Ascorbic acid oxidation and DNA scission catalyzed by iron and copper chelates
Abstract
The asorbic acid (AH-) auto-oxidation rates catalyzed by copper chelates of 1,10-phenanthroline (OP) or by iron chelates of bleomycin (BLM) are only slightly higher than the oxidation rates catalyzed by the metal ions. AH- oxidation in the presence of DNA is accompanied by degradation of the DNA. The rates of DNA scission by the metal chelates are markedly higher than the rates induced by the free metal ions. AH- oxidation is slowed down in the presence of DNA which forms ternary complexes with the chelates. The ternary complexes react slowly with AH- but induce DNA double strand breaks more efficiently than the free metal chelates. With OP, DNA is degraded by the reaction of the ternary complex, DNA-(OP)2Cu(I), with H2O2. AH- oxidation in the presence of DNA was biphasic, showing a marked rate increase after DNA was cleaved. We suggest that this sigmoidal pattern of the oxidation curves reflects the low initial oxidative activity of the ternary complexes, accelerating as DNA is degraded. Using O2- produced by pulse radiolysis as a reductant, we found that AH- oxidation with (OP)2Cu(II) induced more DNA double strand breaks per single strand break than bipyridine-copper. The site specific DNA damaging reactions indicated by these results are relevant to the mechanism of cytotoxic activities of bleomycin and similar antibiotics or cytotoxic agents.
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Higher doses of vitamin C can behave as a prooxidant.
“Higher doses of vitamin C can behave as a prooxidant [156,168,169]”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [169]
Cites
Free radicals in biology and medicine
Gutteridge, J. M. C. (1991) · General Pharmacology The Vascular System · doi:10.1016/0306-3623(91)90478-o · Cited by 17,178 · see citing works
Role of metals in oxygen radical reactions
Aust, S. D., Morehouse, L. A., & Thomas, C. E. (1985) · Journal of Free Radicals in Biology & Medicine · doi:10.1016/0748-5514(85)90025-x · Cited by 1,150 · see citing works
Kellogg, E. W., & Fridovich, I. (1975) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)40745-x · Cited by 966 · see citing works
Superoxide radical and superoxide dismutase
Fridovich, I. (1972) · Accounts of Chemical Research · doi:10.1021/ar50058a001 · Cited by 472 · see citing works
Activated bleomycin. A transient complex of drug, iron, and oxygen that degrades DNA.
Burger, R. M., Peisach, J., & Horwitz, S. B. (1981) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)68452-8 · Cited by 462 · see citing works
Properties and products of the degradation of DNA by bleomycin and iron(II)
Sausville, E. A., Stein, R. W., Peisach, J., & Horwitz, S. B. (1978) · Biochemistry · doi:10.1021/bi00607a008 · Cited by 337 · see citing works
ON THE MECHANISM OF ACTION OF BLEOMYCIN : SCISSION OF DNA STRANDS IN VITRO AND IN VIVO
Suzuki, H., Nagai, K., Yamaki, H., Tanaka, N., & UMEZAWA, H. (1969) · The Journal of Antibiotics · doi:10.7164/antibiotics.22.446 · Cited by 324 · see citing works
On the cytotoxicity of vitamin C and metal ions
Samuni, A., Aronovitch, J., Godinger, D., Chevion, M., & Czapski, G. (1983) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1983.tb07804.x · Cited by 323 · see citing works
Self-citationSuperoxide‐dependent formation of hydroxyl radicals in the presence of iron salts
Halliwell, B. B. (1978) · FEBS Letters · doi:10.1016/0014-5793(78)80409-8 · Cited by 299 · see citing works
Marshall, L. E., Graham, D. R., Reich, K. A., & Sigman, D. S. (1981) · Biochemistry · doi:10.1021/bi00505a003 · Cited by 231 · see citing works
Fong, K.-L., McCay, P. B., Poyer, J. L., et al. (1976) · Chemico-Biological Interactions · doi:10.1016/0009-2797(76)90130-7 · Cited by 201 · see citing works
Binding of bleomycin to DNA: intercalation of the bithiazole rings
Povirk, L. F., Hogan, M. E., & Dattagupta, N. (1979) · Biochemistry · doi:10.1021/bi00568a015 · Cited by 186 · see citing works
Scarpa, M., Stevanato, R., Viglino, P., et al. (1983) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)32271-3 · Cited by 162 · see citing works
Que, B. G., Downey, K. M., & So, A. G. (1980) · Biochemistry · doi:10.1021/bi00567a007 · Cited by 134 · see citing works
Czapski, G., & Ilan, Y. A. (1978) · Photochemistry and Photobiology · doi:10.1111/j.1751-1097.1978.tb06988.x · Cited by 119 · see citing works
Self-citationGoldstein, S., & Czapski, G. (1986) · Journal of the American Chemical Society · doi:10.1021/ja00269a020 · Cited by 112 · see citing works
Self-citationThe reaction of ferrous EDTA with hydrogen peroxide: Evidence against hydroxyl radical formation
Koppenol, W. H. (1985) · Journal of Free Radicals in Biology & Medicine · doi:10.1016/0748-5514(85)90132-1 · Cited by 89 · see citing works
Reich, K. A., Marshall, L. E., Graham, D. R., et al. (1981) · Journal of the American Chemical Society · doi:10.1021/ja00402a060 · Cited by 62 · see citing works
Czapski, G., & Goldstein, S. (1986) · Free Radical Research Communications · doi:10.3109/10715768609083147 · Cited by 59 · see citing works
Self-citationGoldstein, S., & Czapski, G. (1985) · Inorganic Chemistry · doi:10.1021/ic00201a025 · Cited by 49 · see citing works
Self-citationCopper-bleomycin has no significant DNA cleavage activity
Suzuki, T., Kuwahara, J., & Sugiura, Y. (1985) · Biochemistry · doi:10.1021/bi00339a001 · Cited by 34 · see citing works
UMEZAWA, H. (1979) · Springer eBooks · doi:10.1007/978-1-4612-6191-9_2 · Cited by 30 · see citing works
A novel method for quantitation of favism-inducing agents in legumes
Chevion, M., & Navok, T. (1983) · Analytical Biochemistry · doi:10.1016/0003-2697(83)90355-x · Cited by 22 · see citing works
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Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination
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- Authors
- Aronovitch, J., Godinger, D., Samuni, A., & Czapski, G.
- Affiliations
- Hebrew University of Jerusalem (IL)
- Venue
- Free Radical Research Communications
- Publisher
- Informa UK Limited
- Published
- 1987-01
- Volume
- 2
- Issue
- 4-6
- Pages
- 241-258
- ISSN
- 8755-0199 (ISSN-L)
- OpenAlex
- W1996454694
- Cited by
- 30
- References
- 23
- Citations by year
- 2025: 1 · 2024: 3 · 2023: 1 · 2021: 1 · 2017: 1 · 2012: 1
- FWCI
- 2.61
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Free Radical Research Communications (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Bureau of Land Management
- Topics
- Physical Sciences › Chemistry › Inorganic Chemistry › Metal-Catalyzed Oxygenation Mechanisms
- Health Sciences › Medicine › Oncology › Metal complexes synthesis and properties
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Bioactive Compounds and Antitumor Agents
- Keywords
- ascorbic acid oxidation, DNA cleavage, copper chelates, iron chelates, 1,10-phenanthroline, bleomycin, DNA double-strand breaks, hydrogen peroxide, superoxide, cytotoxicity mechanism
- MeSH terms
- Ascorbic Acid, Bleomycin, Catalysis, Copper, DNA, DNA Damage, Hydrogen Peroxide, Iron Chelating Agents, Kinetics, Osmolar Concentration, Oxidation-Reduction, Phenanthrolines, Spectrophotometry, Ultraviolet, Superoxides
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