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 mice, 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) size, (b) presence of a diagnostic restriction site, and (c) direct sequencing. Our results indicate that nascent mouse liver bears a subpopulation of cells which contain a mutation in codon 61 of Ha-ras, specifically an A to G transition at position 2. Therefore, the detection of this mutation in chemically induced mouse liver tumors does not demonstrate that the chemical in question acts as a mutagen. It might act by a nongenotoxic mechanism, i.e., by facilitating a clonal expansion of cells bearing this spontaneous mutation.