Metabolic consequences of DNA damage: alteration in purine metabolism following poly(ADP ribosyl)ation in human T-lymphoblasts.
The effect of DNA damage caused by N-methyl-N'-nitro-nitrosoguanidine (MNNG) on poly(ADP-ribose) synthesis, NAD levels, and purine nucleotide metabolism was studied in human T-lymphoblasts. Excessive DNA breaks caused by MNNG activated poly(ADP-ribose) polymerase and rapidly consumed intracellular NAD. NAD depletion was followed by rapid catabolism of ATP as well as induction of total purine nucleotide catabolism leading to excretion of purine catabolic products. MNNG-treated cells were not able to replenish the intracellular nucleotide pools due to the depletion of intracellular ATP and phosphoribosylpyrophosphate pools which are required for de novo purine biosynthesis. Inhibition of poly(ADP-ribose) polymerase by 3-aminobenzamide prevented both the depletion of NAD pools and the associated changes in purine nucleotide metabolism.
D000225:Adenine / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D001549:Benzamides / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage; D005998:Glycine / Q000378:metabolism; D006801:Humans; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology; D009243:NAD / Q000378:metabolism; D009536:Niacinamide / Q000378:metabolism; D009702:Nucleoside Diphosphate Sugars / Q000096:biosynthesis*; D011064:Poly Adenosine Diphosphate Ribose / Q000096:biosynthesis*; D011687:Purines / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism*
D001549:Benzamides; D009702:Nucleoside Diphosphate Sugars; D011687:Purines; D009243:NAD; D008769:Methylnitronitrosoguanidine; D009536:Niacinamide; D011064:Poly Adenosine Diphosphate Ribose; C025160:3-aminobenzamide; D000255:Adenosine Triphosphate; D000225:Adenine; D005998:Glycine