The effect of aflatoxins on the incorporation of RNA and protein precursors by isolated hepatocytes.

Hepatocytes prepared by a simplified enzymatic technique were active in the incorporation of RNA and protein precursors into acid-insoluble material. The incorporation of RNA precursors was very markedly inhibited by low levels of aflatoxin B1 and G1 but not by aflatoxins B2 and G2. The activity of mixed function oxidases (MFO), the drug-metabolizing system of the endoplasmic reticulum, could be suppressed in these cells by SKF525A or stimulated by NADPH. SKF525A caused a reduction in the inhibition by aflatoxin B1 of the incorporation of RNA precursor into macromolecules. This finding suggests that a metabolite of aflatoxin B1 is the actual inhibitor of RNA synthesis in the cells. Measurement of lactate dehydrogenase activity showed these cells to be leaky on incubation at 37 degrees C and thus not suitable for studies of protein secretion.