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Inhibition by Urethan of the Synthesis of Free and Membrane-bound Ribosomal RNA in Regenerating Liver¹

Department of Pharmacology, Emory University, Atlanta, Georgia 30322

The response of normal and regenerating liver to the hepatocarcinogen urethan was evaluated by means of an examination of the synthesis of free and membrane-bound ribosomal RNA. Partial hepatectomy results in a five- to ninefold elevation of the incorporation of orotic acid-5-³H into free and membrane-bound ribosomal RNA 18 hr after operation; no noticeable changes occurred in the specific activity of uridine triphosphate during this regenerative period. Treatment of animals with 1 g of urethan per kg, 6 or 12 hr after operation, resulted in 50% inhibition of the incorporation of orotic acid into free and membrane-bound ribosomal RNA in partially hepatectomized rats but not in sham-operated animals. Administration of an equivalent dose of the noncarcinogenic analog methyl carbamate did not affect RNA synthesis in either group of animals. The specific activity of uridine triphosphate in 18-hr regenerating liver was not significantly altered by treatment of animals with urethan 6 hr after operation. Fractionation of ribosomal RNA into 18 S and 28 S components revealed that inhibition of incorporation of orotic acid-5-³H by urethan was equally pronounced on both constituents. Analysis of nucleolar RNA by double labeling with methionine-methyl-³H and orotic acid-6-¹⁴C showed preferential inhibition by urethan of both methylation and synthesis of nucleolar RNA but that not of extranucleolar RNA. These results are consistent with the differential inhibition by urethan of the synthesis of ribosomal precursor and ribosomal RNA of regenerating liver but not of normal liver.

¹ Publication 2001 of the Division of Basic Health Sciences of Emory University. This study was supported by Grant SO 1-RR-05364 from the NIH.

Received 12/26/72. Accepted 4/ 6/73.