Activation of bleomycin A2 to a DNA-damaging intermediate by phorbol ester-stimulated human polymorphonuclear leukocytes.
Metabolically stimulated polymorphonuclear leukocytes (PMNs) generate reactive oxygen metabolites that are capable not only of damaging biomolecules but also of possibly activating exogenous chemicals to reactive intermediates which interact with target molecules. This study examined this later concept and the results demonstrated that the interaction of bleomycin A2 with phorbol ester-stimulated human PMNs resulted in DNA deoxyribose cleavage, a process mediated by an activated bleomycin intermediate. Superoxide dismutase (SOD) significantly inhibited bleomycin-mediated DNA deoxyribose cleavage, indicating the involvement of reactive oxygen. Based on these observations it is plausible that other chemicals, including carcinogens, may be activated by metabolically stimulated PMNs to intermediates which react with biomolecules.
D001711:Biotransformation; D001761:Bleomycin / Q000378:metabolism* / Q000633:toxicity; D002374:Catalase / Q000494:pharmacology; D004247:DNA / Q000378:metabolism*; D003855:Deoxyribose / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D010704:Phorbols / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D010704:Phorbols; D001761:Bleomycin; D003855:Deoxyribose; D004247:DNA; D002374:Catalase; D013482:Superoxide Dismutase; D013755:Tetradecanoylphorbol Acetate