Abstract
A mouse hepatoma cell line, Hepa-1, is highly sensitive to the toxic effects of Aflatoxin B 1 (AFB 1). Half maximal survival (LD 50) of cells occurs at 0.068 ug AFB 1/ml. Benzo(a)anthracene, which induces aryl hydrocarbon hydroxylase and cytochrome P 1-450 in Hepa-1, causes a slight increase in the toxicity of AFB 1 (LD 50 = 0.034 ug/ml). An aryl hydrocarbon hydroxylase- and cytochrome P 1-450-deficient mutant of Hepa-1 is, however, over 100 times more resistant to AFB 1 than Hepa-1. Almost no decline in survival is observed at 5 ug AFB 1/ml. Cytochrome P 1-450 thus effects strongly on the cytotoxicity of AFB 1 in these cells. The basal activity in Hepa-1 is enough to elicit an almost full toxic effect. AFB 1, although a substrate for cytochrome P 1-450, does not act as an inducer of aryl hydrocarbon hydroxylase.
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