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

Abstract

Listen

Translate article

This investigation was concerned with the effects of certain hepatocarcinogens ingested for long- or short-term intervals upon selected responses of rat liver to specific hepatotoxic stimuli. Rats fed ad libitum for long (3 to 45 weeks) periods or force-fed for short (3 days) periods purified diets containing a single hepatocarcinogen, ethionine, N-2-fluorenylacetamide, 3′-methyl-4-dimethylaminoazobenzene, or thioacetamide, were subjected to the acute administration of a single hepatotoxic agent, such as puromycin, actinomycin D, sparsomycin, hypertonic NaCl or CCl 4, and hepatic protein synthesis ( in vitro) and polyribosomal aggregation were evaluated. Relating to in vitro protein synthesis, in long-term experiments, puromycin induced less inhibition in the experimental groups than in the control (basal diet) group; and actinomycin D inhibited all groups similarly; while in the short-term experiments, puromycin induced less inhibition in the experimental groups than in the control group; actinomycin D inhibited he basal and ethionine groups more than the other groups; sparsomycin induced variable degrees of inhibition, with the ethionine group showing the most and the N-2-fluorenylacetamide and thioacetamide groups showing the least; hypertonic NaCl markedly inhibited all groups similarly; and CCl 4 induced somewhat variable degrees of inhibition, with the thioacetamide group showing less than the other groups. In a few long-term experiments where hepatomas were evaluated in relation to surrounding liver tissue, puromycin administration induced less inhibition in the hepatomas than in the surrounding liver while actinomycin D administration induced similar inhibition in both groups. In general, in all experiments the degree of polyribosomal disagregation was parallel to that of inhibition of protein synthesis ( in vitro). The results reveal that the livers of rats fed purified diets containing selected hepatocarcinogens responded in a variable manner in regard to protein synthesis ( in vitro) and status of polyribosomal aggregation to the acute administration of selected hepatotoxic agents.