Trans- and cis-DNA adduct concentration in epidermis from mouse and rat skin treated ex vivo with benzo[a]pyrene diol epoxide and its corresponding chlorohydrin

Benzo[a]pyrene diol epoxide, a metabolite of benzo[a]pyrene (BaP), and chlo rohydrin, the reaction product of chloride and the epoxide, form in vitro t he same trans- and cis-stereoisomeric DNA adducts, but in different proport ions. In this study, we asked whether the DNA adduct concentration can be k ept the same by applying the appropriate dose of (+/-)-7r,8t-dihydroxy-9t, 10t-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (anti-BPDE)and (+/-)-7r, 8t,9t- trihydroxy-10c-chloro-7,8,9,10- l-tetrahydrobenzo[a] pyrene (tmns-BPDCH) to rodent skin and whether the DNA adducts formed differ only in their trans- and cis-stereoisomerism. Skin from C57B16 mice, spontaneous hypertension r ats (SHR) and Sprague-Dawley (SD) rats was treated ex vivo immediately afte r the death of the animals with anti-BPDE and its corresponding bay region chlorohydrin tmns-BPDCH and the epidermis was analyzed for DNA adducts 1h a fter the application. We found that adduct formation at the exocyclic amino groups of deoxyguanosine and deoxyadenosine in epidermal DNA followed a li near dose-response within 6-100 nmol/cm(2) with both chemicals. In order to achieve the same adduct concentration in mouse, spontaneous hypertension r at (SHR), and Sprague-Dawley (SD) rat skin, respectively, a 37-, 23- and 10 -fold lower dose of anti-BPDE than of trans-BPDCH had to be applied. The or der of 2 ' -deoxyguanosine (dGuo) adduct concentration with anti-BPDE was s imilar to what has been reported, but the order with tmns-BPDCH was (+)-cis -BPDE-N-2-dGuo adduct > (+)-trans-BPDE-N-2-dGuo = (-)-trans-BPDE-N-2-dGuo > (-)-cis-BPDE-N-2-dGuo in mouse skin. Irrespective of species or strain, a significantly higher proportion of cis-adducts was obtained after treatment with trans-BPDCH than after treatment with anti-BPDE. Therefore, DNA adduc t concentration can be kept the same by applying the appropriate dose of an ti-BPDE and trans-BPDCH to rodent skin and the DNA adducts formed differ on ly in their trans- and cis-stereoisomerism. (C) 2001 Elsevier Science B.V. All rights reserved.