期刊
TOXICOLOGY IN VITRO
卷 23, 期 4, 页码 736-743出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.tiv.2009.03.004
关键词
Aryl hydrocarbon receptor; Polychlorinated biphenyls; Hydroxylated PCB; Recombinant yeast assay; beta-Naphthoflavone; 3 ',4,5 '-Trichlorobiphenyl-2-ol (2 '-OH-CB39); 3 ',4,4 '-Trichlorobiphenyl-3-ol (3 '-OH-CB37)
类别
The toxicities of polychlorinated biphenyls (PCBs) are thought to be mediated mainly by the aryl hydrocarbon receptor (AhR). However, little is known about changes to AhR-mediated effects caused by metabolic conversion of PCBs. To investigate whether hydroxylation affects the affinity of PCBs for the AhR, we measured the AhR agonistic activity of mono-hydroxylated PCBs (mono-OH-PCBs) and their non-hydroxylated analogs (PCBs) using yeast cells transduced with the human AhR and its response pathway. Fifty-two of 84 tested OH-PCBs and 12 of 24 PCBs exhibited AhR agonistic effects. Of 49 OH-PCBs that had the same chlorination patterns as the tested PCBs, 26 had activities that were more than twice those of their analogous PCBs, or became activated if their non-hydroxylated analogs were inactive. In particular, 31,4,5'-trichlorobiphenyl-2-ol and 3',4,4'-trichlorobiphenyl-3-ol were 37- and 22-fold more potent than their non-hydroxylated analogs and were 1.42 times and 1.08 times, respectively, as active as a standard, beta-naphthoflavone. The activities of only 5 OH-PCBs were reduced to less than half those of their non-hydroxylated counterparts. No tested PCBs were inactivated by the presence of a hydroxyl group. These findings underscore the need to rethink the toxicological evaluation of hydroxylated metabolites of PCBs and their abundance in the environment. (C) 2009 Elsevier Ltd. All rights reserved.
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