Some studies on the relationship between the cytotoxicity of aflatoxin B1 to rat hepatocytes and metabolism of the toxin

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Abstract
Aflatoxin B1 (AFB1) caused marked, rapid (1 h) inhibition of RNA synthesis and subsequent cytotoxic response in isolated and primary cultured hepatocytes, from control rats, which were known to metabolize AFB1. A rat liver epithelial-derived cell line, BL8L, was less susceptible to these effects of AFB1. These cells had no detectable AFB1 metabolizing capacity, but a less potent, antimitotic action of AFB1 was observed in the BL8L cell line. AFB1 probably required metabolism to exert its acute cytotoxic action which was found at low AFB1 concentrations, although a direct antimitotic effect, independent of metabolism, was seen in dividing cells. Phenobarbitone and 3-methylcholanthrene in vivo pretreatments, known inducers of AFB1 metabolism, resulted in reduced AFB1 inhibition of RNA synthesis and cytotoxicity in hepatocytes, but only at lower concentrations of AFB1 used; cells from AFB1 fed rats were less susceptible to AFB1 toxicity at all concentrations used. This resistance to cytotoxicity of AFB1 involved detoxification mechanisms, primarily the formation of polar conjugates of AFB1 metabolites such as glutathione conjugates. These cell culture systems were useful for studying association between metabolism and cytotoxicty of AFB1 and other xenobiotics.