METHYLATION OF TRANSFER RNA AND OF RIBOSOMAL RNA IN RAT LIVER IN INTACT ANIMAL AND EFFECT OF CARCINOGENS

The methylation of transfer RNA (tRNA) and of ribosomal RNA (rRNA) was studied in normal animals and in animals fed diets containing the carcinogens dimethylnitrosamine, aflatoxin or ethionine. The rats were injected with [14C]methionine, and the nucleic acids were isolated, hydrolysed with HClO4 and analysed by column chromatography on Dowex-50. The level of labelling of each methylated base in tRNA was increased by the carcinogenic treatment. The increase probably does not reflect merely an increased rate of synthesis of tRNA, as each methylated base increases to a different extent in precancerous liver, in contrast to the situation in intestine, where the labelling of the different methylated bases is higher than in liver, but each is increased to a similar extent. Also, in precancerous liver, the increase in protein synthesis, judged by the incorporation of [14C]methionine into protein, is in most cases much less than the increased methylation of tRNA, while in intestine the incorporation of [14C]-methionine into protein and the methylation of tRNA exceed the values in liver in equal proportions. There also appears to be a change in composition of the major bases of tRNA during carcinogenesis produced by dimethylnitrosamine and by aflatoxin. These results add evidence to the view that there is a change in the relative abundance of different species of tRNA synthesised during carcinogenesis, the change being towards more highly methylated species. In the case of rRNA there is an increase in labelling of each methylated base, but the increase may correlate with an increased synthesis of rRNA. There is evidence for a change in the kinetics of the reactions leading to the formation of rRNA precursor. © 1969.