共平面与非共平面多氯联苯经不同CYP酶代谢活化为致突变物（英文）
作者单位：Department of ToxicologySchool of Public HealthSouthern Medical University
会议名称：《2017环境与公共健康学术会议暨中国环境科学学会环境医学与健康分会、中国毒理学会生化与分子毒理专业委员会2017年年会》
会议日期：2017年
学科分类：100405[医学-卫生毒理学] 1004[医学-公共卫生与预防医学(可授医学、理学学位)] 10[医学]
关 键 词：Cytochrome P450(CYP) Coplanarity Gene mutations Micronuclei Polychlorinated biphenyl
摘 要：Polychlorinated biphenyls(PCBs) are persistent organic pollutants and human carcinogens,currently still released from various human activities including e-waste *** PCBs may activate the aromatic hydrocarbon receptor and thus stimulate various cellular ***-coplanar PCBs,however,are supposed to exert carcinogenic effects after metabolic activation to mutagenic *** recently identified that some non-coplanar PCBs are potent promutagens subsequent to activation by human CYP2E1,as indicated by their induction of micronuclei and gene mutations in Chinese hamster V79-derived cells expressing human CYP2E1 and human hepatocyte(L-02) *** human CYP2E1-mediated mutagenicity of PCBs demonstrated structure-activity relationships featured by selective activation of congeners with one of the chlorine substituents being ortho-positioned(conferring a non-coplanar configuration).Particularly,induction of mutagenic responses to 2,3,4’-(PCB 22) and 2,3,3’-trichlorobiphenyl(PCB 20) in human CYP2E1-expressing V79-derived cells was more potent than that to iV-nitrosodimemylamine,a CYP2El-dependent *** the other hand,these non-coplanar PCBs showed no or weak activities in V79-derived cell lines expressing other CYPs,i.e.,human CYP1A1,1A2,1B1,or ***,PCB 20 and 22 induced micronuclei in L-02 cells,and this effect was blocked by specific CYP2E1 inhibition,wherein the effects of benzo[a]pyrene(activated by CYP1A1) and aflatoxin B(activated by CYP1A2 and CYP3A4) were *** 3,3’4,4’-tetra-(PCB 77)and 3,4,4’,5-tetrachlorobiphenyl(PCB 81) were both inactive in V79-derived cells expressing human CYP2E1;however,in the cell lines expressing human CYP1B1 or 1A2,coplanar PCB 81 and3,3’4,4’,5-pentachlorobiphenyl(PCB 126) induced micronuclei in a concentration-dependent manner,though they were inactive in the Hprt mutagenicity *** summary,our investigations suggest that both coplanar and non-coplanar PCBs are promutag