Hypochlorous acid potentiates hydrogen peroxide-mediated DNA-strand breaks in human mononuclear leucocytes

Abstract

In this study the formation of DNA single-strand breaks in MNL in close proximity to activated phagocytes, or in contact with added H 2O 2 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 (NaN 3), to the system was associated with less damage after 1–2 h incubation and a faster repair rate. Exposure of MNL to added reagent H 2O 2 (12–100 μM) was also accompanied by DNA damage. Addition of reagent HOCl (3–25 μM) did not induce any DNA-strand breaks. However, when combined with H 2O 2 (12.5 μM), HOCl increased H 2O 2-mediated DNA damage and compromised the repair process. Interactions between the phagocyte-derived reactive oxidants H 2O 2 and HOCl are probably involved in the etiology of inflammation-related cancer.