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Transfer RNA Methylase Activity and Capacity during Aflatoxin B₁-induced Hepatocellular Carcinogenesis¹

Department of Nutrition and Food Science, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139

Transfer RNA methylase (tRNA methylase) activity and capacity were monitored in whole-rat-liver preparations during the induction of hepatocellular carcinomas by an 8-week aflatoxin B₁ dosing regimen that produced minimal toxic effects. Significant phases of elevated tRNA methylase capacity occurred at 6 to 9 weeks (20%) and 24 to 29 weeks (40%). No significant change in tRNA methylase activity was noted over the course of the 55-week experiment. Higher aflatoxin B₁ doses, producing acute toxic liver damage, resulted in elevated tRNA methylase activity (50%) and capacity (30%) at least as early as 1 week after dosing.

Experiments with individual nodular lesions excised from livers of rats continuously fed a diet containing 2 ppm aflatoxin B₁ demonstrated similarly elevated tRNA methylase activities and capacities in hyperplastic (preneoplastic) nodules, with and without histological evidence of carcinoma.

¹ Financial support was provided by Grant 5-PO1-ES-00597 from National Institute of Environmental Health Services and Contract NIH NO1-CP-43265 from the National Cancer Institute.

² To whom requests for reprints should be addressed, at 77 Massachusetts Avenue, Room 56-212, Massachusetts Institute of Technology, Cambridge, Mass. 02139.

Received 2/ 5/75. Accepted 3/ 8/76.

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