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

The polycyclic aromatic hydrocarbon, 7,12-dimethyl benz[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, resulted in extensive formation of hydrocarbon-deoxyribonucleoside adducts. Sephadex LH-20 and reverse-phase h.p.l.c. and spectrofluorometric analysis of these adducts demonstrate that at least one adducts results from the binding of 7, 12-dimethylbenz [a] anthracene-1,2,3,4-tetrahydro-3,4,-dihydroxy-1,2,-oxide. In these experiments, employing i.p. administration of the hydrocarbon, a second more polar adduct was observed. Evidence is presented that this adduct results from the formation of a monohydroxymethyl-methyl-benz [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 first 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.