Isolated hepatocytes are capable of excreting aflatoxin metabolites

The intra- and extra-cellular concentrations of AFB1, AFM1, AFP1, AFQ1 and their conjugates were quantitatively determined after 60 min of incubation with [3H]-AFB1 (1500 pmol/10(8) cells). Comparing the total concentrations of water-soluble conjugates, the eight fold greater amounts found in the medium (718 pmol) than in the cell (86 pmol) indicate that these detoxication products were excreted soon after they were formed. When the cells were perturbed with butylated hydroxyanisole (BHA), a noncompetitive inhibitor of the mixed-function oxidases, accumulations of intracellular AFB1 and extracellular AFB1 were observed. In a cell-free microsomal system, the AFB1 was metabolized at a slower rate than in intact cells. When the activation of AFB1 is blocked, the accumulation of intracellular AFB1 and decreased internalization of AFB1 suggest that AFB1 uptake, translocation of AFB1 from site of entry to site of actions, oxidation by cytochrome P-450-dependent monoxygenase, metabolic detoxication and conjugation reactions, and excretion of water soluble metabolites are linked.