Effects of the co-carcinogen catechol on benzo[a]pyrene metabolism and DNA adduct formation in mouse skin

We have studied the effects of the co-carcinogen catechol (1,2-dihydroxybenzene)on the metabolic activation of ³H] benzoa]pyrene (BaP) inmouse skin, in vivo and on the binding of BaP metabolites toDNA and protein at intervals from 0.5–24 h. Upon topicalapplication of 0.015 mg ³H]BaP and 0.25 or 0.5 mg catecholper mouse, catechol had little effect on the total amount of³H]BaP metabolized in mouse skin, but it affected the relativeproportions of ³H]BaP metabolites. Catechol (0.5 mg/mouse)decreased the proportion of watersoluble ³H]BaP metabolites,ethyl acetate-soluble polar metabolites and quinones, but doubledthe levels of unconjugated 3-hydroxy-BaP at all measured intervalsafter treatment. Catechol also caused a small increase in thelevels of trans-7,8-dihydroxy-7,8-dihydroBaP and trans-9,10-dihydroxy-9,10-dihydroBaP0.5 h after treatment. Two hours after treatment, the levelsof these metabolites subsided to those of the controls. Catecholdid not affect the levels of glutathione conjugates of BaP.However, it caused a decrease in glucuronide and sulphate conjugateformation from BaP. Catechol caused an 2-fold increase in theformation of anti-7, 8-dihydroxy-9, 10-epoxy-7, 8, 9, 10-tetrahydroBaP(BPDE) DNA adducts and elevated the ratio of anti-syn-BPDE-DNAadducts 1.6 to 2.9-fold. Catechol treatment increased the radioactivityassociated with epidermal proteins after ³H]BaP application.Because catechol increased levels of 3-hydroxyBaP, we consideredthe possibility that 3-hy-droxyBaP might enhance the tumor initiatingactivities of BaP or BPDE in mouse skin; a bioassay demonstratedthat this was not the case. The results of this study indicatethat one important effect of catechol related to its co-carcinogenicityis its ability to enhance formation of anti-BPDE-DNA adductsin mouse skin.