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Transfer RNA Methylase Activity in Normal Monkey Liver and in Carcinogen-induced Hepatoma

Human Tumor Cell Biology Branch [T. P. W., R. C. G.], Laboratory of Chemical Pharmacology [R. H. A.], and Laboratory of Pathology [R. W. O.], National Cancer Institute, NIH, Bethesda, Maryland 20014

Hepatomas were induced in monkeys by the administration of N-nitrosodiethylamine. An -fetoprotein, not normally found in adult monkeys, was present in the serum of the majority of the animals with the liver tumor. Frequently, the test for serum -fetoprotein was positive prior to any histological evidence of a cancer. With tRNA from Escherichia coli K₁₂W₆ or from normal adult monkey liver or hepatoma as methyl acceptor, an increasing degree of methylation was found with the tRNA methylases in tissue extracts from normal adult monkey liver, premalignant liver, liver from newborn monkeys, and hepatoma, respectively. These observations suggest that a change in specificity of tRNA methylation occurs during chemical carcinogenesis with N-nitrosodiethylamine. The increase in tRNA methylation by extracts of premalignant liver also suggests that changes in tRNA methylase activity occur prior to, or as an early manifestation of, malignant conversion.

Further study showed the presence of an inhibitor of tRNA methylases in extracts from normal adult monkey liver but not in extracts of normal newborn liver and hepatoma. Thus, multiple factors may be involved which account for the differences observed in the tRNA methylases.

Received 11/30/70. Accepted 3/31/71.