EFFECTS OF CARBON TETRACHLORIDE AND ETHIONINE ON RNA SYNTHESIS IN VIVO AND IN ISOLATED RAT LIVER NUCLEI

Carbon tetrachloride and ethionine were administered to male and female rats. The effects of CCl4 were measured on RNA formation in vivo and on the capacity of isolated rat liver nuclei to incorporate UTP and ATP into RNA in vitro. During the first 3 hr after CCl4 administration no differences were found when orotate incorporation into liver RNA was studied. Nuclei isolated from CCl4-treated animals had the same composition as controls, and incorporated UTP and ATP as well as controls. RNase activity was unchanged. Chromatin and DNA, isolated from nuclei, assayed with E. coli RNA polymerase were identical. At later times, 12 hr, RNA formation measured with isolated nuclei was increased. Similar studies with ethionine revealed that nuclei from both male and female rat livers were less active than controls, and could not be restored by cofactor addition. There were no differences in nuclear composition, nuclear RNase, or in the capacity of chromatin or DNA to act as template when incubated with E. coli RNA polymerase. Microsomes from ethionine-treated female rats showed decreased endogenous amino acid incorporation concomitantly with decreased RNA formation. Ethionine-treated male rats showed no differences from control even though RNA formation was depressed. Addition of synthetic messenger, Poly U, stimulated microsomes from treated animals to greater specific activity than controls, and cell sap from treated animals was more active than controls. It is concluded that CCl4 intoxication does not alter RNA formation early in the course of the intoxication and stimulates RNA formation 12 hr after administration. Ethionine treatment decreases RNA formation. © 1969.