Dose response for benzo(a)pyrene adducts in mouse epidermal DNA.

The dose dependency of the binding of benzo(a)pyrene (BaP) with DNA of mouse epidermis was investigated. BaP-conjugated epidermal DNA was isolated and enzymatically degraded to deoxyribonucleosides. The BaP-DNA adducts were separated by Sephadex LH-20 column or high-performance liquid chromatography. Two major BaP-DNA adducts were found. One was in the region of the elution profile that contained polycyclic aromatic hydrocarbons adducted to deoxyribonucleosides. The other adduct was eluted from Sephadex LH-20 and high-performance liquid chromatography columns before the deoxyribonucleosides and after deoxyribonucleotides. Both adducts of BaP in epidermal DNA reached a maximum 7 hr after a single skin application, and subsequently little, if any, loss of adducts was observed for 49 hr. Both adducts varied as a linear function for topical doses in the range from 0.01 to 300 microgram/mouse. The formation of DNA adducts by BaP occurred in proportion to dose at doses several orders of magnitude below those that are feasible to test for carcinogenicity.