High frequency of K-ras mutations in spontaneous and vinyl carbamate-induced lung tumors of relatively resistant B6CF1 (C57BL/6J x BALB/cJ) mice.

The murine K-ras proto-oncogene is hypothesized to be a pulmonary adenoma susceptibility gene. This postulate is supported by the previous demonstration of a preference for mutation of the K-ras allele from the susceptible parent in lung tumors of A/J x C3H F1 mice. We have examined K-ras activation in control and vinyl carbamate (VC) (single dose 0.03 mumol/g i.p.) treated B6CF1 mice, the progeny of resistant C57BL/6J and intermediately sensitive BALB/cJ parents. Thirty-four of 37 tumors from VC-treated mice and 17 of 23 from controls contained activating K-ras mutations. The spectra of mutations in codons 12 and 61 of K-ras were similar for the two groups, except that 7 tumors from VC-treated mice had A-->T transversions in the second base of codon 61; none were observed in tumors from saline-treated animals. PCR-based genotyping of first exon K-ras mutations revealed that the vast majority (15 of 18) of the mutations were in the BALB/cJ allele. Furthermore, the three tumors with mutated C57BL/6J K-ras were among the smallest tumors analyzed. These results are consistent with previous findings in other mouse hybrids showing parental bias for K-ras mutations and suggest that mutation of the allele of the susceptible parent may provide a growth advantage to the tumor.