Benzo(a)pyrene Metabolism in Primary Cultures of Mouse Epidermal Cells and Untransformed and Transformed Epidermal Cell Lines¹

The metabolism of [³H]benzo(a)pyrene [B(a)P] by cultures of primary mouse epidermal cells and untransformed and transformed epidermal cell lines was investigated. All three cell types effectively metabolized [³H]B(a)P. The major organic solvent-extractable metabolites found intracellularly in primary cultures were trans-7,8-dihydro-7,8-dihydroxybenzo(a)pyrene and 3-hydroxybenzo(a)pyrene, although quantities of 9-hydroxybenzo(a)pyrene, trans-9,10-dihydro-9,10-dihydroxybenzo(a)pyrene, and quinones also were present. The major organic solvent-soluble metabolites found in the extracellular medium were trans-9,10-dihydro-9,10-dihydroxybenzo(a)pyrene and trans-7,8-dihydro-7,8-dihydroxybenzo(a)pyrene, with smaller quantities of unconjugated phenols and quinones. The major water-soluble metabolites found in the extracellular medium were conjugated with glucuronic acid [primarily 3-hydroxybenzo(a)pyrene and several quinones]. No sulfate conjugates of [³H]B(a)P metabolites were detected.

[³H]B(a)P metabolism was similar in cultures of untransformed and transformed epidermal cell lines but differed from the primary cultures. The major intracellular and extracellular organic solvent-soluble metabolites were diols. Little or no unconjugated phenols were detected. Both the untransformed and transformed epidermal cell lines converted [³H]B(a)P to water-soluble metabolites, primarily glucuronide conjugates. In contrast to the primary cells, a major pathway of trans-7,8-dihydro-7,8-dihydroxybenzo(a)pyrene metabolism in the untransformed and transformed cell lines was to a glucuronide conjugate. Primary mouse epidermal cells provide an important model system for studying factors affecting the activation and detoxification of hydrocarbon carcinogens.