Strain-specific tumorigenesis in mouse skin induced by the carcinogen, 15,16-dihydro-11-methylcyclopenta[a]phenanthren-17-one, and its relation to DNA adduct formation and persistence

The incidence of skin tumors has been studied in three strains of mice, namely, TO, C57BL, and DBA/2, after treatment with the carcinogen 15,16-dihydro-11-methylcyclopenta[a]phenanthren-17-one. After either a single dose followed by croton oil promotion or a continual dose of the carcinogen, tumors were observed in the TO and C57BL strains, with the TO mice having the shorter mean latent period. The DBA/2 mice, however, appeared to be resistant to tumor formation by either treatment. To understand the mechanism of resistance, several criteria have been investigated. Metabolism of the carcinogen was assessed in terms of the total DNA adduct formation and the pattern of individual adducts after separation by high-pressure liquid chromatography, and no major differences between the three strains was found. Similarly, the rates of disappearance of the individual adducts when measured over 14 days posttreatment were not strain specific. Persistent binding of the carcinogen after 2 months was found in all three strains and could be reduced markedly if croton oil was administered throughout this period. The ability of the phorbol esters to cause biochemical changes in both sensitive and resistant strains was indicated by the induction of ornithine decarboxylase in each of the three strains after treatment with either croton oil or its active component, 12-O-tetradecanoylphorbol-13-acetate.