Journal article
Breaking the dogma: PCB-derived semiquinone free radicals do not form covalent adducts with DNA, GSH, and amino acids
Environmental science and pollution research international, Vol.23(3), pp.2138-2147
02/2016
DOI: 10.1007/s11356-015-5007-4
PMCID: PMC4767158
PMID: 26396011
Abstract
Covalent bond formations of free radical metabolites with biomolecules like DNA and proteins are thought to constitute a major mechanism of toxicity and carcinogenesis. Glutathione (GSH) is generally accepted as a radical scavenger protecting the cell. In the present study, we investigated a semiquinone radical (SQ(●-)) metabolite of the semivolatile 4-chlorobiphenyl, using electron paramagnetic resonance spectroscopy, and oxygen consumption. Proton nuclear magnetic resonance ((1)H NMR) and liquid chromatography-mass spectrometry (LC-MS) were also employed to elucidate the radical interaction with DNA, amino acids, and GSH. We found that DNA and oligonucleotides stabilized SQ(●-) by electron delocalization in the π-stacking system, resulting in persistent radical intercalated, rather than forming a covalent bond with SQ(●-). This finding was strongly supported by the semiempirical calculation of the semioccupied molecular orbital and the linear combination of the atomic orbitals, indicating 9.8 kcal mol(-1) energy gain. The insertion of SQ(●-) into the DNA strand may result in DNA strand breaks and interruption of DNA replication process or even activate radical mediated secondary reactions. The presence of amino acids resulted in a decrease of the electron paramagnetic resonance (EPR) signal of SQ(●-) and correlated with their isoelectric points. The pH shifts the equilibrium of the dianions of hydroquinone and influenced indirectly the formation of SQ(●-). Similar findings were observed with GSH and Cys. GSH and Cys functioned as indirect radical scavengers; their activities depend on their chemical equilibria with the corresponding quinones, and their further reaction via Michael addition. The generally accepted role of GSH as radical scavenger in biological systems should be reconsidered based upon these findings, questioning the generally accepted view of radical interaction of semiquinones with biologically active compounds, like DNA, amino acids, proteins, and radical scavengers like GSH.
Details
- Title: Subtitle
- Breaking the dogma: PCB-derived semiquinone free radicals do not form covalent adducts with DNA, GSH, and amino acids
- Creators
- Orarat Wangpradit - Sirindhorn College of Public Health, BanSuan, Muang, Chonburi, 2000, ThailandAsif Rahaman - Department of Chemistry, City College of New York, Convent Avenue at 138th St., New York, NY, 10031, USAS V Santhana Mariappan - Central High-Field NMR Research Facility, Department of Chemistry, The University of Iowa, Iowa, IA, 52242, USAGarry R Buettner - Free Radical and Radiation Biology Program, The University of Iowa, Iowa, IA, 52242, USALarry W Robertson - Department of Occupational and Environmental Health, The University of Iowa, 100 Oakdale Campus, Iowa, IA, 52242, USAGregor Luthe - Luthe-Pharma, Fabrikstrasse 3, 48599, Gronau. g.luthe@luthe-pharma.com
- Resource Type
- Journal article
- Publication Details
- Environmental science and pollution research international, Vol.23(3), pp.2138-2147
- DOI
- 10.1007/s11356-015-5007-4
- PMID
- 26396011
- PMCID
- PMC4767158
- NLM abbreviation
- Environ Sci Pollut Res Int
- ISSN
- 0944-1344
- eISSN
- 1614-7499
- Publisher
- Springer Science and Business Media LLC; Germany
- Grant note
- P30 ES005605 / NIEHS NIH HHS R01 GM073929 / NIGMS NIH HHS P30 ES05605 / NIEHS NIH HHS P42 ES013661 / NIEHS NIH HHS P30 CA086862 / NCI NIH HHS R01 CA169046 / NCI NIH HHS
- Language
- English
- Date published
- 02/2016
- Academic Unit
- Occupational and Environmental Health; Radiation Oncology; Iowa Superfund Research Program
- Record Identifier
- 9984002467302771
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