Allele-specific activation and expression of the K-ras gene in hybrid mouse lung tumors induced by chemical carcinogens.
A mouse hybrid, (C3H x A/J)F1 or C3A, was developed by crossing male A/J mice (high lung tumor susceptibility) with female C3H mice (low lung tumor susceptibility). The lung tumor responses of the C3A mice to dimethylnitrosamine (DMN) or benzo[a]pyrene (B[a]P) were found to be intermediate between those of the two parental strains. Mutational activation of the K-ras gene was found at a high frequency in both the B[a]P- and DMN-induced C3A lung tumors. To explore the genetic basis of the K-ras gene involvement in mouse lung tumor susceptibility, the parental origin of the K-ras oncogene in the chemically induced C3A lung tumors was determined. K-ras oncogenes were found on the allele inherited from the susceptible A/J parent in 14/16 of DMN-induced tumors and 15/17 of B[a]P-induced tumors from C3A mice. Furthermore, the K-ras mRNA transcribed from the A/J allele was 5-20 times more than C3H K-ras transcripts in 10/10 DMN-induced and 10/10 B[a]P-induced C3A lung tumors. These data suggest that an activated A/J K-ras allele could be more tumorigenic than an activated C3H allele due to the differential expression of the two alleles in lung cells.
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Department of Pathology, Medical College of Ohio, Toledo 43699.
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Wang
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Stoner
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D000483:Alleles; D000818:Animals; D003043:Cocarcinogenesis; D004128:Dimethylnitrosamine; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras; D008175:Lung Neoplasms / Q000139:chemically induced* / Q000235:genetics*; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D008809:Mice, Inbred C3H; D009154:Mutation; D016133:Polymerase Chain Reaction / Q000379:methods; D018807:Polymorphism, Single-Stranded Conformational
D004128:Dimethylnitrosamine