Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001430 (adenoma)
 21,222 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Young, rapidly growing mice are greatly more responsive to the adenoma-inducing influence of urethane than are those just arriving at maturity. This is manifest both in the proportion of animals developing the tumors and in their number per individual. An amount of urethane per gram body weight which suffices to induce adenomas in only an occasional 8-week-old animal will cause them to appear in quantity in more than half the 3-week-old mice injected. There is an almost absolute inverse correlation between the rate of growth of the pulmonary tissue between the ages of 2 and 10 weeks and the response to urethane in terms of adenomas. Hence the conclusion seems justified that the natural proliferative activity of the alveolar cells during youth plays a major part in the formation of the tumors. After the 6th week the age differences become relatively slight, yet there is reason to think that they continue in some degree as life goes on. Urethane has no effect to promote multiplication of the cells it has rendered neoplastic, its whole role being to initiate neoplastic change. The abnormalities induced by urethane in the nucleus of normal and neoplastic cells, as observed by previous workers, have suggested that the substance brings about the adenomatous state by acting upon the nucleus. But colchicine, also a karyolytic poison causing pronounced nuclear changes, does not alter in the least the yield of adenomas to urethane when administered concurrently. Nor does fasting influence the yield, though it markedly reduces mitotic activity. The meaning of these facts is discussed.
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PMID:Age of the host and other factors affecting the production with urethane of pulmonary adenomas in mice. 1483 93

Urethane is a carcinogen to which there is widespread exposure through the consumption of fermented foods and alcoholic beverages. In this study, we have assessed the carcinogenicity of urethane in combination with ethanol. Male and female B6C3F(1) mice (48 mice per sex per group) were exposed to 0, 10, 30, or 90 ppm urethane in the presence of 0%, 2.5%, or 5% ethanol in drinking water ad libitum for two years, at which time the extent of tumorigenesis was assessed. Additional mice (four per sex per group) received the same doses for four weeks to assess serum levels of urethane and ethanol, DNA adduct formation, and the induction of microsomal cytochromes P450, cell proliferation, and apoptosis. Urethane decreased cell replication in the livers of female, but not male, mice, decreased cell replication in the lungs of both sexes, and induced cytochrome P450 2E1 in the livers of female mice. Hepatic levels of the DNA adduct 1,N(6)-ethenodeoxyadenosine were increased by exposure to urethane and decreased by treatment with ethanol. Animal weights and survival were not affected by ethanol; in contrast, urethane administration decreased body weights and survival. Urethane caused dose-dependent increases in liver, lung, and harderian gland adenoma or carcinoma and hemangiosarcoma of the liver and heart in both sexes, mammary gland and ovarian tumors in females, and squamous cell papilloma or carcinoma of the skin and forestomach in males. The increase in hepatocellular tumors occurred in a relatively linear manner and was attributed to the formation of 1,N(6)-ethenodeoxyadenosine in hepatic DNA coupled with an increase in cell replication. Hemangiosarcomas were observed only at the 90 ppm urethane dose and were probably a result of high-dose urethane-induced toxicity. Lung alveolar/bronchiolar and harderian gland adenoma or carcinoma increased in a relatively linear manner, suggestive of a genotoxic mechanism for tumor induction. Ethanol induced a dose-dependent trend in hepatocellular adenoma or carcinoma in male mice, with the incidence being marginally increased at the highest dose. In female mice administered 10 ppm and 90 ppm urethane, ethanol caused dose-related increases in alveolar/bronchiolar adenoma or carcinoma and hemangiosarcoma of the heart, respectively. This may be due to ethanol decreasing the first-pass clearance of urethane, thus, increasing systemic distribution. In male mice a different relationship was observed: ethanol caused a dose-related decrease in alveolar/bronchiolar and harderian gland adenoma or carcinoma in mice administered 30 ppm urethane.
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PMID:Effect of ethanol on the tumorigenicity of urethane (ethyl carbamate) in B6C3F1 mice. 1558 91

Ethyl carbamate is mutagenic and produces DNA-adducts in vivo, and is carcinogenic in rodent bioassays. Dose-response modelling of the data for alveolar and bronchiolar adenoma or carcinoma in male and female mice combined gave a BMDL(10) of 0.25 mg/kg-bw/day. The dietary exposure from consumption of foods and non-alcoholic beverage was estimated to be 1 microg/person/day (15 ng/kg-bw/day), while the exposure of a high-percentile consumer of alcoholic beverages was estimated to be 5 microg/person per day (80 ng/kg-bw/day). The corresponding calculated MOEs were 16600 and 3125, respectively.
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PMID:Application of the margin of exposure (MoE) approach to substances in food that are genotoxic and carcinogenic: example: ethyl carbamate (CAS 51-79-6). 2011 56


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