dose effect relationship could not be thoroughly assessed

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

International Nuclear Information System (INIS)

Benson, J.M.; Barr, E.B.; Lundgren, D.L.; Nikula, K.J.

1994-01-01

Carbon tetrachloride (CCl 4 ) has been used extensively in the nuclear weapons industry, so it is possible that nuclear plant workers have been exposed to CCl 4 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 CCl 4 is 5 ppm; however, concentrations of CCl 4 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 CCl 4 by CDF register (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 239 Pu nitrate 239 Pu(NO 3 ) 4

Rift Valley fever virus infection in golden Syrian hamsters.

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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.

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

Science.gov (United States)

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

2015-03-01

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

Mutagenicity of comfrey (Symphytum Officinale) in rat liver

OpenAIRE

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

2005-01-01

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

Mutagenicity of comfrey (Symphytum Officinale) in rat liver.

Science.gov (United States)

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

2005-03-14

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

Distinct functional characteristics of levocabastine sensitive rat neurotensin NT2 receptor expressed in Chinese hamster ovary cells.

Science.gov (United States)

Yamada, M; Yamada, M; Lombet, A; Forgez, P; Rostène, W

1998-01-01

Neurotensin has been shown to produce pharmacological effects both in brain and periphery. Several of these effects are mediated by a high-affinity neurotensin NT1 receptor. On the other hand, a low-affinity levocabastine-sensitive neurotensin NT2 receptor was molecularly cloned from rodent brain recently. In this study, in contrast to NT1 receptor, levocabastine (a histamine H1 receptor antagonist) and SR48692 (an antagonist for NT1 receptor) strongly stimulated intracellular Ca2+ mobilization in transfected Chinese hamster ovary cells expressing rat NT2 receptor, thus acting as potent NT2 receptor. Furthermore, despite of their affinities for NT2 receptor, the Ca2+ responses to potent NT1 agonists, neurotensin or JMV449 ([Lys8-(CH2NH)-Lys9]Pro-Tyr-Ile-Leu, a peptidase resistant analogue of neurotensin) were much smaller than that observed with SR48692. These findings suggest that NT1 and NT2 receptors present distinct functional characteristics and that SR48692 may act as a potent agonist for NT2 receptor.

Susceptibility to radiation-induced mammary carcinoma in genetically resistant Copenhagen rats

International Nuclear Information System (INIS)

Kamiya, Kenji; Nitta, Yumiko; Gould, M.N.

2000-01-01

The objective of this experiment was to compare the cellular basis of mammary cancer induction by a chemical carcinogen with induction by ionizing radiation in three strains of rats (inbred that have different genetic susceptibilities: COP rats, F344 rats, and WF rats). Rats were given a single intraperitoneal injection of 50 mg MNU/kg body weight as a mammary-tumor-inducing chemical carcinogen and were irradiated with a 3.0 Gy dose of 60 Co gamma rays at a dose rate of 26.58±1.19 cGy/min. The rats were inspected weekly, and they were killed and necropsied whenever palpable tumors were detected or they became moribund. The histopathological and immunohistochemical characteristics of the mammary tumors were investigated. A transplantation experiment using selected primary mammary tumors that developed in COP rats exposed to gamma rays was also performed to investigate the transplantability of mammary tumors induced by ionizing radiation. The sensitivity of the WF and F344 rats and the resistance of the COP rats to mammary carcinoma induction by the chemical carcinogen MNU was confirmed. In contrast to the chemical carcinogens, no difference in susceptibility to radiation induction of mammary carcinomas was detected among the three strains of rats, and immunohistochemical examination indicated that the radiation-induced carcinomas consisted of more highly differentiated cells than the MNU-induced cancers. The results of the experiment appear to support the hypothesis that differentiated mammary gland tissue is more resistant to chemical carcinogens than to cancer induction by radiation. The authors conclude that radiation-induced cancers in rats may develop via different pathways or from different cell populations than chemically induced cancers. (K.H.)

Susceptibility to radiation-induced mammary carcinoma in genetically resistant Copenhagen rats

Energy Technology Data Exchange (ETDEWEB)

Kamiya, Kenji; Nitta, Yumiko [Hiroshima Univ. (Japan). Research Inst. for Radiation Biology and Medicine; Gould, M.N.

2000-07-01

The objective of this experiment was to compare the cellular basis of mammary cancer induction by a chemical carcinogen with induction by ionizing radiation in three strains of rats (inbred that have different genetic susceptibilities: COP rats, F344 rats, and WF rats). Rats were given a single intraperitoneal injection of 50 mg MNU/kg body weight as a mammary-tumor-inducing chemical carcinogen and were irradiated with a 3.0 Gy dose of {sup 60} Co gamma rays at a dose rate of 26.58{+-}1.19 cGy/min. The rats were inspected weekly, and they were killed and necropsied whenever palpable tumors were detected or they became moribund. The histopathological and immunohistochemical characteristics of the mammary tumors were investigated. A transplantation experiment using selected primary mammary tumors that developed in COP rats exposed to gamma rays was also performed to investigate the transplantability of mammary tumors induced by ionizing radiation. The sensitivity of the WF and F344 rats and the resistance of the COP rats to mammary carcinoma induction by the chemical carcinogen MNU was confirmed. In contrast to the chemical carcinogens, no difference in susceptibility to radiation induction of mammary carcinomas was detected among the three strains of rats, and immunohistochemical examination indicated that the radiation-induced carcinomas consisted of more highly differentiated cells than the MNU-induced cancers. The results of the experiment appear to support the hypothesis that differentiated mammary gland tissue is more resistant to chemical carcinogens than to cancer induction by radiation. The authors conclude that radiation-induced cancers in rats may develop via different pathways or from different cell populations than chemically induced cancers. (K.H.)

Transoral tracheal intubation of rodents using a fiberoptic laryngoscope.

Science.gov (United States)

Costa, D L; Lehmann, J R; Harold, W M; Drew, R T

1986-06-01

A fiberoptic laryngoscope which allows direct visualization of the deep pharynx and epiglottis has been developed for transoral tracheal intubation of small laboratory mammals. The device has been employed in the intubation and instillation of a variety of substances into the lungs of rats, and with minor modification, has had similar application in mice, hamsters, and guinea pigs. The simplicity and ease of handling of the laryngoscope permits one person to intubate large numbers of enflurane anesthetized animals either on an open counter top or in a glove-box, as may be required for administration of carcinogenic materials. Instillation of 7Be-labeled carbon particles into the lungs of mice, hamsters, rats, and guinea pigs resulted in reasonably consistent interlobal distribution of particles for each test animal species with minimal tracheal deposition. However, actual lung tissue doses of carbon exhibited some species dependence.

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

Science.gov (United States)

Dunkelberg, H

1983-04-01

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

Changes of 67Ga-citrate accumulation in the rat liver during feeding with chemical carcinogen 3'-Methyl-4-dimethylaminoazobenzene

International Nuclear Information System (INIS)

Sasaki, Toru; Kojima, Shuji; Kubodera, Akiko.

1982-01-01

The changes of 67 Ga-citrate( 67 Ga) in the rat liver during feeding with chemical carcinogen 3'-methyl- 4-dimethylaminoazobenzene (3'-Me-DAB) were studied for 20 weeks. The results were shown as follows: Elevated 67 Ga accumulation in the rat liver was first observed at 3rd week after the start of 3'-Me-DAB feeding. There was decrease from the 3-week level at about the 6th week, followed by a sustained increase. The accumulation of 67 Ga in the gram liver at 20th week was about 2.3 times higher than that of the control. There was close correlation between the 67 Ga accumulation pattern and the patterns of the hepatic #betta#-glutamyltranspeptidase and glucose-6-phosphate dehydrogenase activities at l ate stages during hepatocarcinogenesis. In subcellular distribution of 67 Ga, remarkable changes were seen in 800 x g fraction. Grom these studies, it is suggested that 67 Ga may bind with components in 800 x g fraction, concerned with one pathological changes induced by 3'-Me-DAB. (author)

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

Science.gov (United States)

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

2014-04-01

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

Impact of beta-naphthoflavone on genotoxicity of food-derived carcinogens.

Science.gov (United States)

Hodek, Petr; Krizkova, Jitka; Frei, Eva; Singh, Rajinder; Arlt, Volker M; Stiborova, Marie

2011-01-01

Benzo[a]pyrene (BaP) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) are carcinogens, which frequently occur in the human diet. Their metabolic activation to reactive species binding to DNA is mediated by cytochromes P450 (CYPs) 1A1 and 1A2. Thus, levels and activities of these CYPs are crucial for initiation of BaP- and PhPI-mediated carcinogenesis. Here, the effect of CYP1A1/2 induction due to their prototype flavonoid inducer, β-naphthoflavone (BNF), on BaP- and PhPI-derived DNA adduct formation in rats was examined. Male rats pretreated with BNF were treated with a single dose of either carcinogen by oral gavage. Nuclease P1 version of 32P-postlabeling assay and online column-switching liquid chromatography-electrospray ionization-tandem mass spectrometry were used to detect and quantify covalent DNA adducts formed by BaP and PhIP in-vivo, respectively. Expression of CYP1A1/2 enzymes was examined by Western blot. Enzymatic activities of CYP1A1/2 were assessed using their marker substrates (ethoxyresorufin and methoxyresorufin). Treatment of rats with a single dose of BNF produced an increase in levels CYP1A1/2 and CYP1A1 proteins in liver and small intestine, respectively. An increase in CYP1A1 protein expression found in both organs correlated well with specific activities of these CYPs. The CYP1A1 expression levels and its specific activity in small intestine decreased along the length of the organ, being highest in its proximal part and lowest in its distal part. The BNF induction of CYP1A1/2 resulted in a significant increase in the formation of BaP- and PhIP-DNA adducts in liver and in the distal part of the small intestine, respectively. Thus, pretreatment of rats with BNF did not prevent the PhIP and BaP activation, but vice versa, enhanced their genotoxicity. The results of this study demonstrate that the administration of only a single dose of CYP-inducing flavonoid prior to the intake of food carcinogens may increase the risk of a tumor

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

International Nuclear Information System (INIS)

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

1987-01-01

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

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

International Nuclear Information System (INIS)

Renner, H.W.

1982-01-01

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

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.

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

Science.gov (United States)

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

1983-01-01

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

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

International Nuclear Information System (INIS)

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

2008-01-01

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

Chronic carcinogenicity study of gasoline vapor condensate (GVC) and GVC containing methyl tertiary-butyl ether in F344 rats.

Science.gov (United States)

Benson, Janet M; Gigliotti, Andrew P; March, Thomas H; Barr, Edward B; Tibbetts, Brad M; Skipper, Betty J; Clark, Charles R; Twerdok, Lorraine

2011-01-01

Chronic inhalation studies were conducted to compare the toxicity and potential carcinogenicity of evaporative emissions from unleaded gasoline (GVC) and gasoline containing the oxygenate methyl tertiary-butyl ether (MTBE; GMVC). The test materials were manufactured to mimic vapors people would be exposed to during refueling at gas stations. Fifty F344 rats per gender per exposure level per test article were exposed 6 h/d, 5 d/wk for 104 wk in whole body chambers. Target total vapor concentrations were 0, 2, 10, or 20 g/m³ for the control, low-, mid-, and high-level exposures, respectively. Endpoints included survival, body weights, clinical observations, organs weights, and histopathology. GVC and GMVC exerted no marked effects on survival or clinical observations and few effects on organ weights. Terminal body weights were reduced in all mid- and high-level GVC groups and high-level GMVC groups. The major proliferative lesions attributable to gasoline exposure with or without MTBE were renal tubule adenomas and carcinomas in male rats. GMV exposure led to elevated testicular mesothelioma incidence and an increased trend for thyroid carcinomas in males. GVMC inhalation caused an increased trend for testicular tumors with exposure concentration. Mid- and high-level exposures of GVC and GMVC led to elevated incidences of nasal respiratory epithelial degeneration. Overall, in these chronic studies conducted under identical conditions, the health effects in F344 rats following 2 yr of GVC or GMVC exposure were comparable in the production of renal adenomas and carcinomas in male rats and similar in other endpoints.

Chronic Carcinogenicity Study of Gasoline Vapor Condensate (GVC) and GVC Containing Methyl Tertiary-Butyl Ether in F344 Rats

Science.gov (United States)

Benson, Janet M.; Gigliotti, Andrew P.; March, Thomas H.; Barr, Edward B.; Tibbetts, Brad M.; Skipper, Betty J.; Clark, Charles R.; Twerdok, Lorraine

2011-01-01

Chronic inhalation studies were conducted to compare the toxicity and potential carcinogenicity of evaporative emissions from unleaded gasoline (GVC) and gasoline containing the oxygenate methyl tertiary-butyl ether (MTBE; GMVC). The test materials were manufactured to mimic vapors people would be exposed to during refueling at gas stations. Fifty F344 rats per gender per exposure level per test article were exposed 6 h/d, 5 d/wk for 104 wk in whole body chambers. Target total vapor concentrations were 0, 2, 10, or 20 g/m3 for the control, low-, mid-, and high-level exposures, respectively. Endpoints included survival, body weights, clinical observations, organs weights, and histopathology. GVC and GMVC exerted no marked effects on survival or clinical observations and few effects on organ weights. Terminal body weights were reduced in all mid- and high-level GVC groups and high-level GMVC groups. The major proliferative lesions attributable to gasoline exposure with or without MTBE were renal tubule adenomas and carcinomas in male rats. GMV exposure led to elevated testicular mesothelioma incidence and an increased trend for thyroid carcinomas in males. GVMC inhalation caused an increased trend for testicular tumors with exposure concentration. Mid- and high-level exposures of GVC and GMVC led to elevated incidences of nasal respiratory epithelial degeneration. Overall, in these chronic studies conducted under identical conditions, the health effects in F344 rats following 2 yr of GVC or GMVC exposure were comparable in the production of renal adenomas and carcinomas in male rats and similar in other endpoints. PMID:21432714

Activation and detoxification metabolism of urban air pollutants 2-nitrobenzanthrone and carcinogenic 3-nitrobenzanthrone by rat and mouse hepatic microsomes.

Science.gov (United States)

Stiborova, Marie; Cechova, Tereza; Borek-Dohalska, Lucie; Moserova, Michaela; Frei, Eva; Schmeiser, Heinz H; Paca, Jan; Arlt, Volker M

2012-01-01

2-Nitrobenzanthrone (2-NBA) has recently been detected in ambient air particulate matter. Its isomer 3-nitrobenzanthrone (3-NBA) is a potent mutagen and suspected human carcinogen identified in diesel exhaust. Understanding which enzymes are involved in metabolism of these toxicants is important in the assessment of individual susceptibility. Here, metabolism of 2-NBA and 3-NBA by rat and mouse hepatic microsomes containing cytochromes P450 (CYPs), their reductase (NADPH:CYP reductase), and NADH:cytochrome b5 reductase was investigated under anaerobic and aerobic conditions. In addition, using the same microsomal systems, 2-NBA and 3-NBA were evaluated to be enzymatically activated under anaerobic conditions to species generating 2-NBA- and 3-NBA-derived DNA adducts. High performance liquid chromatography (HPLC) with ultraviolet (UV) detection was employed for the separation and characterization of 2-NBA and 3-NBA metabolites formed by hepatic microsomes of rats and mice under the anaerobic and aerobic conditions. Microsomal systems isolated from the liver of the control (untreated) rats and rats pretreated with Sudan I, β-naphthoflavone (β-NF), phenobarbital (PB), ethanol and pregnenolon 16α-carbonitrile (PCN), the inducers of cytochromes P450 (CYP) 1A1, 1A1/2, 2B, 2E1 and 3A, respectively, were used in this study. Microsomes of mouse models, a control mouse line (wild-type, WT) and Hepatic Cytochrome P450 Reductase Null (HRN) mice with deleted gene of NADPH:CYP reductase in the liver, thus absenting this enzyme in their livers, were also employed. To detect and quantify the 2-NBA- and 3-NBA-derived DNA adducts, the 32P postlabeling technique was used. Both reductive metabolite of 3-NBA, 3-aminobenzanthrone (3-ABA), found to be formed predominantly under the anaerobic conditions, and two 3-NBA oxidative metabolites, whose structures have not yet been investigated, were formed by several microsomal systems used in the study. Whereas a 3-NBA reductive metabolite

Imaging study of pancreatic ductal adenocarcinomas in Syrian hamsters using X-ray micro-computed tomography (CT)

International Nuclear Information System (INIS)

Kitahashi, Tsukasa; Mutoh, Michihiro; Tsurusaki, Masakatsu

2010-01-01

X-ray computed tomography (CT) has been used for diagnoses of human pancreatic cancer. Although micro-CT is a useful approach to evaluate macromorphology of organs/tissue also in animal models, reports on pancreatic tumors are limited. In this study, the utility of micro-CT was assessed in characterizing chemically induced pancreatic tumors in Syrian hamsters. Hamsters treated with or without N-nitrosobis(2-oxopropyl)amine (BOP) were injected with the antispasmodic agent, scopolamine butylbromide, and contrast agents, 5 or 10 mL/kg body weight of iopamidol or Fenestra VC at 18-38 weeks, then examined by micro-CT scanning with a respiratory gating system. Both peristaltic and respiratory movements were substantially suppressed by the combination of scopolamine butylbromide treatment and the respiratory gating system, resulting in improvements of image qualities. Iopamidol clearly visualized the pancreatic parenchyma and contrasted the margins among the pancreas and other abdominal organs/tissue. Meanwhile Fenestra VC predominantly contrasted abdominal vascular systems, but the margins among pancreas and other organs/tissue remained obscure. Six pancreatic tumors of 4-13 mm in diameter were detected in four of 15 animals, but not the five tumors of 1-4 mm in diameter. The inner tumor images were heterogeneously or uniformly visualized by iopamidol and Fenestra VC. Overall, iopamidol could clearly contrast between pancreatic parenchyma and the tumors as compared with Fenestra VC. All tumors confirmed were histopathologically diagnosed as pancreatic ductal adenocarcinomas. Thus, micro-CT could be useful to evaluate the carcinogenic processes and preventive methods of pancreatic cancer in hamsters and to assess the novel contrast agents for detection of small pancreatic cancer in humans. (author)

Production and purification of polyclonal anti-hamster ...

African Journals Online (AJOL)

. ... IgG showed high titer and high specificity in the designed ELISA. Purified antibody and its conjugation with HRP are used in research and diagnosis of hamster disease. Key words: Production, purification, hamster immunoglobulins.

The effect of new probiotic strain Lactobacillus plantarum on counts of coliforms, lactobacilli and bacterial enzyme activities in rats exposed to N,N-dimethylhydrazine (chemical carcinogen

Directory of Open Access Journals (Sweden)

Denisa Čokášová

2012-01-01

Full Text Available The aim of the present study was to evaluate the effect of the new probiotic strain Lactobacillus plantarum on chemically induced carcinogenesis in rats. Sprague dowley rats (n = 33 were divided into control and experimental groups and were fed a conventional laboratory diet. In the experimental group, rats were treated with the probiotic at the dose of 1 × 109 CFU (colony-forming units/ml. Two weeks after the beginning of the trial, N,N-dimethylhydrazine (chemical carcinogen injections were applied s.c. at the dose of 21 mg/kg b.w., 5 × weekly. At the end of the 8-month experimental period, faeces samples were taken from the rats and used for laboratory analysis. The counts of lactobacilli and coliforms and bacterial enzyme activity were determined. The probiotic strain L. plantarum as single species or in combination with oil (Lini oleum virginale decreased the count of total coliforms and increased lactobacilli in faeces of rats. Application of probiotic microorganisms significantly (P < 0.05 decreased the activities of bacterial enzymes (β-galactosidase and β-glucuronidase compared to the control group rats. The results of this study indicate that probiotic microorganisms could exert a preventive effect on colon carcinogenesis induced by N,N-dimethylhydrazine.

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.

Mutagenic and epigenetic influence of caffeine on the frequencies of UV-induced ouabain-resistant Chinese hamster cells

International Nuclear Information System (INIS)

Chang, Chia-Cheng; Philipps, C.; Trosko, J.E.; Hart, R.W.

1977-01-01

Caffeine, given as a post-treatment to UV-irradiated Chinese hamster cells in vitro, modified the frequency of induced mutations at the ouabain resistance locus. Mutation frequencies were increased when caffeine was added only for the DNA repair and mutation fixation period. When caffeine was added after the DNA repair and mutation fixation period, or immediately after DNA damage and for the entire repair and selection period, mutation frequencies were reduced. A hypothesis, given to explain both results, is that caffeine, by blocking a constitutive 'error-free' postreplication repair process, allows an 'error-prone' DNA repair process to produce many mutations. Moreover, caffeine, possibly by modifying C-AMP metabolism, causes a repression of induced mutations which, in effect, explains its anti-mutagenic and anti-carcinogenic properties

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

Science.gov (United States)

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

1987-05-01

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

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

International Nuclear Information System (INIS)

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

1993-01-01

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

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

Science.gov (United States)

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

2015-01-01

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

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.

In vitro and in vivo studies of the carcinogenic, toxic and genotoxic activities of the air pollutants SO2 and NOx, separately and in combination with carcinogenic polycyclic aromatic hydrocarbons and N-nitrosamines. In vivo- und in vitro-Studien zur carcinogenen, toxischen und genschaedigenden Wirkung von Luftschadstoffen (SO sub 2 , NO sub x , PAH, N-Nitrosoverbindungen, allein und in Kombination)

Energy Technology Data Exchange (ETDEWEB)

Schmezer, P; Zeller, W J; Klein, R G; Pool-Zobel, B L [Deutsches Krebsforschungszentrum, Heidelberg (Germany, F.R.). Inst. fuer Toxikologie und Chemotherapie

1990-04-01

Previous studies with different in vitro cell systems had shown that the DNA-damaging activity of several carcinogens may be decreased by SO{sub 2} and NO{sub x}. Experiments to elucidate possible mechanisms responsible for the observed effects were conducted. Comparative studies with the DNA-repair inhibitor novobiocin revealed that the reduction of benzo(a)pyrene (BaP) induced DNA-single strand breaks (DNA-SSB) in fetal hamster lung cells (FHLC) is probably caused by an inhibition of DNA-repair processes. Experiments with the Salmonella typhimurium mutagenicity assay showed that neither SO{sub 2} nor NO{sub x} influence the overall rate of BaP metabolism. Although it has been shown that both gases are able to influence appropriate enzyme activities, the net yield of mutagenic BaP metabolites is not altered. Finally, new investigations with primary rat hepatocytes revealed that no decrease of N-nitrosamine genotoxicity (DNA-SBB) was observed following simultaneous gas and nitrosamine exposure. With this system experiments are underway to elucidate if, in contrast, local influences (lung, nasal mucosa) are triggered by the in vivo combination treatment (SO{sub 2} and N-nitrosodimethylamine, NDMA). The present status of an ongoing inhalation study for carcinogenic activity of NDMA with and without the simultaneous application of the air pollutants is reported. The histopathological analysiss of the treatment groups receiving only NDMA exposure showed that even with an exposure as low as 0.04 ppm NDMA in the breathing air, which leads to a daily intake of 10 {mu}g NDMA/kg during 207 days of application, a 36% rate of tumor induction was observed.

Induction of lyme arthritis in LSH hamsters

International Nuclear Information System (INIS)

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

1988-01-01

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

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

International Nuclear Information System (INIS)

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

2009-01-01

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

Histaminergic regulation of seasonal metabolic rhythms in Siberian hamsters.

Science.gov (United States)

I'anson, Helen; Jethwa, Preeti H; Warner, Amy; Ebling, Francis J P

2011-06-01

We investigated whether histaminergic tone contributes to the seasonal catabolic state in Siberian hamsters by determining the effect of ablation of histaminergic neurons on food intake, metabolic rate and body weight. A ribosomal toxin (saporin) conjugated to orexin-B was infused into the ventral tuberomammillary region of the hypothalamus, since most histaminergic neurons express orexin receptors. This caused not only 75-80% loss of histaminergic neurons in the posterior hypothalamus, but also some loss of other orexin-receptor expressing cells e.g. MCH neurons. In the long-day anabolic state, lesions produced a transient post-surgical decrease in body weight, but the hamsters recovered and maintained constant body weight, whereas weight gradually increased in sham-lesioned hamsters. VO(2) in the dark phase was significantly higher in the lesioned hamsters compared to shams, and locomotor activity also tended to be higher. In a second study in short days, sham-treated hamsters showed the expected seasonal decrease in body weight, but weight remained constant in the lesioned hamsters, as in the long-day study. Lesioned hamsters consumed more during the early dark phase and less during the light phase due to an increase in the frequency of meals during the dark and decreased meal size during the light, and their cumulative food intake in their home cages was greater than in the control hamsters. In summary, ablation of orexin-responsive cells in the posterior hypothalamus blocks the short-day induced decline in body weight by preventing seasonal hypophagia, evidence consistent with the hypothesis that central histaminergic mechanisms contribute to long-term regulation of body weight. Copyright © 2011 Elsevier Inc. All rights reserved.

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

International Nuclear Information System (INIS)

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

2004-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2004-10-01

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

20neon ion- and x-ray-induced mammary carcinogenesis in female rats

International Nuclear Information System (INIS)

Shellabarger, C.J.; Baum, J.W.; Holtzman, S.; Stone, J.P.

1983-01-01

One of the proposed uses of heavy ion irradiation is to image lesions of the human female breast. The rat model system was chosen to assess the carcinogenic potential of heavy ion irradiation in the belief that data obtained from rat studies would have a qualitatively predictive value for the human female. Accordingly, female rats were exposed to 20 Ne ions at the BEVALAC and studied for the development of mammary neoplasia for 312 +- 2 days at Brookhaven along with rats exposed concurrently to x-irradiation or to no irradiation. As the dose of either type of radiation was increased the percent of rats with mammary adenocarcinomas, and the percent of rats with mammary fibroadenomas, tended to increase. At a prevalence of 20%, the RBE for 20 Neon ions for mammary adenocarcinomas was estimated to be larger than 5 and for mammary fibroadenomas the RBE was estimated to be less than 2. No conclusion was reached concerning whether or not the RBE might vary with dose. We suggest that 20 Ne ions do have a carcinogenic potential for rat mammary tissue and that this carcinogenic potential is likely to be greater than for x-irradiation. (DT)

Colon of the rat

International Nuclear Information System (INIS)

Lindstroem, C.G.; Rosengren, J.-E.; Fork, F.-T.

1979-01-01

The anatomy and radiologic appearance of the colon in rats are described on the basis of 300 animals treated with carcinogenic agents and 40 normal rats. The macroscopic and microscopic appearance of the mucosa varies in the different parts of the colon. Lymphoid plaques are normal structures. The results justify a new anatomic nomenclature. (Auth.)

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

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.

Blood proteins as carcinogen dosimeters

International Nuclear Information System (INIS)

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

1986-01-01

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

Obeticholic acid raises LDL-cholesterol and reduces HDL-cholesterol in the Diet-Induced NASH (DIN) hamster model.

Science.gov (United States)

Briand, François; Brousseau, Emmanuel; Quinsat, Marjolaine; Burcelin, Rémy; Sulpice, Thierry

2018-01-05

The use of rat and mouse models limits the translation to humans for developing novel drugs targeting nonalcoholic steatohepatitis (NASH). Obeticholic acid (OCA) illustrates this limitation since its dyslipidemic effect in humans cannot be observed in these rodents. Conversely, Golden Syrian hamsters have a lipoprotein metabolism mimicking human dyslipidemia since it does express the cholesteryl ester transfer protein (CETP). We therefore developed a Diet-Induced NASH (DIN) hamster model and evaluated the impact of OCA. Compared with chow fed controls, hamsters fed for 20 weeks with a free-choice (FC) diet, developed obesity, insulin resistance, dyslipidemia and NASH (microvesicular steatosis, inflammation, hepatocyte ballooning and perisinusoidal to bridging fibrosis). After 20 weeks of diet, FC fed hamsters were treated without or with obeticholic acid (15mg/kg/day) for 5 weeks. Although a non-significant trend towards higher dietary caloric intake was observed, OCA significantly lowered body weight after 5 weeks of treatment. OCA significantly increased CETP activity and LDL-C levels by 20% and 27%, and reduced HDL-C levels by 20%. OCA blunted hepatic gene expression of Cyp7a1 and Cyp8b1 and reduced fecal bile acids mass excretion by 64% (P OCA showed a trend towards higher scavenger receptor Class B type I (SR-BI) and lower LDL-receptor hepatic protein expression. OCA reduced NAS score for inflammation (P OCA as observed in humans, and should be useful for evaluating novel drugs targeting NASH. Copyright © 2017 Elsevier B.V. All rights reserved.

Involvement of Pro-Inflammatory Macrophages in Liver Pathology of Pirital Virus-Infected Syrian Hamsters

Directory of Open Access Journals (Sweden)

Corey L. Campbell

2018-05-01

Full Text Available New World arenaviruses cause fatal hemorrhagic disease in South America. Pirital virus (PIRV, a mammarenavirus hosted by Alston’s cotton rat (Sigmodon alstoni, causes a disease in Syrian golden hamsters (Mesocricetus auratus (biosafety level-3, BSL-3 that has many pathologic similarities to the South American hemorrhagic fevers (BSL-4 and, thus, is considered among the best small-animal models for human arenavirus disease. Here, we extend in greater detail previously described clinical and pathological findings in Syrian hamsters and provide evidence for a pro-inflammatory macrophage response during PIRV infection. The liver was the principal target organ of the disease, and signs of Kupffer cell involvement were identified in mortally infected hamster histopathology data. Differential expression analysis of liver mRNA revealed signatures of the pro-inflammatory response, hematologic dysregulation, interferon pathway and other host response pathways, including 17 key transcripts that were also reported in two non-human primate (NHP arenavirus liver-infection models, representing both Old and New World mammarenavirus infections. Although antigen presentation may differ among rodent and NHP species, key hemostatic and innate immune-response components showed expression parallels. Signatures of pro-inflammatory macrophage involvement in PIRV-infected livers included enrichment of Ifng, Nfkb2, Stat1, Irf1, Klf6, Il1b, Cxcl10, and Cxcl11 transcripts. Together, these data indicate that pro-inflammatory macrophage M1 responses likely contribute to the pathogenesis of acute PIRV infection.

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.

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.

Involvement of PSMD10, CDK4, and Tumor Suppressors in Development of Intrahepatic Cholangiocarcinoma of Syrian Golden Hamsters Induced by Clonorchis sinensis and N-Nitrosodimethylamine.

Directory of Open Access Journals (Sweden)

Md Hafiz Uddin

Full Text Available Clonorchis sinensis is a group-I bio-carcinogen for cholangiocarcinoma (CCA. Although the epidemiological evidence links clonorchiasis and CCA, the underlying molecular mechanism involved in this process is poorly understood. In the present study, we investigated expression of oncogenes and tumor suppressors, including PSMD10, CDK4, p53 and RB in C. sinensis induced hamster CCA model.Different histochemical/immunohistochemical techniques were performed to detect CCA in 4 groups of hamsters: uninfected control (Ctrl., infected with C. sinensis (Cs, ingested N-nitrosodimethylamine (NDMA, and both Cs infected and NDMA introduced (Cs+NDMA. The liver tissues from all groups were analyzed for gene/protein expressions by quantitative PCR (qPCR and western blotting.CCA was observed in all hamsters of Cs+NDMA group with well, moderate, and poorly differentiated types measured in 21.8% ± 1.5%, 13.3% ± 1.3%, and 10.8% ± 1.3% of total tissue section areas respectively. All CCA differentiations progressed in a time dependent manner, starting from the 8th week of infection. CCA stroma was characterized with increased collagen type I, mucin, and proliferative cell nuclear antigen (PCNA. The qPCR analysis showed PSMD10, CDK4 and p16INK4 were over-expressed, whereas p53 was under-expressed in the Cs+NDMA group. We observed no change in RB1 at mRNA level but found significant down-regulation of RB protein. The apoptosis related genes, BAX and caspase 9 were found downregulated in the CCA tissue. Gene/protein expressions were matched well with the pathological changes of different groups except the NDMA group. Though the hamsters in the NDMA group showed no marked pathological lesions, we observed over-expression of Akt/PKB and p53 genes proposing molecular interplay in this group which might be related to the CCA initiation in this animal model.The present findings suggest that oncogenes, PSMD10 and CDK4, and tumor suppressors, p53 and RB, are involved in the

Hamster and Murine Models of Severe Destructive Lyme Arthritis

Science.gov (United States)

Munson, Erik; Nardelli, Dean T.; Du Chateau, Brian K.; Callister, Steven M.; Schell, Ronald F.

2012-01-01

Arthritis is a frequent complication of infection in humans with Borrelia burgdorferi. Weeks to months following the onset of Lyme borreliosis, a histopathological reaction characteristic of synovitis including bone, joint, muscle, or tendon pain may occur. A subpopulation of patients may progress to a chronic, debilitating arthritis months to years after infection which has been classified as severe destructive Lyme arthritis. This arthritis involves focal bone erosion and destruction of articular cartilage. Hamsters and mice are animal models that have been utilized to study articular manifestations of Lyme borreliosis. Infection of immunocompetent LSH hamsters or C3H mice results in a transient synovitis. However, severe destructive Lyme arthritis can be induced by infecting irradiated hamsters or mice and immunocompetent Borrelia-vaccinated hamsters, mice, and interferon-gamma- (IFN-γ-) deficient mice with viable B. burgdorferi. The hamster model of severe destructive Lyme arthritis facilitates easy assessment of Lyme borreliosis vaccine preparations for deleterious effects while murine models of severe destructive Lyme arthritis allow for investigation of mechanisms of immunopathology. PMID:22461836

Specific estrogen-induced cell proliferation of cultured Syrian hamster renal proximal tubular cells in serum-free chemically defined media

International Nuclear Information System (INIS)

Oberley, T.D.; Lauchner, L.J.; Pugh, T.D.; Gonzalez, A.; Goldfarb, S.; Li, S.A.; Li, J.J.

1989-01-01

It has long been recognized that the renal proximal tubular epithelium of the hamster is a bona fide estrogen target tissue. The effect of estrogens on the growth of proximal tubule cell explants and dissociated single cells derived from these explant outgrowths has been studied in culture. Renal tubular cells were grown on a PF-HR-9 basement membrane under serum-free chemically defined culture conditions. At 7-14 days in culture, cell number was enhanced 3-fold in the presence of either 17β-estradiol or diethylstilbestrol. A similar 3-fold increase in cell number was also seen at 1 nM 17β-estradiol in subcultured dissociated single tubular cells derived from hamster renal tubular explant outgrowths at 21 days in culture. Concomitant exposure of tamoxifen at 3-fold molar excess in culture completely abolished the increase in cell number seen with 17β-estradiol. The proliferation effect of estrogens on proximal tubular cell growth appears to be species specific since 17β-estradiol did not alter the growth of either rat or guinea pig proximal tubules in culture. In addition, at 7-10 days in culture in the presence of 17β-estradiol, [ 3 H]thymidine labeling of hamster tubular cells was enhanced 3-fold. These results clearly indicate that estrogens can directly induce primary epithelial cell proliferation at physiologic concentrations and provide strong additional evidence for an important hormonal role in the neoplastic transformation of the hamster kidney

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

International Nuclear Information System (INIS)

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

1988-01-01

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)

Clinical Procedures Training for Veterinary Technicians and Investigators using Common Laboratory Animal Species, including: Mice (Mus musculus), Rats (Rattus norvegicus), Hamsters (Mesocricetus auratus), Guinea Pigs (Gavia porcellus), Rabbits (Otyctolagus cuniculus), Ferrets (Mustela putorius furo), Pigs (Sus scrofa), Sheep (Ovis aries), and Goats (Capra hircus)

Science.gov (United States)

2016-08-30

60th Medical Group (AMC), Travis AFB, CA INSTITUTIONAL ANIMAL CARE AND USE COMMITTEE (IACUC) FINAL REPORT SUMMARY (Please !ml all information. Use...Technicians and Investigators using Common Laboratory Animal Species, including: Mice (Mus muscu/us), Rats (Rattus norvegicus), Hamsters (Mesocricetus auratus...DATE: 14 November 2016 FUNDING SOURCE: SG O&M funds LAST TRIENNIAL REVISION DATE: 15 October 2015 1. RECORD OF ANIMAL USAGE: Animal Species: Total

Cystolithiasis in a Syrian hamster: a different outcome | Petrini ...

African Journals Online (AJOL)

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. Keywords: Glucosamine, Hamster, Hesperidin, PEA, Urolithiasis ...

Rat Urinary Bladder Carcinogenesis by Dual-Acting PPARα+γ Agonists

Directory of Open Access Journals (Sweden)

Martin B. Oleksiewicz

2008-01-01

Full Text Available Despite clinical promise, dual-acting activators of PPARα and γ (here termed PPARα+γ agonists have experienced high attrition rates in preclinical and early clinical development, due to toxicity. In some cases, discontinuation was due to carcinogenic effect in the rat urothelium, the epithelial layer lining the urinary bladder, ureters, and kidney pelvis. Chronic pharmacological activation of PPARα is invariably associated with cancer in rats and mice. Chronic pharmacological activation of PPARγ can in some cases also cause cancer in rats and mice. Urothelial cells coexpress PPARα as well as PPARγ, making it plausible that the urothelial carcinogenicity of PPARα+γ agonists may be caused by receptor-mediated effects (exaggerated pharmacology. Based on previously published mode of action data for the PPARα+γ agonist ragaglitazar, and the available literature about the role of PPARα and γ in rodent carcinogenesis, we propose a mode of action hypothesis for the carcinogenic effect of PPARα+γ agonists in the rat urothelium, which combines receptor-mediated and off-target cytotoxic effects. The proposed mode of action hypothesis is being explored in our laboratories, towards understanding the human relevance of the rat cancer findings, and developing rapid in vitro or short-term in vivo screening approaches to faciliate development of new dual-acting PPAR agonist compounds.

Methods for modeling chinese hamster ovary (cho) cell metabolism

DEFF Research Database (Denmark)

2015-01-01

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

Histopathology of Lyme arthritis in LSH hamsters

International Nuclear Information System (INIS)

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

1989-01-01

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

Photoperiodic regulation of the hamster testis: dependence on circadian rhythms

International Nuclear Information System (INIS)

Eskes, G.A.; Zucker, I.

1978-01-01

The testes of hamsters exposed to short days (10 hr of light per day) regress within 13 weeks. Administration of 7.5 percent deuterium oxide to hamsters lengthens the period of free running circadian activity rhythms by 2.2 percent and prevents testicular regression during short-day exposure. This is consistent with predictions derived from an external coincidence model for photoperiodic time measurement: Deuterium oxide changes phase relationships between the light-dark cycle and the circadian system, the hamster's daily photosensitive phase is stimulated with light during short days, and the testes remain large. Conservation of the period of circadian rhythms within narrow limits has adaptive significance for hamster photoperiodism and for the occurrence and phasing of the annual reproductive cycle

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

Science.gov (United States)

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

Modifying factors in rat mammary gland carcinogenesis

International Nuclear Information System (INIS)

Shellabarger, C.J.

1975-01-01

The spontaneous incidence of mammary adenocarcinomas and mammary fibroadenomas in rats was found to be related to the strain of rat studied. Strains of rats that are sensitive to chemical carcinogens in regard to induced mammary neoplasia tend to be the same strains of rats that are sensitive to radiation. Methylcholantrene (MCA) and x-rays appeared to act in an additive fashion on the induction of mammary adenocarcinomas when they were given together. Lactating and older rats lose responsiveness to chemical carcinogens but do not lose responsiveness to radiation. Radiation appears to act in a scopal fashion in the induction of mammary neoplasia. Mammary neoplasia induction was not changed when low LET radiation was split into 2 equal fractions and high LET radiation was more effective than low LET radiation in inducing mammary neoplasia. It is suggested that DMBA can act as an initiator for the induction of mammary adenocarcinomas, that phorbol can act as a promotor, and that viruses may induce mammary neoplasia. Diethylstilbestrol (DES) and radiation appeared to act synergistically in the induction of mammary adenocarcinomas in one strain of rat but not in another strain. (U.S.)

Risk assessment of carcinogens in food

International Nuclear Information System (INIS)

Barlow, Susan; Schlatter, Josef

2010-01-01

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

Risk assessment of carcinogens in food.

Science.gov (United States)

Barlow, Susan; Schlatter, Josef

2010-03-01

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

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......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...

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.

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.

Studies on carcinogenic effect of tritiated water

International Nuclear Information System (INIS)

Zou Shuai; Wang Hui; Li Maohe; Lin Suqin

1994-09-01

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

Effects of calcium and magnesium acetates on tissue distribution of carcinogenic doses of calcium chloride in Wistar rats

International Nuclear Information System (INIS)

Kasprzak, K.S.; Poirier, L.A.

1985-01-01

Previous studies have shown that magnesium, unlike calcium, prevents cadmium carcinogenesis at the subcutaneous injection site, and that neither magnesium nor calcium has any significant influence on the production of testicular tumors by cadmium in rats. The present investigation attempts to disclose the nature of those different effects by comparing the results of administration of both physiological metals on the uptake and distribution of carcinogenic doses of cadmium in rats. Male Wistar rats received a single subcutaneous (s.c.) injection of 109 CdCl 2 (0.02 mmol/kg or 0.04 mmol/kg) and s.c. injections (one daily) of calcium acetate (CaAcet; 0.16 mmol/kg), or magnesium acetate (MgAcet; 4 mmol/kg) or saline on the day before, the day of and the day after the 109 CdCl 2 dosing. The concentration of cadmium in tissues was determined by gamma-counting on the 4th, the 15th and the 45th day after 109 CdCl 2 injection. The concentration of cadmium in tissues on day 4 was ranked as follows: liver > kidney > the injection site skin > pancreas > spleen > heart > lung > distant skin > testes > blood. Administration of CaAcet increased by over 20% and that of MgAcet decreased by over 30% the initial uptake of both cadmium doses at the injection site. The MgAcet may prevent cadmium carcinogenesis by inhiniting the uptake of cadmium by the injection site tissues. In the testis and in all other tissues investigated, except kidney, the effects of the physiological metals were reversed, CaAcet and MgAcet tended to increase the uptake of cadmium. CaAcet exerted no noticeable effects on the uptake of cadmium by the kidney. The observed results of CaAcet and MgAcet administration on the concentration of cadmium in distal tissues seem to depend on the alterations in cadmium uptake at the injection site. (author)

Metabolic influences on circadian rhythmicity in Siberian and Syrian hamsters exposed to long photoperiods.

Science.gov (United States)

Challet, E; Kolker, D E; Turek, F W

2000-01-01

Calorie restriction and other situations of reduced glucose availability in rodents alter the entraining effects of light on the circadian pacemaker located in the suprachiasmatic nuclei. Siberian and Syrian hamsters are photoperiodic species that are sexually active when exposed to long summer-like photoperiods, while both species show opposite changes in body mass when transferred from long to short or short to long days. Because metabolic cues may fine tune the photoperiodic responses via the suprachiasmatic nuclei, we tested whether timed calorie restriction can alter the photic synchronization of the light-entrainable pacemaker in these two hamster species exposed to long photoperiods. Siberian and Syrian hamsters were exposed to 16 h:8 h light:dark cycles and received daily hypocaloric (75% of daily food intake) or normocaloric diet (100% of daily food intake) 4 h after light onset. Four weeks later, hamsters were transferred to constant darkness and fed ad libitum. The onset of the nocturnal pattern of locomotor activity was phase advanced by 1.5 h in calorie-restricted Siberian hamsters, but not in Syrian hamsters. The lack of phase change in calorie-restricted Syrian hamsters was also observed in individuals exposed to 14 h:10 h dim light:dark cycles and fed with lower hypocaloric food (i.e. 60% of daily food intake) 2 h after light onset. Moreover, in hamsters housed in constant darkness and fed ad lib., light-induced phase shifts of the locomotor activity in Siberian hamsters, but not in Syrian hamsters were significantly reduced when glucose utilization was blocked by pretreatment with 500 mg/kg i.p. 2-deoxy-D-glucose. Taken together, these results show that the photic synchronization of the light-entrainable pacemaker can be modulated by metabolic cues in Siberian hamsters, but not in Syrian hamsters maintained on long days.

Hypothalamic over-expression of VGF in the Siberian hamster increases energy expenditure and reduces body weight gain.

Science.gov (United States)

Lewis, Jo E; Brameld, John M; Hill, Phil; Cocco, Cristina; Noli, Barbara; Ferri, Gian-Luca; Barrett, Perry; Ebling, Francis J P; Jethwa, Preeti H

2017-01-01

VGF (non-acronymic) was first highlighted to have a role in energy homeostasis through experiments involving dietary manipulation in mice. Fasting increased VGF mRNA in the Arc and levels were subsequently reduced upon refeeding. This anabolic role for VGF was supported by observations in a VGF null (VGF-/-) mouse and in the diet-induced and gold-thioglucose obese mice. However, this anabolic role for VGF has not been supported by a number of subsequent studies investigating the physiological effects of VGF-derived peptides. Intracerebroventricular (ICV) infusion of TLQP-21 increased resting energy expenditure and rectal temperature in mice and protected against diet-induced obesity. Similarly, ICV infusion of TLQP-21 into Siberian hamsters significantly reduced body weight, but this was due to a decrease in food intake, with no effect on energy expenditure. Subsequently NERP-2 was shown to increase food intake in rats via the orexin system, suggesting opposing roles for these VGF-derived peptides. Thus to further elucidate the role of hypothalamic VGF in the regulation of energy homeostasis we utilised a recombinant adeno-associated viral vector to over-express VGF in adult male Siberian hamsters, thus avoiding any developmental effects or associated functional compensation. Initially, hypothalamic over-expression of VGF in adult Siberian hamsters produced no effect on metabolic parameters, but by 12 weeks post-infusion hamsters had increased oxygen consumption and a tendency to increased carbon dioxide production; this attenuated body weight gain, reduced interscapular white adipose tissue and resulted in a compensatory increase in food intake. These observed changes in energy expenditure and food intake were associated with an increase in the hypothalamic contents of the VGF-derived peptides AQEE, TLQP and NERP-2. The complex phenotype of the VGF-/- mice is a likely consequence of global ablation of the gene and its derived peptides during development, as well

Detection of carcinogen-DNA adducts by radioimmunoassay

International Nuclear Information System (INIS)

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

1977-01-01

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

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...

Involvement of PSMD10, CDK4, and Tumor Suppressors in Development of Intrahepatic Cholangiocarcinoma of Syrian Golden Hamsters Induced by Clonorchis sinensis and N-Nitrosodimethylamine

Science.gov (United States)

Uddin, Md. Hafiz; Choi, Min-Ho; Kim, Woo Ho; Jang, Ja-June; Hong, Sung-Tae

2015-01-01

Background Clonorchis sinensis is a group-I bio-carcinogen for cholangiocarcinoma (CCA). Although the epidemiological evidence links clonorchiasis and CCA, the underlying molecular mechanism involved in this process is poorly understood. In the present study, we investigated expression of oncogenes and tumor suppressors, including PSMD10, CDK4, p53 and RB in C. sinensis induced hamster CCA model. Methods Different histochemical/immunohistochemical techniques were performed to detect CCA in 4 groups of hamsters: uninfected control (Ctrl.), infected with C. sinensis (Cs), ingested N-nitrosodimethylamine (NDMA), and both Cs infected and NDMA introduced (Cs+NDMA). The liver tissues from all groups were analyzed for gene/protein expressions by quantitative PCR (qPCR) and western blotting. Principal Findings CCA was observed in all hamsters of Cs+NDMA group with well, moderate, and poorly differentiated types measured in 21.8% ± 1.5%, 13.3% ± 1.3%, and 10.8% ± 1.3% of total tissue section areas respectively. All CCA differentiations progressed in a time dependent manner, starting from the 8th week of infection. CCA stroma was characterized with increased collagen type I, mucin, and proliferative cell nuclear antigen (PCNA). The qPCR analysis showed PSMD10, CDK4 and p16INK4 were over-expressed, whereas p53 was under-expressed in the Cs+NDMA group. We observed no change in RB1 at mRNA level but found significant down-regulation of RB protein. The apoptosis related genes, BAX and caspase 9 were found downregulated in the CCA tissue. Gene/protein expressions were matched well with the pathological changes of different groups except the NDMA group. Though the hamsters in the NDMA group showed no marked pathological lesions, we observed over-expression of Akt/PKB and p53 genes proposing molecular interplay in this group which might be related to the CCA initiation in this animal model. Conclusions/Significance The present findings suggest that oncogenes, PSMD10 and CDK4

Identification and monitoring of non-radiological carcinogens

Energy Technology Data Exchange (ETDEWEB)

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

1995-09-01

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

Identification and monitoring of non-radiological carcinogens

International Nuclear Information System (INIS)

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

1995-09-01

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

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.

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.

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.

Thermostability of sperm nuclei assessed by microinjection into hamster oocytes

Science.gov (United States)

Nuclei isolated from spermatozoa of various species (golden hamster, mouse, human, rooster, and the fish tilapia) were heated at 60 degrees-125 degrees C for 20-120 min and then microinjected into hamster oocytes to determine whether they could decondense and develop into pronucl...

Construction and characterization of the alpha form of a cardiac myosin heavy chain cDNA clone and its developmental expression in the Syrian hamster.

OpenAIRE

Liew, C C; Jandreski, M A

1986-01-01

A cDNA clone, pVHC1, was isolated from a Syrian hamster heart cDNA library and was compared to the rat alpha (pCMHC21) and beta (pCMHC5) ventricular myosin heavy chain cDNA clones. The DNA sequence and amino acid sequence deducted from the DNA show more homology with pCMHC21 than pCMHC5. This indicates that pVHC1 is an alpha ventricular myosin heavy chain cDNA clone. However, even though pVHC1 shows a high degree of nucleotide and amino acid conservation with the rat myosin heavy chain sequen...

Black tea extract and dental caries formation in hamsters.

Science.gov (United States)

Linke, Harald A B; LeGeros, Racquel Z

2003-01-01

Several studies have suggested that green tea and Oolong tea extracts have antibacterial and anticariogenic properties in vitro and in vivo. The aim of the present study was to determine the effect of a standardized black tea extract (BTE) on caries formation in inbred hamsters on a regular and a cariogenic diet. Eighty hamsters were divided into four groups of 20 animals each. Two groups received a pelleted regular diet (LabChow) with water or BTE ad libitum. The other two groups received a powdered cariogenic diet (Diet 2000, containing 56% sucrose) with water or BTE ad libitum. The animals were kept for 3 months on their respective diets and then were sacrificed. The heads were retained, the jaws were prepared and stained using alizarin mordant red II, and were then scored for dental caries according to the Keyes method. This is the first study indicating that BTE, as compared with water, significantly decreased caries formation by 56.6% in hamsters on a regular diet and by 63.7% in hamsters on a cariogenic diet (P cariogenic diet group BTE, reduced the mandibular caries score of the hamsters slightly more than the maxillary caries score. The fluoride content of the standardized BTE solution was frequently monitored during the experiment; the mean fluoride concentration was found to be 4.22 ppm. A frequent intake of black tea can significantly decrease caries formation, even in the presence of sugars in the diet.

The hamster flank organ model: Is it relevant to man

International Nuclear Information System (INIS)

Franz, T.J.; Lehman, P.A.; Pochi, P.; Odland, G.F.; Olerud, J.

1989-01-01

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

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

Science.gov (United States)

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

2015-05-01

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

Predictive Models for Carcinogenicity and Mutagenicity ...

Science.gov (United States)

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

Infestivity of Demodex canis to hamster skin engrafted onto SCID mice.

Science.gov (United States)

Tani, Kenji; Une, Satoshi; Hasegawa, Atsuhiko; Adachi, Makoto; Kanda, Naoko; Watanabe, Shin-ichi; Nakaichi, Munekazu; Taura, Yasuho

2005-04-01

We demonstrated that Demodex canis was transferred to skin xenografts of a dog and a hamster onto severe combined immunodeficiency mice. After the transfer of mites, the number of eggs, larvae, nymphs and adult mites per gram of canine and hamster xenografts increased, whereas no live mites were detected on murine allograft. These results indicate that D. canis proliferates in hair follicles of dog and hamster skins but not in murine allograft. Therefore, D. canis may have host preference but not strict host-specificity.

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.

Cross-species transcriptomic approach reveals genes in hamster implantation sites.

Science.gov (United States)

Lei, Wei; Herington, Jennifer; Galindo, Cristi L; Ding, Tianbing; Brown, Naoko; Reese, Jeff; Paria, Bibhash C

2014-12-01

The mouse model has greatly contributed to understanding molecular mechanisms involved in the regulation of progesterone (P4) plus estrogen (E)-dependent blastocyst implantation process. However, little is known about contributory molecular mechanisms of the P4-only-dependent blastocyst implantation process that occurs in species such as hamsters, guineapigs, rabbits, pigs, rhesus monkeys, and perhaps humans. We used the hamster as a model of P4-only-dependent blastocyst implantation and carried out cross-species microarray (CSM) analyses to reveal differentially expressed genes at the blastocyst implantation site (BIS), in order to advance the understanding of molecular mechanisms of implantation. Upregulation of 112 genes and downregulation of 77 genes at the BIS were identified using a mouse microarray platform, while use of the human microarray revealed 62 up- and 38 down-regulated genes at the BIS. Excitingly, a sizable number of genes (30 up- and 11 down-regulated genes) were identified as a shared pool by both CSMs. Real-time RT-PCR and in situ hybridization validated the expression patterns of several up- and down-regulated genes identified by both CSMs at the hamster and mouse BIS to demonstrate the merit of CSM findings across species, in addition to revealing genes specific to hamsters. Functional annotation analysis found that genes involved in the spliceosome, proteasome, and ubiquination pathways are enriched at the hamster BIS, while genes associated with tight junction, SAPK/JNK signaling, and PPARα/RXRα signalings are repressed at the BIS. Overall, this study provides a pool of genes and evidence of their participation in up- and down-regulated cellular functions/pathways at the hamster BIS. © 2014 Society for Reproduction and Fertility.

Neonatal oocyte development and selective oocyte-killing by X-rays in the Chinese hamster, Cricetulus griseus

Energy Technology Data Exchange (ETDEWEB)

Tateno, H.; Mikamo, K. (Asahikawa Medical Coll. (Japan). Dept. of Biological Sciences)

1984-02-01

The process of ovarian development in neonatal Chinese hamsters aged between 0 and 16 days was studied histologically and quantitatively in both a non-irradiated group and an irradiated group. In the latter, ovaries were exposed to a single dose of 1 Gy X-rays on days 0, 2, 4, 6, 8, 10, 12 and 14 after birth. All oocytes on day 0 were at pachytene, and nearly all of them seemed to develop to dictyate by day 10. A quantitative analysis of age-dependent changes in the distribution of oocytes showed that a marked spontaneous degeneration of oocytes took place twice, i.e. during pachytene (day 0 to day 4) and dictyate (day 12 to day 14). Oocytes of this species were found to be very radioresistant at pachytene, but to become sharply sensitive during the phases between diplotene and early dictyate, suffering an almost complete oocyte-killing after 1 Gy. However, they recovered radioresistance after the onset of the resting stage. The changing aspects of radiosensitivity in the Chinese hamster were shown to be far more marked than in the mouse and the rat, which have been observed by previous investigators.

Indoor air-assessment: Indoor concentrations of environmental carcinogens

International Nuclear Information System (INIS)

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

1991-01-01

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

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

Science.gov (United States)

Frolova, O A; Karpova, M V

2012-01-01

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

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

Science.gov (United States)

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

2017-05-18

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

Arnica Tincture Cures Cutaneous Leishmaniasis in Golden Hamsters

Directory of Open Access Journals (Sweden)

Sara M. Robledo

2018-01-01

Full Text Available In search for potential therapeutic alternatives to existing treatments for cutaneous Leishmaniasis, we have investigated the effect of Arnica tincture Ph. Eur. (a 70% hydroethanolic tincture prepared from flowerheads of Arnica montana L. on the lesions caused by infection with Leishmania braziliensis in a model with golden hamsters. The animals were treated topically with a daily single dose of the preparation for 28 days. Subsequently, the healing process was monitored by recording the lesion size in intervals of 15 days up to day 90. As a result, Arnica tincture fully cured three out of five hamsters while one animal showed an improvement and another one suffered from a relapse. This result was slightly better than that obtained with the positive control, meglumine antimonate, which cured two of five hamsters while the other three showed a relapse after 90 days. This result encourages us to further investigate the potential of Arnica tincture in the treatment of cutaneous Leishmaniasis.

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 Welfare...

Risk Assessment Approaches for Carcinogenic Food Contaminants

OpenAIRE

Gillespie, Zoe; Pulido, Olga; Vavasour, Elizabeth

2011-01-01

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

Kisspeptin and the seasonal control of reproduction in hamsters

DEFF Research Database (Denmark)

Simonneaux, Valérie; Ansel, Laura; Revel, Florent G

2008-01-01

-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 arcuate nucleus of the Syrian hamster is lower in short photoperiod, when animals are sexually quiescent. Notably, intracerebroventricular infusion of Kiss1 gene product, kisspeptin, in hamsters kept in short photoperiod is able to override the inhibitory photoperiod and to reactivate sexual activity...

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

Science.gov (United States)

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

2013-10-04

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

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

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

2014-07-30

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

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

International Nuclear Information System (INIS)

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

2014-01-01

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

Metabolic activation of the bladder carcinogen 4-nitrobiphenyl (NBP)

International Nuclear Information System (INIS)

Swaminathan, S.

1986-01-01

The metabolism of NBP, a dog bladder carcinogen, was examined in vitro using rat liver tissues. NBP was metabolized by enzymes localized both in the microsomes and cytosol. The microsomal enzyme activity was inducible by Aroclor 1254 and phenobarbital. High pressure liquid chromatography analysis of the ethyl acetate extract of the reaction mixture, following incubation of [ 3 H]NBP with NADPH and microsomes, revealed four radioactive and UV absorbing peaks with retention times of 5, 8, 14 and 28 min. The peaks at 8, 14 and 28 min corresponded with 4-aminobiphenyl (ABP), NBP and azoxy biphenyl, respectively. The early eluting component with a retention time of 5 min has been tentatively identified as a ring hydroxylated derivative. In contrast to microsomal metabolism, cytosol-mediated metabolism yielded only one major metabolite identified as ABP. Cytosol-mediate reduction was inhibited by the xanthine oxidase inhibitor allopurinol. In vitro incubation of NBP with NADH and commercial preparations of xanthine oxidase also yielded ABP and the formation of the latter was blocked by allopurinol. Xanthine oxidase catalyzed also the binding of [ 3 H]NBP to DNA and proteins; the binding was inhibited by allopurinol. These data support the hypothesis that the nitro reduction step is involved in the activation of the bladder carcinogen NBP, and that the nitroreductases occur in both the microsomes and cytosol. The cytosolic activity is primarily due to xanthine oxidase

Titanium dioxide: inhalation toxicology and epidemiology.

Science.gov (United States)

Hext, Paul M; Tomenson, John A; Thompson, Peter

2005-08-01

Titanium dioxide (TiO(2)) is manufactured worldwide in large quantities for use in a wide range of applications and is normally considered to be toxicologically inert. Findings of tumours in the lungs of rats exposed chronically to high concentrations of TiO(2), but not in similarly exposed mice or hamsters, suggest that the tumorigenic response may be a rat-specific phenomenon but nonetheless raises concerns for potential human health effects. With the limited toxicological understanding of species differences in response to inhaled TiO(2) and a similarly limited amount of epidemiological information with respect to TiO(2) exposure in the workplace, a consortium of TiO(2) manufacturers in Europe (under the European Chemistry Industry Council; CEFIC) and in North America (under the American Chemistry Council; ACC) initiated a programme of research to investigate inter-species differences as a result of exposure to TiO(2) and to conduct detailed epidemiological surveys of the major manufacturing sites. The toxicology studies exposed rats, mice and hamsters to pigment-grade TiO(2) (PG-TiO(2), 0, 10, 50 and 250 mg m(-3)) or ultrafine TiO(2) (UF-TiO(2), 0, 0.5, 2 and 10 mg m(-3)) for 90 days and the lung burdens and tissue responses were evaluated at the end of the exposure period and for up to 1 year after exposure. Results demonstrated clear species differences. Rats and mice had similar lung burdens and clearance rates while hamsters showed high clearance rates. At high lung particle burdens, rats showed a marked progression of histopathological lesions throughout the post-exposure period while mice and hamsters showed minimal initial lesions with recovery apparent during the post-exposure period. Lung neutrophil responses, a sensitive marker of inflammatory changes, reflected the development or recovery of the histopathological lesions. The use of surface area rather than gravimetric lung burden provided closer correlates of the burden to the biological effect

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...

Photoperiod history differentially impacts reproduction and immune function in adult Siberian hamsters.

Science.gov (United States)

Prendergast, Brian J; Pyter, Leah M

2009-12-01

Seasonal changes in numerous aspects of mammalian immune function arise as a result of the annual variation in environmental day length (photoperiod), but it is not known if absolute photoperiod or relative change in photoperiod drives these changes. This experiment tested the hypothesis that an individual's history of exposure to day length determines immune responses to ambiguous, intermediate-duration day lengths. Immunological (blood leukocytes, delayed-type hypersensitivity reactions [DTH]), reproductive, and adrenocortical responses were assessed in adult Siberian hamsters (Phodopus sungorus) that had been raised initially in categorically long (15-h light/day; 15L) or short (9L) photoperiods and were subsequently transferred to 1 of 7 cardinal experimental photoperiods between 9L and 15L, inclusive. Initial photoperiod history interacted with contemporary experimental photoperiods to determine reproductive responses: 11L, 12L, and 13L caused gonadal regression in hamsters previously exposed to 15L, but elicited growth in hamsters previously in 9L. In hamsters with a 15L photoperiod history, photoperiods history, DTH responses were largely unaffected by increases in day length. Enhancement and suppression of blood leukocyte concentrations occurred at 13L in hamsters with photoperiod histories of 15L and 9L, respectively; however, prior exposure to 9L imparted marked hysteresis effects, which suppressed baseline leukocyte concentrations. Cortisol concentrations were only enhanced in 15L hamsters transferred to 9L and, in common with DTH, were unaffected by photoperiod treatments in hamsters with a 9L photoperiod history. Photoperiod history acquired in adulthood impacts immune responses to photoperiod, but manifests in a markedly dissimilar fashion as compared to the reproductive system. Prior photoperiod exposure has an enduring impact on the ability of the immune system to respond to subsequent changes in day length.

A Syrian golden hamster model recapitulating ebola hemorrhagic fever.

Science.gov (United States)

Ebihara, Hideki; Zivcec, Marko; Gardner, Donald; Falzarano, Darryl; LaCasse, Rachel; Rosenke, Rebecca; Long, Dan; Haddock, Elaine; Fischer, Elizabeth; Kawaoka, Yoshihiro; Feldmann, Heinz

2013-01-15

Ebola hemorrhagic fever (EHF) is a severe viral infection for which no effective treatment or vaccine is currently available. While the nonhuman primate (NHP) model is used for final evaluation of experimental vaccines and therapeutic efficacy, rodent models have been widely used in ebolavirus research because of their convenience. However, the validity of rodent models has been questioned given their low predictive value for efficacy testing of vaccines and therapeutics, a result of the inconsistent manifestation of coagulopathy seen in EHF. Here, we describe a lethal Syrian hamster model of EHF using mouse-adapted Ebola virus. Infected hamsters displayed most clinical hallmarks of EHF, including severe coagulopathy and uncontrolled host immune responses. Thus, the hamster seems to be superior to the existing rodent models, offering a better tool for understanding the critical processes in pathogenesis and providing a new model for evaluating prophylactic and postexposure interventions prior to testing in NHPs.

The toxicological study of plutonium: tumor-inducing effect of plutonium in rats

International Nuclear Information System (INIS)

Chen Rusong; Zhao Yongchan; Wang Shoufang; Li Maohe

1992-09-01

The carcinogenic effects of Pu compounds through different routs of administration are introduced. The following results have been obtained: (1) Pu is really a powerful carcinogenic radionuclide. (2) Osteosarcoma can be induced in rats by plutonium nitrate at low level radiation. The incidence is from 38.9% to 42.9% in the 185 kBq/kg group. (3) Lung cancer can be induced by plutonium dioxide and the biological effect of TLN (thoracic lymph node) is significant. (4) Under the combined treatment of 239 Pu, 90 Sr and 144 Ce, the carcinogenic effects is much greater than their separative effect on rats. (5) By using the method of comparative toxicology, the risk of osteosarcoma induced by Pu in human is about 600/(10 6 man·cGy) which is extrapolated from animal to human. The above conclusions are important for evaluating the potential hazard of Pu to human beings

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

Science.gov (United States)

Dasenbrock, Clemens

2005-09-01

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

Dopamine mediates testosterone-induced social reward in male Syrian hamsters.

Science.gov (United States)

Bell, Margaret R; Sisk, Cheryl L

2013-03-01

Adolescent maturation of responses to social stimuli is essential for adult-typical sociosexual behavior. Naturally occurring developmental changes in male Syrian hamster responses to a salient social cue, female hamster vaginal secretions (VS), provide a good model system for investigating neuroendocrine mechanisms of adolescent change in social reward. Sexually naïve adult, but not juvenile, males show a conditioned place preference (CPP) to VS, indicating that VS is not rewarding before puberty. In this series of experiments, the authors examined the roles of testosterone and dopamine receptor activation in mediating the adolescent gain in positive valence of VS. Experiment 1 showed that testosterone replacement is necessary for gonadectomized adult hamsters to form a CPP to VS. Experiment 2 showed that testosterone treatment is sufficient for juvenile hamsters to form a CPP to VS, and that the dopamine receptor antagonist haloperidol blocks formation of a CPP to VS in these animals. Experiments 3 and 4 demonstrated that the disruption of VS CPP with low doses of haloperidol is the result of a reduction in the attractive properties of VS and not attributable to aversive properties of haloperidol. Together, these studies demonstrate that the unconditioned rewarding properties of a social cue necessary for successful adult sociosexual interactions come about as the result of the pubertal increase in circulating testosterone in male hamsters. Furthermore, this social reward can be prevented by dopamine receptor antagonism, indicating that hypothalamic and/or mesocorticolimbic dopaminergic circuits are targets for hormonal activation of social reward.

Syrian Hamster as an Animal Model for the Study of Human Influenza Virus Infection.

Science.gov (United States)

Iwatsuki-Horimoto, Kiyoko; Nakajima, Noriko; Ichiko, Yurie; Sakai-Tagawa, Yuko; Noda, Takeshi; Hasegawa, Hideki; Kawaoka, Yoshihiro

2018-02-15

Ferrets and mice are frequently used as animal models for influenza research. However, ferrets are demanding in terms of housing space and handling, whereas mice are not naturally susceptible to infection with human influenza A or B viruses. Therefore, prior adaptation of human viruses is required for their use in mice. In addition, there are no mouse-adapted variants of the recent H3N2 viruses, because these viruses do not replicate well in mice. In this study, we investigated the susceptibility of Syrian hamsters to influenza viruses with a view to using the hamster model as an alternative to the mouse model. We found that hamsters are sensitive to influenza viruses, including the recent H3N2 viruses, without adaptation. Although the hamsters did not show weight loss or clinical signs of H3N2 virus infection, we observed pathogenic effects in the respiratory tracts of the infected animals. All of the H3N2 viruses tested replicated in the respiratory organs of the hamsters, and some of them were detected in the nasal washes of infected animals. Moreover, a 2009 pandemic (pdm09) virus and a seasonal H1N1 virus, as well as one of the two H3N2 viruses, but not a type B virus, were transmissible by the airborne route in these hamsters. Hamsters thus have the potential to be a small-animal model for the study of influenza virus infection, including studies of the pathogenicity of H3N2 viruses and other strains, as well as for use in H1N1 virus transmission studies. IMPORTANCE We found that Syrian hamsters are susceptible to human influenza viruses, including the recent H3N2 viruses, without adaptation. We also found that a pdm09 virus and a seasonal H1N1 virus, as well as one of the H3N2 viruses, but not a type B virus tested, are transmitted by the airborne route in these hamsters. Syrian hamsters thus have the potential to be used as a small-animal model for the study of human influenza viruses. Copyright © 2018 American Society for Microbiology.

Sensibility of the hamster (Cricetus auratus to the Treponema pertenue

Directory of Open Access Journals (Sweden)

F. Nery-Guimarães

1955-05-01

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

Orally administered nicotine induces urothelial hyperplasia in rats and mice

International Nuclear Information System (INIS)

Dodmane, Puttappa R.; Arnold, Lora L.; Pennington, Karen L.; Cohen, Samuel M.

2014-01-01

Highlights: • Rats and mice orally administered with nicotine tartrate for total of 4 weeks. • No treatment-related death or whole body toxicity observed in any of the groups. • Urothelium showed simple hyperplasia in treated rats and mice. • No significant change in BrdU labeling index or SEM classification of urothelium. - Abstract: Tobacco smoking is a major risk factor for multiple human cancers including urinary bladder carcinoma. Tobacco smoke is a complex mixture containing chemicals that are known carcinogens in humans and/or animals. Aromatic amines a major class of DNA-reactive carcinogens in cigarette smoke, are not present at sufficiently high levels to fully explain the incidence of bladder cancer in cigarette smokers. Other agents in tobacco smoke could be excreted in urine and enhance the carcinogenic process by increasing urothelial cell proliferation. Nicotine is one such major component, as it has been shown to induce cell proliferation in multiple cell types in vitro. However, in vivo evidence specifically for the urothelium is lacking. We previously showed that cigarette smoke induces increased urothelial cell proliferation in mice. In the present study, urothelial proliferative and cytotoxic effects were examined after nicotine treatment in mice and rats. Nicotine hydrogen tartrate was administered in drinking water to rats (52 ppm nicotine) and mice (514 ppm nicotine) for 4 weeks and urothelial changes were evaluated. Histopathologically, 7/10 rats and 4/10 mice showed simple hyperplasia following nicotine treatment compared to none in the controls. Rats had an increased mean BrdU labeling index compared to controls, although it was not statistically significantly elevated in either species. Scanning electron microscopic visualization of the urothelium did not reveal significant cytotoxicity. These findings suggest that oral nicotine administration induced urothelial hyperplasia (increased cell proliferation), possibly due to a

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

International Nuclear Information System (INIS)

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

2008-01-01

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

High local carcinogenic activity of 1,3-dimethyl-3-phenyl-1-nitrosourea and its inactivation by intravenous application in rats: comparison of in vivo findings with the in vitro direct and a combined in vivo/in vitro sister chromatid exchange assay in V79-E cells.

Science.gov (United States)

Thust, R; Martin, J; Mendel, J; Schreiber, D

1987-02-01

1,3-Dimethyl-3-phenyl-1-nitrosourea (DMPNU) is a very potent local carcinogen in rats and induces a 100% frequency of forestomach carcinomas when applied i.g. in two different dosages (10 applications of 0.3 or 0.03 mmol/kg body wt, respectively, at 14-day intervals), but it is inactive upon i.v. administration (10 applications of 0.03 mmol/kg body wt at 14-day intervals). By means of the direct sister chromatid exchange (SCE) assay in V79-E cells in the presence of rat blood, serum or plasma, respectively, as well as by a 'host-mediated' SCE assay (in which the agent was given i.v. to rats, and blood taken from the animal was checked for the recovery of genotoxic activity in cell cultures), we tried to elucidate the unexpected lack of carcinogenic activity of i.v. DMPNU. The direct SCE assay revealed a drastic reduction of DMPNU genotoxicity by rat blood, serum or plasma, respectively, which is abolished by the esterase inhibitor diisopropylfluorophosphate. In the 'host-mediated' SCE assay a genotoxic activity of DMPNU was only recoverable after a very high i.v. dose and when the blood added to the cell cultures had been taken from the rat heart within 1 min after DMPNU administration in vivo. 1-Methyl-1-nitrosourea (MNU) and 1-methyl-3-phenyl-1-nitrosourea (MPNU) were used as positive controls in these experiments and also gave a lower response than theoretically expected, but the relative loss of activity with the latter compounds was much lower than with DMPNU. It is assumed that an esterase in rat blood effectively decomposes this trisubstituted nitrosourea. Problems of the novel 'host-mediated' SCE assay are discussed.

Genetic susceptibility to mammary carcinogenesis in rats

Energy Technology Data Exchange (ETDEWEB)

Kamiya, Kenji; Nitta, Yumiko [Hiroshima Univ. (Japan). Research Inst. for Radiation Biology and Medicine

1999-06-01

The Copenhagen (COP) rat strain has previously been shown to be genetically resistant to chemical induction of breast cancer, while Wistar/Furth (WF) and Fischer 344 (F344) animals are relatively susceptible. We have compared the carcinogenic response of these three strains of rats to N-methyl-N-nitrosourea (MNU) with that to {sup 60}Co gamma rays. High incidences of mammary carcinomas were induced by MNU in the F344 and WF rats (100%), whereas the COP strain proved resistant (11.8%). In contrast, radiation-induced mammary carcinomas in COP rats developed in a similar incidence (37.0%) to those in the F344 (22.6%) and WF (26.9%) strains. The low incidence of papillary carcinomas in MNU-treated COP rats appeared to be directly related to the COP genetic resistance controlled by the Mcs genes. Ionizing radiation did, however, induce papillary carcinomas in all the three strains of rats. These carcinomas were more differentiated than MNU-induced cancers with regard to the two mammary differentiation markers, rat milk fat globule membrane (R-MFGM) and {alpha}-smooth muscle actin ({alpha}-SMA). Furthermore, ionizing radiation but not MNU induced mammary adenomas in all three strains, especially in COP rats. Such adenomas had differentiation marker profiles similar to these of carcinomas induced by {sup 60}Co gamma rays. When transplanted into syngenic hosts, growth of adenomas was 17 {beta}-estradiol (E{sub 2})-dependent and they progressed to carcinomas. Furthermore, one microcarcinoma was observed to develop from adenoma tissue in a radiation-exposed COP rat. The findings suggest that radiation and chemical carcinogens are likely to induce mammary cancers through different pathways or from different cell populations. The induction of relatively high incidences of mammary carcinomas and adenomas by radiation in COP rats may correlate with the genetically modulated and highly differentiated physiological status of their mammary glands. (author)

Hamsters' (Mesocricetus auratus) memory in a radial maze analog: the role of spatial versus olfactory cues.

Science.gov (United States)

Tonneau, François; Cabrera, Felipe; Corujo, Alejandro

2012-02-01

The golden hamster's (Mesocricetus auratus) performance on radial maze tasks has not been studied a lot. Here we report the results of a spatial memory task that involved eight food stations equidistant from the center of a circular platform. Each of six male hamsters depleted the food stations along successive choices. After each choice and a 5-s retention delay, the hamster was brought back to the center of the platform for the next choice opportunity. When only one baited station was left, the platform was rotated to evaluate whether olfactory traces guided hamsters' choices. Results showed that despite the retention delay hamsters performed above chance in searching for food. The choice distributions observed during the rotation probes were consistent with spatial memory and could be explained without assuming guidance by olfactory cues. The radial maze analog we devised could be useful in furthering the study of spatial memory in hamsters.

[Purification of arsenic-binding proteins in hamster plasma after oral administration of arsenite].

Science.gov (United States)

Wang, Wenwen; Zhang, Min; Li, Chunhui; Qin, Yingjie; Hua, Naranmandura

2013-01-01

To purify the arsenic-binding proteins (As-BP) in hamster plasma after a single oral administration of arsenite (iAs(III)). Arsenite was given to hamsters in a single dose. Three types of HPLC columns, size exclusion, gel filtration and anion exchange columns, combined with an inductively coupled argon plasma mass spectrometer (ICP MS) were used to purify the As-BP in hamster plasma. SDS-PAGE was used to confirm the arsenic-binding proteins at each purification step. The three-step purification process successfully separated As-BP from other proteins (ie, arsenic unbound proteins) in hamster plasma. The molecular mass of purified As-BP in plasma was approximately 40-50 kD on SDS-PAGE. The three-step purification method is a simple and fast approach to purify the As-BP in plasma samples.

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

International Nuclear Information System (INIS)

Ward, E.J.; Stewart, B.W.

1987-01-01

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 [ 3 H]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)

Chromium carcinogenicity: California strategies.

Science.gov (United States)

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

1989-10-01

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

Secondhand smoke induces hepatic apoptosis and fibrosis in hamster fetus.

Science.gov (United States)

Huang, Chien-Wei; Horng, Chi-Ting; Huang, Chih-Yang; Cho, Ta-Hsiung; Tsai, Yi-Chang; Chen, Li-Jeng; Hsu, Tsai-Ching; Tzang, Bor-Show

2016-09-01

Secondhand smoke (SHS) is an important health issue worldwide. Inhaling SHS during pregnancy could cause abnormalities in the internal tissues of newborns, which may then impair fetal development and even cause severe intrauterine damage and perinatal death. However, the understanding of cytopathic mechanisms of SHS by maternal passive smoking on fetus liver during pregnancy is still limited. This study analyzed the effects of high-dose SHS (SHSH) on fetus liver using a maternal passive smoking animal model. Experiments showed that hepatic matrix metalloproteinase-9 activity and terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling-positive cells were significantly increased in livers from fetuses of hamsters treated with SHSH. Similarly, expressions of both extrinsic and intrinsic apoptotic molecules were significantly higher in livers from fetuses of hamsters exposed to SHSH. Additionally, significantly increased inflammatory proteins, including transforming growth factor β, inducible nitric oxide synthase, and interleukin 1β, and fibrotic signaling molecules, including phosphorylated Smad2/3, SP1, and α-smooth muscle actin, were observed in the fetus livers from hamsters treated with SHSH. This study revealed that SHSH not only increased apoptosis through intrinsic and extrinsic pathways in the livers of fetuses from hamsters exposed to SHSH but also augmented hepatic fibrosis via Smad2/3 signaling. © The Author(s) 2015.

A new species of Giardia Künstler, 1882 (Sarcomastigophora: Hexamitidae) in hamsters.

Science.gov (United States)

Lyu, Zhangxia; Shao, Jingru; Xue, Min; Ye, Qingqing; Chen, Bing; Qin, Yan; Wen, Jianfan

2018-03-20

Giardia spp. are flagellated protozoan parasites that infect humans and many other vertebrates worldwide. Currently seven species of Giardia are considered valid. Here, we report a new species, Giardia cricetidarum n. sp. in hamsters. Trophozoites of G. cricetidarum n. sp. are pear-shaped with four pairs of flagella and measure on average 14 μm (range 12-18 μm) in length and 10 μm (range 8-12 μm) in width. The trophozoites of the new species are generally larger and stouter than those of most of the other Giardia spp. and exhibit the lowest length/width ratio (c.1.40) of all recognized Giardia species. Cysts of G. cricetidarum n. sp. are ovoid and measure on average 11 μm (range 9-12 μm) in length and 10 μm (range 8-10 μm) in width and are indistinguishable from the cysts of other Giardia species. Molecular phylogenetic analyses based on beta-giardin, small subunit rRNA, and elongation factor-1 alpha loci all demonstrated that G. cricetidarum n. sp. is genetically distinct from all currently accepted Giardia spp. Investigation of the host range indicated that the new species was only found in hamsters (including Phodopus sungorus, P. campbelli and Mesocricetus auratus), while all the other described mammal-parasitizing species (G. muris, G. microti and G. intestinalis) each infect multiple hosts. Cross-transmission studies further demonstrated the apparent host specificity of G. cricetidarum n. sp. as it only infected hamsters. Trophozoites were found in high numbers in hamster intestines (5 × 10 5 - 5 × 10 6 ) and was rarely detected co-infecting with other Giardia spp. in the common hamster, suggesting it has some advantages in parasitizing hamsters. This study has identified a new species of Giardia, which appears to be specific to hamsters, and together with the three other mammal-parasitizing Giardia species with different host ranges, may be able to be used as a model system for the study of evolutionary divergence of host parasitism strategies in

Human chromosome-specific changes in a human-hamster hybrid cell line (AL) assessed by fluorescent in situ hybridization (fish)

International Nuclear Information System (INIS)

Geard, Charles R.; Jenkins, Gloria

1995-01-01

(translocations) were readily scored and found to equate with the complementary asymmetrical exchanges (dicentrics). That is, nonlethal stable changes, which might be of concern in carcinogenic processes, complement lethal, unstable changes. Interstitial deletions that may contribute to the loss of antioncogenes as well as to lethality are also readily detected with enhanced levels detected at higher doses. The high level of induced terminal deletions and of incomplete dicentrics and translocations indicate a partial failure of interaction between lesions induced in human and hamster DNA, and suggest that such interspecies interactions lack the fidelity of intraspecies DNA lesion interactions. This suggests caution in the use of such model systems as indicators of human cell responsiveness

Effects of hyperthermia on the hamster immune system

International Nuclear Information System (INIS)

Gangavalli, R.; Cain, C.A.; Tompkins, W.A.F.

1984-01-01

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 (41 0 C; 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

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. © 2013 International Society of Zoological Sciences, Institute of Zoology/Chinese Academy of Sciences and Wiley Publishing Asia Pty Ltd.

Diurnal rhythms in gonadotropins and progesterone in lactating and photoperiod induced acyclic hamsters

International Nuclear Information System (INIS)

Bridges, R.S.; Goldman, B.D.

1975-01-01

Levels of LH, FSH, and progesterone in serum were measured in lactating hamsters and in hamsters in which acyclicity was induced with altered photoperiod. Lactating hamsters were found to have low titers of LH, FSH, and progesterone in serum at 0900 (lights on 0500--1900) on Days 4, 9, 14, and 19 of lactation and increased levels of these hormones at 1600. Levels of LH and FSH in serum at both 0900 and 1600 remained relatively constant throughout lactation. In contrast, levels of progesterone in serum obtained at both 0900 and 1600 sampling times increased as lactation progressed. Ovariectomy on Day 9 of lactation reduced serum levels of progesterone at both 0900 and 1600 and eliminated the afternoon surge in progesterone in animals bled 5 days after surgery. The levels and pattern of LH in serum remained unchanged after ovariectomy in lactating hamsters. However, serum FSH levels in the ovariectomized, lactating animals were elevated at both 0900 and 1600 when compared to levels present in intact, lactating hamsters bled at the same times. Females which were acyclic due to altered photoperiod displayed similar patterns of LH, FSH, and progesterone in serum. Levels of LH, FSH, and progesterone in serum were low at 1000 (lights on 0500--1500) and were increased 2 to 10 fold at 1500. Ovariectomy was followed by lower progesterone levels in serum at 1000 and 1500 and eliminated the afternoon rise of this hormone. Serum levels of LH were unaffected by ovariectomy. As in lactating hamsters, levels of FSH in serum were elevated 3--4 days following ovariectomy at both bleeding times, but the levels were higher at 1500. These results indicate that acyclicity induced by lactation or exposure to a short photoperiod is characterized by similar diurnal patterns of circulating hormones in the hamster

Environmental exposure to carcinogens in northwestern Cameroon ...

African Journals Online (AJOL)

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

Autoradiographic localization of tritiated dihydrotestosterone in the flank organ of the albino hamster

International Nuclear Information System (INIS)

Lucky, A.W.; Eisenfeld, A.J.; Visintin, I.

1985-01-01

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 ( [ 3 H]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. [ 3 H]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 [ 3 H]DHT in animals pretreated with excessive quantities of unlabeled DHT. Steroid metabolites of [ 3 H] 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

Impact of wheel running on chronic ethanol intake in aged Syrian hamsters.

Science.gov (United States)

Brager, Allison J; Hammer, Steven B

2012-10-10

Alcohol dependence in aging populations is seen as a public health concern, most recently because of the significant proportion of heavy drinking among "Baby Boomers." Basic animal research on the effects of aging on physiological and behavioral regulation of ethanol (EtOH) intake is sparse, since most of this research is limited to younger models of alcoholism. Here, EtOH drinking and preference were measured in groups of aged Syrian hamsters. Further, because voluntary exercise (wheel-running) is a rewarding substitute for EtOH in young adult hamsters, the potential for such reward substitution was also assessed. Aged (24 month-old) male hamsters were subjected to a three-stage regimen of free-choice EtOH (20% v/v) or water and unlocked or locked running wheels to investigate the modulatory effects of voluntary wheel running on EtOH intake and preference. Levels of fluid intake and activity were recorded daily across 60 days of experimentation. Prior to wheel running, levels of EtOH intake were significantly less than levels of water intake, resulting in a low preference for EtOH (30%). Hamsters with access to an unlocked running wheel had decreased EtOH intake and preference compared with hamsters with access to a locked running wheel. These group differences in EtOH intake and preference were sustained for up to 10 days after running wheels were re-locked. These results extend upon those of our previous work in young adult hamsters, indicating that aging dampens EtOH intake and preference. Voluntary wheel running further limited EtOH intake, suggesting that exercise could offer a practical approach for managing late-life alcoholism. Copyright © 2012 Elsevier Inc. All rights reserved.

Respiratory carcinogenicity assessment of soluble nickel compounds.

Science.gov (United States)

Oller, Adriana R

2002-10-01

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

Immunologic methods for monitoring carcinogen exposure

Science.gov (United States)

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

1993-03-01

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

Functional evidence for alternative ANG II-forming pathways in hamster cardiovascular system

NARCIS (Netherlands)

Nishimura, H; Buikema, H; Baltatu, O; Ganten, D; Urata, H

1998-01-01

Like human chymase, hamster chymase is an ANG II-forming enzyme, but pathophysiological roles of chymase are still unknown. We determined the functional conversion of ANG I and [Pro(11), D-Ala(12)]ANG I, a chymase-selective substrate, to ANG II in the hamster cardiovascular system. ANG I and

How many food additives are rodent carcinogens?

Science.gov (United States)

Johnson, F M

2002-01-01

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

Vasopressin differentially modulates aggression and anxiety in adolescent hamsters administered anabolic steroids.

Science.gov (United States)

Morrison, Thomas R; Ricci, Lesley A; Melloni, Richard H

2016-11-01

Adolescent Syrian hamsters (Mesocricetus auratus) treated with anabolic/androgenic steroids display increased offensive aggression and decreased anxiety correlated with an increase in vasopressin afferent development, synthesis, and neural signaling within the anterior hypothalamus. Upon withdrawal from anabolic/androgenic steroids, this neurobehavioral relationship shifts as hamsters display decreased offensive aggression and increased anxiety correlated with a decrease in anterior hypothalamic vasopressin. This study investigated the hypothesis that alterations in anterior hypothalamic vasopressin neural signaling modulate behavioral shifting between adolescent anabolic/androgenic steroid-induced offensive aggression and anxiety. To test this, adolescent male hamsters were administered anabolic/androgenic steroids and tested for offensive aggression or anxiety following direct pharmacological manipulation of vasopressin V1A receptor signaling within the anterior hypothalamus. Blockade of anterior hypothalamic vasopressin V1A receptor signaling suppressed offensive aggression and enhanced general and social anxiety in hamsters administered anabolic/androgenic steroids during adolescence, effectively reversing the pattern of behavioral response pattern normally observed during the adolescent exposure period. Conversely, activation of anterior hypothalamic vasopressin V1A receptor signaling enhanced offensive aggression in hamsters exposed to anabolic/androgenic steroids during adolescence. Together, these findings suggest that the state of vasopressin neural development and signaling in the anterior hypothalamus plays an important role in behavioral shifting between aggression and anxiety following adolescent exposure to anabolic/androgenic steroids. Copyright © 2016 Elsevier Inc. All rights reserved.

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

International Nuclear Information System (INIS)

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

2010-01-01

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

Modeling the dual pacemaker system of the tau mutant hamster.

Science.gov (United States)

Oda, G A; Menaker, M; Friesen, W O

2000-06-01

Circadian pacemakers in many animals are compound. In rodents, a two-oscillator model of the pacemaker composed of an evening (E) and a morning (M) oscillator has been proposed based on the phenomenon of "splitting" and bimodal activity peaks. The authors describe computer simulations of the pacemaker in tau mutant hamsters viewed as a system of mutually coupled E and M oscillators. These mutant animals exhibit normal type 1 PRCs when released into DD but make a transition to a type 0 PRC when held for many weeks in DD. The two-oscillator model describes particularly well some recent behavioral experiments on these hamsters. The authors sought to determine the relationships between oscillator amplitude, period, PRC, and activity duration through computer simulations. Two complementary approaches proved useful for analyzing weakly coupled oscillator systems. The authors adopted a "distinct oscillators" view when considering the component E and M oscillators and a "system" view when considering the system as a whole. For strongly coupled systems, only the system view is appropriate. The simulations lead the authors to two primary conjectures: (1) the total amplitude of the pacemaker system in tau mutant hamsters is less than in the wild-type animals, and (2) the coupling between the unit E and M oscillators is weakened during continuous exposure of hamsters to DD. As coupling strength decreases, activity duration (alpha) increases due to a greater phase difference between E and M. At the same time, the total amplitude of the system decreases, causing an increase in observable PRC amplitudes. Reduced coupling also increases the relative autonomy of the unit oscillators. The relatively autonomous phase shifts of E and M oscillators can account for both immediate compression and expansion of activity bands in tau mutant and wild-type hamsters subjected to light pulses.

Identifying occupational carcinogens: an update from the IARC Monographs.

Science.gov (United States)

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

2018-05-16

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

Molecular cloning and sequence analysis of hamster CENP-A cDNA

Directory of Open Access Journals (Sweden)

Valdivia Manuel M

2002-05-01

Full Text Available Abstract Background The centromere is a specialized locus that mediates chromosome movement during mitosis and meiosis. This chromosomal domain comprises a uniquely packaged form of heterochromatin that acts as a nucleus for the assembly of the kinetochore a trilaminar proteinaceous structure on the surface of each chromatid at the primary constriction. Kinetochores mediate interactions with the spindle fibers of the mitotic apparatus. Centromere protein A (CENP-A is a histone H3-like protein specifically located to the inner plate of kinetochore at active centromeres. CENP-A works as a component of specialized nucleosomes at centromeres bound to arrays of repeat satellite DNA. Results We have cloned the hamster homologue of human and mouse CENP-A. The cDNA isolated was found to contain an open reading frame encoding a polypeptide consisting of 129 amino acid residues with a C-terminal histone fold domain highly homologous to those of CENP-A and H3 sequences previously released. However, significant sequence divergence was found at the N-terminal region of hamster CENP-A that is five and eleven residues shorter than those of mouse and human respectively. Further, a human serine 7 residue, a target site for Aurora B kinase phosphorylation involved in the mechanism of cytokinesis, was not found in the hamster protein. A human autoepitope at the N-terminal region of CENP-A described in autoinmune diseases is not conserved in the hamster protein. Conclusions We have cloned the hamster cDNA for the centromeric protein CENP-A. Significant differences on protein sequence were found at the N-terminal tail of hamster CENP-A in comparison with that of human and mouse. Our results show a high degree of evolutionary divergence of kinetochore CENP-A proteins in mammals. This is related to the high diverse nucleotide repeat sequences found at the centromere DNA among species and support a current centromere model for kinetochore function and structural

Toxicology and carcinogenesis studies of nitrofurantoin (CAS No. 67-20-9) in F344/n rats and B6C3F1 mice (feed studies). Technical report

Energy Technology Data Exchange (ETDEWEB)

French, J.E.

1989-09-01

Two-year toxicology and carcinogenesis studies were conducted by administering diets containing 0, 600, or 1,300 ppm nitrofurantoin to groups of 50 female rats for 103 weeks. Groups of 50 male rats and 50 mice of each sex were fed diets containing 0, 1,300 or 2,500 ppm for 103 weeks. Under the conditions of these 2-year feed studies, there was some evidence of carcinogenic activity of nitrofurantoin for male F344/N rats as shown by increased incidences of uncommon kidney tubular cell neoplasms. Uncommon osteosarcomas of the bone and neoplasms of the subcutaneous tissue were observed in dosed male rats. Incidences of interstitial cell adenomas of the testis and neoplasms of the preputial gland were decreased in the 2,500-ppm group of male rats. There was no evidence of carcinogenic activity of nitrofurantoin for female F344/N rats fed diets containing 600 ppm or 1,300 ppm for 2 years. Female rats may have been able to tolerate higher doses. There was no evidence of carcinogenic activity of nitrofurantoin for male B6C3F(1) mice fed diets containing 1,300 ppm or 2,500 ppm for 2 years. There was clear evidence of carcinogenic activity of nitrofurantoin for female B6C3F(1) mice as shown by increased incidences of tubular adenomas, benign mixed tumors, and granulosa cell tumors of the ovary.

Track segment studies with Chinese hamster cells

International Nuclear Information System (INIS)

Bird, R.P.

1984-01-01

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

Constitutive overexpression of a growth-regulated gene in transformed Chinese hamster and human cells

International Nuclear Information System (INIS)

Anisowicz, A.; Bardwell, L.; Sager, R.

1987-01-01

Comparison by subtractive hybridization of mRNAs revealed a moderately abundant message in highly tumorigenic CHEF/16 cells present at very low levels in closely related nontumorigenic CHEF/18 cells. After cloning and sequencing the corresponding cDNA, computer comparison showed closest homology with the human connective tissue-activating peptide III (CTAP III). The human tumor cell cDNA hybridizing with the Chinese hamster clone was isolated, sequenced, and found to have closer similarity to the Chinese hamster gene than to CTAP III. Thus, the cloned cDNAs from Chinese hamster and human cells represent a different gene, named gro. Studies of its transcriptional regulation have shown that expression is tightly regulated by growth status in normal Chinese hamster and human cells and relaxed in the tumorigenic cells so far examined

In vivo genotoxicity of furan in F344 rats at cancer bioassay doses

International Nuclear Information System (INIS)

Ding, Wei; Petibone, Dayton M.; Latendresse, John R.; Pearce, Mason G.; Muskhelishvili, Levan; White, Gene A.; Chang, Ching-Wei; Mittelstaedt, Roberta A.; Shaddock, Joseph G.; McDaniel, Lea P.; Doerge, Daniel R.; Morris, Suzanne M.; Bishop, Michelle E.; Manjanatha, Mugimane G.; Aidoo, Anane; Heflich, Robert H.

2012-01-01

Furan, a potent rodent liver carcinogen, is found in many cooked food items and thus represents a human cancer risk. Mechanisms for furan carcinogenicity were investigated in male F344 rats using the in vivo Comet and micronucleus assays, combined with analysis of histopathological and gene expression changes. In addition, formamidopyrimidine DNA glycosylase (Fpg) and endonuclease III (EndoIII)-sensitive DNA damage was monitored as a measure of oxidative DNA damage. Rats were treated by gavage on four consecutive days with 2, 4, and 8 mg/kg bw furan, doses that were tumorigenic in 2-year cancer bioassays, and with two higher doses, 12 and 16 mg/kg. Rats were killed 3 h after the last dose, a time established as producing maximum levels of DNA damage in livers of furan-treated rats. Liver Comet assays indicated that both DNA strand breaks and oxidized purines and pyrimidines increased in a near-linear dose-responsive fashion, with statistically significant increases detected at cancer bioassay doses. No DNA damage was detected in bone marrow, a non-target tissue for cancer, and peripheral blood micronucleus assays were negative. Histopathological evaluation of liver from furan-exposed animals produced evidence of inflammation, single-cell necrosis, apoptosis, and cell proliferation. In addition, genes related to apoptosis, cell-cycle checkpoints, and DNA-repair were expressed at a slightly lower level in the furan-treated livers. Although a mixed mode of action involving direct DNA binding cannot be ruled out, the data suggest that furan induces cancer in rat livers mainly through a secondary genotoxic mechanism involving oxidative stress, accompanied by inflammation, cell proliferation, and toxicity. -- Highlights: ► Furan is a potent rodent liver carcinogen and represents a human cancer risk. ► Furan induces DNA damage in rat liver at cancer bioassay doses. ► Furan induces oxidative stress, inflammation and cell proliferation in rat liver. ► Expression of

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.

Delay of behavioral estrus in hamsters and phenobarbital.

Science.gov (United States)

Alleva, J J

1989-01-01

The onset of behavioral estrus was used as a phase marker of the hamster timing system in SLD 16:8 (dark 20:00-04:00). TZ was injected between 11:00 of cycle day 3 and noon of cycle day 4 when onset of estrus was determined. At no time did injection of TZ cause a phase advance in SLD 16:8. Small delays of estrus resulted from 11:00-16:00 injections but marked delays began with the 17:00 injection. Phenobarbital was injected between noon and 19:30 on cycle day 3. Injections between noon and 16:00 had no effect but all later injections beginning at 17:00 delayed estrus, the 17:30 injection causing the greatest delay. Diazepam also markedly delayed estrus when tested at 17:30. These results with three drugs support results with light pulses that 18:00 in SLD 16:8 marks the same phase of the 24-h hamster timing system as the onset of wheel running does in DD, LL, and WLD. These findings with three GABA potentiators extend to SLD previous evidence based on the onset of wheel running in DD, LL and WLD that GABA may be involved in hamster timekeeping and its responses to light and drugs.

The neem limonoids azadirachtin and nimbolide inhibit hamster cheek pouch carcinogenesis by modulating xenobiotic-metabolizing enzymes, DNA damage, antioxidants, invasion and angiogenesis.

Science.gov (United States)

Priyadarsini, Ramamurthi Vidya; Manikandan, Palrasu; Kumar, Gurram Harish; Nagini, Siddavaram

2009-05-01

The neem tree has attracted considerable research attention as a rich source of limonoids that have potent antioxidant and anti-cancer properties. The present study was designed to evaluate the chemopreventive potential of the neem limonoids azadirachtin and nimbolide based on in vitro antioxidant assays and in vivo inhibitory effects on 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis. Both azadirachtin and nimbolide exhibited concentration-dependent anti-radical scavenging activity and reductive potential in the order: nimbolide > azadirachtin > ascorbate. Administration of both azadirachtin and nimbolide inhibited the development of DMBA-induced HBP carcinomas by influencing multiple mechanisms including prevention of procarcinogen activation and oxidative DNA damage, upregulation of antioxidant and carcinogen detoxification enzymes and inhibition of tumour invasion and angiogenesis. On a comparative basis, nimbolide was found to be a more potent antioxidant and chemopreventive agent and offers promise as a candidate agent in multitargeted prevention and treatment of cancer.

Differential effect of lithium on the circadian oscillator in young and old hamsters

International Nuclear Information System (INIS)

Iwahana, Eiko; Hamada, Toshiyuki; Uchida, Ayumi; Shibata, Shigenobu

2007-01-01

Lithium is one of the most commonly used drugs in the prophylaxis and treatment of bipolar disorder. It is also known to lengthen circadian period in several organisms. Previously, we reported that there was the association between lengthening circadian period by lithium and GSK-3 protein and its enzyme activity in the mouse suprachiasmatic nucleus (SCN). In this study, we show that lithium affects the circadian oscillator in young and old hamster SCN, in an age-dependent manner. We found that basal levels of phosphorylated GSK-3 (pGSK-3) protein expression in old hamsters are much lower than that in young hamsters. Furthermore, in the old hamsters, lithium did not affect the period of the locomotor activity rhythm or pGSK-3 expression, while changing period and pGSK-3 in the younger animals. These results indicate that the content of pGSK-3 in the SCN has an important role in age-dependent effects of lithium on the circadian oscillator

After infection with Leishmania infantum, Golden Hamsters (Mesocricetus auratus) become more attractive to female sand flies (Lutzomyia longipalpis).

Science.gov (United States)

Nevatte, T M; Ward, R D; Sedda, L; Hamilton, J G C

2017-07-21

In Brazil, human and canine visceral leishmaniasis is caused by infection with Leishmania infantum, a Protist parasite transmitted by blood-feeding female Lutzomyia longipalpis sand flies. The objective of this study was to determine if the odour of hamsters, infected with Le. infantum, was more attractive than the odour of the same hamsters, before they were infected. The attractiveness of odour collected from individual hamsters (n = 13), before they were infected, was compared in a longitudinal study, with the attractiveness of the odour of the same hamster in a Y-tube olfactometer bioassay, at a late stage of infection. The odour of six of the golden hamsters was significantly more attractive to 50% of the female sand flies at the end of infection compared to before infection and the odour of four of the golden hamsters was significantly more attractive to 75% of the female sand flies at the end of infection. These results strongly indicate that hamsters infected with Le. infantum become significantly more attractive to a greater proportion of female sand flies as the infection progresses.

Environmental carcinogenic agents and cancer prevention. Risk assessment and management

International Nuclear Information System (INIS)

Tsugane, Shoichiro

2013-01-01

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

FELASA recommendations for the health monitoring of mouse, rat, hamster, guinea pig and rabbit colonies in breeding and experimental units.

Science.gov (United States)

Mähler Convenor, M; Berard, M; Feinstein, R; Gallagher, A; Illgen-Wilcke, B; Pritchett-Corning, K; Raspa, M

2014-07-01

The microbiological quality of experimental animals can critically influence animal welfare and the validity and reproducibility of research data. It is therefore important for breeding and experimental facilities to establish a laboratory animal health monitoring (HM) programme as an integrated part of any quality assurance system. FELASA has published recommendations for the HM of rodent and rabbit colonies in breeding and experimental units (Nicklas et al. Laboratory Animals, 2002), with the intention of harmonizing HM programmes. As stated in the preamble, these recommendations need to be adapted periodically to meet current developments in laboratory animal medicine. Accordingly, previous recommendations have been revised and shall be replaced by the present recommendations. These recommendations are aimed at all breeders and users of laboratory mice, rats, Syrian hamsters, guinea pigs and rabbits as well as diagnostic laboratories. They describe essential aspects of HM, such as the choice of agents, selection of animals and tissues for testing, frequency of sampling, commonly used test methods, interpretation of results and HM reporting. Compared with previous recommendations, more emphasis is put on the role of a person with sufficient understanding of the principles of HM, opportunistic agents, the use of sentinel animals (particularly under conditions of cage-level containment) and the interpretation and reporting of HM results. Relevant agents, testing frequencies and literature references are updated. Supplementary information on specific agents and the number of animals to be monitored and an example of a HM programme description is provided in the appendices. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Effect of deuterium on the circadian period and metabolism in wild-type and tau mutant Syrian hamsters

NARCIS (Netherlands)

Oklejewicz, M; Hut, RA; Daan, S

2000-01-01

Homozygous tau mutant Syrian hamsters (tau-/-) have a free-running circadian period (tau) around 20 h and a proportionally higher metabolic rate compared with wild-type hamsters (tau+/+) with a period of circa 24 h. In this study, we applied deuterium oxide (D2O) to hamsters to test whether

Environmental exposure to carcinogens in northwestern Cameroon

African Journals Online (AJOL)

EB

2013-09-03

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

Experimental treatment with sodium stibogluconate of hamsters infected with Leishmania (Leishmania) chagasi and Leishmania (Leishmania) amazonensis Tratamento experimental com stibogluconato de sódio em hamsters infectados com Leishmania (Leishmania) chagasi e Leishmania (Leishmania) amazonensis

OpenAIRE

Elizabeth M. de Figueiredo; Jaime Costa e Silva; Reginaldo P. Brazil

1999-01-01

The present paper reports the experimental treatment of hamsters infected with Leishmania chagasi and Leishmania amazonensis with sodium stibogluconate (20mg/kg/day x 20 days). Only with L. chagasi did the treatment result in the complete elimination of parasites from the spleen. However, no parasitological cure was achieved in hamsters infected with L. amazonensis.O presente trabalho é um relato do tratamento experimental de hamsters infectado com Leishmania chagasi e Leishmania amazonensis ...

EPA's evaluation of the carcinogenic potential of glyphosate

Science.gov (United States)

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

Effect of various chemicals on the metabolism of benzo(a)pyrene by cultured rat colon

DEFF Research Database (Denmark)

Autrup, Herman; Harris, Curtis C.; Fugaro, Steven

1977-01-01

The effect of various co- and anti-carcinogens of colon carcinogenesis on the metabolism of benzo(a)pyrene (BP) in cultured rat colon is reported. Rat colon enzymatically converted BP into metabolites which bind to cellular macromolecules i.e., DNA and protein. Activity of aryl hydrocarbon...

The effects of environmental chemical carcinogens on the microRNA machinery.

Science.gov (United States)

Izzotti, A; Pulliero, A

2014-07-01

The first evidence that microRNA expression is early altered by exposure to environmental chemical carcinogens in still healthy organisms was obtained for cigarette smoke. To date, the cumulative experimental data indicate that similar effects are caused by a variety of environmental carcinogens, including polycyclic aromatic hydrocarbons, nitropyrenes, endocrine disruptors, airborne mixtures, carcinogens in food and water, and carcinogenic drugs. Accordingly, the alteration of miRNA expression is a general mechanism that plays an important pathogenic role in linking exposure to environmental toxic agents with their pathological consequences, mainly including cancer development. This review summarizes the existing experimental evidence concerning the effects of chemical carcinogens on the microRNA machinery. For each carcinogen, the specific microRNA alteration signature, as detected in experimental studies, is reported. These data are useful for applying microRNA alterations as early biomarkers of biological effects in healthy organisms exposed to environmental carcinogens. However, microRNA alteration results in carcinogenesis only if accompanied by other molecular damages. As an example, microRNAs altered by chemical carcinogens often inhibits the expression of mutated oncogenes. The long-term exposure to chemical carcinogens causes irreversible suppression of microRNA expression thus allowing the transduction into proteins of mutated oncogenes. This review also analyzes the existing knowledge regarding the mechanisms by which environmental carcinogens alter microRNA expression. The underlying molecular mechanism involves p53-microRNA interconnection, microRNA adduct formation, and alterations of Dicer function. On the whole, reported findings provide evidence that microRNA analysis is a molecular toxicology tool that can elucidate the pathogenic mechanisms activated by environmental carcinogens. Copyright © 2014 Elsevier GmbH. All rights reserved.

Effect of aflatoxin-B1 doses simulating natural food contamination reproductive steroid hormones in rats

International Nuclear Information System (INIS)

Gamal, M.H.; EL-Banna, I.M.

2002-01-01

Aflatoxin B1 (AFB1) is the most toxic metabolite synthesized by aspergillus flavus. The mycotoxins was found to be endemic contaminant in underdeveloped countries and in egypt was documented as a pollutant of a wide variety of products for human and animal nutrition. Carcinogenic and mutagenic effects of AFB1 has been investigated extensively, while very scare information is available about other possible endocrine effects of the toxin which might precedes carcinogenic effects. This study was performed to investigate the effects of in vivo administration of AFB1 via intraperitoneal injection (I.P) in adult male rats to show its effects on rat reproductive function and to illucidate the effects of acute, chronic and sub toxic (endimomemitic) AFB1 doses on male rat steroid function. Intraperitoneal injection (I.P) of AFB 1 doses in adult male rats revealed that AFB1 caused significant decrease in serum testosterone and cortisol (early), while a significant increase was observed in progesterone (P 4 ) and Estrodial (E 2 ) (late)

The accumulation of 134Cs in heart and skeletal muscle of healthy and dystrophic hamsters

International Nuclear Information System (INIS)

Szentkuti, L.; Breitrueck, H.; Giese, W.

1976-01-01

he accumulation of cesium-134 in heart and skeletal muscle of healthy and dystrophic hamsters was compared. It was lower in dystrophic hamsters than in normal ones after only a single dose of cesium-134. The 134 Cs-concentrations of heart and 'red' skeletal muscle were different between normal and dystrophic hamsters. When the isotope had equilibrated in the animals differences in 134 Cs-accumulation in muscle tissue between normal and dystrophic hamsters were even more obvious. The faster elimination of cesium-134 from the body as affected by muscular dystrophy was due to a reduction of 134 Cs-accumulation in muscle tissue. The reduced ability of damaged muscles to accumulate Cs-ions offers the possibility to use Cs-isotopes in diagnosis of skeletal muscle dystrophy. (author)

Effects of diazepam on Mycobacterium bovis-induced infection in hamsters

Directory of Open Access Journals (Sweden)

Righi D.A.

1999-01-01

Full Text Available The in utero exposure of hamsters to low doses of diazepam results in impaired host defense against Mycobacterium bovis during adulthood. Delayed developmental immunotoxicity, however, represents a specific situation that might not be general. The present experiment was undertaken to investigate the effects of diazepam on hamster resistance to M. bovis using adult animals. The effects of diazepam treatment on serum cortisol levels were also studied. Adult hamsters (N = 10 for each group were treated with diazepam (E1 = 1.0, E2 = 2.0 or E3 = 3.0 mg kg-1 day-1 subcutaneously or with control solution (C for 30 days. Seven days after the beginning of the treatment, the animals received identical inoculum concentrations of M. bovis. Hamsters treated with the higher (2.0 and 3.0 mg kg-1 day-1 doses of diazepam exhibited: 1 increased granuloma areas in the liver (C = 1.81 ± 1.39, E2 = 10.29 ± 4.64 and E3 = 15.80 ± 4.82 and lung (C = 0.54 ± 0.55, E2 = 6.28 ± 3.85 and E3 = 6.31 ± 3.56 and 2 increased scores of M. bovis colony-forming units isolated from liver (C = 2.0, E2 = 3.0 and E3 = 3.5, lung (C = 1.0, E2 = 3.0 and E3 = 3.5 and spleen (C = 1.0, E2 = 2.5 and E3 = 4.0. These effects were dose dependent, and were not detected or were less severe in animals treated with the lowest (1.0 mg/kg dose of diazepam as well as in those of the control group. Furthermore, diazepam treatment (3.0 mg kg-1 day-1 for 30 days increased (E3 = 71.32 ± 2.99; N = 10 the serum levels of cortisol compared to control hamsters (C = 22.61 ± 2.75; N = 10. The present data, that demonstrate an impaired defense against M. bovis in adult hamsters treated with diazepam, were tentatively explained on the basis of a direct and/or indirect action of diazepam on the cytokine network. The effects may be related to stimulation of peripheral benzodiazepine receptor binding sites (PBR by macrophages and/or lymphocytes, or they may be mediated by PBR stimulation of the adrenals.

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

Energy Technology Data Exchange (ETDEWEB)

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

2004-05-20

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

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

International Nuclear Information System (INIS)

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

2004-01-01

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

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

International Nuclear Information System (INIS)

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

2017-01-01

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

X-ray induced dominant lethal mutations in mature and immature oocytes of guinea-pigs and golden hamsters

International Nuclear Information System (INIS)

Cox, B.D.; Lyon, M.F.

1975-01-01

The induction of dominant lethal mutations by doses of 100-400 rad X-rays in oocytes of the guinea-pig and golden hamster was studied using criteria of embryonic mortality. For both species higher yields were obtained from mature than from immature oocytes. Data on fertility indicated that in the golden hamster immature oocytes were more sensitive to killing by X-rays than mature oocytes but that the converse was true in the guinea-pig. The dose-response relationship for mutation to dominant lethals in pre-ovulatory oocytes of guinea-pigs and golden hamsters was linear, both when based on pre- and post-implantation loss only. The rate per unit dose was higher for the golden hamster, and the old golden hamsters were possibly slightly more sensitive than young ones

Identification of hamster inducible nitric oxide synthase (iNOS) promoter sequences that influence basal and inducible iNOS expression

Science.gov (United States)

Saldarriaga, Omar A.; Travi, Bruno L.; Choudhury, Goutam Ghosh; Melby, Peter C.

2012-01-01

IFN-γ/LPS-activated hamster (Mesocricetus auratus) macrophages express significantly less iNOS (NOS2) than activated mouse macrophages, which contributes to the hamster's susceptibility to intracellular pathogens. We determined a mechanism responsible for differences in iNOS promoter activity in hamsters and mice. The HtPP (1.2 kb) showed low basal and inducible promoter activity when compared with the mouse, and sequences within a 100-bp region (−233 to −133) of the mouse and hamster promoters influenced this activity. Moreover, within this 100 bp, we identified a smaller region (44 bp) in the mouse promoter, which recovered basal promoter activity when swapped into the hamster promoter. The mouse homolog (100-bp region) contained a cis-element for NF-IL-6 (−153/−142), which was absent in the hamster counterpart. EMSA and supershift assays revealed that the hamster sequence did not support the binding of NF-IL-6. Introduction of a functional NF-IL-6 binding sequence into the hamster promoter or its alteration in the mouse promoter revealed the critical importance of this transcription factor for full iNOS promoter activity. Furthermore, the binding of NF-IL-6 to the iNOS promoter (−153/−142) in vivo was increased in mouse cells but was reduced in hamster cells after IFN-γ/LPS stimulation. Differences in the activity of the iNOS promoters were evident in mouse and hamster cells, so they were not merely a result of species-specific differences in transcription factors. Thus, we have identified unique DNA sequences and a critical transcription factor, NF-IL-6, which contribute to the overall basal and inducible expression of hamster iNOS. PMID:22517919

Social housing and social isolation: Impact on stress indices and energy balance in male and female Syrian hamsters (Mesocricetus auratus).

Science.gov (United States)

Ross, Amy P; Norvelle, Alisa; Choi, Dennis C; Walton, James C; Albers, H Elliott; Huhman, Kim L

2017-08-01

Although Syrian hamsters are thought to be naturally solitary, recent evidence from our laboratory demonstrates that hamsters may actually prefer social contact. Hamsters increase their preference for a location associated with an agonistic encounter regardless of whether they have "won" or "lost". It has also been reported that social housing as well as exposure to intermittent social defeat or to a brief footshock stressor increase food intake and body mass in hamsters. By contrast, it has also been suggested that housing hamsters in social isolation causes anxiety-induced anorexia and reductions in body mass selectively in females. The purpose of this study was to determine the physiological consequences of housing hamsters in social isolation versus in social groups. Male and female hamsters were housed singly or in stable groups of 5 for 4weeks after which they were weighed and trunk blood was collected. In addition, fat pads and thymus and adrenal glands were extracted and weighed. Serum and fecal cortisol were measured using an enzyme-linked immunoassay. Housing condition had no effect on serum or fecal cortisol, but socially housed hamsters displayed modest thymus gland involution. Socially housed females weighed more than did any other group, and socially housed females and males had more fat than did socially isolated hamsters. No wounding or tissue damage occurred in grouped hamsters. Overall, these data suggest that Syrian hamsters tolerate both stable social housing and social isolation in the laboratory although social housing is associated with some alteration in stress-related and bioenergetic measures. Copyright © 2017 Elsevier Inc. All rights reserved.

Evidence of lung cancer risk from animal studies

International Nuclear Information System (INIS)

Cross, F.T.

1988-03-01

Human epidemiological data provide the most important basis for assessing risks of radon exposures. However, additional insight into the nature of exposure-response relationships is provided by animal experimentation and dosimetric determinations. Animal studies have now been conducted for more than 50 years to examine the levels of pollutants in underground mines that were responsible for the respiratory effects observed among miners. This work has emphasized respiratory cancer and the interaction of radon with other agents, such as ore dust, diesel-engine-exhaust fumes and cigarette smoke. The more recent data on radon-daughter inhalation exposures were provided by two American research centers, The University of Rochester (UR) and the Pacific Northwest Laboratory (PNL), and by the Compagnie Generale des Matieres Nucleaires (COGEMA) laboratory in France. Approximately 2000 mice, 100 rats and 80 dogs were employed in the completed UR studies, begun in the mid 1950s; 800 hamsters, 5000 rats and 100 dogs in the ongoing PNL studies, begun in the late 1960s; and 10,000 rats in the ongoing COGEMA studies, also begun in the late 1960s. More complete updated biological effects, data resulting from chronic radon-daughter inhalation exposures of mice, hamsters, rats and beagle dogs were examined. Emphasis on the carcinogenic effects of radon-decay product exposure, including the influences of radon-daughter exposure rate, unattached fraction and disequilibrium, and co-exposures to other pollutants. Plausible values for the radon (radon-daughter) lifetime lung-cancer risk coefficients are also provided. 13 refs., 1 fig., 1 tab

The multitude and diversity of environmental carcinogens

International Nuclear Information System (INIS)

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

2007-01-01

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

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

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Omema SALAH

2009-04-01

Full Text Available 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

Carcinogenic and mutagenic properties of chemicals in drinking water

Energy Technology Data Exchange (ETDEWEB)

Bull, R J

1985-12-01

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

Is ionizing radiation regulated more stringently than chemical carcinogens

International Nuclear Information System (INIS)

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

1989-01-01

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

Monosodium glutamate-induced arcuate nucleus damage affects both natural torpor and 2DG-induced torpor-like hypothermia in Siberian hamsters.

Science.gov (United States)

Pelz, Kimberly M; Routman, David; Driscoll, Joseph R; Kriegsfeld, Lance J; Dark, John

2008-01-01

Siberian hamsters (Phodopus sungorus) have the ability to express daily torpor and decrease their body temperature to approximately 15 degrees C, providing a significant savings in energy expenditure. Daily torpor in hamsters is cued by winterlike photoperiods and occurs coincident with the annual nadirs in body fat reserves and chronic leptin concentrations. To better understand the neural mechanisms underlying torpor, Siberian hamster pups were postnatally treated with saline or MSG to ablate arcuate nucleus neurons that likely possess leptin receptors. Body temperature was studied telemetrically in cold-acclimated (10 degrees C) male and female hamsters moved to a winterlike photoperiod (10:14-h light-dark cycle) (experiments 1 and 2) or that remained in a summerlike photoperiod (14:10-h light-dark cycle) (experiment 3). In experiment 1, even though other photoperiodic responses persisted, MSG-induced arcuate nucleus ablations prevented the photoperiod-dependent torpor observed in saline-treated Siberian hamsters. MSG-treated hamsters tended to possess greater fat reserves. To determine whether reductions in body fat would increase frequency of photoperiod-induced torpor after MSG treatment, hamsters underwent 2 wk of food restriction (70% of ad libitum) in experiment 2. Although food restriction did increase the frequency of torpor in both MSG- and saline-treated hamsters, it failed to normalize the proportion of MSG-treated hamsters undergoing photoperiod-dependent torpor. In experiment 3, postnatal MSG treatments reduced the proportion of hamsters entering 2DG-induced torpor-like hypothermia by approximately 50% compared with saline-treated hamsters (38 vs. 72%). In those MSG-treated hamsters that did become hypothermic, their minimum temperature during hypothermia was significantly greater than comparable saline-treated hamsters. We conclude that 1) arcuate nucleus mechanisms mediate photoperiod-induced torpor, 2) food-restriction-induced torpor may also be

Steroid metabolism in pregnant hamster. I

International Nuclear Information System (INIS)

Marchut, M.

1980-01-01

Quartered placentae from 12- and 15-day pregnant hamsters were incubated with 14 C labelled pregnenolone and progesterone and the products of their conversion were identified by chromatographic and isotope dilution methods. Pregnenolone was converted to progesterone, 7α-hydroxypregnenolone, 7α-hydroxyprogesterone, 3α-hydroxy-5β-pregnan-20-one, 3β-hydroxy-5α-pregnan-20-one, 3α-hydroxy-5α-pregnan-20-one, 5β-pregnane-3,20-dione and 5α-pregnane-3,20-dione. Except for 7α-hydroxypregnenolone, the same metabolites were identified in the incubates of the placental tissue with progesterone. Thus, the activity of Δ 5 -3β-hydroxysteroid dehydrogenase and Δsup(5→4) isomerase, 7α-hydrΔ 4 -5β- and Δ 4 -5α-reductase enzyme systems was shown in the hamster placenta. The formation of androgens from pregnenolone, progesterone and their 17-hydroxy-derivatives was not observed. There was also no evidence of the formation of estrogens from the above C-21 steroid precursors. (author)

Effects of aqueous cinnamon extract on chemically-induced carcinoma of hamster cheek pouch mucosa

Directory of Open Access Journals (Sweden)

Samah K. Ezzat

2017-12-01

Full Text Available This study aimed to investigate the effects of aqueous cinnamon extract (ACE on 7, 12-Dimethylbenz[a]anthracene (DMBA-induced oral carcinogenesis in hamster cheek pouch (HCP mucosa. Sixty male Syrian hamsters were randomly divided into six equal groups. The hamsters of groups I, II and III received no treatment, DMBA and ACE respectively, for 16 weeks. Groups IV and V were handled as group II and concomitantly treated with ACE for the same period and additionally group V received ACE for other 16 weeks after the stoppage of DMBA application. Group VI hamsters were handled as group III and additionally received DMBA for other 16 weeks after the stoppage of ACE supplementation. Hamsters of each group were euthanized according to the experimental schedule. The buccal pouches were and prepared for H&E stain, PAS reagent, CD3 and PDGF immunohistochemical reactivity. All groups showed dysplastic changes with varying degrees except groups I and III. Deep invasive carcinomas were recorded in 90% of the samples of group II, 60% of group IV, 50% of group V and 40% of group VI. From the previous results, it can be concluded that ACE has the potentiality preventing oral cancer initiation better than inhibiting oral cancer progression.

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

NARCIS (Netherlands)

Hadi, M; Dragovic, S.; van Swelm, R; Herpers, B; van de Water, B.; Russel, RG; Commandeur, J.N.M.; Groothuis, G.M.

2013-01-01

N-acetyl-meta-aminophenol (AMAP) is generally considered as a non-toxic regioisomer of the wellknown 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

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

International Nuclear Information System (INIS)

Amlacher, E.; Rudolph, C.

1978-01-01

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

An overview of PNL radon experiments with reference to epidemiological data

International Nuclear Information System (INIS)

Cross, F.T.; Palmer, R.F.; Busch, R.H.; Dagle, G.E.; Filipy, R.E.; Ragan, H.A.

1986-01-01

Biological effects observed in dogs and rodents after the inhalation of radon and radon daughters have included, primarily, respiratory carcinoma, pulmonary fibrosis, emphysema, and life-span shortening. Extrapulmonary lesions observed are not considered significant except for certain hematological effects. In this paper we present biological effects data resulting from chronic exposures of hamsters, rats, and beagle dogs. Emphasis is placed on the carcinogenic effects of radon and radon daughters, including the influences of radon-daughter exposure rate, unattachment fraction, and disequilibrium and of concomitant exposure to other pollutants. These data are correlated with results from human epidemiological studies. Plausible values for the radon (radon-daughter) lifetime lung-cancer risk coefficient are provided. 30 refs., 3 tabs

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

International Nuclear Information System (INIS)

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

1987-01-01

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

Transplantation of hamster lung lesions induced by 239PuO2 or benz(a)pyrene

International Nuclear Information System (INIS)

McDonald, K.E.; Sanders, C.L.

1980-01-01

None(0%) of 1000 recipients of lung lesions for 239 PuO 2 -exposed hamsters that were transplanted into other hamsters' cheek pouches, developed tumors, whereas 90% of transplants from benz(a)pyrene-induced lung lesions were malignant

Tamoxifen induces regression of estradiol-induced mammary cancer in ACI.COP-Ept2 rat model

OpenAIRE

Ruhlen, Rachel L.; Willbrand, Dana M.; Besch-Williford, Cynthia L.; Ma, Lixin; Shull, James D.; Sauter, Edward R.

2008-01-01

The ACI rat is a unique model of human breast cancer in that mammary cancers are induced by estrogen without carcinogens, irradiation, xenografts or transgenic manipulations. We sought to characterize mammary cancers in a congenic variant of the ACI rat, the ACI.COP-Ept2. All rats with estradiol implants developed mammary cancers in 5–7 months. Rats bearing estradiol-induced mammary cancers were treated with tamoxifen for three weeks. Tamoxifen reduced tumor mass, measured by magnetic resonan...

Effect of Antiviral Agents in Equine Abortion Virus-Infected Hamsters1

Science.gov (United States)

Lieberman, Melvin; Pascale, Andrea; Schafer, Thomas W.; Came, Paul E.

1972-01-01

Equine abortion virus, a member of the herpesvirus group, produces a lethal infection in hamsters. With this system, the protective effect of certain inhibitors of deoxyribonucleic acid viruses, inducers of interferon and exogenous interferon, was evaluated. Of the various agents studied, 9-β-d-arabinofuranosyladenine markedly suppressed mortality, and 5-iodo-2′-deoxyuridine, distamycin A, and N-ethylisatin β-thiosemicarbazone were inactive. Of the inducers tested, statolon, ultraviolet-irradiated Newcastle disease virus, and polyriboinosinic:polyribocytidylic acid (poly I:C) were protective, and endotoxin, polyacrylic acid, and polymethacrylic acid did not protect. Administration of exogenous interferon did not afford protection. Statolon and ultraviolet-irradiated Newcastle disease virus induced circulating interferon in hamsters, whereas poly I:C, endotoxin, and polyacrylic acid did not produce interferon. Because of the severity of the disease produced in hamsters by equine abortion virus, lack of protective activity by an agent in this system should not preclude possible efficacy against other members of the herpesvirus group. PMID:4376907

Influence of N-methyl-N-nitrosourea, testosterone, and N-(4-hydroxyphenyl)-all-trans-retinamide on prostate cancer induction in Wistar-Unilever rats.

Science.gov (United States)

McCormick, D L; Rao, K V; Dooley, L; Steele, V E; Lubet, R A; Kelloff, G J; Bosland, M C

1998-08-01

The influence of chemical carcinogen, hormonal stimulation, and chronic dietary administration of the synthetic retinoid, N-(4-hydroxyphenyl)-all-trans-retinamide (4-HPR), on the induction of prostate cancer in male Wistar-Unilever rats was determined. Three different tumor induction regimens were used: (a) a single i.v. dose of 50 mg of N-methyl-N-nitrosourea (MNU) per kg body weight, followed by chronic androgen stimulation via s.c. implantation of two silastic capsules containing 40 mg testosterone each; (b) a single i.v. dose of 50 mg of MNU per kg body weight (no testosterone treatment); and (c) chronic androgen stimulation with implanted testosterone capsules (no MNU treatment). In a fourth series of animals, the incidence of spontaneous prostate tumors was determined in groups of rats receiving neither carcinogen nor hormone stimulation. Within each series, parallel groups of animals were fed a control (vehicle-supplemented) diet or control diet supplemented with 4-HPR beginning 1 day after carcinogen administration; retinoid administration was continuous until termination of the study at 450 days. The incidence of accessory sex gland cancer in rats treated sequentially with MNU + testosterone was >60%, in comparison with cancer incidences of Unilever rats.

Ozone acts alone and synergistically with ionizing radiation to induce in vitro neoplastic transformation

Energy Technology Data Exchange (ETDEWEB)

Borek, C; Zaider, M; Ong, A; Mason, H; Witz, G

1986-09-01

Ozone, a major chemical oxidant in the atmosphere, is an environmental air pollutant whose ability to act as a direct carcinogen is unclear. Using in vitro transformation, a technique which permits the study of oncogenesis in the absence of host specific effects, it is reported for the first time that ozone (5 p.p.m. for 5 min) induces neoplastic transformation in vitro in both primary hamster embryo cells and mouse fibroblast cultures (C3H/10-1/2). Exposure of the hamster and mouse cells to ozone also results in enhanced levels of free radical-mediated lipid peroxidation products. The carcinogenic interaction between ozone and ionizing radiation is also reported. Exposure of the cells to 3 or 4 Gy of ..gamma..-rays, 2 h prior to O/sub 3/ treatment, results in markedly enhanced rates of transformation, statistically consistent with a synergistic interaction between the agents. The results demonstrate that O/sub 3/ acts as a direct carcinogen and co-carcinogen on susceptible cells, therefore having important consequences for public health.

Castration, dopamine and food choice: a cost/benefit test in male hamsters.

Science.gov (United States)

Chu, Lucy; Wood, Ruth I

2002-10-17

Testosterone is essential for copulation, and contributes to sexual motivation. In addition, castrated males are fatter and less active, suggesting that androgens may play a role in non-sexual behaviors, including food-related responses. To test this hypothesis, male hamsters were trained with a cost/benefit test, which compares operant responding for more-preferred food versus ad libitum consumption of lab chow. Males were tested before and after castration. The effect of the dopamine antagonist, haloperidol, on instrumental responses in intact and castrated males was also determined. Food-deprived hamsters responded vigorously for 45 mg Bio-Serv pellets in daily 30-min tests (665 presses, 6.0+/-0.9 g). When lab chow was available, males continued to respond for pellets (3.6+/-0.6 g) over chow ad libitum (1.2+/-0.3 g). Dopamine is central to this response because haloperidol (1.0 mg/kg i.p.) reversed food intake (pellets: 0.5+/-0.1 g; chow 2.0+/-0.5 g). Castration had no effect on operant responding for pellets alone (6.6+/-0.7 g). When chow was present, castrates consumed an even greater proportion of their total food intake as pellets [6.0+/-0.4 g pellets (92%), 1.6+/-0.5 g chow (8%), vs. 75 and 25%, respectively, for intact males]. This is contrary to our original hypothesis. In addition, castration did not change the effects of haloperidol on food intake: (0.4+/-0.1 g pellets; 1.6+/-0.5 g chow). These results support previous findings in rats that dopamine affects response allocation in a cost/benefit test. However, they do not support the hypothesis that testosterone modifies the allocation of food-related responses.

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.

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

Isolation of two chloroethylnitrosourea-sensitive Chinese hamster cell lines

International Nuclear Information System (INIS)

Hata, H.; Numata, M.; Tohda, H.; Yasui, A.; Oikawa, A.

1991-01-01

1-[(4-Amino-2-methylpyrimidin-5-yl)methyl]-3-(2-chloroethyl)-3- nitrosourea hydrochloride (ACNU), a cancer chemotherapeutic bifunctional alkylating agent, causes chloroethylation of DNA and subsequent DNA strand cross-linking through an ethylene bridge. We isolated and characterized two ACNU-sensitive mutants from mutagenized Chinese hamster ovary cells and found them to be new drug-sensitive recessive Chinese hamster mutants. Both mutants were sensitive to various monofunctional alkylating agents in a way similar to that of the parental cell lines CHO9. One mutant (UVS1) was cross-sensitive to UV and complemented the UV sensitivity of all Chinese hamster cell lines of 7 established complementation groups. Since UV-induced unscheduled DNA synthesis was very low, a new locus related to excision repair is thought to be defective in this cell line. Another ACNU-sensitive mutant, CNU1, was slightly more sensitive to UV than the parent cell line. CNU1 was cross-sensitive to 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea and slightly more sensitive to mitomycin C. No increased accumulation of ACNU and a low level of UV-induced unscheduled DNA synthesis in this cell as compared with the parental cell line suggest that there is abnormality in a repair response of this mutant cell to some types of DNA cross-links

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. Copyright © 2014 Elsevier Inc. All rights reserved.

Efficacy of a New Recrystallized Enrofloxacin Hydrochloride-Dihydrate against Leptospirosis in a Hamster Model.

Science.gov (United States)

Carrascosa, Alma; Gutierrez, Lilia; De la Peña, Alejandro; Candanosa, Irma E; Tapia, Graciela; Sumano, Hector

2017-11-01

A trial on Syrian hamsters ( Mesocricetus auratus ) infected with Leptospira interrogans serovar Canicola was established to compare treatment efficacies of daily intramuscular (i.m.) injections of either 10 mg/kg of 5% enrofloxacin (Baytril [BE]; Bayer Animal Health, Mexico) or the same dose of enrofloxacin hydrochloride-dihydrate (enro-C). Hamsters were experimentally infected via the oral submucosa with 400 microorganisms/animal, in a sequential time schedule aligned to the initial treatment day, and were treated in groups as follows: a group treated with 5% enrofloxacin daily for 7 days after 24 h of infection (group BE 24 ); a group treated as described for group BE 24 but with enro-C (enro-C 24 ); a group also treated with 5% enrofloxacin but starting at 72 h after infection (BE 74 ); a group treated as described for group BE 74 but with injection of enro-C (enro-C 74 ). An untreated-uninfected control group (group CG - ) and an infected-untreated control group (group CG + ) were assembled ( n = 18 in all groups). Weights and temperatures of the hamsters were monitored daily for 28 days. After hamsters were euthanatized or following death, necropsy, histopathology, macroscopic agglutination tests (MAT), bacterial culture, and PCR were performed. The mortality rates were 38.8% in group BE 24 and 100% in group BE 74 No mortality was observed in group enro-C 24 , and 11.1% mortality was recorded in group enro-C 74 The mortality rates in groups CG + and CG - were 100% and zero, respectively. Combined necropsy and histopathologic findings revealed signs of septicemia and organ damage in groups BE 24 , BE 72 , and CG + Groups enro-C 24 and CG - showed no lesions. Moderated lesions were registered in 3 hamsters in group enro-C 72 MAT results were positive in 83.3% of BE 24 hamsters (83.3%) and 100% of BE 72 and CG + hamsters; MAT results were positive in 16.7% in group Enro-C 24 and 38.9% in group enro-C 72 Only 4/18 were PCR positive in group enro-C 72 and only 1

Risk assessment of DNA-reactive carcinogens in food.

Science.gov (United States)

Jeffrey, A M; Williams, G M

2005-09-01

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

The effect of dietary vitamin A on NO2 exposure on the hamster lung

International Nuclear Information System (INIS)

Kim, J.C.

1978-01-01

The effect of dietary vitamin A and NO2 exposure on the hamster lung was evaluated by histopathology, electron microscopy, and thymidine uptake studies. Hamsters were maintained on deficient (0 micrograms), adequate (100 micrograms), and high (200 micrograms) dose levels of vitamin A while being exposed repeatedly to 10 ppm of NO2 for 5 hours once a week over an 8-week period. Hamsters of the deficient group exhibited clinical and morphologic changes characteristic of vitamin A deficiency. Animals maintained on adequate and high dose levels of vitamin A were not affected by vitamin A deficiency. Hypertrophy and hyperplasia of the epithelial cells of the terminal bronchiolar alveolar region of lungs of adequately and highly dosed animals were greater than those observed in the deficient animals, when NO2 exposure was given. However, the extent of the lesions observed in all three groups was less than that seen in normal hamsters given a single, 5-hour NO2 exposure. Ultrastructural changes observed in vitamin A-deficient hamsters exposed to NO2 were hypertrophy and hyperplasia of bronchiolar epithelial cells, diffuse loss of cilia, membrane damage, and mitochondrial damage manifested by calcium deposition. Tritiated thymidine uptake studies of lungs of animals exposed repeatedly revealed a rather erratic cell renewal pattern following NO2 exposure in comparison to the group of animals exposed singly

Adrenal hormones mediate melatonin-induced increases in aggression in male Siberian hamsters (Phodopus sungorus).

Science.gov (United States)

Demas, Gregory E; Polacek, Kelly M; Durazzo, Alfredo; Jasnow, Aaron M

2004-12-01

Among the suite of seasonal adaptations displayed by nontropical rodents, some species demonstrate increased territorial aggression in short compared with long day lengths despite basal levels of testosterone. The precise physiological mechanisms mediating seasonal changes in aggression, however, remain largely unknown. The goal of the present study was to examine the role of melatonin, as well as adrenal hormones, in the regulation of seasonal aggression in male Siberian hamsters (Phodopus sungorus). In Experiment 1, male Siberian hamsters received either daily (s.c.) injections of melatonin (15 microg/day) or saline 2 h before lights out for 10 consecutive days. In Experiment 2, hamsters received adrenal demedullations (ADMEDx), whereas in Experiment 3 animals received adrenalectomies (ADx); control animals in both experiments received sham surgeries. Animals in both experiments subsequently received daily injections of melatonin or vehicle as in Experiment 1. Animals in all experiments were tested using a resident-intruder model of aggression. In Experiment 1, exogenous melatonin treatment increased aggression compared with control hamsters. In Experiment 2, ADMEDx had no effect on melatonin-induced aggression. In Experiment 3, the melatonin-induced increase in aggression was significantly attenuated by ADx. Collectively, the results of the present study demonstrate that short day-like patterns of melatonin increase aggression in male Siberian hamsters and suggest that increased aggression is due, in part, to changes in adrenocortical steroids.

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.

Pulmonary collagen metabolism in irradiated hamsters and those treated with corticosteroids

International Nuclear Information System (INIS)

Pickrell, J.A.; Straus, F.C.; Halliwell, W.H.; Jones, R.K.

1976-01-01

Syrian hamsters were exposed to 90 Y in fused aluminosilicate particles to produce pulmonary fibrosis. Irradiated hamsters and contols were treated with Depomedrol, arresting the developing fibrosis. All hamsters receiving steroid showed a reduced incorporation of 14 C-proline into noncollagen protein during the 3-19 wk period after exposure. Collagen synthesis relative to noncollagen protein synthesis was decreased five-fold in these animals at early times after exposure and during high steroid dosage, but had returned to control levels after considerable time at lower steroid dosage. Collagen synthesis in irradiated animals not receiving steroids was elevated during the same time period and collagen synthesis in irradiated hamsters treated with steroid was intermediate between that in radiation animals and in control or steroid animals. Collagen breakdown was elevated to the same level as in irradiated animals, and collagen content was normal and well below that of irradiated animals. These and previous data indicate that steroid treatment delays development of pulmonary fibrosis in animals irradiated with fibrogenic doses of 90 Y in fused aluminosilicate particles. Experiments incubating BAPN or Depomedrol with L-929 or WI-38 fibroblasts in vitro were performed to note any effect of these agents upon fibroblast proliferation, cellular collagen processing or collagen synthesis. Steroids frequently reduced fibroblast proliferation and altered cellular collagen processings to reflect an increased proportion of collagen breakdown products. These changes reflect the importance of fibroblast proliferation in developing pulmonary fibrosis

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

on the gonadotrophic axis in the Syrian hamster. We show that acute central injection of RFRP-3 induces c-Fos expression in GnRH neurons and increases LH, FSH, and testosterone secretion. Moreover, chronic central administration of RFRP-3 restores testicular activity and Kiss1 levels in the arcuate nucleus of hamsters...

Serotonergic modulation of hippocampal pyramidal cells in euthermic, cold-acclimated, and hibernating hamsters

Science.gov (United States)

Horrigan, D. J.; Horwitz, B. A.; Horowitz, J. M.

1997-01-01

Serotonergic fibers project to the hippocampus, a brain area previously shown to have distinctive changes in electroencephalograph (EEG) activity during entrance into and arousal from hibernation. The EEG activity is generated by pyramidal cells in both hibernating and nonhibernating species. Using the brain slice preparation, we characterized serotonergic responses of these CA1 pyramidal cells in euthermic, cold-acclimated, and hibernating Syrian hamsters. Stimulation of Shaffer-collateral/commissural fibers evoked fast synaptic excitation of CA1 pyramidal cells, a response monitored by recording population spikes (the synchronous generation of action potentials). Neuromodulation by serotonin (5-HT) decreased population spike amplitude by 54% in cold-acclimated animals, 80% in hibernating hamsters, and 63% in euthermic animals. The depression was significantly greater in slices from hibernators than from cold-acclimated animals. In slices from euthermic animals, changes in extracellular K+ concentration between 2.5 and 5.0 mM did not significantly alter serotonergic responses. The 5-HT1A agonist 8-hydroxy-2(di-n-propylamino)tetralin mimicked serotonergic inhibition in euthermic hamsters. Results show that 5-HT is a robust neuromodulator not only in euthermic animals but also in cold-acclimated and hibernating hamsters.

Multi-walled carbon nanotubes (NM401) induce ROS-mediated HPRT mutations in Chinese hamster lung fibroblasts

Energy Technology Data Exchange (ETDEWEB)

Rubio, Laura [Grup de Mutagènesi, Departament de Genètica i de Microbiologia, Facultat de Biociències, Universitat Autònoma de Barcelona, Bellaterra (Spain); El Yamani, Naouale [Health Effects Laboratory-MILK, NILU-Norwegian Institute for Air Research, Kjeller (Norway); Kazimirova, Alena [Department of Biology, Slovak Medical University, Bratislava (Slovakia); Dusinska, Maria, E-mail: maria.dusinska@nilu.no [Health Effects Laboratory-MILK, NILU-Norwegian Institute for Air Research, Kjeller (Norway); Marcos, Ricard, E-mail: ricard.marcos@uab.es [Grup de Mutagènesi, Departament de Genètica i de Microbiologia, Facultat de Biociències, Universitat Autònoma de Barcelona, Bellaterra (Spain); CIBER Epidemiología y Salud Pública, Instituto de Salud Carlos III, Madrid (Spain)

2016-04-15

Although there is an important set of data showing potential genotoxic effects of nanomaterials (NMs) at the DNA (comet assay) and chromosome (micronucleus test) levels, few studies have been conducted to analyze their potential mutagenic effects at gene level. We have determined the ability of multi-walled carbon nanotubes (MWCNT, NM401), to induce mutations in the HPRT gene in Chinese hamster lung (V79) fibroblasts. NM401, characterized in the EU NanoGenotox project, were further studied within the EU Framework Programme Seven (FP7) project NANoREG. From the proliferation assay data we selected a dose-range of 0.12 to 12 µg/cm{sup 2} At these range we have been able to observe significant cellular uptake of MWCNT by using transmission electron microscopy (TEM), as well as a concentration-dependent induction of intracellular reactive oxygen species. In addition, a clear concentration-dependent increase in the induction of HPRT mutations was also observed. Data support a potential genotoxic/ carcinogenic risk associated with MWCNT exposure. - Highlights: • MWCNT were tested in V79 cells. • Cellular uptake of MWCNT was detected using TEM. • Intracellular ROS induction was observed after MWCNT exposure. • MWCNT induced a concentration-dependent increase of HPRT mutations.

Multi-walled carbon nanotubes (NM401) induce ROS-mediated HPRT mutations in Chinese hamster lung fibroblasts

International Nuclear Information System (INIS)

Rubio, Laura; El Yamani, Naouale; Kazimirova, Alena; Dusinska, Maria; Marcos, Ricard

2016-01-01

Although there is an important set of data showing potential genotoxic effects of nanomaterials (NMs) at the DNA (comet assay) and chromosome (micronucleus test) levels, few studies have been conducted to analyze their potential mutagenic effects at gene level. We have determined the ability of multi-walled carbon nanotubes (MWCNT, NM401), to induce mutations in the HPRT gene in Chinese hamster lung (V79) fibroblasts. NM401, characterized in the EU NanoGenotox project, were further studied within the EU Framework Programme Seven (FP7) project NANoREG. From the proliferation assay data we selected a dose-range of 0.12 to 12 µg/cm 2 At these range we have been able to observe significant cellular uptake of MWCNT by using transmission electron microscopy (TEM), as well as a concentration-dependent induction of intracellular reactive oxygen species. In addition, a clear concentration-dependent increase in the induction of HPRT mutations was also observed. Data support a potential genotoxic/ carcinogenic risk associated with MWCNT exposure. - Highlights: • MWCNT were tested in V79 cells. • Cellular uptake of MWCNT was detected using TEM. • Intracellular ROS induction was observed after MWCNT exposure. • MWCNT induced a concentration-dependent increase of HPRT mutations.

Mycotoxins as human carcinogens-the IARC Monographs classification.

Science.gov (United States)

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

2017-02-01

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

Long-term organ culture of adult rat colon

DEFF Research Database (Denmark)

Shamsuddin, A.K.M.; Barrett, L.A.; Autrup, Herman

1978-01-01

. The effect of in vivo carcinogen pretreatment was also studied. The explant culture from control untreated animals showed good epithelial differentiation with crypts until 6 weeks. In contrast, the explants from animals pretreated with 4 weekly doses of azoxymethane consistently showed epithelial......Colon explants from adult rats were maintained in culture for over 3 months in our laboratories with good epithelial preservation and cellular differentiation. The light and transmission electron microscopic features of rat colon mucosa during the culture period are described. In all the explants...

The influence of sex and diet on the characteristics of hibernation in Syrian hamsters.

Science.gov (United States)

Trefna, Marie; Goris, Maaike; Thissen, Cynthia M C; Reitsema, Vera A; Bruintjes, Jojanneke J; de Vrij, Edwin L; Bouma, Hjalmar R; Boerema, Ate S; Henning, Robert H

2017-07-01

Research on deep hibernators almost exclusively uses species captured from the wild or from local breeding. An exception is Syrian hamster (Mesocricetus auratus), the only standard laboratory animal showing deep hibernation. In deep hibernators, several factors influence hibernation quality, including body mass, sex and diet. We examined hibernation quality in commercially obtained Syrian hamsters in relation to body mass, sex and a diet enriched in polyunsaturated fatty acids. Animals (M/F:30/30, 12 weeks of age) were obtained from Harlan (IN, USA) and individually housed at 21 °C and L:D 14:10 until 20 weeks of age, followed by L:D 8:16 until 27 weeks. Then conditions were changed to 5 °C and L:D 0:24 for 9 weeks to induce hibernation. Movement was continuously monitored with passive infrared detectors. Hamsters were randomized to control diet or a diet 3× enriched in linoleic acid from 16 weeks of age. Hamsters showed a high rate of premature death (n = 24, 40%), both in animals that did and did not initiate torpor, which was unrelated to body weight, sex and diet. Time to death (31.7 ± 3.1 days, n = 12) or time to first torpor bout (36.6 ± 1.6 days, n = 12) was similar in prematurely deceased hamsters. Timing of induction of hibernation and duration of torpor and arousal was unaffected by body weight, sex or diet. Thus, commercially obtained Syrian hamsters subjected to winter conditions showed poor survival, irrespective of body weight, sex and diet. These factors also did not affect hibernation parameters. Possibly, long-term commercial breeding from a confined genetic background has selected against the hibernation trait.

Transmission and adaptation of chronic wasting disease to hamsters and transgenic mice: evidence for strains.

Science.gov (United States)

Raymond, Gregory J; Raymond, Lynne D; Meade-White, Kimberly D; Hughson, Andrew G; Favara, Cynthia; Gardner, Donald; Williams, Elizabeth S; Miller, Michael W; Race, Richard E; Caughey, Byron

2007-04-01

In vitro screening using the cell-free prion protein conversion system indicated that certain rodents may be susceptible to chronic wasting disease (CWD). Therefore, CWD isolates from mule deer, white-tailed deer, and elk were inoculated intracerebrally into various rodent species to assess the rodents' susceptibility and to develop new rodent models of CWD. The species inoculated were Syrian golden, Djungarian, Chinese, Siberian, and Armenian hamsters, transgenic mice expressing the Syrian golden hamster prion protein, and RML Swiss and C57BL10 wild-type mice. The transgenic mice and the Syrian golden, Chinese, Siberian, and Armenian hamsters had limited susceptibility to certain of the CWD inocula, as evidenced by incomplete attack rates and long incubation periods. For serial passages of CWD isolates in Syrian golden hamsters, incubation periods rapidly stabilized, with isolates having either short (85 to 89 days) or long (408 to 544 days) mean incubation periods and distinct neuropathological patterns. In contrast, wild-type mouse strains and Djungarian hamsters were not susceptible to CWD. These results show that CWD can be transmitted and adapted to some species of rodents and suggest that the cervid-derived CWD inocula may have contained or diverged into at least two distinct transmissible spongiform encephalopathy strains.

A hamster model for Marburg virus infection accurately recapitulates Marburg hemorrhagic fever.

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Marzi, Andrea; Banadyga, Logan; Haddock, Elaine; Thomas, Tina; Shen, Kui; Horne, Eva J; Scott, Dana P; Feldmann, Heinz; Ebihara, Hideki

2016-12-15

Marburg virus (MARV), a close relative of Ebola virus, is the causative agent of a severe human disease known as Marburg hemorrhagic fever (MHF). No licensed vaccine or therapeutic exists to treat MHF, and MARV is therefore classified as a Tier 1 select agent and a category A bioterrorism agent. In order to develop countermeasures against this severe disease, animal models that accurately recapitulate human disease are required. Here we describe the development of a novel, uniformly lethal Syrian golden hamster model of MHF using a hamster-adapted MARV variant Angola. Remarkably, this model displayed almost all of the clinical features of MHF seen in humans and non-human primates, including coagulation abnormalities, hemorrhagic manifestations, petechial rash, and a severely dysregulated immune response. This MHF hamster model represents a powerful tool for further dissecting MARV pathogenesis and accelerating the development of effective medical countermeasures against human MHF.

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.

Dietary Carcinogens and Anticarcinogens.

Science.gov (United States)

Ames, Bruce N.

1983-01-01

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

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

Science.gov (United States)

Pease, Camilla; Rücker, Thomas; Birk, Thomas

2016-03-21

Since the iron-age and throughout the industrial age, humans have been exposed to iron oxides. Here, we review the evidence from epidemiology, toxicology, and lung bioavailability as to whether iron oxides are likely to act as human lung carcinogens. Current evidence suggests that observed lung tumors in rats result from a generic particle overload effect and local inflammation that is rat-specific under the dosing conditions of intratracheal instillation. This mode of action therefore, is not relevant to human exposure. However, there are emerging differences seen in vitro, in cell uptake and cell bioavailability between "bulk" iron oxides and "nano" iron oxides. "Bulk" particulates, as defined here, are those where greater than 70% are >100 nm in diameter. Similarly, "nano" iron oxides are defined in this context as particulates where the majority, usually >95% for pure engineered forms of primary particulates (not agglomerates), fall in the range 1-100 nm in diameter. From the weight of scientific evidence, "bulk" iron oxides are not genotoxic/mutagenic. Recent evidence for "nano" iron oxide is conflicting regarding genotoxic potential, albeit genotoxicity was not observed in an in vivo acute oral dose study, and "nano" iron oxides are considered safe and are being investigated for biomedical uses; there is no specific in vivo genotoxicity study on "nano" iron oxides via inhalation. Some evidence is available that suggests, hypothetically due to the larger surface area of "nano" iron oxide particulates, that toxicity could be exerted via the generation of reactive oxygen species (ROS) in the cell. However, the potential for ROS generation as a basis for explaining rodent tumorigenicity is only apparent if free iron from intracellular "nano" scale iron oxide becomes bioavailable at significant levels inside the cell. This would not be expected from "bulk" iron oxide particulates. Furthermore, human epidemiological evidence from a number of studies suggests that

Memory for individual scent in hamsters (Mesocricetus auratus) as assessed by habituation methods.

Science.gov (United States)

Johnston, R E

1993-06-01

The memory of hamsters (Mesocricetus auratus) for the flank scent of other male hamsters was investigated in a series of habituation experiments. In 2 types of habituation tasks (Experiments 1 and 2), male hamsters habituated to the flank scent of 1 male and then increased their level of investigation to that of a novel male; similar results were obtained when the intervals between trials ranged from 1 s to 2 days. When the test trial was 10 or 21 days after habituation (Experiment 3), males discriminated between familiar and novel flank scents at 10 days but not at 21 days. The results demonstrate recognition of familiar and unfamiliar individual odors and excellent memory for these differences. Habituation techniques yield extremely robust results and may be useful for investigations of other aspects of individual signatures.

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

International Nuclear Information System (INIS)

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

2012-01-01

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

NORMAL GENE EXPRESSION IN MALE F344 RAT NASAL TRANSITIONAL/RESPIRATORY EPITHELIUM

Science.gov (United States)

Abstract The nasal epithelium is an important target site for chemically-induced toxicity and carcinogenicity in rodents. Gene expression profiles were determined in order to provide normal baseline data for nasal transitional/respiratory epithelium from healthy rats. Ce...

Identification of Radiation Effects on Carcinogenic Food Estimated by Ames Test

International Nuclear Information System (INIS)

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

2016-01-01

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

Biomarkers of carcinogen exposure and early effects.

OpenAIRE

2006-01-01

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

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

Science.gov (United States)

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

2017-10-02

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

Post-initiation chlorophyllin exposure does not modulate aflatoxin-induced foci in the liver and colon of rats

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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.

Quantitative structure activity relationship for the computational prediction of nitrocompounds carcinogenicity

International Nuclear Information System (INIS)

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

2006-01-01

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

Carcinogenicity assessment of water-soluble nickel compounds.

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

2009-01-01

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

Carcinogenic compounds in alcoholic beverages: an update.

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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.

A review of mammalian carcinogenicity study design and potential effects of alternate test procedures on the safety evaluation of food ingredients.

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Hayes, A W; Dayan, A D; Hall, W C; Kodell, R L; Williams, G M; Waddell, W D; Slesinski, R S; Kruger, C L

2011-06-01

of test procedures, dose selection, histopathology procedures, application of historical control data, statistical evaluations and whether statistical extrapolations are supported by, or are beyond the limits of, the data generated. Without due consideration, there can be result conflicting data interpretations and uncertainty about the relevance of a study's results to human risk. This paper discusses the critical elements of rodent (rat) carcinogenicity studies, particularly with respect to the study of food ingredients. It also highlights study practices and procedures that can detract from the appropriate evaluation of human relevance of results, indicating the importance of adherence to international consensus protocols, such as those detailed by OECD. Copyright © 2010. Published by Elsevier Inc.

Cystolithiasis in a Syrian hamster: a different outcome

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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.

Determination of elements in blood of golden hamster by NAA; Determinacao de elementos em sangue de hamster dourado usando AAN

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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)

Comparison of gene expression profiles altered by comfrey and riddelliine in rat liver.

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Guo, Lei; Mei, Nan; Dial, Stacey; Fuscoe, James; Chen, Tao

2007-11-01

Comfrey (Symphytum officinale) is a perennial plant and has been consumed by humans as a vegetable, a tea and an herbal medicine for more than 2000 years. It, however, is hepatotoxic and carcinogenic in experimental animals and hepatotoxic in humans. Pyrrolizidine alkaloids (PAs) exist in many plants and many of them cause liver toxicity and/or cancer in humans and experimental animals. In our previous study, we found that the mutagenicity of comfrey was associated with the PAs contained in the plant. Therefore, we suggest that carcinogenicity of comfrey result from those PAs. To confirm our hypothesis, we compared the expression of genes and processes of biological functions that were altered by comfrey (mixture of the plant with PAs) and riddelliine (a prototype of carcinogenic PA) in rat liver for carcinogenesis in this study. Groups of 6 Big Blue Fisher 344 rats were treated with riddelliine at 1 mg/kg body weight by gavage five times a week for 12 weeks or fed a diet containing 8% comfrey root for 12 weeks. Animals were sacrificed one day after the last treatment and the livers were isolated for gene expression analysis. The gene expressions were investigated using Applied Biosystems Rat Whole Genome Survey Microarrays and the biological functions were analyzed with Ingenuity Analysis Pathway software. Although there were large differences between the significant genes and between the biological processes that were altered by comfrey and riddelliine, there were a number of common genes and function processes that were related to carcinogenesis. There was a strong correlation between the two treatments for fold-change alterations in expression of drug metabolizing and cancer-related genes. Our results suggest that the carcinogenesis-related gene expression patterns resulting from the treatments of comfrey and riddelliine are very similar, and PAs contained in comfrey are the main active components responsible for carcinogenicity of the plant.

Regulation of intestinal immune response by selective removal of the anterior, posterior, or entire pituitary gland in Trichinella spiralis infected golden hamsters.

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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.

Zyflamend reduces LTB4 formation and prevents oral carcinogenesis in a 7,12-dimethylbenz[alpha]anthracene (DMBA)-induced hamster cheek pouch model.

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Yang, Peiying; Sun, Zheng; Chan, Diana; Cartwright, Carrie A; Vijjeswarapu, Mary; Ding, Jibin; Chen, Xiaoxin; Newman, Robert A

2008-11-01

Aberrant arachidonic acid metabolism, especially altered cyclooxygenase and 5-lipoxygenase (LOX) activities, has been associated with chronic inflammation as well as carcinogenesis in human oral cavity tissues. Here, we examined the effect of Zyflamend, a product containing 10 concentrated herbal extracts, on development of 7,12-dimethylbenz[alpha]anthracene (DMBA)-induced inflammation and oral squamous cell carcinoma (SCC). A hamster cheek pouch model was used in which 0.5% DMBA was applied topically onto the left cheek pouch of male Syrian golden hamsters either three times per week for 3 weeks (short term) or 6 weeks (long term). Zyflamend was then applied topically at one of three different doses (25, 50 and 100 microl) onto the left cheek pouch three times for 1 week (short-term study) or chronically for 18 weeks. Zyflamend significantly reduced infiltration of inflammatory cells, incidence of hyperplasia and dysplastic lesions, bromodeoxyuridine-labeling index as well as number of SCC in a concentration-dependent manner. Application of Zyflamend (100 microl) reduced formation of leukotriene B(4) (LTB(4)) by 50% compared with DMBA-treated tissues. The reduction of LTB(4) was concentration dependent. The effect of Zyflamend on inhibition of LTB(4) formation was further confirmed with in vitro cell-based assay. Adding LTB(4) to RBL-1 cells, a rat leukemia cell line expressing high levels of 5-LOX and LTA(4) hydrolase, partially blocked antiproliferative effect of Zyflamend. This study demonstrates that Zyflamend inhibited LTB(4) formation and modulated adverse histopathological changes in the DMBA-induced hamster cheek pouch model. The study suggests that Zyflamend might prevent oral carcinogenesis at the post-initiation stage.

Regulation of intestinal immune response by selective removal of the anterior, posterior, or entire pituitary gland in Trichinella spiralis infected golden hamsters.

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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.

The Hamster Model for Identification of Specific Antigens of Taenia solium Tapeworms

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Ochoa-Sánchez, Alicia; Jiménez, Lucía; Landa, Abraham

2011-01-01

Humans acquire taeniasis by ingesting pork meat infected with Taenia solium cysticerci, which are the only definitive hosts of the adult stage (tapeworm) and responsible for transmitting the human and porcine cysticercosis. Hence, detection of human tapeworm carriers is a key element in the development of viable strategies to control the disease. This paper presents the identification of specific antigens using sera from hamsters infected with T. solium tapeworms analyzed by western blot assay with crude extracts (CEs) and excretion-secretion antigens (E/S Ag) obtained from T. solium cysticerci and tapeworms and extracts from other helminthes as controls. The hamster sera infected with T. solium tapeworms recognized specific bands of 72, 48, 36, and 24 kDa, in percentages of 81, 81, 90, and 88%, respectively, using the T. solium tapeworms E/S Ag. The antigens recognized by these hamster sera could be candidates to improve diagnosis of human T. solium taeniasis. PMID:22253530

Dorsal shaving affects concentrations of faecal cortisol metabolites in lactating golden hamsters

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Ohrnberger, Sarah A.; Brinkmann, Katharina; Palme, Rupert; Valencak, Teresa G.

2018-02-01

Breeding of golden hamsters is classically performed at thermal conditions ranging from 20 to 24 °C. However, growing evidence suggests that lactating females suffer from heat stress. We hypothesised that shaving females dorsally to maximise heat dissipation may reduce stress during reproduction. We thus compared faecal cortisol metabolites (FCM) from shaved golden hamster mothers with those from unshaved controls. We observed significantly lower FCM levels in the shaved mothers ( F 1,22 = 8.69, p = 0.0075) pointing to lower stress due to ameliorated heat dissipation over the body surface. In addition, we observed 0.4 °C lower mean subcutaneous body temperatures in the shaved females, although this effect did not reach significance ( F 1,22 = 1.86, p = 0.18). Our results suggest that golden hamsters having body masses being more than four times that of laboratory mice provide a very interesting model to study aspects of lactation and heat production at the same time.

Zika virus infection of adult and fetal STAT2 knock-out hamsters.

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Siddharthan, Venkatraman; Van Wettere, Arnaud J; Li, Rong; Miao, Jinxin; Wang, Zhongde; Morrey, John D; Julander, Justin G

2017-07-01

Zika virus (ZIKV) infection was investigated in adult and fetal STAT2 knock-out (KO) hamsters. Subcutaneous injection of ZIKV of adults resulted in morbidity, mortality, and infection of the uterus, placenta, brain, spinal cord, and testicles, thus providing an opportunity to evaluate congenital ZIKV infection in a second rodent species besides mice. ZIKV-infected cells with morphologies of Sertoli cells and spermatogonia were observed in the testes, which may have implications for sexual transmission and male sterility. Neonates exposed as fetuses to ZIKV at 8 days post-coitus were not smaller than controls. Nevertheless, infectious virus and ZIKV RNA was detected in some, but not all, placentas and fetal brains of KO hamsters. STAT2 KO hamsters may be useful for addressing sexual transmission, pathogenesis, routes of fetal infection, and neurological disease outcomes, and may also be used in antiviral or vaccine studies to identify intervention strategies. Copyright © 2017. Published by Elsevier Inc.

The Hamster Model for Identification of Specific Antigens of Taenia solium Tapeworms

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Alicia Ochoa-Sánchez

2011-01-01

Full Text Available Humans acquire taeniasis by ingesting pork meat infected with Taenia solium cysticerci, which are the only definitive hosts of the adult stage (tapeworm and responsible for transmitting the human and porcine cysticercosis. Hence, detection of human tapeworm carriers is a key element in the development of viable strategies to control the disease. This paper presents the identification of specific antigens using sera from hamsters infected with T. solium tapeworms analyzed by western blot assay with crude extracts (CEs and excretion-secretion antigens (E/S Ag obtained from T. solium cysticerci and tapeworms and extracts from other helminthes as controls. The hamster sera infected with T. solium tapeworms recognized specific bands of 72, 48, 36, and 24 kDa, in percentages of 81, 81, 90, and 88%, respectively, using the T. solium tapeworms E/S Ag. The antigens recognized by these hamster sera could be candidates to improve diagnosis of human T. solium taeniasis.

Mutagenic and carcinogenic properties of drinking water

International Nuclear Information System (INIS)

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

1985-01-01

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

Andrographolide Ameliorates Beta-Naphthoflavone-Induced CYP1A Enzyme Activity and Lipid Peroxidation in Hamsters with Acute Opisthorchiasis.

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Udomsuk, Latiporn; Chatuphonprasert, Waranya; Jarukamjorn, Kanokwan; Sithithaworn, Paiboon

2016-01-01

Opisthorchis viverrini (OV) infection generates oxidative stress/free radicals and is considered as a primary cause ofcholangiocarcinoma since it primarily triggers sclerosing cholangitis. In this study, the impacts of andrographolide on acute opisthorchaisis in β-naphthoflavone (BNF)-exposed hamsters were investigated. Ethoxyresorufin O-deethylase (EROD) and methoxyresorufin O-demethylase (MROD) activities and Thiobarbituric acid reaction substances (TBARS) assay of andrographolide in acute opisthorchiasis in the BNF-exposed hamsters were assessed. The results showed that andrographolide ameliorated the hepatic CYP1A1 and CYP1A2 activities by decreases of the specific enzymatic reactions of EROD and MROD, respectively, in the BNF-exposed hamsters. Moreover, andrographolide lowered the formation of malondialdehyde in the livers and brains of the hamsters. These observations revealed the promising chemo-protective and antioxidant activities of andrographolide via suppression of the specific EROD and MROD reactions and lipid peroxidation against acute opisthorchiasis in the BNF-exposed hamsters.

Combination of aging and dimethylhydrazine treatment causes an increase in cancer-stem cell population of rat colonic crypts.

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Levi, Edi; Misra, Sandhya; Du, Jianhua; Patel, Bhaumik B; Majumdar, Adhip P N

2009-07-31

Aging is associated with increased incidence of colon cancers. It is also becoming evident that cancer stem cells (CSC) play a vital role in the pathogenesis and prognosis of colon cancer. Recently, we reported the presence of colon cancer stem-like cells in macroscopically normal mucosa in patients with adenomatous polyps and that they increase with aging, suggesting that aging may predispose the colon to carcinogenesis. In the current study we have examined the combined effects of aging and carcinogen exposure on the status of colon CSCs in an experimental model. We used young (4-6 months) and aged (22-24 months) rats and exposed them to the carcinogen, dimethylhydroxide (DMH). We investigated the expression of colon cancer stem cell markers, CD44, CD166, EpCam, and ALDH1 as well as EGFR expression in normal colonic crypt epithelium following carcinogen treatment. Our results demonstrate that aging per se or carcinogen treatment alone causes an increase in the number of colon cancer stems cells, as evidenced by increased immunoreactive-CSC-markers positive cells in the colonic mucosa. In aged rats, carcinogen exposure results in a more pronounced increase in colon cancer stem cells. Our study shows that in aging colon the effects of carcinogens are more pronounced, and an increase in colon CSCs is one of the earliest changes preceding tumor development. Moreover, the current investigation of the use of a panel of immunohistochemical markers of colon CSC can potentially serve as a prognostic marker during screening for colon cancer.

Negligible colon cancer risk from food-borne acrylamide exposure in male F344 rats and nude (nu/nu mice-bearing human colon tumor xenografts.

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Jayadev Raju

Full Text Available Acrylamide, a possible human carcinogen, is formed in certain carbohydrate-rich foods processed at high temperature. We evaluated if dietary acrylamide, at doses (0.5, 1.0 or 2.0 mg/kg diet reflecting upper levels found in human foods, modulated colon tumorigenesis in two rodent models. Male F344 rats were randomized to receive diets without (control or with acrylamide. 2-weeks later, rats in each group received two weekly subcutaneous injections of either azoxymethane (AOM or saline, and were killed 20 weeks post-injections; colons were assessed for tumors. Male athymic nude (nu/nu mice bearing HT-29 human colon adenocarcinoma cells-derived tumor xenografts received diets without (control or with acrylamide; tumor growth was monitored and mice were killed 4 weeks later. In the F344 rat study, no tumors were found in the colons of the saline-injected rats. However, the colon tumor incidence was 54.2% and 66.7% in the control and the 2 mg/kg acrylamide-treated AOM-injected groups, respectively. While tumor multiplicity was similar across all diet groups, tumor size and burden were higher in the 2 mg/kg acrylamide group compared to the AOM control. These results suggest that acrylamide by itself is not a "complete carcinogen", but acts as a "co-carcinogen" by exacerbating the effects of AOM. The nude mouse study indicated no differences in the growth of human colon tumor xenografts between acrylamide-treated and control mice, suggesting that acrylamide does not aid in the progression of established tumors. Hence, food-borne acrylamide at levels comparable to those found in human foods is neither an independent carcinogen nor a tumor promoter in the colon. However, our results characterize a potential hazard of acrylamide as a colon co-carcinogen in association with known and possibly other environmental tumor initiators/promoters.

Adapting to alcohol: Dwarf hamster (Phodopus campbelli) ethanol consumption, sensitivity, and hoard fermentation.

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Lupfer, Gwen; Murphy, Eric S; Merculieff, Zoe; Radcliffe, Kori; Duddleston, Khrystyne N

2015-06-01

Ethanol consumption and sensitivity in many species are influenced by the frequency with which ethanol is encountered in their niches. In Experiment 1, dwarf hamsters (Phodopus campbelli) with ad libitum access to food and water consumed high amounts of unsweetened alcohol solutions. Their consumption of 15%, but not 30%, ethanol was reduced when they were fed a high-fat diet; a high carbohydrate diet did not affect ethanol consumption. In Experiment 2, intraperitoneal injections of ethanol caused significant dose-related motor impairment. Much larger doses administered orally, however, had no effect. In Experiment 3, ryegrass seeds, a common food source for wild dwarf hamsters, supported ethanol fermentation. Results of these experiments suggest that dwarf hamsters may have adapted to consume foods in which ethanol production naturally occurs. Copyright © 2015 Elsevier B.V. All rights reserved.

Recent developments in carcinogenic risk assessment

International Nuclear Information System (INIS)

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

1989-01-01

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

METABOLISM, GENOTOXICITY, AND CARCINOGENICITY OF COMFREY

Science.gov (United States)

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

2018-01-01

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

Metabolism, genotoxicity, and carcinogenicity of comfrey.

Science.gov (United States)

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

2010-10-01

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

Risk assessment of DNA-reactive carcinogens in food

International Nuclear Information System (INIS)

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

2005-01-01

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

Effect of DNA type on response of DNA biosensor for carcinogens

Science.gov (United States)

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

2013-11-01

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

EFEK VITAMIN C DALAM MEDIUM DMEM TERHADAP PERTUMBUHAN SEL PARU-PARU FETUS HAMSTER SECARA IN VITRO

Directory of Open Access Journals (Sweden)

Ema Kurnia W,

2012-09-01

Full Text Available Penelitian ini dilakukan dengan tujuan untuk mengetahui efek vitamin C dalam medium DMEM terhadap pertumbuhan sel paru-paru fetus hamster secara in vitro dan untuk mengetahui pada konsentrasi berapakah vitamin C dalam medium DMEM yang berpengaruh paling efektif terhadap pertumbuhan sel paru-paru fetus hamster secara in vitro. Penelitian ini merupakan penelitian eksperimental dengan 6 perlakuan dan 2 ulangan. Masing-masing perlakuan tersebut adalah vitamin C dengan konsentrasi 0mM (kontrol, 5mM, 10mM, 15mM, 20mM, dan 25mM. Vitamin C dengan berbagai konsentrasi tersebut ditambahkan ke dalam medium DMEM dan selanjutnya digunakan untuk menumbuhkan sel paru-paru fetus hamster. Sel paru-paru fetus hamster diisolasi dari fetus hamster berumur 2 hari, ditumbuhkan dalam medium DMEM yang sudah ditambah dengan vitamin C dengan berbagai konsentrasi dan diinkubasi dalam inkubator CO2 5% pada suhu 370C selama beberapa hari sampai biakan sel-sel tersebut konfluen. Setelah konfluenbiakan sel diamati persentase konfluen, viabilitas dan abnormalitas sel. Hasil penelitian menunjukkan bahwa vitamin C dengan konsentrasi 0mM (kontrol, 5mM, 10mM, 15mM, 20mM, dan 25mM dalam medium DMEM mampu menghasilkan persentase konfluen berturut-turut 50%, 65%, 72.5%, 82.5%, 87.5%, dan 92.5% dan persentase viabilitas sel sebesar 89%, 94.5%, 94%, 93%, 94%, dan 96.5%. Sedangkan konsentrasi vitamin C yang efektif terhadap pertumbuhan sel paru-paru fetus hamster secara in vitro adalah konsentrasi 25mM.

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)

Fatty acid and lipidomic data in normal and tumor colon tissues of rats fed diets with and without fish oil

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Zora Djuric

2017-08-01

Full Text Available Data is provided to show the detailed fatty acid and lipidomic composition of normal and tumor rat colon tissues. Rats were fed either a Western fat diet or a fish oil diet, and half the rats from each diet group were treated with chemical carcinogens that induce colon cancer (azoxymethane and dextran sodium sulfate. The data show total fatty acid profiles of sera and of all the colon tissues, namely normal tissue from control rats and both normal and tumor tissues from carcinogen-treated rats, as obtained by gas chromatography with mass spectral detection. Data from lipidomic analyses of a representative subset of the colon tissue samples is also shown in heat maps generated from hierarchical cluster analysis. These data display the utility lipidomic analyses to enhance the interpretation of dietary feeding studies aimed at cancer prevention and support the findings published in the companion paper (Effects of fish oil supplementation on prostaglandins in normal and tumor colon tissue: modulation by the lipogenic phenotype of colon tumors, Djuric et al., 2017 [1].

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

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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.

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

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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.

Detection of Leishmania infantum DNA in hamsters infested with ticks collected from naturally infected dogs

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Valter dos Anjos Almeida

2016-12-01

Full Text Available ABSTRACT. Almeida V. dos A., da Hora T.N., Leça Júnior N.F., Carvalho F.S., da Silva A.L., Wenceslau A.A., Albuquerque G.R. & Silva F.L. Detection of Leishmania infantum DNA in hamsters infested with ticks collected from naturally infected dogs. [Detecção do DNA de Leishmania infantum em hamsters infestados com carrapatos coletados de cães naturalmente infectados.] Revista Brasileira de Medicina Veterinária, 38(4:329-333, 2016. Departamento de Ciências Agrárias e Ambientais, Universidade Estadual de Santa Cruz, Campus Soane Nazaré de Andrade, Hospital Veterinário, Km 16, Rodovia Jorge Amado, Ilhéus, BA 45662-900, Brasil. E-mail: fabiana.lessa@gmail.com The aim of this study was to investigate the role of Rhipicephalus sanguineus, the brown dog tick, in the transmission of Leishmania infantum. To accomplish this, we used 24 adult golden hamsters of both genders, and divided them into two groups: a control group (n = 4 and an experimental group (n = 20. The animals from the experimental group were infested with ticks obtained from dogs naturally infected with L. infantum. Hamsters of the control group were not infested and were maintained at the same conditions, as the infested animals. After three months of observation, animals were euthanized and they were posted to obtain samples of their blood, spleen, liver, lymph nodes, and skin. These samples were then processed by histopathology, immunohistochemistry, and polymerase chain reaction (PCR. Fourteen hamsters (70% of the experimental group tested PCR-positive for L. infantum DNA in samples of buffy coat. The results of this study indicated that R. sanguineus ticks can transmit some forms or parts of L. infantum to parasitized hamsters.

Vasopressin immunoreactivity and release in the suprachiasmatic nucleus of wild-type and tau mutant Syrian hamsters

NARCIS (Netherlands)

Van der Zee, EA; Oklejewicz, M; Jansen, K; Daan, S; Gerkema, MP

2002-01-01

Despite the prominent role of the Syrian hamster (Mesocricetus auratus) in studies of circadian rhythms, there are no data available on the temporal dynamics of the neuropeptide vasopressin (AVP), a major output system of the suprachiasmatic nucleus (SCN). We studied the hamster SCN-AVP system in

Food restriction attenuates oxidative stress in brown adipose tissue of striped hamsters acclimated to a warm temperature.

Science.gov (United States)

Zhang, Ji-Ying; Zhao, Xiao-Ya; Wang, Gui-Ying; Wang, Chun-Ming; Zhao, Zhi-Jun

2016-05-01

It has been suggested that the up-regulation of uncoupling proteins (UCPs) decreases reactive oxygen species (ROS) production, in which case there should be a negative relationship between UCPs expression and ROS levels. In this study, the effects of temperature and food restriction on ROS levels and metabolic rate, UCP1 mRNA expression and antioxidant levels were examined in the brown adipose tissue (BAT) of the striped hamsters (Cricetulus barabensis). The metabolic rate and food intake of hamsters which had been restricted to 80% of ad libitum food intake, and acclimated to a warm temperature (30°C), decreased significantly compared to a control group. Hydrogen peroxide (H2O2) levels were 42.9% lower in food restricted hamsters than in the control. Malonadialdehyde (MDA) levels of hamsters acclimated to 30°C that were fed ad libitum were significantly higher than those of the control group, but 60.1% lower than hamsters that had been acclimated to the same temperature but subject to food restriction. There were significantly positive correlations between H2O2 and, MDA levels, catalase activity, and total antioxidant capacity. Cytochrome c oxidase activity and UCP1 mRNA expression significantly decreased in food restricted hamsters compared to the control. These results suggest that warmer temperatures increase oxidative stress in BAT by causing the down-regulation of UCP1 expression and decreased antioxidant activity, but food restriction may attenuate the effects. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

Science.gov (United States)

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

2014-01-01

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

Efficacy of UV-irradiated larval vaccine of Ancylostoma ceylanicum (Looss, 1911) in golden hamsters (Merocricetus auratus)

International Nuclear Information System (INIS)

Menon, S.; Bhopale, M.K.

1985-01-01

A vaccination trial in golden hamsters with UV-irradiated infective larvae of Ancylostoma ceylanicum was attempted. One oral vaccination of hamsters with 100 infective larvae irradiated by means of UV-tube (390 nm) at different time intervals induced the development of resistance. As the time exposure of irradiation was increased, there was a corresponding decrease in the subsequent worm establishment. A high level of protection afforded by larvae irradiated for 15 min UV-exposure was recorded giving 99.0% and 95.0% worm reduction against the challenge doses of 100 and 1000 normal larvae respectively. There was no marked difference in worm establishment in hamsters vaccinated either orally or subcutaneously, followed by oral challenge. In the vaccinated hamsters, the manifestations of resistance at 15 min UV-exposure were shown by marked reduction in worm establishment and highly reduced epg in pellets with significantly higher blood haemoglobin levels compared with those given normal larvae as vaccine and challenge controls. (author)

Experience-independent development of the hamster circadian visual system.

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August Kampf-Lassin

2011-04-01

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.

Smoking out carcinogens

OpenAIRE

Baines, David; Griffiths, Huw; Parker, Jane

2016-01-01

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

Twenty-six-week oral carcinogenicity study of 3-monochloropropane-1,2-diol in CB6F1-rasH2 transgenic mice.

Science.gov (United States)

Lee, Byoung-Seok; Park, Sang-Jin; Kim, Yong-Bum; Han, Ji-Seok; Jeong, Eun Ju; Son, Hwa-Young; Moon, Kyoung-Sik

2017-01-01

The carcinogenic potential of 3-monochloro-1,2-propanediol (3-MCPD) was evaluated in a short-term carcinogenicity testing study using CB6F1 rasH2-Tg (rasH2-Tg) mice. 3-MCPD is found in many foods and food ingredients as a result of storage or processing and is regarded as a carcinogen since it is known to induce Leydig cell and kidney tumors in rats. Male and female rasH2-Tg mice were administered 3-MCPD once daily by oral gavage at doses of 0, 10, 20, and 40 mg/kg body weight (bw) per day for 26 weeks. As a positive control, N-methyl-N-nitrosourea (MNU) was administered as a single intraperitoneal injection (75 mg/kg). In 3-MCPD-treated mice, there was no increase in the incidence of neoplastic lesions compared to the incidence in vehicle control mice. However, 3-MCPD treatment resulted in an increased incidence of tubular basophilia in the kidneys and germ cell degeneration in the testes, with degenerative germ cell debris in the epididymides of males at 20 and 40 mg/kg bw per day. In 3-MCPD-treated females, vacuolation of the brain and spinal cord was observed at 40 mg/kg bw per day; however, only one incidence of vacuolation was observed in males. Forestomach and cutaneous papilloma and/or carcinoma and lymphoma were observed in most rasH2 mice receiving MNU treatment. We concluded that 3-MCPD did not show carcinogenic potential in the present study using rasH2-Tg mice. The findings of this study suggest that the carcinogenic potential of 3-MCPD is species specific.

THE FAILURE OF CHLOROFORM ADMINISTERED IN THE DRINKING WATER TO INDUCE RENAL TUBULAR CELL NEOPLASIA IN MALE F344/N RATS

Science.gov (United States)

The failure of chloroform administered in drinking water to induce renal tubular cell neoplasia in male F344/N rats Chloroform (TCM) has been demonstrated to be a renal carcinogen in the male Osborne-Mendel rat when administered either by corn oil gavage or in drin...

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)...

[Prokaryotic expression of Leptospira interrogans groEL gene and immunoprotection of its products in hamsters].

Science.gov (United States)

Li, Xiaoyu; Wang, Yinhuan; Yan, Jie; Cheng, Dongqing

2013-03-01

To construct a prokaryotic expression system of groEL gene of Leptospira interrogans serogroup Icterohaemorrhagia serovar Lai strain Lai, and to determine the immunoprotective effect of recombinant GroEL protein (rGroEL) in LVG hamsters. The groEL gene was amplified by high fidelity PCR and the amplification products were then sequenced. A prokaryotic expression system of groEL gene was constructed using routine genetic engineering technique. SDS-PAGE plus Bio-Rad Gel Image Analyzer was applied to examine the expression and dissolubility of rGroEL protein while Ni-NTA affinity chromatography was used to extract the expressed rGroEL. The immunoprotective rate in rGroEL-immunized LVG hamsters was determined after challenge with L.interrogans strain Lai. The cross agglutination titers of sera from immunized hamsters with different L.interrogans serogroups were detected using MAT. The nucleotide and amino acid sequences of the cloned groEL gene were the same as those reported in GenBank. The constructed prokaryotic expression system of groEL gene expressed soluble rGroEL. The immunoprotective rates of 100 and 200 μg rGroEL in LVG hamsters were 50.0 % and 75.0%, respectively. The sera from the rGroEL-immunized LVG hamsters agglutinated all the L.interrogans serogroups tested with different levels. The GroEL protein is a genus-specific immunoprotective antigen of L.interrogans and can be used to develop an universal genetically engineering vaccine of Leptospira.

Gadolinium diethylenetriamine pentaacetic acid enhanced magnetic resonance imagings in cardiomyopathic hamsters. Histopathologic correlation

International Nuclear Information System (INIS)

Aso, Hiroko

1995-01-01

To assess the significance of gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA)-enhanced magnetic resonance (MR) imaging, the findings were correlated with histopathological findings in cardiomyopathic hamsters (Bio 14.6). In hamsters given 1 mBq of Gd-DTPA, autoradiography revealed uptake of Gd-DTPA corresponding to the fibrotic tissue. According to the degree of fibrosis and inflammation, the tissue was graded into three. The ratio of contrast enhancement in the fibrotic area to that in the normal area was significantly higher in grade 1 than grades 2 and 3, and in grade 2 than grade 3. Next, hamsters in various age groups were given 0.2 mmol/kg intravenously. In the age group of 2-5 month, contrast enhancement was homogeneously observed in the entire myocardium. In the age group of 8-10 years, it was entirely observed, partly with heterogeneous enhancement. In the age group of 11-12 years, contrast enhancement was not different from that in the normal hamsters. Histological examination revealed that fibrosis changed from grade 1 through grade 3 with advancing age. In conclusion, MR imaging for myocardiopathy showed signal intensity reflecting the fibrotic tissue. Contrast enhancement of MR imaging was stronger when much more inflammatory cells were involved and fibrotic tissues were filled with much more blood vessels. Thus MR imaging may be a promising tool for evaluating the severity of myocardiopathy. (N.K.)

Carcinogenicity of petroleum lubricating oil distillates: effects of solvent refining, hydroprocessing, and blending.

Science.gov (United States)

Halder, C A; Warne, T M; Little, R Q; Garvin, P J

1984-01-01

Certain refining processes were investigated to determine their influence on the dermal carcinogenic activity of petroleum-derived lubricating oil distillates. Specifically, the effects of solvent refining, hydroprocessing, a combination of both processes, and the blending of oils processed using each technique were evaluated in standard mouse skin-painting bioassays. The refining process used as well as the level or severity of treatment greatly influenced the carcinogenic outcome of processed lubricating oils. Solvent refining at severities normally used appeared to eliminate carcinogenicity. In contrast, hydroprocessing alone at mild levels of treatment was successful only in reducing the carcinogenic potency; severe hydroprocessing conditions were necessary to eliminate carcinogenic activity without the use of additional refining processes. Carcinogenic activity could also be eliminated by following moderate solvent refining with mild hydroprocessing. Blending of hydroprocessed oils with solvent-refined oils resulted in a substantial reduction or even elimination of carcinogenic activity. However, the degree of protection obtained varied with the particular distillates used and appeared largely dependent on the inherent biological activity of the hydroprocessed oil.

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

International Nuclear Information System (INIS)

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

2016-01-01

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

Relative potency estimation for synthetic petroleum skin carcinogens.

OpenAIRE

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

1981-01-01

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

7-Glutathione-pyrrole and 7-cysteine-pyrrole are potential carcinogenic metabolites of pyrrolizidine alkaloids.

Science.gov (United States)

He, Xiaobo; Xia, Qingsu; Fu, Peter P

2017-04-03

Many pyrrolizidine alkaloids (PAs) are hepatotoxic, genotoxic, and carcinogenic phytochemicals. Metabolism of PAs in vivo generates four (±)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP)-DNA adducts that have been proposed to be responsible for PA-induced liver tumor formation in rats. In this present study, we determined that the same set of DHP-DNA adducts was formed upon the incubation of 7-glutathione-DHP and 7-cysteine-DHP with cultured human hepatocarcinoma HepG2 cells. These results suggest that 7-glutathione-DHP and 7-cysteine-DHP are reactive metabolites of PAs that can bind to cellular DNA to form DHP-DNA adducts in HepG2 cells, and can potentially initiate liver tumor formation.

Effect of arsenite on the DNA repair of UV-irradiated Chinese hamster ovary cells

International Nuclear Information System (INIS)

Lee-Chen, S.F.; Yu, C.T.; Jan, K.Y.

1992-01-01

Arsenite, an ubiquitous human carcinogen, has been shown to enhance the cytotoxicity, mutagenicity and clastogenicity of UV light in mammalian cells. Arsenite may exert its co-genotoxic effects by inhibiting DNA repair. Results from alkaline sucrose gradient sedimentation show that arsenite did not accumulate UV-induced DNA strand breaks in Chinese hamster ovary (CHO) K1 cells as aphidicolin plus hydroxyurea (HU) did. These data indicate that arsenite did not inhibit the activity of DNA polymerase α in UV repair. Treatment with arsenite before UV irradiation slightly reduced the DNA strand breaks accumulated by cytosine β-D-arabinofuranoside (AraC) plus HU. This effect implies that arsenite only slightly inhibited the incision of UV-induced DNA adducts. The low molecular weight DNA accumulated by post-UV incubation with AraC plus HU shifted to high molecular weight upon the incubation of cells in drug-free medium, but this shifting was prohibited by the presence of arsenite. This suggests that arsenite inhibited the rejoining of DNA strand breaks. When a pulse-chase labelling procedure was applied on UV-irradiated cells, the chain elongation of nascent DNA was strongly inhibited by post-incubation with arsenite. These data show that arsenite inhibited post-replication repair in UV-irradiated cells. Therefore, the steps inhibited by arsenite in UV-induced cells. Therefore, the steps inhibited by arsenite in UV-induced DNA repair in CHO K1 cells are different from human fibroblasts. (author)

Effect of arsenite on the DNA repair of UV-irradiated Chinese hamster ovary cells

Energy Technology Data Exchange (ETDEWEB)

Lee-Chen, S.F.; Yu, C.T.; Jan, K.Y. (Academia Sinica, Taipei, (Taiwan). Institute of Zoology)

1992-01-01

Arsenite, an ubiquitous human carcinogen, has been shown to enhance the cytotoxicity, mutagenicity and clastogenicity of UV light in mammalian cells. Arsenite may exert its co-genotoxic effects by inhibiting DNA repair. Results from alkaline sucrose gradient sedimentation show that arsenite did not accumulate UV-induced DNA strand breaks in Chinese hamster ovary (CHO) K1 cells as aphidicolin plus hydroxyurea (HU) did. These data indicate that arsenite did not inhibit the activity of DNA polymerase [alpha] in UV repair. Treatment with arsenite before UV irradiation slightly reduced the DNA strand breaks accumulated by cytosine [beta]-D-arabinofuranoside (AraC) plus HU. This effect implies that arsenite only slightly inhibited the incision of UV-induced DNA adducts. The low molecular weight DNA accumulated by post-UV incubation with AraC plus HU shifted to high molecular weight upon the incubation of cells in drug-free medium, but this shifting was prohibited by the presence of arsenite. This suggests that arsenite inhibited the rejoining of DNA strand breaks. When a pulse-chase labelling procedure was applied on UV-irradiated cells, the chain elongation of nascent DNA was strongly inhibited by post-incubation with arsenite. These data show that arsenite inhibited post-replication repair in UV-irradiated cells. Therefore, the steps inhibited by arsenite in UV-induced cells. Therefore, the steps inhibited by arsenite in UV-induced DNA repair in CHO K1 cells are different from human fibroblasts. (author).

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

Science.gov (United States)

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

2013-02-12

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

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...

Basking hamsters reduce resting metabolism, body temperature and energy costs during rewarming from torpor.

Science.gov (United States)

Geiser, Fritz; Gasch, Kristina; Bieber, Claudia; Stalder, Gabrielle L; Gerritsmann, Hanno; Ruf, Thomas

2016-07-15

Basking can substantially reduce thermoregulatory energy expenditure of mammals. We tested the hypothesis that the largely white winter fur of hamsters (Phodopus sungorus), originating from Asian steppes, may be related to camouflage to permit sun basking on or near snow. Winter-acclimated hamsters in our study were largely white and had a high proclivity to bask when resting and torpid. Resting hamsters reduced metabolic rate (MR) significantly (>30%) when basking at ambient temperatures (Ta) of ∼15 and 0°C. Interestingly, body temperature (Tb) also was significantly reduced from 34.7±0.6°C (Ta 15°C, not basking) to 30.4±2.0°C (Ta 0°C, basking), which resulted in an extremely low (thermal conductance. Induced torpor (food withheld) during respirometry at Ta 15°C occurred on 83.3±36.0% of days and the minimum torpor MR was 36% of basal MR at an average Tb of 22.0±2.6°C; movement to the basking lamp occurred at Tb50%) during radiant heat-assisted rewarming; however, radiant heat per se without an endogenous contribution by animals did not strongly affect metabolism and Tb during torpor. Our data show that basking substantially modifies thermal energetics in hamsters, with a drop of resting Tb and MR not previously observed and a reduction of rewarming costs. The energy savings afforded by basking in hamsters suggest that this behaviour is of energetic significance not only for mammals living in deserts, where basking is common, but also for P. sungorus and probably other cold-climate mammals. © 2016. Published by The Company of Biologists Ltd.

VGF-derived peptide, TLQP-21, regulates food intake and body weight in Siberian hamsters.

Science.gov (United States)

Jethwa, Preeti H; Warner, Amy; Nilaweera, Kanishka N; Brameld, John M; Keyte, John W; Carter, Wayne G; Bolton, Neil; Bruggraber, Michael; Morgan, Peter J; Barrett, Perry; Ebling, Francis J P

2007-08-01

The Siberian hamster survives winter by decreasing food intake and catabolizing abdominal fat reserves, resulting in a sustained, profound loss of body weight. VGF gene expression is photoperiodically regulated in the hypothalamus with significantly higher expression in lean Siberian hamsters. The aim of this study was to investigate the role of VGF in regulating these seasonal cycles by determining the effects of a VGF-derived peptide (TLQP-21) on food intake and body weight. Acute intracerebroventricular administration of TLQP-21 decreased food intake, and chronic treatment caused a sustained reduction in food intake and body weight and decreased abdominal fat depots. Behavioral analysis revealed that TLQP-21 reduced meal size but not the frequency of feeding bouts, suggesting a primary action on satiety. Hamsters treated with TLQP-21 lost a similar amount of weight as a pair-fed group in which food intake was matched to that of the TLQP-21-treated group. Central or peripheral treatment with TLQP-21 did not produce a significant effect on resting metabolic rate. We conclude that the primary action of TLQP-21 is to decrease food intake rather than increase energy expenditure. TLQP-21 treatment caused a decrease in UCP-1 mRNA in brown adipose tissue, but hypothalamic expression of orexigenic and anorexigenic neuropeptide genes remained unchanged after TLQP-21 treatment, although compensatory increases in NPY and AgRP mRNA were observed in the pair-fed hamsters. The effects of TLQP-21 administration are similar to those in hamsters in short days, suggesting that increased VGF activity may contribute to the hypophagia that underlies the seasonal catabolic state.

Carcinogen risk assessment

International Nuclear Information System (INIS)

Hazelwoold, R.N.

1987-01-01

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

Hamster endogenous retrovirus (HaER) - distinct properties of structural proteins and DNA polymerase

International Nuclear Information System (INIS)

Goldschmied-Reouven, A.; Yaniv, A.

1983-01-01

The structural proteins as well as some features of the RNA-dependent DNA polymerase of the hamster endogenous retrovirus (HaER) were examined. The polypeptide pattern of this virus is substantially different from that of other known retroviruses in containing major polypeptides with molecular weights of 68000, 59000, 27000, 24000 daltons. Double antibody competitive radioimmunoassays showed that the HaER particles do not share any detectable antigenic relatedness with the murine viruses' p30, but manifest a considerable relatedness with the feline leukemia virus p27 and a slight cross-reactivity with the rat virus major protein. The RNA-dependent DNA polymerase of HaER virus has a molecular size of approximately 73000 daltons and in contrast to other mammalian retroviruses shows no significant preference for Mn 2+ over Mg 2+ . Apart from the lack of antigenic relatedness between the HaER virus proteins and the p30 protein of murine viruses, there is also no antigenic relatedness between HaER and murine viruses insofar as their DNA polymerase is concerned. (Author)

Behavioral and hormonal changes associated with the infective dose in experimental taeniasis in golden hamsters (Mesocricetus auratus).

Science.gov (United States)

Domínguez-Roldan, Rosa; Hallal-Calleros, Claudia; Sciutto, Edda; Hernández, Marisela; Aguirre-Flores, Virginio; García-Jiménez, Sara; Báez-Saldaña, Armida; Flores-Pérez, Fernando Iván

2016-07-01

It has been reported that behavioral changes relate to infection in different parasitoses. However, the relation between the extent of the behavioral changes and the magnitude of the infection has been scarcely studied. The aim of this study was to evaluate the relationship between different doses of infection and the behavioral changes induced in the experimental Taenia pisiformis taeniasis in golden hamsters. Groups of nine hamsters were infected with three or six T. pisiformis metacestodes. The locomotor activity was quantified daily in an open field test during the 21 days after infection; anxiety test was performed in an elevated plus-maze with a dark/light area at 7, 14 and 21 days post-infection, and serum cortisol levels were determined by radioimmunoassay before infection and at day 22 after infection. The challenge itself induced modifications on behavior and cortisol levels in hamsters, with or without successful infection (taenia development). Animals challenged with three metacestodes induced a decrease in locomotor activity and an increase in anxiety in infected animals. A higher and earlier decrease in locomotor activity and increased anxiety levels were observed in hamsters challenged with six cysticerci, which were accompanied by higher levels of sera cortisol at the end of the experiment. At necropsy, 44-55% of hamster became infected with an efficiency of implantation of 22-26%, challenged with three or six cysticerci respectively. The challenge of hamsters with metacestodes, promote behavioral changes in an extent dependent on the magnitude of the challenge, disregarding the effectiveness of the infection. Copyright © 2016 Elsevier Inc. All rights reserved.

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

Effect of prenatal and postnatal photoperiod on spermatogenic development in the Djungarian hamster (Phodopus sungorus sungorus)

NARCIS (Netherlands)

van Haaster, L. H.; van Eerdenburg, F. J.; de rooij, D. G.

1993-01-01

The effect of the pre- and postnatal daylength on the start of spermatogenesis and further testicular development from day 4 up to day 127 was investigated in Djungarian hamsters. Hamsters were either gestated under long (16 h light:8 h dark) photoperiod and reared under long or short (4 h light:20

Mutagenicity of 8-methoxypsoralen and long-wave ultraviolet irradiation in V-79 Chinese hamster cells

International Nuclear Information System (INIS)

Burger, P.M.; Simons, J.W.I.M.

1979-01-01

The effect of 8-methoxypsoralen (8-MOP) and long-wave ultraviolet irradiation (UVA) on cell killing and mutation induction was studied in V-79 Chinese hamster cells. No effect was observed after treatment with 8-MOP alone (50 μg/ml, 4 h), UVA alone (9000 J/m 2 ), or 8-MOP metobolized by rat-liver microsomes. Combined treatment with 8-MOP and UVA induced both cell killing and mutation. This was also observed under conditins approaching patient treatment with PUVA photochemotherapy with respect to the concentration of 8-MOP in the skin and the amount of UVA received by the epidermal cells. A simple relation proved to apply for mutation induction under different treatment conditions: 5.5 X 10 -8 per J/m 2 per μg 8-MOP/ml. On this basis the mutation induction in dividing cells per session of PUVA-photochemotherapy amounts to 12.4 X 10 -5 , which is probably an over-estimation. (Auth.)

Early Postnatal Development of the South African Hamster ...

African Journals Online (AJOL)

The South African Hamster Mystromys albicaudatus has been bred in the laboratory of the Medical Ecology Centre since 1941. It is of interest taxonomically in that it is the sole representative left in Africa of the subfamily Cricetinae (Davis 1962). It has been used in Medical Research on poliomyelitis, benign histoplasmosis, ...

Carcinogen-induced damage to DNA

International Nuclear Information System (INIS)

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

1979-01-01

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

Voluntary exercise increases resilience to social defeat stress in Syrian hamsters.

Science.gov (United States)

Kingston, Rody C; Smith, Michael; Lacey, Tiara; Edwards, Malcolm; Best, Janae N; Markham, Chris M

2018-05-01

Exposure to social stressors can cause profound changes in an individual's well-being and can be an underlying factor in the etiology of a variety of psychopathologies, such as post-traumatic stress disorder (PTSD). In Syrian hamsters, a single social defeat experience results in behavioral changes collectively known as conditioned defeat (CD), and includes an abolishment of territorial aggression and the emergence of high levels of defensive behaviors. In contrast, voluntary exercise has been shown to promote stress resilience and can also have anxiolytic-like effects. Although several studies have investigated the resilience-inducing effects of voluntary exercise after exposure to physical stressors, such as restraint and electric shock, few studies have examined whether exercise can impart resilience in response to ethologically-based stressors, such as social defeat. In Experiment 1, we tested the hypothesis that voluntary exercise can have anxiolytic-like effects in socially defeated hamsters. In the elevated plus maze, the exercise group exhibited a significant reduction in risk assessment, a commonly used index of anxiety, compared to the no-exercise group. In the open-field test, animals in the exercise group exhibited a significant reduction in locomotor behavior and rearing, also an indication of an anxiolytic-like effect of exercise. In Experiment 2, we examined whether exercise can reverse the defeat-induced potentiation of defensive behaviors using the CD model. Socially defeated hamsters in the exercise group exhibited significantly lower levels of defensive/submissive behaviors compared to the no-exercise group upon exposure to the resident aggressor. Taken together, these results are among the first to suggest that voluntary exercise may promote resilience to social defeat stress in Syrian hamsters. Copyright © 2018 Elsevier Inc. All rights reserved.

Protective effect of black seed oil of nigella sativa in rats during tumour induction and radiotherapy

International Nuclear Information System (INIS)

Hussein, H.I.M.

2007-01-01

the present study was conducted to evaluate the potency of nigella sativa freshly crushed seeds (0.42 g/kg body weight) or oil ( 2.5 ml/kg body weight) for preventing tumor induction through exposure of rats to a common pollutant (1,4- dioxane) as a promoter under condition of the presence of an initiator ( N-nitrosodiethylamine). the antitumor effect was evaluated alone or in combination with low doses of γ-irradiation as a route of cancer treatment. female swiss albino rats were administered orally twice weekly with nigella sativa before and during exposure of rats to the carcinogenic compounds. animals were exposed to 3 doses of radiation (3 Gy/dose) day after day 2 weeks before the end of the experiment . the animals were sacrificed after one week of radiation, homocysteine, glutathione, lipid peroxide, GGT activity, nitric oxide, total protein, albumin and bilirubin levels were estimated in blood after 7 and 12 months from the start of the experiment .this work also includes histopathological study.rats injected with the carcinogenic compounds showed marked elevation in homocysteine, GGT activity, nitric oxide, bilirubin and lipid peroxide levels accompanied by a significant decrease in glutathione, total proteins and albumin levels

Autoradiography in fetal golden hamsters treated with tritiated diethylnitrosamine

International Nuclear Information System (INIS)

Reznik-Schueller, H.M.; Hague, B.F. Jr.

1981-01-01

Tritiated diethylnitrosamine was administered to female Syrian golden hamsters on each of the last 4 days (days 12-15) of pregnancy. The distribution of bound radioactivity was monitored by light microscopic autoradiography of fetal tracheas and livers, the placentas, and the maternal livers. In the trachea, the fetal target organ, bound radioactivity was restricted to the respiratory epithelium, where diethylnitrosamine-induced tracheal tumors arise. Mucous cells and nonciliated stem cells were identified as the principal sites of binding; other cell types within the tracheal epithelium contained only small amounts of bound radioactivity. The level of binding observed in the fetal trachea increased steadily from day 12 to day 15, which correlated well with the levels of differentiation of this tissue during this period. This observation also agrees with the previously reported observation that tumor incidence increases from 40 to 95% in Syrian golden hamsters between days 12 and 15

Foetal exposure to food and environmental carcinogens in human beings.

Science.gov (United States)

Myöhänen, Kirsi; Vähäkangas, Kirsi

2012-02-01

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

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...

Diphenylarsinic acid, a chemical warfare-related neurotoxicant, promotes liver carcinogenesis via activation of aryl hydrocarbon receptor signaling and consequent induction of oxidative DAN damage in rats

International Nuclear Information System (INIS)

Wei, Min; Yamada, Takanori; Yamano, Shotaro; Kato, Minoru; Kakehashi, Anna; Fujioka, Masaki; Tago, Yoshiyuki; Kitano, Mistuaki; Wanibuchi, Hideki

2013-01-01

Diphenylarsinic acid (DPAA), a chemical warfare-related neurotoxic organic arsenical, is present in the groundwater and soil in some regions of Japan due to illegal dumping after World War II. Inorganic arsenic is carcinogenic in humans and its organic arsenic metabolites are carcinogenic in animal studies, raising serious concerns about the carcinogenicity of DPAA. However, the carcinogenic potential of DPAA has not yet been evaluated. In the present study we found that DPAA significantly enhanced the development of diethylnitrosamine-induced preneoplastic lesions in the liver in a medium-term rat liver carcinogenesis assay. Evaluation of the expression of cytochrome P450 (CYP) enzymes in the liver revealed that DPAA induced the expression of CYP1B1, but not any other CYP1, CYP2, or CYP3 enzymes, suggesting that CYP1B1 might be the enzyme responsible for the metabolic activation of DPAA. We also found increased oxidative DNA damage, possibly due to elevated CYP1B1 expression. Induction of CYP1B1 has generally been linked with the activation of AhR, and we found that DPAA activates the aryl hydrocarbon receptor (AhR). Importantly, the promotion effect of DPAA was observed only at a dose that activated the AhR, suggesting that activation of AhR and consequent induction of AhR target genes and oxidative DNA damage plays a vital role in the promotion effects of DPAA. The present study provides, for the first time, evidence regarding the carcinogenicity of DPAA and indicates the necessity of comprehensive evaluation of its carcinogenic potential using long-term carcinogenicity studies. - Highlights: • DPAA, an environmental neurotoxicant, promotes liver carcinogenesis in rats. • DPAA is an activator of AhR signaling pathway. • DPAA promoted oxidative DNA damage in rat livers. • AhR target gene CYP 1B1 might be involved in the metabolism of DPAA

Diphenylarsinic acid, a chemical warfare-related neurotoxicant, promotes liver carcinogenesis via activation of aryl hydrocarbon receptor signaling and consequent induction of oxidative DAN damage in rats

Energy Technology Data Exchange (ETDEWEB)

Wei, Min; Yamada, Takanori; Yamano, Shotaro; Kato, Minoru; Kakehashi, Anna; Fujioka, Masaki; Tago, Yoshiyuki; Kitano, Mistuaki; Wanibuchi, Hideki, E-mail: wani@med.osaka-cu.ac.jp

2013-11-15

Diphenylarsinic acid (DPAA), a chemical warfare-related neurotoxic organic arsenical, is present in the groundwater and soil in some regions of Japan due to illegal dumping after World War II. Inorganic arsenic is carcinogenic in humans and its organic arsenic metabolites are carcinogenic in animal studies, raising serious concerns about the carcinogenicity of DPAA. However, the carcinogenic potential of DPAA has not yet been evaluated. In the present study we found that DPAA significantly enhanced the development of diethylnitrosamine-induced preneoplastic lesions in the liver in a medium-term rat liver carcinogenesis assay. Evaluation of the expression of cytochrome P450 (CYP) enzymes in the liver revealed that DPAA induced the expression of CYP1B1, but not any other CYP1, CYP2, or CYP3 enzymes, suggesting that CYP1B1 might be the enzyme responsible for the metabolic activation of DPAA. We also found increased oxidative DNA damage, possibly due to elevated CYP1B1 expression. Induction of CYP1B1 has generally been linked with the activation of AhR, and we found that DPAA activates the aryl hydrocarbon receptor (AhR). Importantly, the promotion effect of DPAA was observed only at a dose that activated the AhR, suggesting that activation of AhR and consequent induction of AhR target genes and oxidative DNA damage plays a vital role in the promotion effects of DPAA. The present study provides, for the first time, evidence regarding the carcinogenicity of DPAA and indicates the necessity of comprehensive evaluation of its carcinogenic potential using long-term carcinogenicity studies. - Highlights: • DPAA, an environmental neurotoxicant, promotes liver carcinogenesis in rats. • DPAA is an activator of AhR signaling pathway. • DPAA promoted oxidative DNA damage in rat livers. • AhR target gene CYP 1B1 might be involved in the metabolism of DPAA.

Oxidative metabolites of diethylstilbestrol in the fetal Syrian golden hamster

International Nuclear Information System (INIS)

Maydl, R.; Metzler, M.

1984-01-01

14 C-Diethylstilbestrol was administered orally, intraperitoneally, and intrafetally to 15-day pregnant hamsters at a dose of 20 mg/kg body weight, and the radioactivity was determined in the fetus, placenta, and maternal liver after 6 hours. Significant amounts of radioactivity were found in these tissues in every case, indicating maternal-fetal and fetal-maternal transfer of diethylstilbestrol. Part of the radioactivity found in the tissues could not be extracted even after excessive washing. This implied the presence of reactive metabolites. In the fetal and placental extracts, eight oxidative metabolites of diethylstilbestrol were identified by mass fragmentography as hydroxy- and methoxy-derivatives of diethylstilbestrol, pseudodiethylstilbestrol, and dienestrol. The presence of oxidative metabolites in the hamster fetus and the covalent binding to tissue macromolecules are possibly associated with the fetotoxic effects of diethylstilbestrol

Inhibitory effect of vitamin D-binding protein-derived macrophage activating factor on DMBA-induced hamster cheek pouch carcinogenesis and its derived carcinoma cell line.

Science.gov (United States)

Toyohara, Yukiyo; Hashitani, Susumu; Kishimoto, Hiromitsu; Noguchi, Kazuma; Yamamoto, Nobuto; Urade, Masahiro

2011-07-01

This study investigated the inhibitory effect of vitamin D-binding protein-derived macrophage-activating factor (GcMAF) on carcinogenesis and tumor growth, using a 9,10-dimethyl-1,2-benzanthracene (DMBA)-induced hamster cheek pouch carcinogenesis model, as well as the cytocidal effect of activated macrophages against HCPC-1, a cell line established from DMBA-induced cheek pouch carcinoma. DMBA application induced squamous cell carcinoma in all 15 hamsters of the control group at approximately 10 weeks, and all 15 hamsters died of tumor burden within 20 weeks. By contrast, 2 out of the 14 hamsters with GcMAF administration did not develop tumors and the remaining 12 hamsters showed a significant delay of tumor development for approximately 3.5 weeks. The growth of tumors formed was significantly suppressed and none of the hamsters died within the 20 weeks during which they were observed. When GcMAF administration was stopped at the 13th week of the experiment in 4 out of the 14 hamsters in the GcMAF-treated group, tumor growth was promoted, but none of the mice died within the 20-week period. On the other hand, when GcMAF administration was commenced after the 13th week in 5 out of the 15 hamsters in the control group, tumor growth was slightly suppressed and all 15 hamsters died of tumor burden. However, the mean survival time was significantly extended. GcMAF treatment activated peritoneal macrophages in vitro and in vivo, and these activated macrophages exhibited a marked cytocidal effect on HCPC-1 cells. Furthermore, the cytocidal effect of activated macrophages was enhanced by the addition of tumor-bearing hamster serum. These findings indicated that GcMAF possesses an inhibitory effect on tumor development and growth in a DMBA-induced hamster cheek pouch carcinogenesis model.

Genotoxicity of Swimming Pool Water and Carcinogenicity of Drinking Water

Science.gov (United States)

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

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

Science.gov (United States)

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

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.

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

Science.gov (United States)

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

2008-07-01

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

Experimental pulmonary carcinogenesis by radon and its daughters

International Nuclear Information System (INIS)

Sato, Fumiaki

1989-01-01

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

Het effect van hamsterbeheer op de overwintering bij hamsters

NARCIS (Netherlands)

Beek, van der M.; Ligtenberg, H.; Haye, la M.J.J.

2006-01-01

De afgelopen decennia is het aantal hamsters (Cricetus cricetus) in Nederland sterk afgenomen. Door onderzoek te verrichten naar de levenscyclus en naar de effecten van agrarisch beheer is getracht de afname te verklaren en oplossingen aan te dragen. In voorjaar 2006 is een verkennend onderzoek

In vitro and in vivo studies of the carcinogenic, toxic and genotoxic activities of the air pollutants SO/sub 2/ and NO/sub x/, separately and in combination with carcinogenic polycyclic aromatic hydrocarbons and N-nitrosamines

Energy Technology Data Exchange (ETDEWEB)

Zeller, W J; Klein, R G; Pool, B L; Schmezer, P; Horsch, F; Filby, W G; Fund, N; Gross, S; Hanisch, B; Kilz, E; Seidel, A [comps.

1988-04-01

In the course of our studies directed at elucidating biological effects of the air pollutants SO/sub 2/ and NO/sub x/ it was found, that the activity of lactate dehydrogenase (LDH) is inhibited by SO/sub 2/. This effect was observed in vitro and in vivo and is based on a sulfite- and not on a sulfate-mediated action. NO/sub x/ and SO/sub 2/ reduce DNA single strand breaks induced by B(a)P in fetal hamster lung cells in vitro and SO/sub 2/ reduces DNA single strand breaks induced by AMMN in primary cultures of rat hepatocytes. The postulated mechanisms of action are discussed. Sulfite itself induces DNA-amplification in SV40 transformed CO60 cells; but an increase in the amplification rate induced by B(a)P or 7,12-DMBA was not observed. The in vitro genotoxicity (DNA single strand breaks) of 3 nitrosamines (AMMN, NDMA, NMBzA) is reduced in rat hepatocytes from donor animals pretreated with 50 ppm SO/sub 2/ for 2 weeks. Inhalation of NO/sub x/ by rats reduced the activities of AHH, NDMA-D and GST in hepatocytes and of GST in lung cells. Following SO/sub 2/ inhalation NDMA-D activity in the liver is increased and GST activity in the lung is decreased. In a current in vivo long-term inhalation study of NDMA+-SO/sub 2/ or NO/sub x/ first tumors of the nasal cavity are already observed after a total dose of 2 mg NDMA/animal.

Effects of combined exposure of F344 rats to radiation and chronically inhaled cigarette smoke

International Nuclear Information System (INIS)

Finch, G.L.; Nikula, K.J.; Barr, E.B.

1995-01-01

Nuclear workers may be exposed to radiation in various forms, such as low-LET γ-irradiation or α-irradiation from inhaled 239 PuO 2 particles. These workers may then have increased risk for lung cancer compared to the general population. Of additional concern is the possibility that interactions between radiation and other carcinogens may increase the risk of cancer induction, compared to the risks from either type of agent alone. An important and common lung carcinogen is cigarette smoke. The purpose of this project is to better determine the combined effects of chronically inhaled cigarette smoke and either inhaled 239 PuO 2 or external, thoracic X-irradiation on the induction of lung cancer in rats. Histologic and dosimetric evaluations of rats in the CS + 239 PuO 2 study continue, and the study of CS + X rays is beginning

Enhancement of postreplication repair in Chinese hamster cells

International Nuclear Information System (INIS)

D'Ambrosio, S.M.; Setlow, R.B.

1976-01-01

Alkaline sedimentation profiles of pulse-labeled DNA from Chinese hamster cells showed that DNA from cells treated with N-acetoxy-acetylaminofluorene or ultraviolet radiation was made in segments smaller than those from untreated cells. Cells treated with a small dose (2.5 μM) of N-acetoxy-acetylaminofluorene or(2.5 J . m -2 ) 254-nm radiation, several hours before a larger dose (7 to 10 μM) of N-acetoxy-acetylaminofluorene or 5.0 J . m -2 of 254-nm radiation, also synthesized small DNA after the second dose. However, the rate at which this small DNA was joined together into parental size was appreciably greater than in absence of the small dose. This enhancement of postreplication repair (as a result of the initial small dose) was not observed when cells were incubated with cycloheximide between the two treatments. The results suggest that N-acetoxy-acetylaminofluorene and ultraviolet-damaged DNA from Chinese hamster cells are repaired by similar postreplicative mechanisms that require de novo protein synthesis for enhancement

Induction of prophage lambda by chlorinated organics: Detection of some single-species/single-site carcinogens

Energy Technology Data Exchange (ETDEWEB)

DeMarini, D.M.; Brooks, H.G. (Environmental Protection Agency, Research Triangle Park, NC (United States))

1992-01-01

Twenty-eight chlorinated organic compounds were evaluated for their ability to induce DNA damage using the Microscreen prophage-induction assay in Escherichia coli. Comparison of the performance characteristics of the prophage-induction and Salmonella assays to rodent carcinogenicity assays showed that the prophage-induction assay had a somewhat higher specificity than did the Salmonella assay (70% vs. 50%); sensitivity, concordance, and positive and negative predictivity were similar for the two microbial assays. The Microscreen prophage-induction assay failed to detect eight carcinogens, perhaps due to toxicity or other unknown factors; five of these eight carcinogens were detected by the Salmonella assay. However, the prophage-induction assay did detect six carcinogens that were not detected by the Salmonella assay, and five of these were single-species, single-site carcinogens, mostly mouse liver carcinogens. Some of these carcinogens, such as the chloroethanes, produce free radicals, which may be the basis for their carcinogenicity and ability to induce prophage. The prophage-induction (or other SOS) assay may be useful in identifying some genotoxic chlorinated carcinogens that induce DNA damage that do not revert the standard Salmonella tester strains.

Autoimmunity in type 1 diabetes mellitus: a rat model

International Nuclear Information System (INIS)

Liu, Z.

1987-01-01

In this study, we have sought to isolate in vitro, from acutely diabetic BB rats, cytotoxic T lymphocytes, which exhibit specific cytotoxicity toward islet cells. Thoracic duct lymphocytes (TDL) from acutely diabetic BB rats cultured with irradiated MHC matched (RT1.u) islet cells and dendritic cells in vitro were shown to be specifically cytotoxic to MHC matched and mismatched allogeneic (RT1.1) and xenogeneic (hamster) islet target cells in a 3 H-leucine release assay. Two cell lines (V1A8 and V1D11) derived from the TDL culture showed similar patterns of non-MHC restricted islet cell killing which could be blocked by islet cells and cultured rat insulinoma cells (RIN5mF) but not by non-islet cells of various tissue origins. Both V1A8 and V1D11 were not cytotoxic to Natural Killer (NK) sensitive target cells, G1TC and YAC-1. Conventional surface markers for rat helper and suppressor/cytotoxic T cells were not detectable on either cell lines. The V1D11 cell line was positive for W 3/13 (rat T/NK marker) on OX-19 (rat T/macrophage marker), whereas the V1A8 cell line was only positive for W 3/13

Hypothalamic ventricular ependymal thyroid hormone deiodinases are an important element of circannual timing in the Siberian hamster (Phodopus sungorus.

Directory of Open Access Journals (Sweden)

Annika Herwig

Full Text Available Exposure to short days (SD induces profound changes in the physiology and behaviour of Siberian hamsters, including gonadal regression and up to 30% loss in body weight. In a continuous SD environment after approximately 20 weeks, Siberian hamsters spontaneously revert to a long day (LD phenotype, a phenomenon referred to as the photorefractory response. Previously we have identified a number of genes that are regulated by short photoperiod in the neuropil and ventricular ependymal (VE cells of the hypothalamus, although their importance and contribution to photoperiod induced physiology is unclear. In this refractory model we hypothesised that the return to LD physiology involves reversal of SD expression levels of key hypothalamic genes to their LD values and thereby implicate genes required for LD physiology. Male Siberian hamsters were kept in either LD or SD for up to 39 weeks during which time SD hamster body weight decreased before increasing, after more than 20 weeks, back to LD values. Brain tissue was collected between 14 and 39 weeks for in situ hybridization to determine hypothalamic gene expression. In VE cells lining the third ventricle, expression of nestin, vimentin, Crbp1 and Gpr50 were down-regulated at 18 weeks in SD photoperiod, but expression was not restored to the LD level in photorefractory hamsters. Dio2, Mct8 and Tsh-r expression were altered by SD photoperiod and were fully restored, or even exceeded values found in LD hamsters in the refractory state. In hypothalamic nuclei, expression of Srif and Mc3r mRNAs was altered at 18 weeks in SD, but were similar to LD expression values in photorefractory hamsters. We conclude that in refractory hamsters not all VE cell functions are required to establish LD physiology. However, thyroid hormone signalling from ependymal cells and reversal of neuronal gene expression appear to be essential for the SD refractory response.

Changes in responsiveness of rat tracheal epithelial cells to growth factors during preneoplastic transformation in cell culture

International Nuclear Information System (INIS)

Thomassen, D.G.

1988-01-01

Preneoplastic rat tracheal epithelial (RTE) cell lines require fewer growth factors for clonal proliferation in culture than normal cells. Serum-free media missing various combinations of growth factors (e.g., cholera toxin, serum albumin, epidermal growth factor, hydrocortisone) required for proliferation of normal, but not preneoplastic, RTE cells can be used to select for carcinogen-induced preneoplastic variants having an increased proliferative potential in culture. These results suggest that reductions in growth factor requirements are primary events in the carcinogenic process. (author)

Enhanced replication of UV-damaged Simian virus 40 DNA in carcinogen-treated mammalian cells

International Nuclear Information System (INIS)

Maga, J.A.

1983-01-01

The replication of UV-damaged Simian virus 40 (SV40) in carcinogen-treated monkey cells has been studied to elucidate the mechanism of carcinogen-enhanced reactivation. Carcinogen enhanced reactivation is the observed increase in UV-irradiated virus survival in host cells treated with low doses of carcinogen compared to UV-irradiated virus survival in untreated hosts. Carcinogen treatment of monkey kidney cells with either N-acetoxy-2-acetylaminofluorene (AAAF) or UV radiation leads to an enhanced capacity to replicate UV-damaged virus during the first round of infection. To further define the mechanism leading to enhanced replication, a detailed biochemical analysis of replication intermediates in carcinogen-treated cells was performed. Several conclusions can be drawn. First enhanced replication can be observed in the first four rounds of replication after UV irradiation of viral templates. The second major finding is that the relaxed circular intermediate model proposed for the replication of UV-damaged templates in untreated cells appears valid for replication of UV-damaged templates in carcinogen-treated cells. Possible mechanisms and the supporting evidence are discussed and future experiments outlined

S-(3-Aminobenzanthron-2-yl)cysteine in the globin of rats as a novel type of adduct and possible biomarker of exposure to 3-nitrobenzanthrone, a potent environmental carcinogen.

Science.gov (United States)

Linhart, Igor; Hanzlíková, Iveta; Mráz, Jaroslav; Dušková, Šárka

2017-10-01

3-Nitrobenzanthrone (3-NBA), a potent environmental mutagen and carcinogen, is known to be activated in vivo to 3-benzanthronylnitrenium ion which forms both NH and C2-bound adducts with DNA and also reacts with glutathione giving rise to urinary 3-aminobenzanthron-2-ylmercapturic acid. In this study, acid hydrolysate of globin from rats dosed intraperitoneally with 3-NBA was analysed by HPLC/MS to identify a novel type of cysteine adduct, 3-aminobenzanthron-2-ylcysteine (3-ABA-Cys), confirmed using a synthesised standard. The 3-ABA-Cys levels in globin peaked after single 3-NBA doses of 1 and 2 mg/kg on day 2 to attain 0.25 and 0.49 nmol/g globin, respectively, thereafter declining slowly to 70-80% of their maximum values during 15 days. After dosing rats for three consecutive days with 1 mg 3-NBA/kg a significant cumulation of 3-ABA-Cys in globin was observed. 3-ABA-Cys was also found in the plasma hydrolysate. Herein, after dosing with 1 and 2 mg 3-NBA/kg the adduct levels peaked on day 1 at 0.15 and 0.51 nmol/ml plasma, respectively, thereafter declining rapidly to undetectable levels on day 15. In addition, sulphinamide adducts were also found in the exposed rats, measured indirectly as 3-aminobenzanthrone (3-ABA) split off from globin by mild acid hydrolysis. Levels of both types of adducts in the globin samples parallelled very well with 3-ABA/3-ABA-Cys ratio being around 1:8. In conclusion, 3-ABA-Cys is the first example of arylnitrenium-cysteine adduct in globin representing a new promising class of biomarkers to assess cumulative exposures to aromatic amines, nitroaromatics and heteroaromatic amines.

Food derived carcinogenic amnoimidazoazaarenes

DEFF Research Database (Denmark)

Frandsen, Henrik

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

Andes Virus M Genome Segment is Not Sufficient to Confer the Virulence Associated With Andres Virus in Syrian Hamsters

National Research Council Canada - National Science Library

McElroy, A

2004-01-01

...) in North and South America, respectively. Although ANDV causes a lethal HPS-like disease in hamsters, SNV, and all other HPS-associated hantaviruses that have been tested, cause asymptomatic infections of laboratory animals, including hamsters...

Red algae (Gelidium amansii) hot-water extract ameliorates lipid metabolism in hamsters fed a high-fat diet.

Science.gov (United States)

Yang, Tsung-Han; Yao, Hsien-Tsung; Chiang, Meng-Tsan

2017-10-01

The purpose of this study was to investigate the effects of Gelidium amansii (GA) hot-water extracts (GHE) on lipid metabolism in hamsters. Six-week-old male Syrian hamsters were used as the experimental animals. Hamsters were divided into four groups: (1) control diet group (CON); (2) high-fat diet group (HF); (3) HF with GHE diet group (HF + GHE); (4) HF with probucol diet group (HF + PO). All groups were fed the experimental diets and drinking water ad libitum for 6 weeks. The results showed that GHE significantly decreased body weight, liver weight, and adipose tissue (perirenal and paraepididymal) weight. The HF diet induced an increase in plasma triacylglycerol (TG), total cholesterol (TC), low-density lipoprotein cholesterol and very-low-density lipoprotein cholesterol levels. However, GHE supplementation reversed the increase of plasma lipids caused by the HF diet. In addition, GHE increased fecal cholesterol, TG and bile acid excretion. Lower hepatic TC and TG levels were found with GHE treatment. GHE reduced hepatic sterol regulatory element-binding proteins (SREBP) including SREBP 1 and SREBP 2 protein expressions. The phosphorylation of adenosine monophosphate (AMP)-activated protein kinase (AMPK) protein expression in hamsters was decreased by the HF diet; however, GHE supplementation increased the phosphorylation of AMPK protein expression. Our results suggest that GHE may ameliorate lipid metabolism in hamsters fed a HF diet. Copyright © 2017. Published by Elsevier B.V.

Red algae (Gelidium amansii hot-water extract ameliorates lipid metabolism in hamsters fed a high-fat diet

Directory of Open Access Journals (Sweden)

Tsung-Han Yang

2017-10-01

Full Text Available The purpose of this study was to investigate the effects of Gelidium amansii (GA hot-water extracts (GHE on lipid metabolism in hamsters. Six-week-old male Syrian hamsters were used as the experimental animals. Hamsters were divided into four groups: (1 control diet group (CON; (2 high-fat diet group (HF; (3 HF with GHE diet group (HF + GHE; (4 HF with probucol diet group (HF + PO. All groups were fed the experimental diets and drinking water ad libitum for 6 weeks. The results showed that GHE significantly decreased body weight, liver weight, and adipose tissue (perirenal and paraepididymal weight. The HF diet induced an increase in plasma triacylglycerol (TG, total cholesterol (TC, low-density lipoprotein cholesterol and very-low-density lipoprotein cholesterol levels. However, GHE supplementation reversed the increase of plasma lipids caused by the HF diet. In addition, GHE increased fecal cholesterol, TG and bile acid excretion. Lower hepatic TC and TG levels were found with GHE treatment. GHE reduced hepatic sterol regulatory element-binding proteins (SREBP including SREBP 1 and SREBP 2 protein expressions. The phosphorylation of adenosine monophosphate (AMP-activated protein kinase (AMPK protein expression in hamsters was decreased by the HF diet; however, GHE supplementation increased the phosphorylation of AMPK protein expression. Our results suggest that GHE may ameliorate lipid metabolism in hamsters fed a HF diet.

Cutaneous leishmaniasis in the dorsal skin of hamsters: a useful model for the screening of antileishmanial drugs.

Science.gov (United States)

Robledo, Sara M; Carrillo, Lina M; Daza, Alejandro; Restrepo, Adriana M; Muñoz, Diana L; Tobón, Jairo; Murillo, Javier D; López, Anderson; Ríos, Carolina; Mesa, Carol V; Upegui, Yulieth A; Valencia-Tobón, Alejandro; Mondragón-Shem, Karina; Rodríguez, Berardo; Vélez, Iván D

2012-04-21

Traditionally, hamsters are experimentally inoculated in the snout or the footpad. However in these sites an ulcer not always occurs, measurement of lesion size is a hard procedure and animals show difficulty to eat, breathe and move because of the lesion. In order to optimize the hamster model for cutaneous leishmaniasis, young adult male and female golden hamsters (Mesocricetus auratus) were injected intradermally at the dorsal skin with 1 to 1.5 x l0(7) promastigotes of Leishmania species and progression of subsequent lesions were evaluated for up to 16 weeks post infection. The golden hamster was selected because it is considered the adequate bio-model to evaluate drugs against Leishmania as they are susceptible to infection by different species. Cutaneous infection of hamsters results in chronic but controlled lesions, and a clinical evolution with signs similar to those observed in humans. Therefore, the establishment of the extent of infection by measuring the size of the lesion according to the area of indurations and ulcers is feasible. This approach has proven its versatility and easy management during inoculation, follow up and characterization of typical lesions (ulcers), application of treatments through different ways and obtaining of clinical samples after different treatments. By using this method the quality of animal life regarding locomotion, search for food and water, play and social activities is also preserved.

Morpho-chemical characterization and surface properties of carcinogenic zeolite fibers

International Nuclear Information System (INIS)

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

2016-01-01

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

Toxic and carcinogenic agents in dry and moist snuff.

Science.gov (United States)

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

1987-12-01

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

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.

Evaluation of 4,4'-diaminodiphenyl ether in the rat comet assay: Part of the Japanese Center for the Validation of Alternative Methods (JaCVAM)-initiative international validation study of in vivo rat alkaline comet assay.

Science.gov (United States)

Priestley, Catherine C; Walker, Joanne S; O'Donovan, Michael R; Doherty, Ann T

2015-07-01

As a part of the Japanese Center for the Validation of Alternative Methods (JaCVAM)-initiative international validation study of the in vivo rat alkaline comet assay, 4,4'-diaminodiphenyl ether (DPE), a known rodent genotoxic carcinogen, was tested in this laboratory. Sprague Dawley rats (7-9 weeks of age) were given three oral doses of DPE, 24 and 21 h apart and liver or stomach sampled 3h after the final dose. Under the conditions of the test, no increases in DNA damage in liver and stomach were observed with DPE (up to 200 mg/kg/day). A dose-dependent decrease in DNA migration, compared to vehicle controls, was noted for DPE in rat stomach. Further analysis is required to elucidate fully whether this decrease is a consequence of the mode of action or due to the toxicity of DPE. What is perhaps surprising is the inability of the comet assay to detect a known rat genotoxic carcinogen in liver. Further investigation is needed to clarify whether this apparent lack of response results from limited tissue exposure or metabolic differences between species. This finding highlights a need for careful consideration of study design when evaluating assay performance as a measure of in vivo genotoxicity. Copyright © 2015 Elsevier B.V. All rights reserved.

Indoor air - assessment: Methods of analysis for environmental carcinogens

International Nuclear Information System (INIS)

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

1990-06-01

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

Caffeine induces metformin anticancer effect on fibrosarcoma in hamsters.

Science.gov (United States)

Popović, D J; Lalošević, D; Miljković, D; Popović, K J; Čapo, I; Popović, J K

2018-04-01

We investigated the effect of metformin and caffeine on fibrosarcoma in hamsters. 32 Syrian golden hamsters of both sexes, weighing approximately 100 g, were randomly allocated to 3 experimental and 2 control groups, with a minimum of 6 animals per group. 2 x 106 BHK-21/C13 cells in 1 ml were injected subcutaneously into the animals' back in 4 groups. The first experimental group started peroral treatment with metformin 500 mg/kg daily, the second with caffeine 100 mg/kg daily and the third with a combination of metformin 500 mg/kg and caffeine 100 mg/kg daily, via a gastric probe 3 days before tumor inoculation. After 2 weeks, when the tumors were approximately 2 cm in the control group, all animals were sacrificed. The blood was collected for glucose and other analyses. The tumors were excised and weighed and their diameters were measured. The tumor samples were pathohistologically (HE) and immunohistochemically (Ki-67, CD 31, COX IV, GLUT-1, iNOS) assessed and the main organs toxicologically analyzed, including the control animals that had received metformin and caffeine. Tumor volume was determined using the formula LxS2/2, where L was the longest and S the shortest diameter. Ki-67-positive cells in the tumor samples were quantified. Images were taken and processed by software UTHSCSA Image Tools for Windows Version 3.00. Statistical significances were determined by the Student's t-test. The combination of metformin and caffeine inhibited fibrosarcoma growth in hamsters without toxicity. Administration of metformin with caffeine might be an effective and safe approach in novel nontoxic adjuvant anticancer treatment.

In-vivo monitoring of development of cholangiocarcinoma induced with C. sinensis and N-nitrosodimethylamine in Syrian golen hamsters using ultrasonography and magnetic resonance imaging: a preliminary study

Energy Technology Data Exchange (ETDEWEB)

Woo, Hyunsik [SMG-SNU Boramae Medical Center, Department of Radiology, Seoul (Korea, Republic of); Han, Joon Koo; Kim, Jung Hoon [Seoul National University Hospital, Department of Radiology, Seoul (Korea, Republic of); Hong, Sung-Tae [Seoul National University, Department of Parasitology, College of Medicine, Seoul (Korea, Republic of); Uddin, M.H. [Seoul National University, Adult Stem Cell Research Center, Laboratory of Stem Cell and Tumor Biology, Department of Veterinary Public Health, College of Veterinary Medicine, Seoul (Korea, Republic of); Jang, Ja-June [Seoul National University, Department of Pathology, College of Medicine, Seoul (Korea, Republic of)

2017-04-15

The purpose of this study is to evaluate high-resolution ultrasound and magnetic resonance imaging (MRI) in monitoring of cholangiocarcinoma in the hamsters with C. sinensis infection and N-nitrosodimethylamine (NDMA). Twenty-four male Syrian golden hamsters of were divided into four groups composed of five hamsters as control, five hamsters receiving 30 metacercariae of C. sinensis per each hamster, five hamsters receiving NDMA in drinking water, and nine hamsters receiving both metacercariae and NDMA. Ultrasound was performed every other week from baseline to the 12th week of infection. MRI and histopathologic examination was done from the 4th week to 12th week. Cholangiocarcinomas appeared as early as the 6th week of infection. There were 12 cholangiocarcinomas, nine and ten of which were demonstrated by ultrasound and MRI, respectively. Ultrasound and MRI findings of cholangiocarcinomas in the hamsters were similar to those of the mass-forming intrahepatic cholangiocarcinomas in humans. Ultrasound and MRI also showed other findings of disease progression such as periductal increased echogenicity or signal intensity, ductal dilatation, complicated cysts, and sludges in the gallbladder. High-resolution ultrasound and MRI can monitor and detect the occurrence of cholangiocarcinoma in the hamsters non-invasively. (orig.)

In-vivo monitoring of development of cholangiocarcinoma induced with C. sinensis and N-nitrosodimethylamine in Syrian golen hamsters using ultrasonography and magnetic resonance imaging: a preliminary study

International Nuclear Information System (INIS)

Woo, Hyunsik; Han, Joon Koo; Kim, Jung Hoon; Hong, Sung-Tae; Uddin, M.H.; Jang, Ja-June

2017-01-01

The purpose of this study is to evaluate high-resolution ultrasound and magnetic resonance imaging (MRI) in monitoring of cholangiocarcinoma in the hamsters with C. sinensis infection and N-nitrosodimethylamine (NDMA). Twenty-four male Syrian golden hamsters of were divided into four groups composed of five hamsters as control, five hamsters receiving 30 metacercariae of C. sinensis per each hamster, five hamsters receiving NDMA in drinking water, and nine hamsters receiving both metacercariae and NDMA. Ultrasound was performed every other week from baseline to the 12th week of infection. MRI and histopathologic examination was done from the 4th week to 12th week. Cholangiocarcinomas appeared as early as the 6th week of infection. There were 12 cholangiocarcinomas, nine and ten of which were demonstrated by ultrasound and MRI, respectively. Ultrasound and MRI findings of cholangiocarcinomas in the hamsters were similar to those of the mass-forming intrahepatic cholangiocarcinomas in humans. Ultrasound and MRI also showed other findings of disease progression such as periductal increased echogenicity or signal intensity, ductal dilatation, complicated cysts, and sludges in the gallbladder. High-resolution ultrasound and MRI can monitor and detect the occurrence of cholangiocarcinoma in the hamsters non-invasively. (orig.)

The induction by X-rays of chromosome aberrations in male guinea-pigs, golden hamsters and rabbits

International Nuclear Information System (INIS)

Cox, B.D.; Lyon, M.F.

1975-01-01

Translocations induced by X-rays in post-meiotic germ cells of male guinea-pigs, golden hamsters and rabbits were studied cytologically in the F 1 sons of the irradiated males. The percentage of spermatocytes displaying multivalent configurations varied with the translocation, but the average percentage appeared to depend on the species: fewer quadrivalents were observed in hamster than in guinea-pig heterozygotes and most were recorded for rabbit heterozygotes. Chain quadrivalents were more abundant than ring quadrivalents at meiosis for the guinea-pig and hamster in contrast to the mouse. Too few translocation heterozygotes were examined to determine which meiotic configuration was the more prevalent in the rabbit. In all three species, as in the mouse, translocations were found which caused male sterility, due to partial or complete failure of spermatogenesis, although most translocations caused semi-sterility. For these semi-sterile males both the frequency and time of embryonic death in the progeny appeared to be the same as in the mouse. It is concluded that similar types of chromosome aberrations are induced by X-rays in post-meiotic germ cells of male guinea-pigs, rabbits, golden hamsters and mice

In vivo genetic toxicity studies in Chinese hamsters fed irradiated or unirradiated foodstuffs

International Nuclear Information System (INIS)

Altmann, H.

1982-01-01

Two in vivo genetic toxicity studies were performed in Chinese hamsters fed irradiated or unirradiated diets of chicken, fish or dates in order to detect possible mutagenic effects caused by irradiating these foodstuffs. The tests selected for study were: 1. Chromosomal analysis of bone narrow cells and 2. DNA metabolism in spleen cells. Chicken, fish and dates were irradiated with doses of 7, 2.5 and 1 kGy respectively. These investigations were subsequently extended to include the effects of irradiated dried onions, pulses and cocoa beans on DNA metabolism in Chinese hamster spleen cells only. Dried onions were irradiated with doses of 0.15, 9 and 15 kGy, pulses with 10 kGy and cocoa beans with 3.2 to 5 kGy. In addition, a fumigated cocoa bean group was included. No significant differences in chromosomal aberration rate were detected between groups fed irradiated or unirradiated diets. Dried dates, whether irradiated or not, showed some evidence of genetic toxicity in their effect on DNA metabolism in the spleen cells of Chinese hamsters. Both date diets caused more strand breaks DNA than are usual for Chinese hamster spleen cells, but DNA repair was not adversely affected. Chicken, both irradiated and unirradiated, was found to enhance replicative DNA synthesis but had no effect on the DNA repair process. Irradiated fish, however, caused enhanced DNA synthesis compared to unirradiated fish, but also had no adverse effect on DNA repair. Irradiated white beans also enhanced DNA synthesis compared to controls whereas unirradiated samples inhibited synthesis. (orig./MG)

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

Science.gov (United States)

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

2006-10-01

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

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

International Nuclear Information System (INIS)

Morales, M.A.; Bustamante, S.; Hernandez, D.; 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 S and non-S 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.

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.

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.

Bio F1B hamster: a unique animal model with reduced lipoprotein lipase activity to investigate nutrient mediated regulation of lipoprotein metabolism

Directory of Open Access Journals (Sweden)

Cornish Marion L

2007-12-01

Full Text Available Abstract Background Bio F1B hamster is an inbred hybrid strain that is highly susceptible to diet-induced atherosclerosis. We previously reported that feeding a high fat fish oil diet to Bio F1B hamster caused severe hyperlipidaemia. In this study we compared the effects of various diets in the Bio F1B hamster and the Golden Syrian hamster, which is an outbred hamster strain to investigate whether genetic background plays an important role in dietary fat mediated regulation of lipoprotein metabolism. We further investigated the mechanisms behind diet-induced hyperlipidaemia in F1B hamster. Methods The Bio F1B and Golden Syrian hamsters, 8 weeks old, were fed high fat diets rich in either monounsaturated fatty acids, an n-6: n-3 ratio of 5 or a fish oil diet for 4 weeks. Animals were fasted overnight and blood and tissue samples were collected. Plasma was fractionated into various lipoprotein fractions and assayed for triacylglycerol and cholesterol concentrations. Plasma lipoprotein lipase activity was measured using radioisotope method. Microsomal triglyceride transfer protein activity was measured in the liver and intestine. Plasma apolipoproteinB48, -B100 and apolipoprotein E was measured using Western blots. Two-way ANOVA was used to determine the effect of diet type and animal strain. Results The fish oil fed F1B hamsters showed milky plasma after a 14-hour fast. Fish oil feeding caused accumulation of apolipoproteinB48 containing lipoprotein particles suggesting hindrance of triglyceride-rich lipoprotein clearance. There was no significant effect of diet or strain on hepatic or intestinal microsomal triglyceride transfer protein activity indicating that hyperlipidaemia is not due to an increase in the assembly or secretion of lipoprotein particles. F1B hamsters showed significantly reduced levels of lipoprotein lipase activity, which was inhibited by fish oil feeding. Conclusion Evidence is presented for the first time that alterations in

Exposure of F344 rats to aerosols of 239PuO2 and chronically inhaled cigarette smoke

International Nuclear Information System (INIS)

Finch, G.L.; Nikula, K.J.; Barr, E.B.; Bechtold, W.E.; Chen, B.T.; Griffith, W.C.; Hobbs, C.H.; Hoover, M.D.; Mauderly, J.L.

1994-01-01

Nuclear workers may be accidently exposed to radioactive materials such as 239 PuO 2 by inhalation, and thus have increased risk for lung cancer compared to the general population. Of additional concern is the possibility that interactions between radionuclides and other carcinogens may increase the risk of cancer induction. An important and common lung carcinogen is cigarette smoke. This study is being conducted to better determine the combined effects of inhaled 239 PuO 2 and cigarette smoke on the induction of lung cancer in rats

Effects of pelleted or powdered diets containing soy protein or sodium caseinate on lipid concentrations and bile acid excretion in golden Syrian hamsters.

Science.gov (United States)

Butteiger, Dustie N; Krul, Elaine S

2015-08-01

Custom diets are a convenient vector for oral administration of test articles, but the processing and physical form of a diet can affect its nutritional properties and how it is consumed. Here, the authors evaluated the feeding behavior and physiology of golden Syrian hamsters fed diets of either soy or caseinate protein in pelleted or powdered forms for 28 d to determine whether dietary processing and form mediates the physiological effects of dietary proteins. The authors compared body weight, food consumption, serum cholesterol concentration, serum triglyceride concentration, fecal weight and fecal excretion of bile acids between treatment groups. Hamsters fed powdered diets showed higher food consumption than hamsters fed pelleted diets, regardless of protein source. Hamsters fed soy pelleted diets showed lower serum cholesterol concentration and higher fecal excretion of bile acid than hamsters fed caseinate pelleted diets, and serum cholesterol concentration correlated strongly with fecal excretion of bile acid. This correlation suggests that the physiological effects of soy protein on cholesterol and excretion of bile acid might be related or similarly mediated through diet. The differences observed between hamsters on different diets indicate that dietary form can influence both feeding behavior and the physiological effects of a diet in hamsters.

Carcinogenic effects of radiation-introduction

International Nuclear Information System (INIS)

Setlow, R.B.

1976-01-01

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

Comet assay evaluation of six chemicals of known genotoxic potential in rats.

Science.gov (United States)

Hobbs, Cheryl A; Recio, Leslie; Streicker, Michael; Boyle, Molly H; Tanaka, Jin; Shiga, Atsushi; Witt, Kristine L

2015-07-01

As a part of an international validation of the in vivo rat alkaline comet assay (comet assay) initiated by the Japanese Center for the Validation of Alternative Methods (JaCVAM) we examined six chemicals for potential to induce DNA damage: 2-acetylaminofluorene (2-AAF), N-nitrosodimethylamine (DMN), o-anisidine, 1,2-dimethylhydrazine dihydrochloride (1,2-DMH), sodium chloride, and sodium arsenite. DNA damage was evaluated in the liver and stomach of 7- to 9-week-old male Sprague Dawley rats. Of the five genotoxic carcinogens tested in our laboratory, DMN and 1,2-DMH were positive in the liver and negative in the stomach, 2-AAF and o-anisidine produced an equivocal result in liver and negative results in stomach, and sodium arsenite was negative in both liver and stomach. 1,2-DMH and DMN induced dose-related increases in hedgehogs in the same tissue (liver) that exhibited increased DNA migration. However, no cytotoxicity was indicated by the neutral diffusion assay (assessment of highly fragmented DNA) or histopathology in response to treatment with any of the tested chemicals. Therefore, the increased DNA damage resulting from exposure to DMN and 1,2-DMH was considered to represent a genotoxic response. Sodium chloride, a non-genotoxic non-carcinogen, was negative in both tissues as would be predicted. Although only two (1,2-DMH and DMN) out of five genotoxic carcinogens produced clearly positive results in the comet assay, the results obtained for o-anisidine and sodium arsenite in liver and stomach cells are consistent with the known mode of genotoxicity and tissue specificity exhibited by these carcinogens. In contrast, given the known genotoxic mode-of-action and target organ carcinogenicity of 2-AAF, it is unclear why this chemical failed to convincingly increase DNA migration in the liver. Thus, the results of the comet assay validation studies conducted in our laboratory were considered appropriate for five out of the six test chemicals. Copyright © 2015

Enhanced longevity in tau mutant Syrian hamsters, Mesocricetus auratus

NARCIS (Netherlands)

Oklejewicz, Malgorzata; Daan, Serge

The single-gene mutation tau in the Syrian hamster shortens the circadian period by about 20% in the homozygous mutant and simultaneously increases the mass-specific metabolic rate by about 20%. Both effects might be expected to lead to a change in longevity. To test such expectations, the life span

Long-term toxicity and carcinogenicity studies of cake made from chlorinated flour. 1. Studies in rats.

Science.gov (United States)

Fisher, N; Hutchinson, J B; Berry, R; Hardy, J; Ginocchio, A V

1983-08-01

Wistar rats were fed for 104 wk on cake-based diets in which the cake, prepared from unchlorinated flour, or flour treated with 1250 or 2500 ppm chlorine, formed 79% of the diet on a 12.6% moisture basis. A fourth group was fed stock diet 41B. No differences in appearance, health, behaviour or mortalities attributable to the flour treatment were observed. Female but not male mortalities were significantly higher for cake-fed rats than for those fed diet 41B. Dose-related haematological effects were seen at various stages in cake-fed rats. Dose-related increases in plasma alanine and aspartate aminotransferases were noted at 12 months in males but not in females, for whom all the values were elevated. A dose-related diminution in blood sugar at 12 months was seen only in females. A dose-related increase in urinary aspartate aminotransferase was seen only in males. Urinary N-acetylglucosaminidase activity per mg creatinine did not differ significantly between groups. At post mortem a dose-related reduction in spleen weight was found in the females only. The lesions found were those expected in ageing rats, but were observed earlier in rats fed cake. Glomerulonephrosis affected rats fed cake more than those fed diet 41B. Cake diets promoted nephrocalcinosis, unrelated to flour treatment. Increased splenic haematopoiesis occurred in about half of the females in the cake diet groups but less frequently in males or in rats fed diet 41B. Tumours were mainly chromophobe adenomas of the pituitary, common in rats. Insulomas were seen in two males in each of the groups fed on cake made from chlorinated flour, but an earlier form of this tumour was found in all cake groups and its incidence is thus regarded as unrelated to the flour treatment. The incidence of tumours of the reticuloendothelial system was not related to flour treatment. Covalent chlorine concentrations in the perirenal fat of the cake-fed rats were correlated with treatment levels, with values of 50-912 ppm in

Results of screening NCI/NTP nongenotoxic carcinogens and genotoxic noncarcinogens with the ke test

International Nuclear Information System (INIS)

Mendelsohn, M.L.; Bakale, G.; McCreary, R.D.

1989-01-01

The interdependence of the electrophilic and carcinogenic properties of chemicals that was demonstrated two decades ago rekindled interest in the somatic mutation theory of carcinogenesis. Interest in this theory grew with the development of a reverse-mutation bacterial assay in the laboratory of B.N. Ames that permitted the mutagenic properties of the chemicals to be determined quickly and yielded results which indicated that ''carcinogens are mutagens.'' Subsequent validation studies of this bioassay, the Salmonella typhimurium/microsome or ''Ames test,'' by Ames' group and others provided additional support for the correlation between mutagenicity and carcinogenicity which led to the worldwide deployment of the Ames test in thousands of laboratories and to the development of more than 100 other short-term tests that continue to be used to identify potential carcinogens via various end-points of genotoxicity. This document discusses electrophilicity, mutagenicity, and carcinogenicity relationships as well as carcinogen-screening of chemicals. 28 refs., 4 tabs

Effects of combined exposure of F344 rats to radiation and chronically inhaled cigarette smoke

Energy Technology Data Exchange (ETDEWEB)

Finch, G.L.; Nikula, K.J.; Barr, E.B. [and others

1995-12-01

Nuclear workers may be exposed to radiation in various forms, such as low-LET {gamma}-irradiation or {alpha}-irradiation from inhaled {sup 239}PuO{sub 2} particles. These workers may then have increased risk for lung cancer compared to the general population. Of additional concern is the possibility that interactions between radiation and other carcinogens may increase the risk of cancer induction, compared to the risks from either type of agent alone. An important and common lung carcinogen is cigarette smoke. The purpose of this project is to better determine the combined effects of chronically inhaled cigarette smoke and either inhaled {sup 239}PuO{sub 2} or external, thoracic X-irradiation on the induction of lung cancer in rats. Histologic and dosimetric evaluations of rats in the CS + {sup 239}PuO{sub 2} study continue, and the study of CS + X rays is beginning.

Protective effect of dexamethasone on 5-FU-induced oral mucositis in hamsters.

Science.gov (United States)

Ribeiro, Susana Barbosa; de Araújo, Aurigena Antunes; Araújo Júnior, Raimundo Fernandes de; Brito, Gerly Anne de Castro; Leitão, Renata Carvalho; Barbosa, Maisie Mitchele; Garcia, Vinicius Barreto; Medeiros, Aldo Cunha; Medeiros, Caroline Addison Carvalho Xavier de

2017-01-01

Oral mucositis (OM) is an important side effect of cancer treatment, characterized by ulcerative lesions in the mucosa of patients undergoing radiotherapy or chemotherapy, which has marked effects on patient quality of life and cancer therapy continuity. Considering that few protocols have demonstrated efficacy in preventing this side effect, the aim of this study was to examine the effect of dexamethasone (DEX) on OM induced by 5-fluorouracil (5-FU) in hamsters by studying signaling pathways. OM was induced in hamsters by 5-FU followed by mechanical trauma (MT) on day 4. On day 10, the animals were euthanized. The experimental groups included saline, MT, 5-FU, and DEX (0.25, 0.5, or 1 mg/kg). Macroscopic, histopathological, and immunohistochemical analyses as well as immunofluorescence experiments were performed on the oral mucosa of the animals. The oral mucosal samples were analyzed by enzyme-linked immunosorbent assays, and quantitative real-time polymerase chain reaction (qPCR). DEX (0.5 or 1 mg/kg) reduced inflammation and ulceration of the oral mucosa of hamsters. In addition, DEX (1 mg/kg) reduced the cytokine levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and macrophage migration inhibitory factor (MIF). DEX (1 mg/kg) also reduced the immunoexpression of cyclooxygenase (COX)-2, matrix metalloproteinase (MMP)-2, transforming growth factor (TGF)-β, MIF, Smad 2/3, Smad 2/3 phosphorylated and NFκB p65 in the jugal mucosa. Finally, DEX (1 mg/kg) increased interleukin-1 receptor-associated kinase 3 (IRAK-M), glucocorticoid-induced leucine zipper (GILZ), and mitogen-activated protein kinase (MKP1) gene expression and reduced NFκB p65 and serine threonine kinase (AKt) gene expression, relative to the 5-FU group. Thus, DEX improved OM induced by 5-FU in hamsters.

Protective effect of dexamethasone on 5-FU-induced oral mucositis in hamsters.

Directory of Open Access Journals (Sweden)

Susana Barbosa Ribeiro

Full Text Available Oral mucositis (OM is an important side effect of cancer treatment, characterized by ulcerative lesions in the mucosa of patients undergoing radiotherapy or chemotherapy, which has marked effects on patient quality of life and cancer therapy continuity. Considering that few protocols have demonstrated efficacy in preventing this side effect, the aim of this study was to examine the effect of dexamethasone (DEX on OM induced by 5-fluorouracil (5-FU in hamsters by studying signaling pathways. OM was induced in hamsters by 5-FU followed by mechanical trauma (MT on day 4. On day 10, the animals were euthanized. The experimental groups included saline, MT, 5-FU, and DEX (0.25, 0.5, or 1 mg/kg. Macroscopic, histopathological, and immunohistochemical analyses as well as immunofluorescence experiments were performed on the oral mucosa of the animals. The oral mucosal samples were analyzed by enzyme-linked immunosorbent assays, and quantitative real-time polymerase chain reaction (qPCR. DEX (0.5 or 1 mg/kg reduced inflammation and ulceration of the oral mucosa of hamsters. In addition, DEX (1 mg/kg reduced the cytokine levels of tumor necrosis factor (TNF-α, interleukin (IL-1β, and macrophage migration inhibitory factor (MIF. DEX (1 mg/kg also reduced the immunoexpression of cyclooxygenase (COX-2, matrix metalloproteinase (MMP-2, transforming growth factor (TGF-β, MIF, Smad 2/3, Smad 2/3 phosphorylated and NFκB p65 in the jugal mucosa. Finally, DEX (1 mg/kg increased interleukin-1 receptor-associated kinase 3 (IRAK-M, glucocorticoid-induced leucine zipper (GILZ, and mitogen-activated protein kinase (MKP1 gene expression and reduced NFκB p65 and serine threonine kinase (AKt gene expression, relative to the 5-FU group. Thus, DEX improved OM induced by 5-FU in hamsters.

A Consensus Genome-scale Reconstruction of Chinese Hamster Ovary Cell Metabolism

KAUST Repository

Hefzi, Hooman; Ang, Kok  Siong; Hanscho, Michael; Bordbar, Aarash; Ruckerbauer, David; Lakshmanan, Meiyappan; Orellana, Camila  A.; Baycin-Hizal, Deniz; Huang, Yingxiang; Ley, Daniel; Martinez, Veronica  S.; Kyriakopoulos, Sarantos; Jimé nez, Natalia  E.; Zielinski, Daniel  C.; Quek, Lake-Ee; Wulff, Tune; Arnsdorf, Johnny; Li, Shangzhong; Lee, Jae  Seong; Paglia, Giuseppe; Loira, Nicolas; Spahn, Philipp  N.; Pedersen, Lasse  E.; Gutierrez, Jahir  M.; King, Zachary  A.; Lund, Anne  Mathilde; Nagarajan, Harish; Thomas, Alex; Abdel-Haleem, Alyaa M.; Zanghellini, Juergen; Kildegaard, Helene  F.; Voldborg, Bjø rn  G.; Gerdtzen, Ziomara  P.; Betenbaugh, Michael  J.; Palsson, Bernhard  O.; Andersen, Mikael  R.; Nielsen, Lars  K.; Borth, Nicole; Lee, Dong-Yup; Lewis, Nathan  E.

2016-01-01

Chinese hamster ovary (CHO) cells dominate biotherapeutic protein production and are widely used in mammalian cell line engineering research. To elucidate metabolic bottlenecks in protein production and to guide cell engineering and bioprocess

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.

Moesin Is a Biomarker for the Assessment of Genotoxic Carcinogens in Mouse Lymphoma

Science.gov (United States)

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

2012-01-01

1,2-Dibromoethane and glycidol are well known genotoxic carcinogens, which have been widely used in industry. To identify a specific biomarker for these carcinogens in cells, the cellular proteome of L5178Y mouse lymphoma cells treated with these compounds was analyzed by 2-dimensional gel electrophoresis (2-DE) and MALDI-TOF mass spectrometry (MS). Of 50 protein spots showing a greater than 1.5-fold increase or decrease in intensity compared to control cells on a 2-D gel, we focused on the candidate biomarker moesin. Western analysis using monoclonal rabbit anti-moesin confirmed the identity of the protein and its increased level of expression upon exposure to the carcinogenic compounds. Moesin expression also increased in cells treated with six additional genotoxic carcinogens, verifying that moesin could serve as a biomarker to monitor phenotypic change upon exposure to genotoxic carcinogens in L5178Y mouse lymphoma cells. PMID:22358511

Inhibition of fatty acid synthesis decreases very low density lipoprotein secretion in the hamster.

Science.gov (United States)

Arbeeny, C M; Meyers, D S; Bergquist, K E; Gregg, R E

1992-06-01

The hamster was developed as a model to study very low density lipoprotein (VLDL) metabolism, since, as is the case in humans, the hamster liver was found to synthesize apoB-100 and not apoB-48. The effect of inhibiting fatty acid synthesis on the hepatic secretion of VLDL triglyceride (TG) and apolipoprotein (apo) B-100 in this model was then investigated. In an in vivo study, hamsters were fed a chow diet containing 0.15% TOFA (5-tetradecyloxy-2-furancarboxylic acid), an inhibitor of acetyl-CoA carboxylase. After 6 days of treatment, plasma triglyceride and cholesterol levels were decreased by 30.2% and 11.6%, respectively. When the secretion of VLDL-TG by the liver was measured in vivo after injection of Triton WR 1339, TOFA treatment was found to decrease VLDL-TG secretion by 40%. In subsequent in vitro studies utilizing cultured primary hamster hepatocytes, incubation with 20 microM TOFA for 4 h resulted in 98% and 76% inhibition in fatty acid and triglyceride synthesis, respectively; VLDL-TG secretion was decreased by 90%. When hepatocytes were pulsed with [3H]leucine, incubation with TOFA resulted in a 50% decrease in the incorporation of radiolabel into secreted VLDL apoB-100. The results of this study indicate that inhibition of intracellular triglyceride synthesis decreases the secretion of VLDL-TG and apoB-100, and does not result in the secretion of a dense, triglyceride-depleted lipoprotein.

Blood epididymal barrier to [3H]-inulin in intact and vasectomized hamsters

International Nuclear Information System (INIS)

Turner, T.T.; D'Addario, D.A.; Howards, S.S.

1981-01-01

The net transport of [ 3 H]-inulin into the fluids of the hamster seminiferous and caput, corpus, and cauda epididymal tubules was examined in both intact animals and those vasectomized 10 months previously. Mean isotope concentrations in reproductive tract tubule fluids did not exceeded 10 per cent of blood plasma isotope concentrations during the experiment. There were no significant differences in net transport of [ 3 H]-inulin into any of the tubule fluids sampled. Ten months after vasectomy, the seminiferous tubule, and all regions of the epididymal tubule retain the capacity to exclude [ 3 H]-insulin. Thus in the hamster 10 months after vasectomy, the blood testis and blood epididymal barriers to inulin are intact

DIP and DIP + 2 as glutathione oxidants and radiation sensitizers in cultured Chinese hamster cells

International Nuclear Information System (INIS)

Harris, J.W.; Power, J.A.; Kosower, N.S.; Kosower, E.M.

1975-01-01

Two diamide analogues, diazene dicarboxylic acid bis (N'-methyl-piperazide) or DIP, and its bis-N'-methyl iodide salt, or DIP + 2, were tested for their ability to penetrate cultured Chinese hamster cells and oxidize intracellular glutathione. DIP penetrated the cells at a reasonable rate at 18 0 C, 160 nmoles being required to oxidize the endogenous glutathione of 2 x 10 6 cells, but it penetrated very slowly at 0 0 C. DIP + 2 did not effectively oxidize glutathione in Chinese hamster cells, possibly because it did not enter the cels. DIP became toxic after about 10 min of exposure, but its toxicity could be moderated by using anoxic conditions. DIP, but not DIP + 2, sensitized anoxic Chinese hamster cells to X-radiation by a factor of 1.5, an effect that was due entirely to removal of the shoulder from the survival curve. (author)

Detecção de lesões neoplásicas induzidas em mucosa oral de hamster utilizando espectroscopia de fluorescência Detection of induced neoplastic lesions in the oral mucosa of hamsters using fluorescence spectroscopy

Directory of Open Access Journals (Sweden)

Landulfo Silveira Junior

2004-09-01

hamsters, with potential to diagnose neoplastic tissue in vivo. METHODS: Carcinogen DMBA was applied to the right cheek of 31 hamsters weighing 150 ± 10g, three times per week during 12 weeks. One animal was kept as a control (without application of the drug. At the end of this period, the animals were submitted to fluorescence spectroscopy excited by an argon laser (488nm connected to an optical fiber cable. Tissue autofluorescence was analyzed by a spectrograph and a CCD camera with 1024X256 pixels covering the spectral range of 550nm to 700nm. Fluorescence emission spectra were collected in the induced region and normal counter side cheek of all the animals and also in the control animal. After spectroscopy, biopsy was carried out for histopathological analysis. Two diagnosis algorithms, one based on the ratio of spectral regions and another based on Principal Components Analysis (PCA were implemented. RESULTS: Spectral analysis had demonstrated existence of an intense peak in the region of 630nm in neoplastic tissues (attributed to protoporphyrin IX when compared to the normal tissue. The algorithm based on the ratio of two spectral regions had 100% of sensitivity and specificity. The algorithm based on the PCA had 94% and 100% of specificity and sensitivity, respectively. CONCLUSIONS: This work indicates that tissue autofluorescence may be used as a non-invasive technique for diagnosis of the neoplastic oral mucosa.

Determination of elements in blood of golden hamster by NAA

International Nuclear Information System (INIS)

Aguiar, Rodrigo Oliveira de

2009-01-01

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 σ (Two Standard deviations) was 0.011 0.047 gL -1 (Br); 0.11 0.35 gL -1 (Ca); 2.11 3.75 gL -1 (Cl); 1.35 2.79 gL -1 (K), 0.026 0.090 gL -1 (Mg), 1.03 2.51 gL -1 (Na) e 0.97 2.01 gL -1 (S). The knowledge of these limits became possible to perform clinical investigation in this animal model using whole blood. The comparison with the results from human being whole blood estimation (Hamster and human) became possible to check the similarities or physiologic differences, an important data for animal experimentation. (author)

Diuron-induced rat bladder epithelial cytotoxicity.

Science.gov (United States)

Da Rocha, Mitscheli S; Arnold, Lora L; Pennington, Karen L; Muirhead, David; Dodmane, Puttappa R; Anwar, Muhammad M; Battalora, Michael; De Camargo, João Lauro V; Cohen, Samuel M

2012-12-01

Diuron, a substituted urea herbicide, is carcinogenic to the rat urinary bladder at high dietary levels (2500 ppm). To further elucidate the mode of action, this study aimed to determine the time course and sequence of bladder cytotoxic and proliferative changes induced by diuron treatment of male Wistar rats. Rats were randomized into two groups (control and 2500 ppm diuron) and treated for 28 days. Ten rats from each group were terminated on each of study days 1, 3, 7, or 28. Scanning electron micro scopy (SEM) showed urothelial cell swelling beginning on day 1, and by day 28, showed extensive necrosis, exfoliation and piling up of cells suggestive of hyperplasia. No difference in the bromo deoxyuridine labeling index was detected. In a second experiment, rats were randomized into control and diuron-treated groups and treated for 7 days or 8 weeks. After 7 days, transmission electron microscopy showed cell degenerative changes and distention of the cytoplasm, organelles, and nuclei characteristic of cytolysis. This resulted in protrusion of the superficial cells into the lumen, corresponding to the cell swelling observed previously by SEM. After 8 weeks, bladders in the diuron-treated group showed an increased incidence of simple hyperplasia by light microscopy (6/10, p diuron exposure in rats.

Cannabis and tobacco smoke are not equally carcinogenic

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Melamede Robert

2005-10-01

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

Carcinogenic effect of petroleum and its by-products

Energy Technology Data Exchange (ETDEWEB)

Gimadeev, M M

1962-01-01

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

Ethanol-Extracted Brazilian Propolis Exerts Protective Effects on Tumorigenesis in Wistar Hannover Rats.

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Anna Kakehashi

Full Text Available The present study was conducted over a course of 104 weeks to estimate the carcinogenicity of ethanol-extracted Brazilian green propolis (EEP. Groups of 50 male and 50 female Wistar Hannover rats, 6-week-old at commencement were exposed to EEP at doses of 0, 0.5 or 2.5% in the diet. Survival rates of 0.5% and 2.5% EEP-treated male and female rats, respectively, were significantly higher than those of respective control groups. Overall histopathological evaluation of neoplasms in rat tissues after 2 years showed no significant increase of tumors or preneoplastic lesions in any organ of animals administered EEP. Significantly lower incidences of pituitary tumors in 0.5% EEP male and 2.5% EEP female groups, malignant lymphoma/leukemia in both 2.5% EEP-treated males and females and total thyroid tumors in 0.5% EEP male group were found. Administration of EEP caused significant decreases of lymphoid hyperplasia of the thymus and lymph nodes in 2.5% EEP-treated rats, tubular cell hyperplasia of kidneys in all EEP groups, and cortical hyperplasia of adrenals in EEP-treated females. In the blood, significant reduction of neutrophils in all EEP-treated males and band neutrophils in 2.5% EEP-treated females was found indicating lower levels of inflammation. Total cholesterol and triglicerides levels were significantly lower in the blood of 2.5% EEP-treated female rats. In conclusion, under the conditions of the 2-year feeding experiment, EEP was not carcinogenic, did not induce significant histopathological changes in any organ, and further exerted anti-inflammatory and antitumorigenic effects resulting in increase of survival of Wistar Hannover rats.

Application of the key characteristics of carcinogens in cancer hazard identification

Science.gov (United States)

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

2018-01-01

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

Non-parametric photic entrainment of Djungarian hamsters with different rhythmic phenotypes

Czech Academy of Sciences Publication Activity Database

Schöttner, Konrad; Hauer, J.; Weinert, D.

2016-01-01

Roč. 33, č. 5 (2016), s. 506-519 ISSN 0742-0528 Institutional support: RVO:60077344 Keywords : delayed activity onset * Djungarian hamster * free- running period Subject RIV: ED - Physiology Impact factor: 2.562, year: 2016

Effects of high fat diet on incidence of spontaneous tumors in Wistar rats

DEFF Research Database (Denmark)

KRISTIANSEN, E.; Madsen, Charlotte Bernhard; Meyer, Otto A.

1993-01-01

In a 2.5-year carcinogenicity study, two groups, both including male and female Wistar rats, were fed two different diets with 4% and 16% fat. In addition to 4% soybean oil, the high-fat diet contained 12% mono- and diglycerides, of which 85% was stearic acid and 13% palmitic acid...

Combined exposure of F344 rats to beryllium metal and plutonium-239 dioxide

Energy Technology Data Exchange (ETDEWEB)

Finch, G.L.; Carlton, W.W.; Rebar, A.H. [Purdue Univ., Lafayette, IN (United States)] [and others

1995-12-01

Nuclear weapons industry workers have the potential for inhalation exposures to plutonium (Pu) and other agents, such as beryllium (Be) metal. The purpose of this ongoing study is to investigate potential interactions between Pu and Be in the production of lung tumors in rats exposed by inhalation to particles of {sup 239}PuO{sub 2}, Be metal, or these agents in combination. Inhaled Pu deposited in the lung delivers high-linear-energy transfer, alpha-particle radiation and is known to induce pulmonary cancer in laboratory animals. Although the epidemiological evidence implicating Be in the induction of human lung cancer is weak and controversial, various studies in laboratory animals have demonstrated the pulmonary carcinogenicity of Be. As a result, Be is classified as a suspect human carcinogen in the United STates and as a demonstrated human carcinogen by the International Agency for Research on Cancer. This study is in progress.

High frequency stimulation of the entopeduncular nucleus sets the cortico-basal ganglia network to a new functional state in the dystonic hamster.

Science.gov (United States)

Reese, René; Charron, Giselle; Nadjar, Agnès; Aubert, Incarnation; Thiolat, Marie-Laure; Hamann, Melanie; Richter, Angelika; Bezard, Erwan; Meissner, Wassilios G

2009-09-01

High frequency stimulation (HFS) of the internal pallidum is effective for the treatment of dystonia. Only few studies have investigated the effects of stimulation on the activity of the cortex-basal ganglia network. We here assess within this network the effect of entopeduncular nucleus (EP) HFS on the expression of c-Fos and cytochrome oxidase subunit I (COI) in the dt(sz)-hamster, a well-characterized model of paroxysmal dystonia. In dt(sz)-hamsters, we identified abnormal activity in motor cortex, basal ganglia and thalamus. These structures have already been linked to the pathophysiology of human dystonia. EP-HFS (i) increased striatal c-Fos expression in controls and dystonic hamsters and (ii) reduced thalamic c-Fos expression in dt(sz)-hamsters. EP-HFS had no effect on COI expression. The present results suggest that EP-HFS induces a new network activity state which may improve information processing and finally reduces the severity of dystonic attacks in dt(sz)-hamsters.

Identification of Reference Genes for Quantitative Real Time PCR Assays in Aortic Tissue of Syrian Hamsters with Bicuspid Aortic Valve.

Science.gov (United States)

Rueda-Martínez, Carmen; Fernández, M Carmen; Soto-Navarrete, María Teresa; Jiménez-Navarro, Manuel; Durán, Ana Carmen; Fernández, Borja

2016-01-01

Bicuspid aortic valve (BAV) is the most frequent congenital cardiac malformation in humans, and appears frequently associated with dilatation of the ascending aorta. This association is likely the result of a common aetiology. Currently, a Syrian hamster strain with a relatively high (∼40%) incidence of BAV constitutes the only spontaneous animal model of BAV disease. The characterization of molecular alterations in the aorta of hamsters with BAV may serve to identify pathophysiological mechanisms and molecular markers of disease in humans. In this report, we evaluate the expression of ten candidate reference genes in aortic tissue of hamsters in order to identify housekeeping genes for normalization using quantitative real time PCR (RT-qPCR) assays. A total of 51 adult (180-240 days old) and 56 old (300-440 days old) animals were used. They belonged to a control strain of hamsters with normal, tricuspid aortic valve (TAV; n = 30), or to the affected strain of hamsters with TAV (n = 45) or BAV (n = 32). The expression stability of the candidate reference genes was determined by RT-qPCR using three statistical algorithms, GeNorm, NormFinder and Bestkeeper. The expression analyses showed that the most stable reference genes for the three algorithms employed were Cdkn1β, G3pdh and Polr2a. We propose the use of Cdkn1β, or both Cdkn1β and G3pdh as reference genes for mRNA expression analyses in Syrian hamster aorta.

Identification of Reference Genes for Quantitative Real Time PCR Assays in Aortic Tissue of Syrian Hamsters with Bicuspid Aortic Valve.

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Carmen Rueda-Martínez

Full Text Available Bicuspid aortic valve (BAV is the most frequent congenital cardiac malformation in humans, and appears frequently associated with dilatation of the ascending aorta. This association is likely the result of a common aetiology. Currently, a Syrian hamster strain with a relatively high (∼40% incidence of BAV constitutes the only spontaneous animal model of BAV disease. The characterization of molecular alterations in the aorta of hamsters with BAV may serve to identify pathophysiological mechanisms and molecular markers of disease in humans. In this report, we evaluate the expression of ten candidate reference genes in aortic tissue of hamsters in order to identify housekeeping genes for normalization using quantitative real time PCR (RT-qPCR assays. A total of 51 adult (180-240 days old and 56 old (300-440 days old animals were used. They belonged to a control strain of hamsters with normal, tricuspid aortic valve (TAV; n = 30, or to the affected strain of hamsters with TAV (n = 45 or BAV (n = 32. The expression stability of the candidate reference genes was determined by RT-qPCR using three statistical algorithms, GeNorm, NormFinder and Bestkeeper. The expression analyses showed that the most stable reference genes for the three algorithms employed were Cdkn1β, G3pdh and Polr2a. We propose the use of Cdkn1β, or both Cdkn1β and G3pdh as reference genes for mRNA expression analyses in Syrian hamster aorta.

The effect of different radiation exposure combined with prolactin on the carcinogenesis of rat mammary tumors

International Nuclear Information System (INIS)

Yokoro Kenjiro

1984-01-01

Female W/Fu rats were exposed to various doses of respective radiation and some of these irradiated rats further received a continuous supply of prolactin by means of grafting a prolactin producing pituitary tumor as a promoter to make easier the detection of carcinogenic effect of radiation. The results show that, the carcinogenic effect of 2.0 MeV fission neutrons is surprisingly higher than those of others; being about 30, 14 and 4.5 times as high as X-rays, 14.1 MeV fast neutrons and 0.025 eV thermal neutrons respectively. The irradiation field of fission radiation is equivalent to the atomic bomb that exploded in Hiroshima in 1945, so these experimental findings may have some relevance to the recent study on the reassessment of radiation dose of both neutrons and gamma-rays produced by atomic bomb in Hiroshima and Nagasaki

Misoprostol-induced radioprotection of Syrian hamster embryo cells in utero from cell death and oncogenic transformation

International Nuclear Information System (INIS)

Miller, R.C.; LaNasa, P.; Hanson, W.R.

1994-01-01

Misoprostol, a PGE analog, is an effective radioprotector of murine intestine and hematopoietic and hair cell renewal systems. The radioprotective nature of misoprostol was extended to examine its ability to influence clonogenic cell survival and induction of oncogenic transformation in Syrian hamster embryo cells exposed to X rays in utero and assayed in vitro. Hamsters in their 12th day of pregnancy were injected subcutaneously with misoprostal, and 2 h later the pregnant hamsters were exposed to graded doses of X rays. Immediately after irradiation, hamsters were euthanized and embryonic tissue was explanted into culture dishes containing complete growth medium. After a 2-week incubation period, clongenic cell survival and morphologically transformed foci were determined. Survival of misoprostol-treated SHE cells was increased and yielded a dose reduction factor of 1.5 compared to SHE cells treated with X rays alone. In contrast, radiation-induced oncogenic transformation of misoprostol-treated cells was reduced by a factor of 20 compared to cells treated with X rays alone. These studies suggest that misoprostol not only protects normal tissues in vivo from acute radiation injury, but also protects cells, to a large extent, from injury leading to transforming events. 26 refs., 6 figs., 2 tabs

Antigenic specificity and morphologic characteristics of Chlamydia trachomatis, strain SFPD, isolated from hamsters with proliferative ileitis.

Science.gov (United States)

Fox, J G; Stills, H F; Paster, B J; Dewhirst, F E; Yan, L; Palley, L; Prostak, K

1993-10-01

Profound diarrhea associated with proliferating intestinal cells containing intraepithelial campylobacter-like organisms (ICLO) occurs in a variety of mammalian hosts, particularly swine and hamsters. Recently, intracellular bacteria were isolated from proliferative intestinal tissue of hamsters and propagated in intestine cell line 407. Oral inoculation of hamsters with cell culture lysates containing these organisms reproduced the disease in susceptible hamsters. In the present study, an intracellular bacterium from the INT 407 cell line was shown by a variety of techniques to be a member of the genus Chlamydia and has been designated Chlamydia sp. strain SFPD. McCoy cells infected with Chlamydia sp. strain SFPD demonstrated bright fluorescent-stained intracytoplasmic inclusions when examined with fluorescein-labeled species-specific C. trachomatis monoclonal antibodies. The organism also reacted to fluorescein-labeled polyclonal but not monoclonal ICLO "omega" antisera. Ultrastructural examination of the Chlamydia sp. strain SFPD from McCoy cells revealed electrondense elementary bodies and a less electron-dense reticulate-like body that was circular; both features are consistent in morphology to developmental forms of Chlamydia and do not conform to ICLO morphology. Molecular studies, 16S ribosomal sequence analysis, and sequencing of the outer membrane protein confirmed that the isolate is a C. trachomatis closely related to the mouse pneumonitis strain of C. trachomatis.

Fluoride does not induce DNA breakage in Chinese hamster ovary cells in vitro Flúor não induz danos ao DNA em células de ovário de hamster chinês in vitro

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