摘要
多氯联苯(polychlorinated biphenyls,PCBs)属于卤代芳香化合物(halogenated aromatic compounds,HACs)或二噁英类化合物(dioxin-like compounds,DLCs)的范畴。DLCs的体内代谢通常由细胞色素P450 (Cytochrome P450,CYP)超家族中1A家族的一些单氧化酶参与,其中CYP1A2特异地存在于肝细胞中,它在外来化学物的肝脏毒性反应中发挥主要作用。CYP1A2可通过影响甲基试卤灵-O-脱甲基酶(methoxyresorufin-O-demethylase,MROD),而选择性地催化7-甲基试卤灵脱甲基反应。故在本试验中,我们采用未成熟SD大鼠肝细胞微粒体为试验材料,引入2,3,7,8-四氯-二苯基-并-二噁英(2,3,7,8-Tetrachlorobenzo-p-dioxin,TCDD),利用MROD荧光光谱分析法,研究了多种PCBs对7-甲基试卤灵脱甲基反应的抑制作用,进而研究了这些PCBs对CYP1A2的竞争性抑制作用。首次发现,TCDD、3,3’,4,4’-四氯联苯(3,3’,4,4’-tetrachlorobiphenyl,统一编号为PCB 77)和3,3’,4,4’,5-五氯联苯(3,3’,4,4’,5-pentachlorobiphenyl,统一编号为PCB 126)对MROD活性的抑制作用最强,由此说明了这些多氯联苯选择性地高度滞留于肝脏的原因。
Polychlorinated biphenyls (PCBs) fall into the category of halogenated aromatic compounds (HACs) or dioxin-like compounds (DLCs) and are highly lipophilic environmental contaminants. Metabolism of DLCs generally involves monooxygenase enzymes of the CYP 1A family in which CYP 1A2 specifically exists in hepatocytes and is mainly responsible for much more toxic reactions of xenobiotics. In this work, we have examined the role of numerous PCBs as inhibitors of the demethylation of 7-methoxyresorufin, a process that is selectively catalyzed by CYP1A2. 2,3,7,8-Tetrachlorobenzo-p-dioxin (TCDD), 3,3?4,4?tetrachlorobiphenyl (PCB 77) and 3,3?4,4?5-pentachlorobiphenyl (PCB 126) were found to be the strongest inhibitors of methoxyresorufin-O-demethylase (MROD) activity, thus accounting for the high ability of hepatic tissue to selectively sequester these compounds.
出处
《中国农学通报》
CSCD
2004年第1期3-6,共4页
Chinese Agricultural Science Bulletin
基金
中国留学基金委(CSC)和加拿大自然科学工程研究委员会(NSERC)及毒物研究创新基金(TSRI)资助。