Similar sensitivity of human lymphoblast cells proficient or deficient in nucleotide biosynthesis to the cytotoxic and cell cycle effects of 3-aminobenzamide.
3-Aminobenzamide (3AB), a potent inhibitor of poly(ADP-ribose) polymerase, induces cytotoxicity and cell cycle delays in exposed cells. 3AB has been reported to inhibit de novo nucleotide synthesis in human lymphoblasts. To determine if the 3AB-mediated effects are related to this inhibition of DNA synthesis, cytotoxicity and cell cycle progression in human lymphoblastoid cell lines, proficient or deficient in salvage nucleotide synthesis pathways, were determined after exposures to 3AB. In addition, changes in cell cycle progression were followed after treatment with 3-aminobenzoic acid (ABA), a nonactive analog of 3AB, and 5-methylnicotinamide (5MN), a less potent inhibitor of poly(ADP-ribose) synthesis. All three lines responded similarly to the different treatments. Cells deficient in salvage nucleotide synthesis pathways were no more sensitive to the cytotoxic or cell cycle effects of 3AB, ABA or 5MN. Thus, effects on nucleotide synthesis are not responsible for either cytotoxicity or the retarded cell growth found in human lymphoblastoid cells exposed to inhibitors of poly(ADP-ribose) synthesis.
Schwartz
J L
JL
Weichselbaum
R R
RR
D062365:Aminobenzoates / Q000494:pharmacology; D001549:Benzamides / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D019271:Hypoxanthine; D007042:Hypoxanthines / Q000378:metabolism; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009243:NAD / Q000378:metabolism; D009244:NAD+ Nucleosidase / Q000037:antagonists & inhibitors*; D009536:Niacinamide / Q000031:analogs & derivatives / Q000494:pharmacology; D009711:Nucleotides / Q000096:biosynthesis* / Q000097:blood; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D013936:Thymidine / Q000378:metabolism; D062368:meta-Aminobenzoates
D062365:Aminobenzoates; D001549:Benzamides; D007042:Hypoxanthines; D009711:Nucleotides; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D062368:meta-Aminobenzoates; D009243:NAD; D009536:Niacinamide; D019271:Hypoxanthine; C024785:5-methylnicotinamide; C025160:3-aminobenzamide; D009244:NAD+ Nucleosidase; C044855:3-aminobenzoic acid; D013936:Thymidine