Metabolism of benzo[a]pyrene by cultured human hepatocytes from multiple donors.

摘要: Primary hepatocyte cultures from six human donors were established and their abilities to metabolize the polycyclic aromatic hydrocarbon carcinogen benzo[a]pyrene (B[a]P) examined. Cells each donor plated at similar densities (1 X 10(7) cells/100 mm dish). All metabolized B[a]P a significant extent (24-35 nmol in 24 h) h.p.l.c. profiles of organic solvent-soluble glucuronidated metabolites obtained for all donors. The predominant extracellular 9,10- 7,8-dihydrodiols, 9-hydroxy-B[a]P, mixture tetrols, but general ratios these varied widely among cells different In contrast, highly reproducible same treated with either 8 or h after initial plating. There was less variability amounts specific conjugated glucuronic acid by various This could not be correlated cell viability overall levels metabolism. addition, metabolism fresh cryopreserved hepatocytes compared. While there only small reduction level total freezing, 3- 5-fold increase production B[a]P-7,8-dihydrodiol, found both medium as conjugates, tested.