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 µg/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.

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This work was supported by United States Department of Energy Contract EY-76-S-02-2737 and National Institute of Environmental Health Service Grant ES 00260. Presented in part at the Annual Meeting of the American Association for Cancer Research, Washington, D. C., April 1978 (22).

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