Racemic anti-
benzo[c]phenanthrene-3,4-diol-1,2-
epoxide (anti-
B[c]PhDE) is a powerful rat mammary
carcinogen and is one of the most potent diol-
epoxide tumorigens in mouse skin. Activation of ras genes has been proposed to be involved in
tumorigenesis by this and related
polynuclear aromatic hydrocarbon metabolites. Therefore, we analyzed rat mammary
tumors and mouse skin
tumors induced by anti-
B[c]PhDE for mutations at
codons 12, 13 and 61 of the Ki-ras and Ha-ras genes. No Ki-ras mutations were detected in either
tumor type. In the rat mammary
tumors, no Ha-ras mutations in
codons 12 or 13 were observed in 25
tumors analyzed. Only one, a CAA-->CTA mutation, was detected in
codon 61, of 42
tumors analyzed. These results indicate that Ki-ras and Ha-ras mutations are not involved in the induction of rat mammary
tumors by anti-
B[c]PhDE. Mutations in
codon 61 of the Ha-ras gene were common, however, in mouse skin
tumors induced by this diol-
epoxide, being detected in 63% of the
tumors analyzed; 90% of these mutations were CAA-->CTA. A dose-dependent difference in the occurrence of the CAA-->CTA mutations was observed; they were present in 75% of the
tumors induced by a 100 nmol initiating dose of the diol-
epoxide, but in only 34.5% of the
tumors induced by a 400 nmol initiating dose. A CAA-->CTA mutation in
codon 61 of Ha-ras was also detected in one of four
acetone control
tumors. In comparison with previous studies of other
polynuclear aromatic hydrocarbons and their metabolites, the results suggest that the reactivity with
DNA of anti-
B[c]PhDE is one factor involved in the induction of A mutations in Ha-ras genes in mouse skin, but further studies are required to evaluate the significance of these mutations in mouse skin
tumorigenesis.