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

  • 1 January 1981
    • journal article
    • research article
    • Vol. 41  (10) , 4115-4120
Abstract
The formation and repair of DNA adducts of the carcinogen 15,16-dihydro-11-methylcyclopenta[a]phenanthren-17-one have been studied in 3 mouse tissues: liver, lung and skin. Following a single i.m. dose of the carcinogen, DNA adduct formation was observed in all 3 tissues and was highest in liver, which was the resistant to tumor formation by this carcinogen. In skin and lung, tissues susceptible to tumor formation, binding was approximately 1/2 that found in liver. Detailed analysis by high-pressure liquid chromatography [HPLC] of the adducts formed in each of the 3 tissues revealed no major qualitative differences in the 8 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 HPLC. In skin and lung, active removal of the major adducts could not be measured above the normal rate of DNA turnover. In the liver, where the rate of DNA turnover was slower, adducts were removed relatively rapidly with a half-life of .apprx. 2.5 days. Only 1 minor adduct present in skin and liver was removed more rapidly than were the major adducts. 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.