Tumor promoter phorbol-12-myristate-13-acetate induces poly ADP-ribosylation in human monocytes.
The tumor promoter phorbol-12-myristate-13-acetate (PMA) induces rapid poly ADP-ribosylation and a drop in cellular NAD concentration in human monocytes. The antioxidants CuZn-superoxide dismutase, catalase, glutathione peroxidase and butylated-hydroxytoluene inhibit the reaction indicating that active oxygen species produced in the PMA-induced oxidative burst represent intermediates. The inhibitor of ADP-ribosyl-transferase, 3-amino-benzamide, inhibited poly ADP-ribosylation but did not prevent the drop in NAD-levels. PMA also causes the slow accumulation of DNA strand breaks in monocytes. The difference in the kinetics of poly ADP-ribosylation and DNA breakage argues against a simple relationship between the two reactions.
Singh
N
N
Poirier
G
G
Cerutti
P
P
D000975:Antioxidants / Q000494:pharmacology; D001549:Benzamides / Q000494:pharmacology; D004247:DNA / Q000097:blood; D006801:Humans; D066298:In Vitro Techniques; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D009243:NAD / Q000097:blood; D009702:Nucleoside Diphosphate Sugars / Q000097:blood*; D009713:Nucleotidyltransferases / Q000037:antagonists & inhibitors / Q000097:blood; D010704:Phorbols / Q000494:pharmacology*; D011064:Poly Adenosine Diphosphate Ribose / Q000097:blood*; D011065:Poly(ADP-ribose) Polymerases; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D000975:Antioxidants; D001549:Benzamides; D009702:Nucleoside Diphosphate Sugars; D010704:Phorbols; D009243:NAD; D011064:Poly Adenosine Diphosphate Ribose; C025160:3-aminobenzamide; D004247:DNA; D011065:Poly(ADP-ribose) Polymerases; D009713:Nucleotidyltransferases; D013755:Tetradecanoylphorbol Acetate