This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wainfan, E. Articles by Balis, M. E. Search for Related Content PubMed PubMed Citation Articles by Wainfan, E. Articles by Balis, M. E.

Ethionine-induced Changes in Rat Liver Transfer RNA Methylation¹

The Lindsley F. Kimball Research Institute of The New York Blood Center [E. W., F. A. M], and Memorial Sloan-Kettering Cancer Center [M. L. M., M. E. B.], New York, New York 10021

We have confirmed the finding by Rajalakshmi that transfer RNA (tRNA) from livers of ethionine-treated rats can act as a substrate for homologous tRNA-methylating enzymes in vitro. This methyl-deficient tRNA from liver can be methylated in vitro by enzymes from normal or ethionine-treated rats. The in vivo inhibition of tRNA methylation that follows ethionine treatment can be at least partially relieved in vitro.

The liver extracts from ethionine-treated animals contained a low-molecular-weight inhibitor of tRNA methylation. Dialysis of enzyme preparations from ethionine-treated, but not control, rats resulted in large increases in tRNA methylase activity, with either Escherichia coli or homologous tRNA's as substrate. Furthermore, the tRNA methylase activity of control rat liver enzyme extracts was greatly depressed by dialysate from liver homogenates of ethionine-treated rats.

After 5 days of ethionine administration the liver tRNA methylase activities were significantly higher than those of control preparations despite the continued presence of the dialyzable inhibitor(s). The liver tRNA's from these animals were poorer methyl acceptors than those from 3-day-treated rats, although still better than tRNA's from untreated rats.

These observations have been interpreted to indicate that ethionine causes the accumulation in the liver of inhibitors of tRNA methylation. Early in the course of ethionine administration, methyl-deficient tRNA can be isolated. When the period of ethionine treatment is extended, the organism attempts to maintain homeostasis by production of increased amounts of tRNA-methylating enzymes. The increased quantities of these enzymes are able to overcome, at least partially, the effects of the inhibitors and to decrease the extent to which methyl-deficient tRNA is produced.

¹ The work was supported in part by USPHS Grant HL-09011 and National Cancer Institute Grant CA-08748.

Received 5/ 1/75. Accepted 6/20/75.

This article has been cited by other articles:

				S.-W. Choi and J. B. Mason Folate and Carcinogenesis: An Integrated Scheme1-3 J. Nutr., January 1, 2000; 130(2): 129 - 132. [Abstract] [Full Text]