Hypochlorous acid potentiates hydrogen peroxide-mediated DNA-strand breaks in human mononuclear leucocytes.
In this study the formation of DNA single-strand breaks in MNL in close proximity to activated phagocytes, or in contact with added H2O2 and/or HOCl, were evaluated. Neutrophils activated by phorbol myristate acetate (PMA), induced DNA-strand breaks in neighboring lymphocytes which increased after 1-2 h incubation in a repair medium. These DNA-strand breaks could be prevented by the addition of catalase or substitution of the neutrophils with cells from a patient with chronic granulomatous disease. Inclusion of the myeloperoxidase (MPO) inhibitor, sodium azide (NaN3), to the system was associated with less damage after 1-2 h incubation and a faster repair rate. Exposure of MNL to added reagent H2O2 (12-100 microM) was also accompanied by DNA damage. Addition of reagent HOCl (3-25 microM) did not induce any DNA-strand breaks. However, when combined with H2O2 (12.5 microM), HOCl increased H2O2-mediated DNA damage and compromised the repair process. Interactions between the phagocyte-derived reactive oxidants H2O2 and HOCl are probably involved in the etiology of inflammation-related cancer.
Department of Immunology, Faculty of Medicine, University of Pretoria, Republic of South Africa.
C E
CE
Van Rensburg
A M
AM
Van Staden
R
R
Anderson
E J
EJ
Van Rensburg
D000328:Adult; D004249:DNA Damage; D004357:Drug Synergism; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity*; D006997:Hypochlorous Acid / Q000494:pharmacology*; D066298:In Vitro Techniques; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000187:drug effects*; D009152:Mutagenicity Tests; D009504:Neutrophils / Q000276:immunology
D006997:Hypochlorous Acid; D006861:Hydrogen Peroxide