In vivo formation and persistence of DNA adducts in mouse and rat skin exposed to (+/-)-trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene and (+/-)-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene.

The in vivo DNA adduct formation of (+/-)-trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene (BPD) and (+/-)-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (anti-BPDE) were compared and the persistence and disappearance of the adducts in both mouse and rat epidermis determined. BPD (100 nmol/mouse in 150 microliter acetone and 200 nmol/rat in 300 microliter acetone) and anti-BPDE (77 nmol/mouse in 150 microliter tetrahydrofuran and 154 nmol/rat in 300 microliter tetrahydrofuran) were topically applied to 50-day-old male Swiss mice and 35-day-old Wistar rats. To improve the identification of the DNA adducts formed, an acid hydrolysis technique was used to convert the BPD- and anti-BPDE-deoxyribonucleoside adducts formed in mouse and rat skin to BP tetrols. The modified deoxyribonucleosides and BP tetrols obtained by hydrolysis of adducts were isolated by reverse-phase h.p.l.c. At approximately similar doses per unit area of treated skin, the initial total binding of these compounds to epidermal DNA and the level of modified deoxyribonucleosides was approximately 6-fold lower in rat skin epidermis than in mouse skin epidermis. Similar ratios of (+/-)-anti-BPDE-deoxyguanosine (dGuo) to (+/-)-syn-BPDE-dGuo adducts (5.7 and 6.1, determined by h.p.l.c. analysis of BP tetrols obtained by hydrolysis of modified dGuo) were found in both mouse and rat epidermis a short time (6 h) after topical application of (+/-)-trans-BPD. Three hours after topical application of (+/-)-anti-BPDE, the ratios of BP-7,10/8,9-tetrol to 7/8,9,10-tetrol were 9:1 in mouse epidermal DNA and 6:1 in rat epidermal DNA. One and three weeks after application of these two compounds, only (+)-anti-BPDE-dGuo was detected in mouse epidermis; 2 and 0.2% of the initial (+)-anti-BPDE-dGuo level was found to persist in the epidermal DNA from BPD- and anti-BPDE-treated mice respectively. No DNA adducts were detected in rat epidermis 3 weeks after BPD and anti-BPDE treatment. Thus, 3 weeks after topical application of BPD and anti-BPDE to mouse and rat skin, the DNA adducts completely disappeared from rat epidermis while they persisted in mouse epidermis. The results suggest that: the persistence of (+)-anti-BPDE-dGuo may be related to carcinogenesis in mouse epidermis by BPD and anti-BPDE; the complete disappearance of the anti-BPDE-dGuo adduct may also account in part for the relative resistance of tissue from this species to the carcinogenic action of benzo[a]pyrene.