Inhibition by urethan of the synthesis of free and membrane-bound ribosomal RNA in regenerating liver.

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 fiveto 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 l 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 regenerat ing 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