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.
Massey
T E
TE
Environmental Carcinogenesis Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
Devereux
T R
TR
Maronpot
R R
RR
Foley
J F
JF
Anderson
M W
MW
D000483:Alleles; D000818:Animals; D001483:Base Sequence; D002273:Carcinogens; D003062:Codon; D003433:Crosses, Genetic; D017931:DNA Primers; D005260:Female; D011905:Genes, ras; D007113:Immunity, Innate; D008175:Lung Neoplasms / Q000139:chemically induced / Q000235:genetics*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D014520:Urethane / Q000031:analogs & derivatives*
D002273:Carcinogens; D003062:Codon; D017931:DNA Primers; D014520:Urethane; C017963:vinyl carbamate