SPONTANEOUS MUTATION AT CODON-61 OF THE HA-RAS GENE IN THE NASCENT LIVER OF B6C3F1, C3H HE AND C57BL/6 MICE/

DNA was isolated from the liver of young B6C3F1, C3H/He and C57BL/6 mi ce, 6-9 weeks old. A portion of exon 2 of Ha-ras was amplified by PCR allele-specific amplification. The PCR product was identified by (a) s ize, (b) presence of a diagnostic restriction site, and (c) direct seq uencing. Our results indicate that nascent mouse liver bears a subpopu lation of cells which contain a mutation in codon 61 of Ha-ras, specif ically an A to G transition at position 2. Therefore, the detection of this mutation in chemically induced mouse liver tumors does not demon strate that the chemical in question acts as a mutagen. It might act b y a nongenotoxic mechanism, i.e., by facilitating a clonal expansion o f cells bearing this spontaneous mutation.