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 VG 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 VG and urethane- induced lung tumors in rasH2 mice. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.