ENHANCEMENT OF A AFLATOXIN-B1 CYTOTOXICITY IN DIFFERENTIATED RAT HEPATOMA CULTURES BY A PRIOR GLUCOCORTICOID TREATMENT OF THE MONOLAYER

The cytotoxic effect of aflatoxin B1 on cultures of a differentiated rat hepatoma cell line, Faza 967, has been evaluated by scoring the surviving colonies two weeks after briefly exposing the freshly plated cells to the mycotoxin. At the lowest concentration, aflatoxin B1 exhibits no toxicity, unless the cultures have been pretreated with dexamethasone. HF-1, an hepatoma hybrid cell line exhibiting extinction of the hepatic functions and HF1-4, its subclone, that reexpresses all of these functions, have been compared. A 6hrs exposure to 60ng/ml aflatoxin B1 is not toxic for HF1 even after an hormonal treatment, while dexamethasone enhances the effect on HF1-4. Glucocorticoïds have been shown previously to induce, in the differentiated clones, the hydroxylation of bile acid - a cytochrome P-450-mediated reaction ; in contrast, 3-methylcholanthrene, an inducer of benzopyrene hydroxylase in hepatoma cultures, is without effect on bile acid metabolism and on aflatoxin B1 cytotoxicity. These results suggest that in the differentiated hepatoma cells, aflatoxin B1 is converted into a cytotoxic metabolite by a glucocorticoïd-induced monooxygenase belonging to the cytochrome P-450-related group. © 1979.