Reversal by nickel(II) of inhibitory effects of some scavengers of active oxygen species upon hydroxylation of 2'-deoxyguanosine in vitro.
Effects of ethanol (EtOH), mannitol (Man), L-histidine (His) and glutathione (GSH) on the oxidation of 2'-deoxyguanosine (dG) to its 8-hydroxy derivative (8-OH-dG) with H2O2 plus L-ascorbic acid (Ascb) in the absence and presence of Ni(II) were investigated in order to unveil the nature of active oxygen species involved in that oxidation. In the absence of Ni(II), production of 8-OH-dG was inhibited by His much greater than GSH greater than or equal to GSSG (oxidized glutathione) much greater than EtOH, but not by Man. The latter tended to enhance the production of 8-OH-dG. In the presence of Ni(II), the inhibition by His, GSH and GSSG, but not EtOH, was prevented. The results indicate involvement of a 'crypto-hydroxyl' radical as the dG oxidizing species in both the absence and presence of Ni(II). Also, the results provide evidence that Ni(II) complexes with His, GSH and GSSG may lack antioxidant capacity. Moreover, the Ni(II) complex with His was found capable of enhancing 8-OH-dG production by the Ascb+H2O2 system to a greater extent than Ni(II) alone. Likewise, although to a lesser extent, the formation of 8-OH-dG was enhanced by the combination of Ni(II) and Man which do not form complexes at pH 7.4. Since His is a major Ni(II) carrier in animal tissues, the dG oxidation enhancing capacity of the Ni(II) complex with His may contribute to the toxic and carcinogenic effects of Ni(II).
Kasprzak
K S
KS
Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick, MD 21702.
North
S L
SL
Hernandez
L
L
D001205:Ascorbic Acid / Q000378:metabolism; D003849:Deoxyguanosine / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology; D016166:Free Radical Scavengers; D005978:Glutathione / Q000494:pharmacology; D006639:Histidine / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000378:metabolism; D006878:Hydroxides / Q000378:metabolism; D017665:Hydroxyl Radical; D006900:Hydroxylation; D008353:Mannitol / Q000494:pharmacology; D009532:Nickel / Q000494:pharmacology*; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism*
D016166:Free Radical Scavengers; D006878:Hydroxides; D017665:Hydroxyl Radical; D000431:Ethanol; D008353:Mannitol; D006639:Histidine; D009532:Nickel; D006861:Hydrogen Peroxide; D003849:Deoxyguanosine; D005978:Glutathione; D001205:Ascorbic Acid; D010100:Oxygen