COMPOSITION, ASSOCIATED TISSUE METHYLTRANSFERASE ACTIVITY, AND CATABOLIC END PRODUCTS OF TRANSFER-RNA FROM CARCINOGEN-INDUCED HEPATOMA AND NORMAL MONKEY LIVERS

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  • 1 January 1977
    • journal article
    • research article
    • Vol. 37  (1) , 285-292
Abstract
This investigation was designed to explore tRNA methyltransferase activity, urinary excretion levels of tRNA degradation products and tRNA base composition in normal [rhesus] monkeys and those with hepatocellular carcinomas induced by N-nitrosodiethylamine. After the development of the tumor, 24 h urine specimens were collected, the monkeys were sacrificed and the livers were removed for tRNA isolation and methyltransferase activity studies. tRNA methyltransferase activity and capacity and urinary excretion levels for selected tRNA degradation products (pseudouridine, N2,N2-dimethylguanosine, 1-methylinosine, 7-methylguanine and .beta.-aminoisobutyric acid) were elevated for the hepatoma-bearing monkeys when compared to those with normal liver. The isolated tRNA pools were analyzed by high resolution liquid chromatography, and similar base compositions were found for hepatoma-bearing and normal monkeys. With the use of methyl-deficient Escherichia coli tRNA as the methyl receptor and the analytical procedure for tRNA analysis, the methylating ability of tRNA methyltransferases in hepatoma and normal liver extracts was determined. Hepatoma methyltransferase homogenates produced increased levels of 7-methylguanine, N2,N2-dimethylguanine and thymine, while normal liver extracts gave higher levels of N2-methylguanine. These differences were not apparent in the base composition of the tRNA pools. The increased urinary excretion and higher methyltransferase activity of hepatoma-bearing monkeys without an apparent increase in the methylated base content of their tRNA suggest increased tRNA turnover. Subtle changes in the methylated base content of individual isoaccepting tRNA''s would be missed by analyzing the tRNA pools. Variations in the individual tRNA methyltransferase activities of hepatoma and normal liver homogenates indicate a difference in the methylation of their tRNA''s.

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