Molecular Mechanisms of Metal Toxicity and Carcinogenicity
Environmental Health Perspectives 102, Supplement 3, September 1994
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
Xianglin Shi,1 Naresh Dalal,2 and Kazimierz Stanislaw Kasprzak1
1Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick, Maryland; 2Department of Chemistry, West Virginia University, Morgantown, West Virginia
Abstract
Electron spin resonance (ESR) spin trapping was utilized to investigate the generation of free radicals from oxidation of sodium sulfite, nickel(II) sulfite, 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, ß-alanyl-3-methyl-L-histidine (anserine), ß-alanyl-L-histidine (carnosine), 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 and 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. -- Environ Health Perspect 102(Suppl 3):91-96 (1994)
Key words: hydroxyl radical, sulfur trioxide anion radical, sulfite, nickel(II) sulfite, nickel subsulfide, nickel(II) complexes
This paper was presented at the Second International Meeting on Molecular Mechanisms of Metal Toxicity and Carcinogenicity held 10-17 January 1993 in Madonna di Campiglio, Italy.
The authors are grateful to Drs. L. K. Keefer, J. M. Rice, and R. W. Nims for helpful comments and suggestions on the manuscript, and to Kathy Breeze for editorial assistance. The West Virginia University's contribution was supported under grant No. 1134142 from the Bureau of Mines through the Generic Mineral Technology Center for Respirable Dust.
Address correspondence to Dr. K. S. Kasprzak, FCRDC, National Cancer Institute, Building 538, Room 205, Frederick, MD 21702. Telephone (301) 846-5738. Fax (301) 846-5946.
Introduction
It has been shown that sulfur dioxide (SO2) is a major air pollutant (1). In aqueous media it exists in equilibrium with the sulfite ion (SO32-)(2). Sulfite appears to have genotoxic effects (3). It can act as a mutagen or co-mutagen (4) and a co-carcinogen (5). The mechanism of sulfite toxicity is believed to be related to sulfite oxidation processes involving sulfur trioxide radical ion (SO3-) formation (1,6-8). Recent studies have shown that hydroxyl (OH) radical is also generated in the sulfite oxidation pathway (9). This radical may play an important role in sulfite-induced genetic damage. For example, incubation of sulfite with DNA produces 8-hydroxy-2'-deoxyguanosine (8-OH-dG) (10), a marker of oxidative DNA damage (11). It has been reported that Mn(II) (12) and chromate (9) enhance sulfite oxidation either as catalysts or as oxidants. However, it has not been clear whether sulfite oxidation can also be enhanced by other transition metal ions, Ni(II) in particular. Ni(II)-enhanced sulfite oxidation would be highly interesting, since nickel in many physicochemical forms is carcinogenic to humans and animals (13-16). Among nickel compounds, the crystalline sulfides, especially the subsulfide Ni3S2, appear to be the strongest carcinogens (17). Ni3S2 is potentially genotoxic, causing random polymerization of histones in vitro (18), formation of DNA-protein crosslinking bonds (18), and hydroxylation of 2'-deoxyguanosine (dG) to 8-OH-dG in the presence of ambient oxygen (19). The latter reaction can be enhanced by H2O2 (19). Most importantly, Ni3S2 interacts with molecular oxygen and undergoes slow oxidation of both its cationic and anionic constituents to soluble Ni(II) and SO42- (20,21). Oxidation of the sulfur moiety of Ni3S2 is gradual and goes through sulfite as an intermediate (21). Thus, it appears that Ni3S2 yields two products that are capable of damaging DNA.
Unlike other transition metal ions such as Fe(II), Cu(II) and VO2+, Ni(II) does not cause efficient free radical generation from O2, H2O2 or lipid hydroperoxides. However, recent studies (22,23) have shown that reactivity of Ni(II) with those oxygen derivatives can be modulated by chelation, e.g., with certain histidine- and cysteine-containing ligands. We could expect, therefore, that chelation of Ni(II) might also facilitate the stimulatory effect of this cation on sulfite oxidation. Hence, in the present study we investigated free- radical generation during autoxidation of sulfite with Ni(II) added in either non-chelated or chelated form. The results show that in the presence of certain chelators, Ni(II) significantly increased SO3- radical generation and, in addition, caused OH radical generation from sodium sulfite reacting with ambient oxygen. Aqueous suspensions of sparingly soluble nickel(II) sulfite, under ambient atmosphere, generated surface-bound free radicals only in the presence of a chelator. For Ni3S2 suspensions, both a chelator and a stronger oxidant, H2O2, were required for the free radical generation. Cooperation of both constituents of Ni3S2 in free-radical production may explain the exceptionally high carcinogenic potential of this compound.
Materials and Methods
Nickel(II) chloride hexahydrate (NiCl2.6H2O), iron(II) chloride tetrahydrate (FeCl2.4H2O), potassium dichromate (K2Cr2O7), sodium formate (HCOONa), sodium sulfite (Na2SO3), and 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) were purchased from Aldrich Chemical Co. (Milwaukee, WI). Glycylglycylhistidine (GlyGlyHis), tetraglycine (GlyGlyGlyGly), ß-alanyl-3-methyl-L-histidine (anserine), ß-alanyl-L-histidine (carnosine), gamma-aminobutyryl-L-histidine (homocarnosine), L-histidine, glutathione (GSH), penicillamine, albumin, diethylenetriaminepentaacetic acid (DTPA), and deferoxamine were purchased from Sigma Chemical Co. (St. Louis, MO). Nickel(II) sulfite (NiSO3) was purchased from Pfaltz and Bauer, Inc. (Waterbury, CT). Ni3S2 (<30 µm particles) was purchased from INCO, Ltd. (Toronto, Canada). Chelex-100 chelating resin was purchased from Bio-Rad Laboratories (Richmond, CA). The phosphate buffer, pH 7.4, used was treated with Chelex-100 to remove possible transition metal ion contaminants. DMPO solutions were purified using activated charcoal until free radical impurities disappeared as verified by ESR spectroscopy.
ESR Measurements
ESR spin-trapping methodology (24,25) was employed for detecting short-lived free radical intermediates. All ESR measurements were performed with a Varian E3 ESR spectrometer and a flat-cell assembly. Hyperfine splittings were measured (to 0.1 G) directly from the magnetic field separation using tetraperoxochromate (K3CrO8) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) as reference standards. A Bruker ASPECT 2000 computer was used for spectral analyses. Reactants were mixed in test tubes in a total final volume of 250 µl. The reaction mixture was then transferred to a flat cell for ESR measurement. The concentrations given in the figure legends represent final concentrations. All experiments were carried out at room temperature in the presence of air unless otherwise indicated.
Results
Effect of GlyGlyHis and Other Chelators on Ni(II)-mediated Free-Radical Generation in Sodium Sulfite Solution
Figure 1a shows a typical ESR spectrum obtained from an aqueous phosphate buffer solution of 2.5 mM Na2SO3, pH 7.4, under air. The analysis of this spectrum yields the hyperfine splittings of aN = 14.7 G and aH = 16.0 G, which are identical to those reported earlier for a DMPO/SO3- adduct produced in various other reaction systems, and thus documents the formation of SO3- radical in sulfite autoxidation (9,26,27). When 1 mM Ni(II) was added to this solution, the intensity of the free-radical spin-adduct signal increased by about 4-fold without noticeable change in the spectral hyperfine splittings, indicating that Ni(II) catalyzed the sulfite autoxidation and concomitant generation of SO3- free radical. Addition of 2 mM GlyGlyHis to a mixture of 2.5 mM sulfite and 1 mM Ni(II) increased the signal intensity about 4-fold, compared with that in the absence of GlyGlyHis, and 15-fold versus that obtained by autoxidation of sulfite alone. The time course of free radical generation is shown in Figure 2. Formation of the radicals reached its saturation level in about 5 min, indicating a relatively fast reaction. A sodium sulfite solution containing GlyGlyHis without Ni(II) yielded the free radicals in amounts comparable to those obtained from autoxidation of the sulfite alone (Figure 1d). A mixture of Ni(II) and GlyGlyHis without sulfite did not generate any detectable amounts of free radicals (Figure 1e).
Figure 1. ESR spectra, recorded 3 min after reactions were initiated, from phosphate buffer solutions (pH 7.4) of various combinations of 100 mM DMPO, 2.5 mM Na2SO3, 1 mM NiCl2, and 2 mM GlyGlyHis. The ESR spectrometer settings were: receiver gain, 2.0 x 105; time constant, 0.3 sec; modulation amplitude, 10 G; scan time, 8 min; magnetic field, 3470 + 50 G.
Figure 2. Time course of free radical spin adduct generation from a mixture of 100 mM DMPO, 2.5 mM Na2SO3, 1 mM NiCl2, and 2 mM GlyGlyHis. Other experimental conditions were the same as those described in the legend to Figure 1.
Analysis of the spectrum in Figure 1c revealed that the hyperfine splittings were different from those shown in Figure 1b. These differences might be due to the trapping of other radicals in addition to SO3-. The spectrum in Figure 1c seemed to be a superposition of those from the DMPO adducts of SO3- and OH radicals. To test this possibility, we used the well-known reaction of K2Cr2O7 with Na2SO3 to generate the SO3- radicals (9,28). As shown in Figure 3a, this reaction generated the typical DMPO/SO3- adduct, with hyperfine splittings of aN = 14.7 G and aH = 16.1 G. We also used the Fenton reagent to generate authentic DMPO/OH adduct, with hyperfine splittings of aN = aH = 14.9 G (Figure 3b). An ASPECT 2000 computer was used to combine various percentages of the DMPO/SO3- and DMPO/OH adduct spectra. The profile in Figure 3c, which corresponded most closely with the spectrum in Figure 1c, was a combination of 65% DMPO/SO3- and 35% DMPO/OH. To ascertain whether OH radicals were indeed produced in the sulfite oxidation in the presence of Ni(II) and GlyGlyHis, formate was used as an OH radical scavenger. It was added to a mixture containing 2.5 mM sodium sulfite, 1 mM Ni(II) and 2 mM GlyGlyHis at concentrations of up to 0.8 M. The resulting spectrum is shown in Figure 4a. Formate caused the appearance of DMPO/COO- adduct, suggesting that OH radical was indeed being produced in the mixture of sodium sulfite, Ni(II), and GlyGlyHis.
Figure 3. ESR spectra recorded from phosphate buffer solutions (pH 7.4) containing 60 mM DMPO and (a) 1 mM Na2SO3 plus 0.1 mM K2Cr2O7, (b) 1 mM H2O2 plus 0.05 mM FeCl2. (c) Computer-simulated spectrum of 65% DMPO/SO3- and 35% DMPO/OH. Note that spectrum c closely resembles that in Figure 1c.
Figure 4. ESR spectra, recorded 3 min after reactions were initiated, from a phosphate buffer solution (pH 7.4) of 100 mM DMPO, 2.5 mM Na2SO3, 1 mM NiCl2, 0.6 M sodium formate, and 2 mM GlyGlyHis. (a) Under ambient oxygen, (b) under argon. The ESR spectrometer settings were the same as those described in the legend to Figure 1.
An experiment carried out under argon showed a significant decrease in the overall spectral intensity (Figure 4b). Thus, the free radical generation from the mixture of sodium sulfite, Ni(II), and GlyGlyHis required molecular oxygen. The residual free radical generation observed under argon may be due to remnants of oxygen dissolved in the reaction mixture.
Figure 5a shows the ESR spectrum obtained from a mixture containing 1 mM Ni(II), 2.5 mM sulfite, 2 mM GlyGlyHis, and 2 mM deferoxamine. The latter caused only a slight decrease in the overall spectral intensity (compare Figures 5a and 1c). Moreover, upon addition of deferoxamine, the second peak of the spectrum exhibited a doublet, similar to that in Figure 3a. This indicates that the major spin adduct obtained in this case was DMPO/SO3-. Hence, deferoxamine inhibited OH generation to a greater degree than SO3- generation. Addition of DTPA sharply reduced the spectral intensity (Figure 5b). In the absence of GlyGlyHis, deferoxamine and DTPA decreased the enhancing effect of Ni(II) on free radical generation from autoxidation of sulfite alone (compare Figures 5c and 5d with Figure 1b).
Figure 5. ESR spectra, recorded 3 min after reactions were initiated, from phosphate buffer solutions (pH 7.4) of various combinations of 100 mM DMPO, 2.5 mM Na2SO3, 1 mM NiCl2, 2 mM GlyGlyHis, 2 mM deferoxamine, and 2 mM DTPA. The ESR spectrometer settings were the same as those described in the legend to Figure 1.
Several other Ni(II) chelators, such as GlyGlyGlyGly, histidine, anserine, carnosine, homocarnosine, GSH, penicillamine, and albumin at 2 mM concentrations were also tested for their effect on 1 mM Ni(II)-mediated free radical generation from 2.5 mM sodium sulfite at pH 7.4. Of these chelators, only albumin had a significant enhancement effect. Albumin doubled the peak intensity of the free radical adducts compared with the intensity produced in the mixture of Na2SO3 and NiCl2. For comparison, under the same condition, 2 mM GlyGlyHis increased the intensity by a factor of 6.
Effect of GlyGlyHis on Free Radical Generation in Nickel(II) Sulfite Suspension
Figure 6 shows a spectrum obtained from sparingly soluble NiSO3 (50 mg/ml) suspended in phosphate buffer (pH 7.4) in the presence of 2 mM GlyGlyHis. The spectral intensity reached its saturation level in about 4 min. Without GlyGlyHis, NiSO3 suspension did not generate any significant amounts of free radicals. The broad peaks in the spectra obtained (Figure 6a, 6b) suggest that the majority of the free radicals generated were surface-located and had a limited motion in the NiSO3 suspension (29). Since the spectrum consisted of only four peaks, it can be assigned to a combination of DMPO/SO3- and DMPO/OH as discussed in the previous section. However, the broadness of the peaks made it difficult to determine the ratio of DMPO/SO3- to DMPO/OH.
Figure 6. ESR spectra, recorded from phosphate buffer solutions (pH 7.4) of 100 mM DMPO, 50 mg/ml NiSO3 and 2 mM GlyGlyHis. (a) Spectrum recorded 1 min after reaction initiation; (b) spectrum recorded 4 min after reaction initiation. (c) Same as (a) but without GlyGlyHis. The ESR spectrometer settings were the same as those described in the legend to Figure 1.
Effect of GlyGlyHis on Free Radical Generation in Nickel Subsulfide Suspension
Figure 7a and 7b shows the spectra obtained from a suspension of 50 mg/ml Ni3S2 in phosphate buffer (pH 7.4) in the presence of 2 mM GlyGlyHis and 5 mM H2O2. These spectra were recorded at time intervals of 1 min and 3.5 min, respectively. The DMPO free radical adducts shown in Figure 7b were present in solution, as indicated by the relatively narrow spectral peaks (compared with Figure 6b). Like that in Figure 6b, the spectrum in Figure 7b can be assigned to a combination of DMPO/SO3- and DMPO/OH. The control reaction of Ni(II) and GlyGlyHis with H2O2 also generated a relatively strong spin adduct signal (Figure 7c). Computer analysis indicated that this signal consisted of 50% DMPO/superoxide radical (O2-) adduct with hyperfine splittings of aN = 14.2 G, aH = 11.4 G and aH_ = 1.3 G and DMPO/OH adduct with hyperfine splittings of aN = aH = 14.9 G, in concordance with those reported earlier (30). Since the spectrum in Figure 7b consisted of only four peaks, it appeared that in contrast to the case for Ni(II), no detectable amount of O2- was produced from H2O2 by Ni3S2 in the presence of GlyGlyHis. Ni3S2 suspension containing GlyGlyHis or H2O2 alone did not generate any significant amounts of free radicals (Figure 7d, e).
Figure 7. ESR spectra, recorded 1 min after the reactions were initiated, from phosphate buffer solutions (pH 7.4) of 100 mM DMPO and (a) 50 mg/ml Ni3S2, 5 mM H2O2, and 2 mM GlyGlyHis, (b) Same as (a) but the spectrum was recorded 4 min after the reaction was initiated. (c) Same as (b) but 1 mM NiCl2 used in place of Ni3S2. (d) Same as (a) but without H2O2. (e) Same as (b) but without GlyGlyHis. The spectrometer settings were the same as those in the legend to Figure 1.
Figures 6b and 7b show that the intensities of the two spectra, representing NiSO3 and Ni3S2, respectively, are comparable but the linewidth of the former is very broad. Since the integration of the spectrum represents the amount of free radicals generated, the relative yield of free radical production by Ni3S2 was much lower than that by NiSO3.
Discussion
It has been known that Ni(II) does not easily react with oxidants to produce free radical species (31,32). However, its reactivity toward molecular oxygen, H2O2, and lipid hydroperoxides can be greatly enhanced by coordination with certain chelating agents, including GlyGlyHis (22,23,30,32,33). Likewise, the results obtained in the present study show that while Ni(II) can increase SO3-radical generation from sulfite to some extent, Ni(II) chelated with the oligopeptide GlyGlyHis is far more effective. Most importantly, in addition to SO3- radical, chelated Ni(II) markedly enhances generation of OH radicals in this system. Unlike GlyGlyHis, other histidyl chelators, including anserine, carnosine, homocarnosine, and histidine itself, as well as some thiol-containing chelators such as GSH and penicillamine, did not affect the Ni(II)-enhanced free radical generation from sodium sulfite. It is noteworthy that all these chelators have been shown to enhance Ni(II)-mediated free radical generation from model lipid hydroperoxides, cumene hydroperoxide and t-butyl hydroperoxide (22,23). Similarly, GlyGlyGlyGly, which appeared to lack any effect on Ni(II) action in the present study, has been reported to enhance Ni(II)-promoted free radical generation from H2O2 (30). It appears, therefore, that the enhancing effect of various Ni(II) chelates on free radical production in the case of oxidation of different substrates depends on the chemistry of those substrates.
The present study also shows that besides assisting Ni(II) in the enhancement of free radical production by autoxidation of the sulfite anion in solution, GlyGlyHis could as well increase radical production from sparingly soluble NiSO3 particles in aqueous suspension. In contrast, Ni3S2 suspension, alone or in the presence of GlyGlyHis, did not generate a detectable amount of free radicals under ambient oxygen. Free radicals could be detected in the Ni3S2/GlyGlyHis system only after the addition of H2O2. Unlike in the suspension of NiSO3 in which SO3- and OH radicals were associated mainly with the particle surface (broad ESR peaks), the same radicals generated in the Ni3S2 system were detectable in the solution (narrow peaks). The reason for this difference is not clear. It may be due to the different physicochemial properties of the two systems, e.g., different distribution of Ni(II) and sulfite between the aqueous and the solid phases and the presence of H2O2. Apparently, H2O2 functioned as a Ni3S2 oxidant to produce Ni(II) and sulfite, a mixture facilitating generation of SO3- and OH, especially in the presence of GlyGlyHis, as discussed above. It also seems possible that Ni(II), derived from Ni3S2 and chelated with GlyGlyHis, reacted with H2O2 to yield OH and O3- radicals, as described elsewhere (30). Both, *OH and O2- could, in turn, react with sulfite to produce SO3- radicals (34,35). However, no DMPO/O2- adduct was detected, which argues against but does not exclude the second scenario.
It is now generally believed that SO3- radical can cause many adverse effects while reacting with biological molecules. These include oxidation of methionine (36), diphosphopyridine nucleotides (37), and lipids (38); destruction of ß-carotene (8) and tryptophan (36); addition to double bonds in unsaturated fatty acids (39); and modification of nucleic acids (7,40). Some of these effects are potentially genotoxic and may contribute to carcinogenesis (3-5). The genotoxicity of OH radical, also generated by sulfite oxidation, is well recognized (41). For example, the OH radical generated by sodium sulfite autoxidation was reported to be capable of producing promutagenic 8-OH-dG in DNA (10). The observed enhancement of OH radical production from sulfite by Ni(II) chelated with GlyGlyHis and albumin may be involved in the mechanism(s) of carcinogenesis by nickel(II) sulfides, the strongest nickel carcinogens. Both Ni(II) and sulfite are derived from oxidative dissolution of Ni3S2 and crystalline NiS (20, 21). Albumin and other proteins having metal binding sites of the GlyGlyHis type are major tissue Ni(II) carriers (42). All these reagents, together with H2O2 may thus act in concert to generate genotoxic radicals from nickel sulfides. H2O2 may originate from cellular metabolic or pathogenic processes; e.g., sulfides of nickel and cadmium induce H2O2 formation by polymorphonuclear leukocytes (43). In concordance with this assumption, in the presence of molecular oxygen, Ni3S2 was found to cause hydroxylation of dG to 8-OH-dG in vitro. The yield of 8-OH-dG was greatly enhanced by H2O2 (19). Ni3S2 and NiSO3 were also found to produce another potentially mutagenic effect, i.e., deamination of 5-methyl-2'-deoxycytidine to thymidine (44). NiSO3 was much more active in this reaction than the well-known deaminating agent, sodium bisulfite. Thus, the exceptionally high carcinogenic potential of Ni3S2 compared to other nickel derivatives (17) may be due to the ability of both the metal and sulfide constituents of the molecule to enhance generation of genotoxic free radicals.
References and Notes
1. Gunnison AF. Sulphite toxicity: a critical review of in vitro and in vivo data. Food Cosmet Toxicol 19:667-682 (1981).
2. Neta P, Huie RE. Free-radical chemistry of sulfite. Environ Health Perspect 64:209-217 (1985).
3. Shapiro R Genetic effects of bisulfite: implications for environmental protection. Basic Life Sci 23:35-60 (1983).
4. Shapiro R. Genetic effects of bisulfite (sulfur dioxide). Mutat Res 39:149-175 (1977).
5. Pauluhn J, Thyssen J, Althoff J, Kimmerle G, Mohr U. Long term inhalation study with benzo[a]pyrene and sulfur dioxide in Syrian golden hamsters. Exp Pathol 28:31 (1985).
6. Brestel ER, Petrone WF, Cohen RA. Lipid peroxides initiate the autoxidation of sulfite with concomitant production of superoxide. J Free Radical Biol Med 2:218-225 (1986).
7. Hayatsu H. Bisulfite modification of nucleic acids and their constituents. Prog Nucleic Acid Res Mol Biol 16:75-124 (1976).
8. Peiser GD, Yang SF. Sulfite-mediated destruction of ß-carotene. J Agric Food Chem 27:446-449 (1979).
9. Shi X, Dalal NS. ESR spin trapping evidence for SO3-- and OH radicals in sulfite oxidation. Res Chem Intermediates 13:103-115 (1990).
10. Kasai H, Nishimura S. Hydroxylation of deoxyguanosine at C-8 position by ascorbic acid and other reducing agents. Nucleic Acids Res 12:2137-2145 (1984).
11. Floyd RA. The role of 8-hydroxyguanosine in carcinogenesis. Carcinogenesis 11:1447-1450 (1990).
12. Inouye B, Ikeda M, Ishida T, Ogata M, Akiyama J, Utsumi K. Participation of superoxide free radical and Mn2+ in sulfite oxidation. Toxicol Appl Pharmacol 46:29-38 (1978).
13. Klein CB, Frenkel K, Costa M. The role of oxidative processes in metal carcinogenesis. Chem Res Toxicol 4:592-604 (1991).
14. Kasprzak KS. The role of oxidative damage in metal carcinogenesis. Chem Res Toxicol 4:604-615 (1991).
15. Coogan TM, Latta DM, Snow ET, Costa M. Toxicity and carcinogenicity of nickel compounds. CRC Crit Rev Toxicol 19: 341-384 (1989).
16. Sunderman FW Jr. Carcinogenic effects of metals. Fed Proc 37:40-46 (1987).
17. Sunderman FW Jr. Carcinogenicity of nickel compounds in animals. In: Nickel in the Human Environment (Sunderman FW Jr, ed). IARC Scientific Publications, No. 53. New York:Oxford University Press, 1984;127-142.
18. Kasprzak KS, Bare RM. In vitro polymerization of histones by carcinogenic nickel compounds. Carcinogenesis 10:621-624 (1989).
19. Kasprzak KS, Hernandez L. Enhancement of hydroxylation and deglycosylation of 2'-deoxyguanosine by carcinogenic nickel compounds. Cancer Res 49:5964-5968 (1989).
20. Kasprzak KS, Sunderman FW Jr. Mechanism of dissolution of nickel subsulfide in rat serum. Res Commun Chem Pathol Pharmacol 16:95-108 (1977).
21. Lee JE, Ciccareli RB, Jennette KW. Solubilization of the carcinogen nickel subsulfide and its interaction with deoxyribonucleic acid and protein. Biochemistry 21:771-778 (1982).
22. Shi X, Dalal NS, Kasprzak KS. Generation of free radicals from lipid hydroperoxides by Ni2+ in the presence of oligopeptides. Arch Biochem Biophys 99:154-162 (1992).
23. Shi X, Dalal NS, Kasprzak KS. Generation of free radicals in reactions of Ni(II)-thiol complexes with molecular oxygen and model lipid hydroperoxides. J Inorg Biochem 50:211-225 (1993).
24. Janzen EG, Blackburn BJ. Detection and identification of short-lived free radicals by electron spin resonance trapping techniques (spin trapping). Photolysis of organolead, -tin, and mercury compounds. J Am Chem Soc 90:5909-5910 (1968).
25. Mottley C, Mason RP. Nitroxide radical adducts in biology:chemistry, applications, and pitfalls. Biol Magn Reson 8:489-546 (1989).
26. Buettner GR. Spin trapping: ESR parameters of spin adducts. Free Radic Biol Med 3:213-303 (1987).
27. Reed GA, Curtis JF, Mottley C, Eling TE, Mason RP. Epoxidation of (+)-7,8-dihydroxy-7,8-dihydrobenzo[
]pyrene during (bi)sulfite autoxidation: activation of a procarcinogen by a cocarcinogen. Proc Natl Acad Sci USA 83:7499-7502 (1986).
28. Shi X, Dalal NS, Jain AC. Antioxidant behavior of caffeine: efficient scavenging of hydroxyl radicals. Food Chem Toxicol 29:1-6 (1991).
29. Wertz JE, Bolton JR. Electron Spin Resonance, 1st ed. New York:Chapman and Hall, 1972; 222.
30. Inoue S, Kawanishi S. ESR evidence for superoxide, hydroxyl radicals and singlet oxygen produced from hydrogen peroxide and nickel(II) complex of glycylglycyl-L-histidine. Biochem Biophys Res Commun 159:445-451 (1989).
31. Tomlinson AAG. Nickel coordination chemistry. Coordination Chem Rev 7:221-296 (1980).
32. Bossu FP, Paniago EB, Margerum DW, Kirksey ST Jr, Kutz JL. Trivalent nickel catalysis of the autoxidation of nickel(II) tetraglycine. Inorg Chem 17:1034-1042 (1978).
33. Bossu FP, Margerum DW. Electrode potentials of nickel(III,II)-peptide complexes. Inorg Chem 16: 1210-1214 (1977).
34. Ozawa T, Kwan T. ESR. studies for chemical modification of biologically active nucleic acids by the sulphite radical anion. J Chem Soc Chem Commun1295-1296 (1983).
35. Covello PS, Thompson JE. Spin trapping evidence for formation of the sulfite radical anion during chloroplast-mediated oxidation of bisulfite ion. Biochim Biophys Acta 843:150-154 (1985).
36. Klebanoff SJ. The sulfite-activated oxidation of reduced pyridine nucleotides by peroxides. Biochim Biophys Acta 48:93-103 (1961).
37. Lizada MCC, Yang SF. Sulfite-induced lipid peroxidation. Lipids 16:189-199 (1981).
38. Yang SF. Sulfoxide formation from methionine or its sulfite analogs during aerobic oxidation of sulfite. Biochemistry 9: 5008-5014 (1970).
39. Southerland WM, Akogyeram CO, Toghrol F, Sloan L, Scherrer R. Interaction of bisulfite with unsaturated fatty acids. J Toxicol Environ Health 10:479-491 (1982).
40. Hayatsu H, Miller RC. The cleavage of DNA by the oxygen-dependent reaction of bisulfite. Biochem Biophys Res Commun 46:20-124 (1972).
41. Halliwell B, Aruoma OI. DNA damage by oxygen-derived species: its mechanism and measurement in mammalian systems. FEBS Lett 281:9-19 (1991).
42. Sarkar B. Biological coordination chemistry of nickel. In: Coordination Chemistry (Laurent JP, ed). Oxford:Pergamon Press, 1980;171-185.
43. Zhong Z, Troll W, Koenig KL, Frenkel K. Carcinogenic sulfide salts of nickel and cadmium induce H2O2 formation by human polymorphonuclear leukocytes. Cancer Res 50:7564-7570 (1990).
44. Kasprzak KS, North SL, Keefer LK. Deamination of 5-methyl-2'-deoxycytidine with carcinogenic nickle subsulfide and its metabolite, nickel(II) sulfite. Proc Am Assoc Cancer Res 32:108 (1991).
Last Update: November 30, 1998
