ADP-ribosyltransferase activity in cultured hepatocytes. Interactions with DNA repair.
A rapid increase in ADP-ribosyltransferase activity was observed when freshly isolated hepatocytes derived from adult rats were established in primary monolayer culture. (ADP-ribose)n-degrading activity remained constant over a period of 48 h of culture. Inhibition of ADP-ribosyltransferase activity with pyridine derivatives, 3-aminobenzamide, theophylline, or thymidine, was accompanied by an enhanced DNA repair synthesis in response to the direct-acting carcinogen, methyl methanesulfonate, or UV irradiation. Three aminobenzamides differing only in the position of the amino group exhibited the same structure-activity relationship in regard to their action on DNA repair synthesis and ADP-ribosyltransferase. Spermine treatment of hepatocytes apparently had an inverse effect on both these cellular functions. The removal of DNA strand breaks following methyl methanesulfonate treatment was accelerated by inhibitors of ADP-ribosyltransferase. The results suggest that ADP-ribosylation interacts with late stages in the process of DNA repair. This interaction apparently is dependent on the nature of damage imposed on chromatin since repair synthesis in response to a number of carcinogens is unaffected by inhibitors of ADP-ribosyltransferase.
D000818:Animals; D002478:Cells, Cultured; D004260:DNA Repair; D004261:DNA Replication; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D008297:Male; D009536:Niacinamide / Q000494:pharmacology; D009713:Nucleotidyltransferases / Q000378:metabolism*; D011065:Poly(ADP-ribose) Polymerases; D051381:Rats; D013096:Spermine / Q000494:pharmacology; D013806:Theophylline / Q000494:pharmacology
D009536:Niacinamide; D013096:Spermine; D013806:Theophylline; D011065:Poly(ADP-ribose) Polymerases; D009713:Nucleotidyltransferases