Correlation of carcinogen-induced unscheduled DNA synthesis and NAD reduction in fresh human lymphocytes.
Incorporation of [3H]thymidine into the DNA of fresh human lymphocytes, treated with various chemical mutagens, was measured and correlated with cellular NAD levels before and after treatment. NAD levels in lymphocytes were significantly reduced following treatment with mutagenic chemicals. Reduction of cellular NAD pools was directly correlated with [3H]thymidine incorporation. As NAD levels decreased, [3H]thymidine incorporation increased. Theophylline, a known inhibitor of poly(ADP-ribose)polymerase, inhibited both the NAD reduction in cells treated with DNA damaging agents and the incorporation of [3H]thymidine into DNA. The inhibitory effect of theophylline on NAD depletion and on [3H]thymidine incorporation was dose and cell number dependent. Near normal responses to carcinogen exposure could be restored to theophylline-treated cells following the removal of theophylline. These data suggest that conversion of NAD to poly(ADP-ribose) may be necessary, or at least closely associated with, DNA repair in human lymphocytes.
D001551:Benz(a)Anthracenes / Q000494:pharmacology; D001580:Benzopyrenes / Q000494:pharmacology; D002273:Carcinogens / Q000494:pharmacology*; D004247:DNA / Q000096:biosynthesis*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism*; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology; D009243:NAD / Q000378:metabolism*; D013806:Theophylline / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism
D001551:Benz(a)Anthracenes; D001580:Benzopyrenes; D002273:Carcinogens; D009243:NAD; D008769:Methylnitronitrosoguanidine; C001903:7-bromomethylbenzanthracene; D004247:DNA; D013806:Theophylline; D013936:Thymidine; D004121:Dimethyl Sulfoxide