Consequences of altered poly(ADP-ribose) metabolism on hepatocyte functions in vitro.
Cultured hepatocytes derived from adult rats were used to determine the consequences of altered poly(ADP-ribose)-metabolism on DNA repair and the expression of hepatocellular functions in vitro. Inhibition of poly(ADP-ribose)-biosynthesis affected the process of DNA repair in response to carcinogens at more than one single step. The expression of two fetal enzymes, gamma-glutamyl transpeptidase and the K-(111) type isozyme of pyruvate kinase, was inhibited in hepatocytes in which poly(ADP-ribose)-biosynthesis was suppressed with 3-aminobenzamide or other inhibitors. Our data show that cellular functions as diverse as DNA repair and gene expression are affected by the same experimental manipulations of poly(ADP-ribose)-metabolism in the same cell. This suggests that poly(ADP-ribose)-modification of chromatin proteins affects a mechanism which is involved in the regulation of more than one chromatin function.
D062365:Aminobenzoates / Q000494:pharmacology; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D004260:DNA Repair; D066298:In Vitro Techniques; D008099:Liver / Q000166:cytology* / Q000201:enzymology; D009244:NAD+ Nucleosidase / Q000378:metabolism*; D009536:Niacinamide / Q000494:pharmacology; D009713:Nucleotidyltransferases / Q000378:metabolism; D010430:Pentosyltransferases / Q000378:metabolism; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D011770:Pyruvate Kinase / Q000378:metabolism; D051381:Rats; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D062365:Aminobenzoates; D001549:Benzamides; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D009536:Niacinamide; C025160:3-aminobenzamide; D005723:gamma-Glutamyltransferase; D010430:Pentosyltransferases; D011065:Poly(ADP-ribose) Polymerases; D011770:Pyruvate Kinase; D009713:Nucleotidyltransferases; D009244:NAD+ Nucleosidase