7,12-Dimethylbenz[a]anthracene - DNA binding in mouse skin: response of different mouse strains and effects of various modifiers of carcinogenesis

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Abstract
7,12-Dimethylbenz[a]anthracene (DMBA)-deoxyribonucleoside adducts formed in mouse skin DNA were quantified in order to determine whether these changed in any systematic fashion under conditions where the tumorigenic activity of DMBA is modified. Similar distributions of adducts were found in male NIH Swiss mice and C57BL mice which exhibit different sensitivities to initiation-promotion using DMBA as initiator, though in both these strains of mice the bay region syn dihydrodiol epoxide is responsible for a greater fraction of total binding at higher DMBA doses. Pretreatment with various chemicals known to inhibit the tumor initiating activity of DMBA in mouse skin did not lead to selective inhibition of the formation of any adduct in female NIH Swiss mice. However, the effects of these agents ranged from a clear inhibition of overall DNA binding (7,8-benzoflavone) to little or no effect on overall binding (butylated hydroxyanisole, butylated hydroxytoluene). The lack of any effect of the antioxidants on DMBA-DNA adduct formation suggests that they may affect some step in tumor initiation other than adduct formation.