Time dependence of ethionine-induced changes in rat liver transfer RNA methylation

Methyl-deficient transfer RNA (tRNA) and subnormal levels of tRNA-methylating enzymes were found in the livers of female rats that had received injections of 250 mg DL-ethionine per kg body weight per day and 120 mg adenine per kg body weight per day for 2 days. Adenine alone had no effect. When the ethionine plus adenine injections were continued for longer periods of time, liver tRNA-methylating enzyme activity measured in vitro gradually increased and exceeded that of the controls. Concurrently, the relative methyl deficiency of liver tRNA decreased. The latter was evident because of the decreased ability of the tRNA to accept methyl groups during in vitro methylation catalyzed by homologous enzymes. Liver tRNA from animals that were treated with ethionine for 7 days could accept only about 40% as many methyl groups as could tRNA from animals that had received ethionine for only 2 days. No further significant change in methyl deficiency of the tRNA was seen when ethionine administration was extended to a total of 14 days. Enzyme preparations from ethionine-treated, but not control, rat livers contained dialyzable substances that inhibited the tRNA methylases and altered the base specificity of these enzymes. Although S-adenosylhomocysteine and S-adenosylethionine were found to be present in the liver preparations, neither of these substances could account for the observed changes in specificity.