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Formation of Covalent DNA Adducts by Enzymatically Activated Carcinogens and Drugs In Vitro and Their Determination by 32P-postlabeling
Published on: March 20, 2018
7,12-Dimethylbenz[a]anthracene-DNA adducts in mouse skin, dermis and epidermis
Abstract:
Female NIH Swiss mice were treated topically with either 0.01 or 0.1 mumol 7,12-[3H]dimethylbenz[a]anthracene and DNA was isolated either from the whole skin, the dermis or the epidermis. Levels of binding to DNA and levels of individual adducts formed were similar in all 3 tissue fractions for a given dose of carcinogen with levels for the epidermis being marginally greater than in the other fractions. In all tissue fractions, the syn dihydrodiol epoxide-deoxyribonucleoside adducts were responsible for a greater fraction of total binding at the higher, than at the lower, carcinogen dose. The mechanism of metabolic activation of 7,12-dimethylbenz[a]anthracene for DNA binding is, therefore, qualitatively the same in both the dermis and epidermis. Quantification of adducts suggests some subtle differences between the DMBA activating systems in dermis and epidermis.
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