COVALENT DNA-ADDUCTS FORMED IN MOUSE EPIDERMIS FROM DIBENZ[AJ]ANTHRACENE - EVIDENCE FOR THE FORMATION OF POLAR ADDUCTS

The formation of deoxyribonucleoside adducts in mouse epidermis has be en examined following topical application of [H-3]dibenz[a,j]anthracen e (DB[a,j]A) or by P-32-postlabeling following topical application of unlabeled DB[a,j]A, DB[a,j]A trans-3,4-diol or the anti- or syn-3,4-di ol 1,2-epoxides. A single topical application of [H-3]DB[a,j]A at a do se of 400 nmol per mouse led to the formation of 11 detectable covalen t DNA adducts. Seven of these DNA adducts were tentatively identified based on cochromatography with marker adducts using high-pressure Liqu id chromatography (HPLC). The presence of both deoxyguanosine (dGuo) a s well. as deoxyadenosine (dAdo) adducts formed from bay-region anti- and syn-3,4-diol 1,2-epoxides of DB[a,j]A was revealed. The major bay- region diol epoxide DNA adduct formed in mouse epidermis following top ical application of [H-3]DB[a,j]A was tentatively identified as the (4 R,3S)-diol (2S,1R)-epoxide bound through trans addition of the exocycl ic amino group of dGuo, although substantial amounts of the correspond ing dAdo adduct were also detected. In addition, a K-region 5,6-oxide- dAdo adduct was tentatively identified in HPLC chromatograms based on cochromatography with an authentic marker adduct. P-32-Postlabeling an alysis of DB[a,j]A-DNA adducts formed in mouse epidermis after topical application of unlabeled compound confirmed the presence of bay-regio n diol epoxide DNA adducts similar to those observed after application of [H-3]DB[a,j]A. However, P-32-postlabeling analysis also revealed t he presence of more polar covalent DNA adducts in epidermal DNA sample s from DB[a,j]A-treated mice. These more polar DNA adducts represented a significant proportion of the P-32-labeled material recovered in HP LC chromatograms. While the exact nature of these adducts remains unkn own at present, they had retention times identical to polar DNA adduct s formed following topical application of DB[a,j]A trans-3,4-diol and may represent bis-dihydrodiol epoxide DNA adducts. The present results indicate that a rather broad spectrum of DNA adducts arises following topical application of DB[a,j]A to mouse epidermis.