Inactivation of poly (ADP-ribose) polymerase by hypochlorous acid.

The effects of the phagocyte-derived reactive oxidants hydrogen peroxide (H2O2) and hypochlorous acid (HOC1) on the activity of poly(ADP-ribose) polymerase (pADP RP), an enzyme involved in DNA repair, and on the induction and repair of DNA strand breaks in human mononuclear leukocytes (MNL) have been investigated in vitro. Exposure of MNL to reagent H2O2 was accompanied by DNA damage and activation of pADP RP. Addition of reagent HOCl (25 microM) was not associated with DNA strand breaks. However, when combined with 150 microM H2O2, HOCl potentiated H2O2-mediated DNA damage, and compromised the repair process. Furthermore, HOCl caused a dose-related decrease in the activity of pADP RP in both control and H2O2-exposed MNL. Interactions between the phagocyte-derived reactive oxidants H2O2 and HOCl are probably involved in the etiology of inflammation-related cancer.