7, 12-Dimethylbenz[a]anthracene-deoxyribonucleoside adduct formation in vivo: evidence for the formation and binding of a monohydroxymethyl-DMBA metabolite to rat liver DNA

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Abstract
The polycyclic aromatic hydrocarbon, 7,12-dimethylbenz[a]anthracene (DMBA), is a potent carcinogen to the female Sprague-Dawley rat and, when administered under conditions that have been shown to produce cancer, results in extensive formation of hydrocarbon-deoxyribonucleoside adducts. Sephadex LH-20 and reverse-phase h.p.l.c. [high-performance liquid chromatography] and spectrofluorometric analysis of these adducts demonstrate that at least 1 adduct results from the binding of 7,12-dimethylbenz[a]anthracene-1,2,3,4-tetrahydro-3,4-dihydroxy-1,2-oxide. In these experiments, which employed i.p. administration of the hydrocarbon, a 2nd more polar adduct was observed. Evidence is presented that this adduct results from the formation of a monohydroxymethyl-methylbenz[a]anthracene-A-ring-diol-epoxide. While both of the monohydroxymethyl-DMBA metabolites have been shown to bind cellular DNA following their administration, this is the 1st evidence of monohydroxymethyl-DMBA-deoxyribonucleoside adducts being formed after the administration of DMBA per se. The evidence suggests that this more polar adduct is a 7-hydroxymethyl-12-methylbenz[a]anthracene-deoxyribonucleoside adduct.