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Mechanism of synergistic DNA damage induced by the hydroquinone metabolite of brominated phenolic environmental pollutants and Cu(II): Formation of DNA-Cu complex and site-specific production of hydroxyl radicals.
Free Radic Biol Med. 2017 03; 104:54-63.FR

Abstract

2,6-Dibromohydroquinone (2,6-DBrHQ) has been identified as an reactive metabolite of many brominated phenolic environmental pollutants such as tetrabromobisphenol-A (TBBPA), bromoxynil and 2,4,6-tribromophenol, and was also found as one of disinfection byproducts in drinking water. In this study, we found that the combination of 2,6-DBrHQ and Cu(II) together could induce synergistic DNA damage as measured by double strand breakage in plasmid DNA and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) formation, while either of them alone has no effect. 2,6-DBrHQ/Cu(II)-induced DNA damage could be inhibited by the Cu(I)-specific chelating agent bathocuproine disulfonate and catalase, but not by superoxide dismutase, nor by the typical hydroxyl radical (•OH) scavengers such as DMSO and mannitol. Interestingly, we found that Cu(II)/Cu(I) could be combined with DNA to form DNA-Cu(II)/Cu(I) complex by complementary application of low temperature direct ESR, circular dichroism, cyclic voltammetry and oxygen consumption methods; and the highly reactive •OH were produced synergistically by DNA-bound-Cu(I) with H2O2 produced by the redox reactions between 2,6-DBrHQ and Cu(II), which then immediately attack DNA in a site-specific manner as demonstrated by both fluorescent method and by ESR spin-trapping studies. Further DNA sequencing investigations provided more direct evidence that 2,6-DBrHQ/Cu(II) caused preferential cleavage at guanine, thymine and cytosine residues. Based on these data, we proposed that the synergistic DNA damage induced by 2,6-DBrHQ/Cu(II) might be due to the synergistic and site-specific production of •OH near the binding site of copper and DNA. Our findings may have broad biological and environmental implications for future research on the carcinogenic polyhalogenated phenolic compounds.

Authors+Show Affiliations

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences and University of Chinese Academy of Sciences, The Chinese Academy of Sciences, Beijing 100085, PR China; School of Public Health, Jining Medical University, Jining, Shandong 272067, PR China.State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences and University of Chinese Academy of Sciences, The Chinese Academy of Sciences, Beijing 100085, PR China.State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences and University of Chinese Academy of Sciences, The Chinese Academy of Sciences, Beijing 100085, PR China.College of Chemistry and Molecular Sciences, Key Laboratory of Biomedical Polymers of Ministry of Education, Wuhan University, Wuhan, Hubei 430072, PR China.State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences and University of Chinese Academy of Sciences, The Chinese Academy of Sciences, Beijing 100085, PR China.State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences and University of Chinese Academy of Sciences, The Chinese Academy of Sciences, Beijing 100085, PR China.State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences and University of Chinese Academy of Sciences, The Chinese Academy of Sciences, Beijing 100085, PR China.State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences and University of Chinese Academy of Sciences, The Chinese Academy of Sciences, Beijing 100085, PR China.State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences and University of Chinese Academy of Sciences, The Chinese Academy of Sciences, Beijing 100085, PR China.State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences and University of Chinese Academy of Sciences, The Chinese Academy of Sciences, Beijing 100085, PR China.State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences and University of Chinese Academy of Sciences, The Chinese Academy of Sciences, Beijing 100085, PR China.State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences and University of Chinese Academy of Sciences, The Chinese Academy of Sciences, Beijing 100085, PR China.College of Chemistry and Molecular Sciences, Key Laboratory of Biomedical Polymers of Ministry of Education, Wuhan University, Wuhan, Hubei 430072, PR China.State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences and University of Chinese Academy of Sciences, The Chinese Academy of Sciences, Beijing 100085, PR China. Electronic address: bzhu@rcees.ac.cn.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28062359

Citation

Shao, Bo, et al. "Mechanism of Synergistic DNA Damage Induced By the Hydroquinone Metabolite of Brominated Phenolic Environmental Pollutants and Cu(II): Formation of DNA-Cu Complex and Site-specific Production of Hydroxyl Radicals." Free Radical Biology & Medicine, vol. 104, 2017, pp. 54-63.
Shao B, Mao L, Qu N, et al. Mechanism of synergistic DNA damage induced by the hydroquinone metabolite of brominated phenolic environmental pollutants and Cu(II): Formation of DNA-Cu complex and site-specific production of hydroxyl radicals. Free Radic Biol Med. 2017;104:54-63.
Shao, B., Mao, L., Qu, N., Wang, Y. F., Gao, H. Y., Li, F., Qin, L., Shao, J., Huang, C. H., Xu, D., Xie, L. N., Shen, C., Zhou, X., & Zhu, B. Z. (2017). Mechanism of synergistic DNA damage induced by the hydroquinone metabolite of brominated phenolic environmental pollutants and Cu(II): Formation of DNA-Cu complex and site-specific production of hydroxyl radicals. Free Radical Biology & Medicine, 104, 54-63. https://doi.org/10.1016/j.freeradbiomed.2016.12.050
Shao B, et al. Mechanism of Synergistic DNA Damage Induced By the Hydroquinone Metabolite of Brominated Phenolic Environmental Pollutants and Cu(II): Formation of DNA-Cu Complex and Site-specific Production of Hydroxyl Radicals. Free Radic Biol Med. 2017;104:54-63. PubMed PMID: 28062359.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mechanism of synergistic DNA damage induced by the hydroquinone metabolite of brominated phenolic environmental pollutants and Cu(II): Formation of DNA-Cu complex and site-specific production of hydroxyl radicals. AU - Shao,Bo, AU - Mao,Li, AU - Qu,Na, AU - Wang,Ya-Fen, AU - Gao,Hui-Ying, AU - Li,Feng, AU - Qin,Li, AU - Shao,Jie, AU - Huang,Chun-Hua, AU - Xu,Dan, AU - Xie,Lin-Na, AU - Shen,Chen, AU - Zhou,Xiang, AU - Zhu,Ben-Zhan, Y1 - 2017/01/03/ PY - 2016/07/11/received PY - 2016/12/30/revised PY - 2016/12/31/accepted PY - 2017/1/8/pubmed PY - 2017/12/15/medline PY - 2017/1/8/entrez KW - 2,6-dibromohydroquinone KW - Cu(II) KW - DNA strand breakage 8-oxo-7,8-dihydro-2'-deoxyguanosine formation KW - Hydroxyl radical KW - Site-specific mechanism SP - 54 EP - 63 JF - Free radical biology & medicine JO - Free Radic Biol Med VL - 104 N2 - 2,6-Dibromohydroquinone (2,6-DBrHQ) has been identified as an reactive metabolite of many brominated phenolic environmental pollutants such as tetrabromobisphenol-A (TBBPA), bromoxynil and 2,4,6-tribromophenol, and was also found as one of disinfection byproducts in drinking water. In this study, we found that the combination of 2,6-DBrHQ and Cu(II) together could induce synergistic DNA damage as measured by double strand breakage in plasmid DNA and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) formation, while either of them alone has no effect. 2,6-DBrHQ/Cu(II)-induced DNA damage could be inhibited by the Cu(I)-specific chelating agent bathocuproine disulfonate and catalase, but not by superoxide dismutase, nor by the typical hydroxyl radical (•OH) scavengers such as DMSO and mannitol. Interestingly, we found that Cu(II)/Cu(I) could be combined with DNA to form DNA-Cu(II)/Cu(I) complex by complementary application of low temperature direct ESR, circular dichroism, cyclic voltammetry and oxygen consumption methods; and the highly reactive •OH were produced synergistically by DNA-bound-Cu(I) with H2O2 produced by the redox reactions between 2,6-DBrHQ and Cu(II), which then immediately attack DNA in a site-specific manner as demonstrated by both fluorescent method and by ESR spin-trapping studies. Further DNA sequencing investigations provided more direct evidence that 2,6-DBrHQ/Cu(II) caused preferential cleavage at guanine, thymine and cytosine residues. Based on these data, we proposed that the synergistic DNA damage induced by 2,6-DBrHQ/Cu(II) might be due to the synergistic and site-specific production of •OH near the binding site of copper and DNA. Our findings may have broad biological and environmental implications for future research on the carcinogenic polyhalogenated phenolic compounds. SN - 1873-4596 UR - https://www.unboundmedicine.com/medline/citation/28062359/Mechanism_of_synergistic_DNA_damage_induced_by_the_hydroquinone_metabolite_of_brominated_phenolic_environmental_pollutants_and_Cu_II_:_Formation_of_DNA_Cu_complex_and_site_specific_production_of_hydroxyl_radicals_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0891-5849(16)31152-2 DB - PRIME DP - Unbound Medicine ER -