The metabolism of aflatoxin B1 by hepatocytes isolated from rats following the in vivo administration of some xenobiotics

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Abstract
Isolated rat hepatocytes, an intact cellular system capable of performing phase I and phase II metabolism, were used to investigate metabolism of aflatoxin B1 [AFB1]. These cells metabolize [14C]AFB1 to aflatoxins M1 and Q1, and to radiolabled polar material, presumably conjugates, as analyzed by h.p.l.c. [high performance liquid chromatography], TLC and radioactive determination. In vivo administration of the mixed function oxidase inducers, phenobarbitone and 3-methylcholanthrene, resulted in enhanced hepatocyte phase I (microsomal) metabolism of AFB1. In contrast to metabolism of AFB1 by in vitro subcellular systems increased production of polar material (conjugated metabolites) derived from [14C]AFB1 was also detected in hepatocytes isolated from these pretreated animals. Formation of AFQ1 by isolated hepatocytes appeared to be mediated by cytochrome P450-linked enzymes whereas cytochrome P448-linked enzymes were apparently involved in AFM1 production. Chronic feeding of aflatoxin B1 to rats enhanced hepatocyte production of conjugated material only and did not elevate cellular cytochrome P450 levels, suggesting that AFB1 is not an inducer of its own primary metabolism. [This study may be applicable to carcinogenesis.].