First Author | Doi ST | Year | 1994 |
Journal | Jpn J Cancer Res | Volume | 85 |
Issue | 8 | Pages | 801-7 |
PubMed ID | 7928625 | Mgi Jnum | J:91176 |
Mgi Id | MGI:3046072 | Doi | 10.1111/j.1349-7006.1994.tb02951.x |
Citation | Doi ST, et al. (1994) Site-specific mutation of the human c-Ha-ras transgene induced by dimethylbenzanthracene causes tissue-specific tumors in mice. Jpn J Cancer Res 85(8):801-7 |
abstractText | Forestomach 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(Leu), 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. |