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.
D000818:Animals; D001374:Azacitidine / Q000378:metabolism / Q000494:pharmacology*; D002467:Cell Nucleus / Q000201:enzymology; D003562:Cytidine / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D008099:Liver / Q000201:enzymology*; D008115:Liver Regeneration; D008745:Methylation; D008780:Methyltransferases / Q000378:metabolism*; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011506:Proteins / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011506:Proteins; D003562:Cytidine; D012313:RNA; D004247:DNA; D008780:Methyltransferases; D001374:Azacitidine