Mutations in the Ha-ras proto-oncogene in spontaneous and chemically induced liver tumours of the CF1 mouse

Abstract

Mutations in codon 61 of the Ha-ras proto-oncogene have been shown to occur with a high frequency in both spontaneous and carcinogen-induced liver tumours of the B6C3F1 mouse. In the present study we analysed the frequency and pattern of Ha-ras mutations in liver tumours in a different strain of mice, namely the CF1 mouse. These liver tumours occurred spontaneously or after administration of either aflatoxin B1, phenobarbital or dieldrin. Mutation analysis was performed by in vitro amplification of DNA using the polymerase chain reaction combined with selective oligonucleotide hybridization. Our results demonstrate the presence of mutations in the Ha-ras gene in liver tumours of the CF1 strain. In total, 6 out of 35 liver tumours of male CF1 mice, two of them occurring after treatment with the tumour promoter phenobarbital solely, contained mutations at either the first or second base of codon 61 of the Ha-ras gene. The types of mutations found in liver tumours of the CF1 mouse were very similar to those described in the B6C3F1 mouse, indicating that mutations in the Ha-ras proto-oncogene may represent a critical event in mouse hepatocarcinogenesis.