Abstract
Dibromoacetonitrile (DBAN) is a disinfection byproduct of chlorination of drinking water. Epidemiological studies indicate that it might present a potential hazard to human health. The present work provides evidence for DBAN activation to cyanide (CN(-)) by the hypoxanthine (HX)/xanthine oxidase (XO)/iron (Fe) system in vitro. Optimum conditions for the oxidation of DBAN to CN(-)were characterized. Addition of the sulfhydryl compounds glutathione, N-acetyl- L-cysteine or dithiothreitol significantly enhanced the rate of CN(-)release. A high positive correlation existed between hydroxyl free radical ((*)OH) generation and CN(-) formation. Addition of the (*)OH scavengers mannitol or dimethylthiourea to the reaction mixtures resulted in a significant decrease in the rate of DBAN oxidation. Addition of the antioxidant enzymes catalase or superoxide dismutase resulted in a significant decrease in the rate of DBAN oxidation. The iron chelator desferrioxamine significantly decreased CN(-) formation. The maximum velocity (V(max)) and Michaelis-Menten constant (K(m)) of the reaction were assessed. Allopurinol competitively inhibited the reaction, while folic acid uncompetitively inhibited the reaction. In conclusion, (*)OH generated by the HX/XO/Fe system are implicated in DBAN oxidation. The present results represent a novel pathway for DBAN activation and might be important in explaining DBAN-induced toxicity.