Acute effects of selected hepatotoxic agents on polyribosomes and protein synthesis in the livers of rats fed purified diets containing hepatocarcinogens.

This investigation was concerned with the acute effect of ethionine, thioacetamide, dimethylnitrosamine (DMN), or aflatoxin B, on hepatic polyribosomes and protein synthesis of rats fed purified diets either ad libitum for 3 to 29 weeks containing 0.025% N-2-fluorenylacetamide (2FAA) or 0.06% 3 -methyl-4-dimethylaminoazobenzene (3 Me-DAB) or by force-feeding for 3 days of diets containing 2-FAA, 3 -Me-DAB, DMN, 0.032% thioacetamide, or 0.25% ethionine. This study revealed that long-term feeding of 2FAA or 3 -Me-DAB diminished the acute toxic effect of ethionine, disaggregation of polyribosomes, and inhibi tion of protein synthesis in liver. Likewise, short-term force-feeding (3 days) of hepatocarcinogens (2-FAA, 3 Me-DAB, DMN, thioacetamide, or ethionine) diminished the acute toxic effect of ethionine on hepatic polyribo somes and protein synthesis. Rats force-fed diets con taining 2-FAA, 3 -Me-DAB, DMN, thioacetamide, or ethio nine for 3 days and then challenged acutely with thioace tamide, DMN, or aflatoxin B, revealed variable responses of hepatic polyribosomes and protein synthesis. Thus, longand short-term feeding of several hepatocarcino gens leads ta a resistance in hepatic polyribosomes and protein synthesis in response to the acute administration of ethionine while rats force-fed for 3 days the same carcinogens and then challenged acutely with carcino gens (thioacetamide, DMN, or aflatoxin B,) other than ethionine develop variable effects.