Site-specific Mutation of the Human c-Ha-ras Transgene Induced by Dimethylbenzanthracene Causes Tissue-specific Tumors in Mice |
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Authors: | Satoru-Takahiro Doi Minoru Kimura Motoya Katsuki |
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Affiliation: | Laboratory of Immunology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya 464;Department of DNA Biology, School of Medicine, Tokai University, Bohseidai, Isehara, Kanagawa 259-11;Department of Molecular and Cellular Biology, Medical Institute of Bioregula-tion, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812 |
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Abstract: | Forestoraach squamous cell carcinomas, lung adenocarcinomas and spleen angiosarcomas were induced by dimethylbenzanthracene (DMBA) in the rasH2 transgenic mouse line carrying human c-Ha-ras genes with their own promoter, encoding the prototype p21 gene product. Fifteen out of 21 mice (71%) developed forestomach squamous cell carcinomas, while 15 out of 21 (71%) had lung adenocarcinomas and 3 out of 21 (14%) showed spleen angiosarcomas within 8 weeks after a single administration of 50 mg/kg DMBA intraperitoneally. Somatic mutation at the 61st codon of the transgenes, from CAG(Gln) to CTG(Len), was detected in all these newly developed tumors. However, non-transgenic littermates demonstrated no tumors at all. These findings provide strong evidence that the somatic mutational activation of human c-Ha- ras genes is a critical event in tumorigenesis and a close relationship is therefore strongly suggested between the tissue-specific development of tumors and the somatic mutation of human c-Ha-ras genes in these rasH2 transgenic mice. |
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Keywords: | Somatic mutation Dimethylbenzanthracene Carcinoma c-Ha-ras gene Transgenic mouse |
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