Metabolism of benzo(a)pyrene by murine embryonal carcinoma cells

Murine embryonal carcinoma (EC) cells were characterized with respect to their ability to metabolize the polycyclic aromatic hydrocarbon, benzo(a)pyrene [B(a)P]. The extent of metabolic activation varied more than 100-fold among the teratocarcinoma-derived cell lines examined. This difference in metabolic activity was correlated with an increase in the formation of specific metabolites that were identified by high-pressure liquid chromatography. Maximal in vitro formation of water-soluble products occurred 24 hr after the addition of [3H]B(a)P to the EC cells. Long-term incubation of EC cells with [3H]B(a)P indicated that, within the initial 24 hr, 2.3% of the input had been taken up by the cells. Subcellular analysis of the distribution of radioactivity indicated that 70 to 80% of intracellular radioactivity was associated with isolated nuclei. Therefore, the intranuclear metabolites of B(a)P were also analyzed by high-pressure liquid chromatography. Embryonal carcinoma cell lines OC15S1 and C86S1 showed significant in vitro toxic effects to B(a)P over a concentration range of 0.05 to 0.3 microgram/ml, whereas F9 and PC13 were resistant to concentrations of B(a)P up to 5 microgram/ml. Equally resistant to B(a)P was the PYS cell line, a differentiated cell type derived from EC cells. Cytotoxicity was related to the extent of metabolic activation of parent compound.