Codon 64 of K-ras gene mutation pattern in hepatocellular carcinomas induced by bleomycin and 1-nitropyrene in A/J mice
Article first published online: 20 FEB 2003
© 2003 Wiley-Liss, Inc.
Teratogenesis, Carcinogenesis, and Mutagenesis
Volume 23, Issue S1, pages 161–170, 2003
How to Cite
Bai, F., Nakanishi, Y., Takayama, K., Pei, X.-H., Inoue, K., Harada, T., Izumi, M. and Hara, N. (2003), Codon 64 of K-ras gene mutation pattern in hepatocellular carcinomas induced by bleomycin and 1-nitropyrene in A/J mice. Teratog. Carcinog. Mutagen., 23: 161–170. doi: 10.1002/tcm.10071
- Issue published online: 20 FEB 2003
- Article first published online: 20 FEB 2003
- lung cancer;
Bleomycin is a radiomimetic antitumor agent with unique genotoxic properties. 1-nitropyrene is an environmental mutagen and carcinogen that undergoes both oxidative and reductive metabolism. In the present study, hepatocellular carcinomas were induced in male A/J mice by the intraperitoneal injection of bleomycin (120 mg/kg) followed by the intraperitoneal administration of 1-nitropyrene (total dose: 1,575 mg/kg). In order to understand the mechanism by which these two compounds induce hepatocellular carcinomas, the incidence and spectrum of mutations in the K-ras proto-oncogene in these hepatocellular carcinomas were analyzed. The hepatocellular carcinomas were induced by the administration of bleomycin and 1-nitropyrene were evaluated for point mutations in exon 1 and exon 2 of the K-ras gene by the polymerase chain reaction and a sequencing analysis. No mutation was found in the hotspots regions of the K-ras gene codon 12, 13, or 61. However, the codon 64 of the K-ras gene mutation was identified in 10 of 10 (100%) hepatocellular carcinomas. All mutations showed the same pattern, which was TAC-CAC transition. Codon 64 of the K-ras gene mutation may thus play an important role in the induction of hepatocellular carcinomas by bleomycin in the existence of 1-nitropyrene. As far as we know, this is the first report of a codon 64 mutation in the K-ras gene in a chemically induced tumor. Teratogenesis Carcinog. Mutagen. Suppl 1:161–170, 2003. © 2003 Wiley-Liss, Inc.