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ras Mutations in 2-Acetylaminofluorene-induced Lung and Liver Tumors from C3H/HeJ and (C3HxA/J)F1 Mice¹

Department of Pathology, Medical College of Ohio, Toledo, Ohio 43699

Previous studies have demonstrated mutagenic specificity of 2-acetylaminofluorene (AAF) in several strains of bacteria and mammalian cells. Examination of AAF-induced B6C3F1 mouse liver tumor DNAs indicates a GT (or CA) transversion in the H-ras gene. In the present study, 6 mouse lung tumors [2 were from C3H/HeJ mice and 4 were from (C3HxA/J)F1 mice] and 20 C3H/HeJ mouse liver tumors induced by AAF were analyzed for the presence of activating mutations in the ras gene by utilizing polymerase chain reaction, single-strand conformation polymorphism, and direct DNA sequencing analysis. All of the lung tumors contained an activated K-ras protooncogene with an AT transversion at the second base of codon 61. The activating mutations in the H-ras gene were detected in 14 of 20 AAF-induced mouse liver tumors with 13 of 14 having a CA transversion at the first base of codon 61 and 1 of 14 having an AT transversion at the second base of codon 61. The selectivity of mutations in the ras oncogene observed in AAF-induced mouse lung and liver tumors, as compared to those in spontaneously occurring mouse lung and liver tumors, suggests that AAF may directly induce point mutations in the ras gene. The difference in the ras mutation spectra between lung and liver tumors induced by AAF indicates that AAF mutagenesis could be tissue-specific.

¹ This investigation was supported by American Cancer Society-Ohio Division (M.Y.) and Ohio Cancer Research Associates, Inc. (M.Y.).

² Present address: Department of Medicine, Medical College of Ohio, Toledo, OH 43699.

³ Present address: Department of Preventive Medicine, Ohio State University, Columbus, OH 43210.

⁴ To whom requests for reprints should be addressed.

Received 3/30/92. Accepted 1/21/93.

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