抄録
The codon 61 of the activated Ha-ras gene is detected most frequently among mutations of proto-oncogenes in spontaneously-occurring hepatocellular tumors in B6C3F1 mice. In the present study, the ras mutations and their patterns in normal liver tissue, foci of cellular alteration (FCA), and hepatocellular tumor from untreated mice were analyzed using the non-RI PCR-SSCP method. The Ha-ras gene with mutated codon 61 was detected in 1.6% (2/122) from normal liver tissues, 16.7% (6/36) from spontaneous FCA tissues, 30.4% (48/158) from spontaneous hepatocellular tumor tissues, and 7.7% (3/39) from normal portion in spontaneous hepatocellular tumor tissues. Furthermore, mutation in the Ha-ras gene was compared between spontaneous and induced hepatocellular proliferative lesions including hepatocellular tumor from archival materials at our Center. Although no clear difference was found between genotoxic carcinogen and non-genotoxic carcinogens in the incidence of Ha-ras gene mutation in the induced tumors, the incidence of Ha-ras gene mutation in FCA, which was induced by genotoxic carcinogen, was higher than that in FCA induced by non-genotoxic carcinogens. These data suggested that to analyze the incidence of Ha-ras gene mutation in proliferative lesions in the livers of B6C3F1 mice, especially in the FCA is useful in evaluation of hepatocarcinogenicity of the chemicals.
