Mutation analysis of vinyl carbamate or urethane induced lung tumors in rasH2 transgenic mice

• Published in: Toxicology letters Vol. 142; no. 1; pp. 111 - 117
• Main Authors: Tomisawa, Masashi, Suemizu, Hiroshi, Ohnishi, Yasuyuki, Maruyama, Chika, Urano, Kohji, Usui, Toshimi, Yasuhara, Kazuo, Tamaoki, Norikazu, Mitsumori, Kunitoshi
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 30.04.2003; Amsterdam Elsevier Science
• Subjects: Animals; Biological and medical sciences; Carcinogenesis, carcinogens and anticarcinogens; Carcinogens - toxicity; Chemical agents; Codon; Crosses, Genetic; Female; Genes, ras - genetics; Human c-Ha- ras gene; Lung Neoplasms - chemically induced; Lung Neoplasms - genetics; Male; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Transgenic; Mutation; Point Mutation; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Polymorphism, Single-Stranded Conformational; rasH2 transgenic mouse; RNA, Neoplasm - chemistry; RNA, Neoplasm - genetics; Tumors; Urethane; Urethane - analogs & derivatives; Urethane - toxicity; Vinyl carbamate; Vinyl carbamate; Urethane; Mutation; rasH2 transgenic mouse; Human c-Ha- ras gene; Lung disease; Respiratory disease; Rodentia; Transgenic animal; Malignant tumor; Organic carbamate; Carcinogen; Vertebrata; Mammalia; Mouse; Human c-Ha-ras gene
• ISSN: 0378-4274; 1879-3169
• DOI: 10.1016/S0378-4274(03)00018-3

Previous studies showed that significant differences in mutation frequency of the human c-Ha- ras transgene between vinyl carbamate (VC)- and ethyl carbamate (urethane)-induced lung tumors were observed in rasH2 mice. It remains unclear why the point mutation frequency is extremely low in VC-induced lung tumors, although this compound is much more carcinogenic than urethane. In this study, we examined the somatic point mutations of the transgene at the RNA level in VC- and urethane-induced lung tumors of rasH2 mice. We did not find any mutation at codon 12 of the transgene in any of these lung tumors, but codon 61 showed frequent mutations in not only urethane-induced lung tumors (15 out of 16) but also VC-induced lung tumors (11 out of 11) in rasH2 mice. These results suggested that point mutations at codon 61 of the transgene play an important role in the carcinogenesis of VC- and urethane- induced lung tumors in rasH2 mice.