title: Molecular mechanism of metal-independent decomposition of organic hydroperoxides by halogenated quinoid carcinogens and the potential biological implications.
abstract: Halogenated quinones (XQ) are a class of carcinogenic intermediates and newly identified chlorination disinfection byproducts in drinking water. Organic hydroperoxides (ROOH) can be produced both by free radical reactions and enzymatic oxidation of polyunsaturated fatty acids. ROOH have been shown to decompose to alkoxyl radicals via catalysis by transition metal ions, which may initiate lipid peroxidation or transform further to the reactive aldehydes. However, it is not clear whether XQ react with ROOH in a similar manner to generate alkoxyl radicals metal-independently. By complementary applications of ESR spin-trapping, HPLC/high resolution mass spectrometric and other analytical methods, we found that 2,5-dichloro-1,4-benzoquinone (DCBQ) could significantly enhance the decomposition of a model ROOH tert-butylhydroperoxide, resulting in the formation of t-butoxyl radicals independent of transition metals. On the basis of the above findings, we detected and identified, for the first time, an unprecedented C-centered quinone ketoxy radical. Then, we extended our study to the more physiologically relevant endogenous ROOH 13-hydroperoxy-9,11-octadecadienoic acid and found that DCBQ could also markedly enhance its decomposition to generate the reactive lipid alkyl radicals and the genotoxic 4-hydroxy-2-nonenal (HNE). Similar results were observed with other XQ. In summary, these findings demonstrated that XQ can facilitate ROOH decomposition to produce reactive alkoxyl, quinone ketoxy, lipid alkyl radicals, and genotoxic HNE via a novel metal-independent mechanism, which may explain partly their potential genotoxicity and carcinogenicity.
authors: †State Key Laboratory of Environmental Chemistry and Ecotoxicology Research Center for Eco-Environmental Sciences, CAS, Beijing 100085, China.
authors: Chun-Hua
authors: CH
authors: Huang
authors: †State Key Laboratory of Environmental Chemistry and Ecotoxicology Research Center for Eco-Environmental Sciences, CAS, Beijing 100085, China.
authors: Fu-Rong
authors: FR
authors: Ren
authors: ‡Key Laboratory of Pollution Processes and Environmental Criteria, MOE, Nankai University, Tianjin 300071, China.
authors: Guo-Qiang
authors: GQ
authors: Shan
authors: †State Key Laboratory of Environmental Chemistry and Ecotoxicology Research Center for Eco-Environmental Sciences, CAS, Beijing 100085, China.
authors: Hao
authors: H
authors: Qin
authors: †State Key Laboratory of Environmental Chemistry and Ecotoxicology Research Center for Eco-Environmental Sciences, CAS, Beijing 100085, China.
authors: Li
authors: L
authors: Mao
authors: †State Key Laboratory of Environmental Chemistry and Ecotoxicology Research Center for Eco-Environmental Sciences, CAS, Beijing 100085, China.
authors: Ben-Zhan
authors: BZ
authors: Zhu
mesh_terms: D000447:Aldehydes / Q000737:chemistry; D016227:Benzoquinones / Q000737:chemistry*; D002273:Carcinogens / Q000737:chemistry*; D005609:Free Radicals; D054879:Halogenation; D008041:Linoleic Acids / Q000737:chemistry; D008054:Lipid Peroxides / Q000737:chemistry; D008670:Metals / Q000737:chemistry; D010084:Oxidation-Reduction; D020122:tert-Butylhydroperoxide / Q000737:chemistry*
chemical_list: D000447:Aldehydes; D016227:Benzoquinones; D002273:Carcinogens; D005609:Free Radicals; D008041:Linoleic Acids; D008054:Lipid Peroxides; D008670:Metals; C038649:13-hydroperoxy-9,11-octadecadienoic acid; C004532:quinone; D020122:tert-Butylhydroperoxide; C027576:4-hydroxy-2-nonenal