Polychlorinated biphenyls (PCBs) as a group of persistent organic pollutants are confirmed human carcinogens; however, their mutagenicity remains mostly unknown. We have reported the mutagenicity of some PCBs with one to four chlorines in mammalian cells expressing human CYP2E1. To further explore the structural requirements for the mutagenicity of PCBs, eight tri- and tetrachlorobiphenyls untested before were investigated for the induction of gene mutations and micronuclei in a V79-derived cell line expressing both human CYP2E1 and sulfotransferase (SULT) 1A1 (V79-hCYP2E1-hSULT1A1), with SULT1A1 activity inhibited by pentachlorophenol, a potent SULT1 inhibitor. 2,2',6-Tri-, 2,3',6-tri, 2,4',6-tri-, and 2,2’,5-trichlorobiphenyls (PCBs 19, 27, 32, and 18, respectively) induced micronuclei and gene mutations in V79-hCYP2E1-hSULT1A1 cells, at potencies slightly higher than 2,6-dichlorobiphenyl, but one order of magnitude below that by 2,3,3’- and 2,3,4’-trichlorobiphenyls as reported recently; in the parental V79-Mz cells, they were nonmutagenic and weak in micronuclei induction. Among the four tetrachlorobiphenyls with varying number of ortho chlorines, 2,3,3',4'-tetrachlorobiphenyl (PCB 56) induced both micronuclei and gene mutations in V79-hCYP2E1-hSULT1A1 cells with a potency greater than the above compounds; however, 2,2',3,3'-tetrachlorobiphenyl was equivocal and 2,2',3,6'-tetra- and 2,2',6,6'-tetrachlorobiphenyls inactive in V79-hCYP2E1-hSULT1A1 cells. Immunofluorescent staining of micronuclei formed by PCBs 32 and 56 in V79-hCYP2E1-hSULT1A1 cells with centromere protein B antibodies indicated that they were predominantly whole chromosomes, implying aneugenic potentials. This study suggests that tri- and tetrachlorobiphenyls with a single ortho chlorine can be most mutagenic under activation by human CYP2E1, and greater numbers of ortho chlorines may cause a drastic decline in the activity, especially for tetrachlorobiphenyls.

多氯联苯（PCBs）作为一种持久性有机污染物，已被证实是人类致癌物。然而，它们的致突变性仍然未知。我们已经报道了一些PCB在表达人CYP2E1的哺乳动物细胞中具有1-4个氯的致突变性。为了进一步探讨PCB致突变性的结构要求，研究了之前未经测试的八种三氯联苯和四氯联苯在表达人CYP2E1和磺基转移酶（SULT）1A1（V79-hCYP2E1）的V79衍生细胞系中诱导基因突变和微核-hSULT1A1），其活性被五氯苯酚（一种有效的SULT1抑制剂）抑制。2,2'，6-Tri-，2,3'，6-tri，2,4'，6-tri-和2,2'，5-三氯联苯（分别为PCB 19、27、32和18 ）诱导V79-hCYP2E1-hSULT1A1细胞中的微核和基因突变，效力略高于2,6-二氯联苯，但比最近报道的2,3,3'-和2,3,4'-三氯联苯低一个数量级；在亲代V79-Mz细胞中，它们是非诱变的，并且在微核诱导方面较弱。在四个四氯联苯中，邻氯，2,3,3'，4'-四氯联苯（PCB 56）诱导V79-hCYP2E1-hSULT1A1细胞中的微核和基因突变，其效力高于上述化合物；但是，2,2'，3,3'-四氯联苯是模棱两可的，而2,2'，3,6'-四氯和2,2'，6,6'-四氯联苯在V79-hCYP2E1-hSULT1A1细胞中是无效的。用着丝粒蛋白B抗体对V79-hCYP2E1-hSULT1A1细胞中PCB 32和56形成的微核进行了免疫荧光染色，表明它们主要是完整的染色体，暗示了潜在的造血潜能。这项研究表明，三和与单一tetrachlorobiphenyls邻氯可以通过人的CYP2E1下激活最诱变，和更多数量的邻 氯可能会导致活性急剧下降，尤其是对于四氯联苯而言。