Oxidative DNA damage by a metabolite of carcinogenic 1-nitropyrene

Nitropyrenes are carcinogenic pollutants, Adduct formation following nitro- reduction is considered to be a major cause of nitropyrene-mediated DNA dam age. We investigated the role of 1-nitrosopyrene, a metabolite of 1-nitropy rene, in causing oxidative DNA damage, using P-32-5'-end-labeled DNA 1-Nitr osopyrene was found to facilitate Cu(II)-mediated DNA damage in the presenc e of NADH, Catalase and a Cu(I)-specific chelator attenuated DNA damage, in dicating the involvement of H2O2 and Cu(I). Typical (OH)-O-. scavenger did not have a significant effect. These results suggest that the main reactive species is probably a DNA-copper-hydroperoxo complex. We also measured 8-o xo-7,8-dihydro-2'-deoxyguanosine formation by 1-nitrosopyrene in the presen ce of Cu(II) and NADH, using an electrochemical detector coupled to a high- pressure liquid chromatograph. We conclude that oxidative DNA damage, in ad dition to DNA adduct formation, may play an important role in the carcinoge nesis of nitropyrenes. (C) 2001 Academic Press.