Benzo[a]pyrene metabolism in human T 47D mammary tumor cells: evidence for sulfate conjugation and translocation of reactive metabolites across cell membranes.

Human mammary tumor T 47D cells were examined for their capacity to metabolize benzo[a]pyrene (BaP) to gain insight into potential metabolic pathways for BaP in human epithelial tissue. Confluent cultures metabolized 95% of 4 microM BaP after 24 h incubation. BaP metabolites were analyzed from culture medium since only residual amounts remained in cells. Tetraols/triols, dihydrodiols, quinones and phenols were either unconjugated or existed as sulfate conjugates. Glucuronide conjugation was minor. Remaining water-soluble (WS) metabolites could be extracted with butanol or removed from culture medium protein with methanol/water and suggestive evidence indicates these may be glutathione conjugates. A portion of BaP-WS metabolites were covalently bound to medium protein. This latter phenomenon is attributed to translocation of reactive BaP metabolites across cell membranes which could potentially occur in vivo during cellular processing of BaP.