Detection of Mutations in the H-ras Proto-Oncogene in Liver Tumours of the CF1 Mouse

Abstract

The B6C3F1 mouse is characterised by a high spontaneous liver tumour frequency and a high susceptibility to chemical carcinogens. Both spontaneous and carcinogen- induced liver tumours of this mouse strain have been shown to contain specific mutations at either the first or second base of codon 61 of the H- ras proto-oncogene (Reynolds et al. 1986; 1987; Wiseman et al. 1986; Stowers et al. 1988). No such mutations, however, have been reported sofar in liver tumours of rats or other mouse strains. The CF1 mouse is very similar to the B6C3F1 mouse with respect to spontaneous liver tumour formation and sensitivity to chemical carcinogens. We were now interested in whether liver tumours of the CF1 mouse also possess mutations in the H-ras proto-oncogene. For this purpose we analysed samples of liver tumours from the CF1 mouse which occurred spontaneously or after carcinogen or promoter treatment for mutations at codon 61 of the H-.. ras gene. Since the CF1 liver tumours were available to us only as formalin- fixed, paraffin-embedded specimens, we first tested whether this material could be used as a source for our analyses. For this purpose we used fixed and embedded material from tumours with known mutations in the H-ras proto-oncogene as a model system.