Covalent binding of benzo[a]pyrene diol epoxide to DNA of mouse skin: in vivo persistence of adducts formation.

Abstract

In the first 9 d after topical application of a single dose of benzo[a]pyrene to the dorsal skin of C3H mice, the half-lives of benzo[a]pyrene diol epoxide-DNA adducts and of DNA were determined to be approximately 5 d. These data indicate that, in proliferating mouse skin, benzo[a]pyrene diol epoxide-DNA lesions are not repaired, but are diluted from the genome at a rate equivalent to DNA turnover (i.e., replication versus degradation). Subsequent to this initial period, benzo[a]pyrene diol epoxide-DNA adduct removal continues, but at a much reduced rate. At 30 d posttreatment with benzo[a]pyrene, approximately 15% of the adducts are still detectable; however, their half-lives had increased to 30 d. Similar experiments with a hairless mouse showed that, although the amount of adduct formation was lower initially, the kinetics of adduct disappearance and persistence were essentially the same as found with the C3H mouse. The data obtained in this work are consistent with the hypothesis that benzo[a]pyrene diol epoxide adducts persist in a subpopulation of skin cells long after their disappearance by DNA turnover would predict.