Catechol-induced alterations in metabolic activation and binding of enantiomeric and racemic 7,8-dihydroxy-7,8-dihydrobenzo[a]pyrenes to DNA in mouse skin

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Abstract
Catechol (1,2-dihydroxybenzene) is a potent co-carcinogen with benzo[a]pyrene (BaP) and with (±)-7,8-dihydroxy-7, 8-dihydrobenzo[a]pyrene (BaP-7, 8-diol) in mouse skin. The effects of catechol on the metabolic activation of (+)- and (−)- [3H]BaP-7,8-diols and on epidermal DNA adduct formation of racemic and enantiomeric [3H]BaP-7, 8-diols were examined by applying the tritlated diols to mouse skin. The major metabolite of the (+)- [3H]BaP-7, 8-diols was the hydrolysis product of (−)- [3H]-7α,8β-diolsepoxy-9β, 10β-epoxy-7,8,9, 10-tetrahydroheiizo[a]pyrene (anti-BPDE). This suggests that a peroxyl radical-mediated pathway Is predominantly responsible for the epoxidation of this diol. Formation of (−)-anti[3H]BPDE from (+)-[3H]BaP-7,8-diol was greater than that of (+)-anti-BPDE from (−)-[3H]BaP-7,8-diol Co-application of catechol with [3H]BaP-7,8-diols inhibited epoxidation of the (+) enantiomer to a greater extent than that of the (−) enantiomer. Catechol decreased the total DNA-binding and the formation of the major adduct with (+)-[3H]BaP-7, 8-diols metabolites but catechol had no significant effect on the binding and formation of (+)-anti- [3H]BPDE-deoxyguanosine the major DNA adduct derived from (−)-[3H]BaP-7,8-diols Co-administration of catechol with (±)-[3H]BaP-7,8-diols increased the ratio of (−)- to (+)-[3H]BaP-7, 8-diols major DNA adducts in mouse skin suggesting that catechol selectively inhibits certain pathways of metabolic activation of (± )-[3H]BaP-7, 8-diols Thus, catechol modifies the tumorigenic activity of (±)- BaP-7 ,8.-diol either by alteration of the relative proportion of various hydrocarbon:DNA adducts or by a totally different as yet unexplored mechanism.

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