This investigation was concerned with the acute effect of ethionine, thioacetamide, dimethylnitrosamine (DMN), or aflatoxin B1 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 (2-FAA) 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 2-FAA or 3′-Me-DAB diminished the acute toxic effect of ethionine, disaggregation of polyribosomes, and inhibition 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 polyribosomes and protein synthesis. Rats force-fed diets containing 2-FAA, 3′-Me-DAB, DMN, thioacetamide, or ethionine for 3 days and then challenged acutely with thioacetamide, DMN, or aflatoxin B1 revealed variable responses of hepatic polyribosomes and protein synthesis. Thus, long- and short-term feeding of several hepatocarcinogens leads to 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 carcinogens (thioacetamide, DMN, or aflatoxin B1) other than ethionine develop variable effects.

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This investigation was supported by USPHS Research Grants CA-14156 and CA-22997 from the National Cancer Institute.

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