Alterations in rat liver
transfer RNA (
tRNA) methyltransferase activities have been observed after liver damage by various chemicals or by partial
hepatectomy. The qualitative and quantitative nature of these activity changes and the time course for their induction have been studied. Since homologous tRNAs are essentially fully modified in vivo, E. coli tRNAs were used as in vitro substrates for the rat liver
enzymes in these studies. Each of the liver-damaging agents tested rapidly caused increases in activities of the
enzyme(s) catalyzing methyl group transfer to tRNAs that have an unmodified
guanine at position 26 from the 5' end of the molecule. This group of tRNAs includes E. coli tRNANfmet, tRNAAla1, tRNALeu1, or Leu2, and tRNASer3 (Group 1). In each case
N2-methylguanine and N2,N2-dimethylguanine represented 90% or more of the products of these in vitro methylations. The product and substrate specificity observed are characteristic of N2-guanine
methyltransferase II (
S-adenosyl-L-methionine :
tRNA (
guanine-2)-
methyltransferase, EC 2.1.1.32). In crude and partially purified preparations derived from livers of both control and treated animals this
enzyme activity was not diminished significantly by exposure to 50 degrees C for min. The same liver-damaging agents induced little or no change in the activities of
enzymes that catalyze methyl group transfer to various other E. coli tRNAs that do not have
guanine at position 26 (Group 2). The results of mixing experiments appear to rule out the likelihood that the observed
enzyme activity changes are due to stimulatory or inhibitory materials present in the
enzyme preparations from control or treated animals. Thus, our experiments indicate that liver damage by each of several different methods, including surgery or administration of chemicals that are strong
carcinogens, hepatotoxins, or
cancer-promoting substances, all produce changes in liver
tRNA methyltransferase activity that represent a selective increase in activity of N2-guanine
tRNA methyltransferase II. It is proposed that the specificity of this change is not fortuitous, but is the manifestation of an as yet unidentified regulatory process.