Formation and persistence of DNA adducts in epidermal and dermal mouse skin exposed to benzo(a)pyrene in vivo.

Tritiated benzo(a)pyrene was applied topically to 35 old male Swiss mice that received 250 nMole (0.63 mCi) per mouse in 150 microliters acetone. At each time point of study, 1, 3 and 7 days, 10 animals were killed, the skin was removed and the susceptible epidermic cells were separated from resistant dermis. The initial level of the total BaP-DNA adduct after 1 day of test was 2 fold higher in epidermic cells; in addition, the concentration of the individual modified deoxyribonucleoside adducts was 4 fold greater in epidermis. However, the nature and the repartition of the modified nucleosides analyzed by high performance liquid chromatography were similar. They were 5 fold more in epidermic cells, except for the (+/-) SynBaP- diolepoxide - deoxyguanosine adduct which was 2 fold more in dermic cells. The major DNA adduct formed in both types of cells was the (+) antiBaP diolepoxide - deoxyguanosine = (+) anti BPDE-dG with 75% of total adduct in epidermic and 55% in dermal cells. The decreased amount of BaP bound to DNA of epidermic and dermic cells may be similar and 90% of (+) anti BPDE-dG was removed after a week of treatment; in addition, a minority that bound with 9OH-BaP was also shown to be persistent. Although the persistence of adduct was 7 fold more important in susceptible epidermal cells than in the resistant dermic population, the nature of adduct repartition and the similar type of excision suggest that other mechanisms are also involved in the biologically different response of epidermis versus dermis to the carcinogenic BaP when it is applied topically.