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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.