Action of Actinomycin D on the GI Tract: Implications for Enzyme Induction Studies

Abstract

Summary

Stomach emptying was significantly inhibited by actinomycin D administration (100 μg/100 g), after a 24-hr fast, to rats intubated with a ¹⁴C-labeled casein hydrolysate. Four hr after intubation 45% of the radioactivity remained in the stomachs of actinomycin D-treated rats; whereas, only 3% was present in those of saline-treated controls. The decreased rate of amino acid incorporation into liver and serum protein reflected the blocked state of the stomachs of drug-treated rats. In addition to the retention of radioactivity there was an actual increase in total stomach content of the animals receiving actinomycin D. In drug-treated rats an increase in stomach content (1.5 ml of fluid) was also observed 4 hr after administration of actinomycin D in fasted rats that were not intubated with casein. In addition, the drug stimulated a bizarre appetite. Treated rats consumed large quantities of wood shavings and neoprene if accessible, besides indulging in a marked degree of coprophagy. The reciprocal relationship between stomach and liver radioactivity levels suggests that failure to observe induction of hepatic enzymes by diet in studies using actinomycin D-treated rats could result from insufficient availability of inducers, rather than the more commonly credited inhibition of RNA synthesis.