Benzo(a)pyrene metabolism and DNA adduct formation in serially cultivated strains of human epidermal keratinocytes.

Six strains of human epidermal keratinocytes were shown to be capable of metabolising benzo(a)pyrene (BP)for at least 40 population doublings in culture. Metabolism was independent of human or mouse fibroblast products, and also the growth rate of the epidermal cultures, at least when cholera toxin and epidermal growth factor were included in the medium. Epidermal strains metabolized and bound to their DNA more BP than human fibroblasts, and themselves exhibited a 2-to 3-fold range of inter-strain variability. Chromatographic analysis of epidermal DNA containing bound BP showed that the major metabolite which had reacted with the DNA was a 7,8 dihydrodiol - 9,10 oxide of BP (the proposed ultimate carcinogenic metabolite of BP).