Suppression of nuclear ADP-ribosyltransferase activity in regenerating rat liver by 5-azacytidine and its relevance to the nuclear methylating activities.

A single administration of 5-azacytidine (5-ACR) to partially hepatectomized rats 24 h following operation resulted in a dose-dependent reduction of nuclear ADP-ribosyltransferase (ADPRT) activity in the liver, when assayed after the nuclei were isolated 22 h after injection. No such a suppression by 5-ACR was observed in the liver of intact rats. Cytidine, a known agent which prevents the incorporation of 5-ACR into DNA, abolished the suppression of ADPRT, when it was given in combination with 5-ACR. The 5-ACR suppressed nuclei from regenerating liver showed no decreased DNA methylating activity, as estimated from the rate of radiolabel transfer from [methyl-3H]SAM to the bulk DNA. The methylation of nuclear RNA and protein was markedly reduced. These results suggest that the incorporation of 5-ACR into nucleic acids inactivates chromatin-bound ADPRT without inhibition of DNA methylation.