Peroxidase-mediated irreversible binding of arylamine carcinogens to DNA in intact polymorphonuclear leukocytes activated by a tumor promoter.
Addition of the tumor promoter phorbol myristate acetate to polymorphonuclear leukocytes results in the oxidation of the arylamine carcinogens; [14C]benzidine, N-[14C]methylaminoazobenzene and [14C]aminofluorene to reactive intermediate(s) that bind irreversibly to the leukocyte DNA. The binding was dependent on oxygen and was decreased by sulfhydryl inhibitors and phenolic antioxidants that inhibit the respiratory burst triggered by the phorbol myristate. Both the binding and the respiratory burst were increased by azide, presumably as a result of intracellular catalase inhibition. However higher concentrations of azide and cyanide prevented binding without affecting the respiratory burst indicating that myeloperoxidase is a catalyst for the binding. Granules isolated from the activated leukocytes and H2O2 catalyzed a cyanide sensitive benzidine binding to calf thymus DNA. Myeloperoxidase and H2O2 also catalysed extensive binding of these arylamines to calf thymus DNA. The leukocytes appear to be a useful model cell for studying one electron oxidation-catalyzed carcinogen activation.
Tsuruta
Y
Y
Subrahmanyam
V V
VV
Marshall
W
W
O'Brien
P J
PJ
D000588:Amines / Q000097:blood / Q000378:metabolism*; D000818:Animals; D001560:Benzidines / Q000378:metabolism; D001665:Binding Sites; D002273:Carcinogens / Q000378:metabolism*; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism; D004247:DNA / Q000097:blood / Q000378:metabolism*; D005449:Fluorenes / Q000378:metabolism; D006168:Guinea Pigs; D009504:Neutrophils / Q000201:enzymology / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D010101:Oxygen Consumption; D009195:Peroxidase / Q000378:metabolism*; D010544:Peroxidases / Q000378:metabolism*; D010704:Phorbols / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013950:Thymus Gland; D010128:p-Aminoazobenzene / Q000031:analogs & derivatives / Q000378:metabolism
D000588:Amines; D001560:Benzidines; D002273:Carcinogens; D005449:Fluorenes; D010704:Phorbols; C029876:benzidine; C012177:2-aminofluorene; D010128:p-Aminoazobenzene; C005202:N-methyl-4-aminoazobenzene; D004247:DNA; D010544:Peroxidases; D009195:Peroxidase; D013755:Tetradecanoylphorbol Acetate