Poly(ADP-ribose) biosynthesis and suicidal NAD+ depletion following carcinogen exposure of mammalian cells.
Hepatocytes were found to be remarkably resistant to suicidal NAD+ depletion due to consumption for chromatin-associated poly(ADP-ribose) biosynthesis, which normally follows infliction of DNA damage in mammalian cells. N-methyl-N'-nitro-N-nitrosoguanidine treatment, which depleted NAD+ levels of confluent fibroblasts to about 40% of controls, did not reduce hepatocellular NAD+ pools, although poly(ADP-ribose) concentrations were concomitantly elevated by 21-fold. This differential behavior, demonstrable also with other carcinogens, can be attributed to the different NAD+ biosynthetic capacities of these cells.
D000818:Animals; D001549:Benzamides / Q000633:toxicity; D002273:Carcinogens / Q000633:toxicity*; D002460:Cell Line; D002478:Cells, Cultured; D004260:DNA Repair; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008769:Methylnitronitrosoguanidine / Q000633:toxicity; D051379:Mice; D009243:NAD / Q000378:metabolism*; D009702:Nucleoside Diphosphate Sugars / Q000096:biosynthesis*; D011064:Poly Adenosine Diphosphate Ribose / Q000096:biosynthesis*; D051381:Rats; D013463:Sulfuric Acid Esters / Q000633:toxicity; D014466:Ultraviolet Rays
D001549:Benzamides; D002273:Carcinogens; D009702:Nucleoside Diphosphate Sugars; D013463:Sulfuric Acid Esters; D009243:NAD; D008769:Methylnitronitrosoguanidine; D011064:Poly Adenosine Diphosphate Ribose; C025160:3-aminobenzamide; C007482:dimethyl sulfate