title: New evidence for toxicity of polybrominated diphenyl ethers: DNA adduct formation from quinone metabolites.
abstract: This study investigated the formation of DNA adducts of polybrominated diphenyl ethers (PBDEs) and the possible mechanisms. DNA adduction was conducted by in vitro reaction of deoxyguanosine (dG) and DNA with PBDE-quinone (PBDE-Q) metabolites, and DNA adducts were characterized by using electrospray ionization tandem mass spectrometry. The results suggested DNA adduction involved Michael Addition between the exocyclic NH(2) group at the N-2 position of dG and the electron-deficient carbon of quinone, followed by reductive cyclization with loss of (bromo-)1-hydroperoxy-benzene or water to form a type I or type II adduct. PBDE-Q with substituted bromine on the quinone ring was proven to be a favorable structure to form a type I adduct, while the absence of bromine on the quinone ring resulted in a type II adduct. Lower reactivity of adduction was also observed with increasing the number of bromine atoms on the phenoxyl ring. Our data clearly demonstrated PBDEs could covalently bind to DNA mediated by quinone metabolites, depending on the degree of bromine substitution. This study opened a new view on the mechanism of toxicity of PBDEs and reported the structure of PBDE-DNA adducts, which might be valuable for the evaluation on potential in vivo formation of PBDE-DNA adducts.
authors: Department of Chemistry, Hong Kong Baptist University, 224 Waterloo Road, Kowloon Tong, Hong Kong SAR, China.
authors: Yongquan
authors: Y
authors: Lai
authors: Minghua
authors: M
authors: Lu
authors: Xiang
authors: X
authors: Gao
authors: Hanzhi
authors: H
authors: Wu
authors: Zongwei
authors: Z
authors: Cai
mesh_terms: D016227:Benzoquinones / Q000378:metabolism* / Q000633:toxicity; D018736:DNA Adducts; D004785:Environmental Pollutants / Q000633:toxicity*; D005411:Flame Retardants / Q000378:metabolism / Q000633:toxicity; D055768:Halogenated Diphenyl Ethers / Q000633:toxicity*; D018570:Risk Assessment; D021241:Spectrometry, Mass, Electrospray Ionization; D018675:Toxicity Tests
chemical_list: D016227:Benzoquinones; D018736:DNA Adducts; D004785:Environmental Pollutants; D005411:Flame Retardants; D055768:Halogenated Diphenyl Ethers; C004532:quinone