Inhibition by chloramphenicol of aminoazo dye carcinogenesis in rat liver: RNA synthesis in isolated liver nuclei

Abstract

RNA synthesis has been measured in isolated rat liver nuclei following pair-feeding of dits containing 0·06% 3′-methyl- 4-dimethylaminoazobenzene ( 3′MeDAB), 2% chloramphenicol (CAP) or both 0·06% 3′MeDAB and 2% CAP for periods of 4 and 10 days. At 4 days, there were significant increases in Mn 2+ (NH 4) 2SO 4- stimulated activity in rats fed CAP or both 3′MeDAB and CAP and a significant increase in the Mg 2+ -stimulated activity in rats fed 3′MeDAB and CAP relative to the control rats. After 10 days of pair-feeding, Mg 2+ -stimulated RNA synthesis was increased in all the treated groups, being significantly greater in the group receiving both 3′MeDAB and CAP than in the group receiving 3′MeDAB alone and Mn 2+ (NH 4) 2SO 4- stimulated RNA synthesis was significantly increased in the group receiving CAP. α-Amanitin was shown to inhibit 88·6% of the Mn 2+ (NH 4) 2SO 4- stimulated activity and 20·6% of the Mg 2+ -stimulated activity. Loss of RNA during the Mg 2+ -stimulated incubation was noted and this was less in the group receiving both 3′MeDAB and CAP than in the other groups, but incubation at 17°C, which prevented the RNA loss, revealed that the differences in incorporation between the groups were not a result of differential loss of RNA during incubation. The RNA/DNA ratio of the isolated nuclei was increased in rats fed CAP and was greater in rats fed both 3′MeDAB and CAP than in rats fed 3′MeDAB alone. The effect of altering the concentration of Mg 2+ in the nuclear isolation medium on subsequent incorporation in vitro was measured; maximal incorporation in the Mg 2+ -stimulated reaction was noted if nuclei were isolated in 10mM Mg 2+ , while the Mn 2+ (NH 4) 2SO 4- stimulated reaction was maximal if 3mM Mg 2+ was used.