title: Poly(ADP-ribose) metabolism in ultraviolet irradiated human fibroblasts.
abstract: Exposure of human fibroblasts to 5 J/m2 of UV light resulted in a rapid increase of up to 1500% in the intracellular content of poly(ADP-ribose) and a rapid depletion of its metabolic precursor, NAD. When added just prior to UV treatment, the poly(ADP-ribose) polymerase inhibitor, 3-aminobenzamide, totally blocked both the increase of poly(ADP-ribose) and decrease in NAD for up to 2.5 h. Addition of 3-aminobenzamide at the time of maximal accumulation of poly(ADP-ribose) resulted in a decrease to basal levels with a half-life of approximately 6 min. The rates of accumulation of poly(ADP-ribose) and depletion of NAD were increased in the presence of either 1-beta-arabinofuranosylcytosine or hydroxyurea. Since these agents are known to cause an additional accumulation of DNA strand breaks following UV irradiation, these data provide evidence for a mechanism in which the rate of poly(ADP-ribose) synthesis following DNA damage is regulated in intact cells by the number of DNA strand breaks. Under conditions in which the synthesis of poly(ADP-ribose) was blocked, DNA repair replication induced by UV light was neither stimulated nor inhibited.
mesh_terms: D002478:Cells, Cultured; D003561:Cytarabine / Q000494:pharmacology; D004260:DNA Repair; D004261:DNA Replication / Q000187:drug effects / Q000528:radiation effects; D005347:Fibroblasts / Q000378:metabolism / Q000528:radiation effects; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology; D007231:Infant, Newborn; D008297:Male; D009243:NAD / Q000378:metabolism / Q000528:radiation effects; D009702:Nucleoside Diphosphate Sugars / Q000528:radiation effects*; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism / Q000528:radiation effects*; D012867:Skin / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects*; D014466:Ultraviolet Rays
chemical_list: D009702:Nucleoside Diphosphate Sugars; D003561:Cytarabine; D009243:NAD; D011064:Poly Adenosine Diphosphate Ribose; D006918:Hydroxyurea