Repair of DNA adducts of the carcinogen 15,16-dihydro-11-methylcyclopenta[a]phenanthren-17-one in mouse tissues and its relation to tumor induction.

The formation and repair of DNA adducts of the carcinogen, 15,16-dihydro-11-methylcyclopenta[a]phenanthren-17-one, have been studied in three mouse tissues, liver, lung, and skin. Following a single i.m. dose of the carcinogen, DNA adduct formation was observed in all three tissues, the highest being found in liver DNA, the tissue resistant to tumor formation by this carcinogen. In skin and lung, the tissues which were susceptible to tumor formation, binding was approximately one-half that found in liver. Detailed analysis by high-pressure liquid chromatography of the adducts formed in each of the three tissues revealed no major qualitative differences in the eight adduct peaks. In vivo removal of the labeled adducts was studied over a 14-day period following initial treatment, and adducts were analyzed at each time point by high-pressure liquid chromatography. In skin and lung, active removal of the major adducts could not be measured above the normal rate of DNA turnover. By contrast, in the liver, where the rate of DNA turnover was slower, adducts were removed relatively rapidly with a half-life of approximately 2.5 days. Only one minor adduct present in both skin and liver was removed more rapidly than were the major adducts. The results suggest that the persistence of carcinogen-DNA adducts coupled with a relatively high rate of cell division may be related to tissue-specific carcinogenesis by this polycyclic ketone.