1999 Fiscal Year Final Research Report Summary
Studies on the elucidation of the enhanced mechanism of chemical carcinogenesis
| Project/Area Number |
09660348
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Applied veterinary science
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| Research Institution | National Institute of Health Sciences |
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Principal Investigator |
MITSUMORI Kunitoshi Div.of Pathology, National Institute of Health Sciences Section Head, 病理部, 室長 (10239296)
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| Co-Investigator(Kenkyū-buntansha) |
YASUHARA Kazuo Div.Of Pathol, National Institute of Health Sciences Senior Scientist, 病理部, 主任研究官 (80174522)
ONODERA Hiroshi Div.Of Pathol, National Institute of Health Sciences Senior Scientisit, 病理部, 主任研究官 (60177285)
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| Project Period (FY) |
1997 – 1999
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| Keywords | transgenic mice / rasH2 mice / p53 deficient mice / human prototype c-Ha-ras gene / p53 supressor oncogene |
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| Research Abstract |
To clarify the mechanism of the enhancement of carcinogenesis by the treatment of genotoxic carcinogens in transgenic mice, the following experiments were performed : (1) Transgenic mice carrying the human prototype c-Ha-ras gene (rasH2 mice) and their wild littermates (non-Tg mice) received an intraperitoneal (ip) injection of urethane. Lung adenomas with high frequency of point mutations of the transgene were induced in treated rasH2 mice. (2) Heterozygous p53 deficient CBA mice [p53 (+/-) CBA mice] and their wold littermates {p53 (+/+) mice] received an ip injection of ethylnitrosourea (ENU). Uterine tumors with high frequency of point mutations of p53 were induced in treated p53 (+/-) mice. The results suggest that point mutations of p53 are responsible for the induction of uterine tumors. (3) Diet containing of p-cresidine was given to rasH2 and non-Tg mice for 26 weeks. Transitional cell papillomas and carcinomas were frequently induced in treated rasH2 mice, but point mutations of the transgene were not related to the tumor induction. (4) p53 (+/-) and p53 (+/+) CBA mice received an ip injection of dimethylnitrosamine (DMN) followed by phenobarbital (PB) for 26 weeks. The incidence of hepatocellular adenomas was significantly increased in p53 (+/-) mice of the DMN+PB group as compared to that in p53 (+/+) mice, but no point mutations of p53 were observed in the induced tumors. (5) Glandular stomach tumors are induced I p53 (+/-) TSG mice by the treatment of methylnitrosourea (MNU) for 10 weeks, but no data were available in p53 (+/-) CBA mice. Therefore, p53 (+/-) and p53 (+/+) CBA mice were given water containing MNU for 26 weeks. The fact that no glandular stomach tumors were induced in these treated mice suggests that the carcinogenic susceptibility is different even in the same p53 (+/-) mice depending on the strain difference or different genetically engineering procedures.
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[Publications] Mitsumori, K., Yasuhara, K., Mori, I., Hayashi, S., Shimo, T., Onodera, H., Nomura, T.and Hayashi, Y.: "Pulmonary fibrosis caused by N-methyl-N-nitrosourethane inhibits lung tumorigenesis by urethane in transgenic mice carrying the human prorotype c-Ha-ras gene."Cancer Letters. 129. 181-190 (1998)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Mitsumori, K., Onodera, H., Shimo, T., Yasuhara, K., Takagi, H., Koujitani, K., Hirose, M., Maruyama, C.and Wakana, S.: "Rapid induction of Uterine tumors with p53 point mutations in heterozygous p53-deficient CBA mice given a single intraperitoneal administration of N-ethyl-N-nitrosourea."Carcinogenesis. 21. 1039-1042 (2000)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Maronpot, R.R, Mitsumori, K., Mann, P., Takaoka, M., Yamamoto, S., Usui, T., Okamiya, H., Nishikawa, S.and Nomura, T.: "Interlaboratory comparison of the CB6F1-Tg rasH2 rapid carcinogenicity testing model."Toxicol ogy. 146. 149-159 (2000)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Takagi, H., Onodera, H., Yasuhara, K., Koujitani, T., Tamura, T., Hirose, M.and Mitsumori, K.: "Lack of carcinogenic sensitivity of the glandular stomach in heterozygous p53 deficient mice given N-methyl-N-nitrosourea in drinking water for 26 weeks."Asian Pacific J.Cancer Prevent.. 1. 299-303 (2000)
Description
「研究成果報告書概要(欧文)」より
