ENHANCED GENERATION OF HYDROXYL RADICAL AND SULFUR-TRIOXIDE ANION-RADICAL FROM OXIDATION OF SODIUM-SULFITE, NICKEL(II) SULFITE, AND NICKEL SUBSULFIDE IN THE PRESENCE OF NICKEL(II) COMPLEXES

Electron spin resonance (ESR) spin trapping was utilized to investigate the generation of free radicals from oxidation of sodium sulfite, nickel(II) subsulfite, and nickel subsulfide (Ni3S2) by ambient oxygen or H2O2 at pH 7.4. The spin trap used was 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). Under ambient oxygen, a solution of sodium sulfite alone generated predominantly sulfur trioxide anion radical (.SO3-) due to the autoxidation of sulfite: Addition of nickel(II) chloride [Ni(II)] enhanced the .SO3- yield about 4-fold. Incubation of sulfite with Ni(II) in the presence of chelators such as tetraglycine, histidine, beta-alanyl-3-methyl-L-histidine (anserine), beta-alanyl-L-histidine (camosine), gamma-aminobutyryl-L-histidine (homocarnosine); glutathione, and penicillamine did not have any significant effect on that enhancement. in contrast, albumin, and especially glycylglycylhistidine (GlyGlyHis), augmented the enhancing effect of Ni(II) by factors of 1.4 acid 4, respectively. Computer simulation analysis of the spin-adduct spectrum and formate scavenging experiment showed that the mixture of sodium sulfite, Ni(II), and GlyGlyHis generated both hydroxyl (.OH) radical and .SO3--radical, in the ratio of approximately 1:2. The free-radical spin adduct intensity reached its saturation level in about 5 min. The yield of the radical adducts could be slightly reduced by deferoxamine and very strongly reduced by diethylenetriaminepentaacetic acid (DTPA). Aqueous suspensions of sparingly soluble nickel(II) sulfite in the presence of air and GlyGlyHis generated surface-located .SO3- and OH radicals. The same radicals were generated in Ni3S2 suspension in the presence of GlyGlyHis and H2O2, indicating sulfite production by oxidation of the sulfide moiety of this compound. In view of the present results, the exceptionally high carcinogenic potential of Ni3S2 appears to be due to the ability of both the nickel and sulfide constituents of the molecule to facilitate the generation of genotoxic radicals.