Differential toxicity of 3-aminobenzamide to wild-type and 6-thioguanine-resistant Chinese hamster cells by interference with pathways of purine biosynthesis.
3-Aminobenzamide is commonly assumed to be a specific inhibitor of poly(ADP-ribose) polymerase. However, it also inhibits de novo synthesis of DNA purines at concentrations of 5 mM and above. A mutant cell line that lacks the ability to incorporate exogenous purines is therefore exceptionally sensitive to the toxic effects of 3-aminobenzamide. This finding has implications for the underlying mechanism of sensitivity to 3-aminobenzamide recently reported in a cell line from an immunodeficient patient, and also implies that many studies using high concentrations of 3-aminobenzamide may not demonstrate a role for poly(ADP-ribose) because of artifacts arising from disturbance of intracellular purine metabolism.
D000818:Animals; D001549:Benzamides / Q000633:toxicity*; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D004261:DNA Replication / Q000187:drug effects*; D004351:Drug Resistance; D005260:Female; D007700:Kinetics; D009154:Mutation; D009698:Nucleoproteins / Q000096:biosynthesis; D010053:Ovary; D013866:Thioguanine / Q000633:toxicity*
D001549:Benzamides; D009698:Nucleoproteins; C025160:3-aminobenzamide; D013866:Thioguanine