Modulation at a cellular level of the thyroid hormone receptor-mediated gene expression by 1,2,5,6,9,10-hexabromocyclododecane (HBCD), 4,4'-diiodobiphenyl (DIB), and nitrofen (NIP).
Previously, we demonstrated that some endocrine disrupting chemicals affected thyroid hormone receptor (TR)-mediated gene expression in HeLaTR cells that stably expressed the human TRalpha1. To examine whether widely used brominated flame retardants and pesticides affect TR-mediated gene expression, those with organohalogen, which is also present in T3, were screened. To monitor the TR-mediated gene expression, HeLaTR cells were transfected with a luciferase gene that was linked to the thyroid hormone responsive element. Thus, transcription of the luciferase gene in HeLaTR cells is driven by TR. By screening 38 chemical agents, it was found that 4,4'-diiodobiphenyl (DIB), markedly, and 1,2,5,6,9,10-hexabromocyclododecane (HBCD) and nitrofen (NIP), to a much lesser extent but significantly, enhanced the expression of the luciferase gene at concentrations that did not affect the growth of HeLaTR cells. DIB also augmented the E2-induced expression of the luciferase gene that was linked to the estrogen responsive element in MCF7 cells, whereas HBCD and NIP did not. These results indicate that DIB augments TR- and ER-mediated gene expression, but HBCD and NIP affect only TR-mediated gene expression. Thus, there is a potential risk that HBCD, DIB, and NIP act as endocrine disrupters in animals and human beings.
Yamada-Okabe
Toshiko
T
Department of Hygiene, School of Medicine, Yokohama City University, 3-9, Fukuura, Kanazawa, Yokohama 236-0004, Japan.
Sakai
Haruya
H
Kashima
Yuji
Y
Yamada-Okabe
Hisafumi
H
D001713:Biphenyl Compounds / Q000633:toxicity*; D049109:Cell Proliferation / Q000187:drug effects; D005411:Flame Retardants / Q000633:toxicity*; D005786:Gene Expression Regulation / Q000187:drug effects; D017930:Genes, Reporter / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D006842:Hydrocarbons, Brominated / Q000633:toxicity*; D008156:Luciferases / Q000235:genetics; D010575:Pesticides / Q000633:toxicity*; D010647:Phenyl Ethers / Q000633:toxicity*; D010957:Plasmids / Q000235:genetics; D011960:Receptors, Estrogen / Q000096:biosynthesis / Q000187:drug effects; D011988:Receptors, Thyroid Hormone / Q000187:drug effects; D014162:Transfection; D014284:Triiodothyronine / Q000494:pharmacology
D001713:Biphenyl Compounds; D005411:Flame Retardants; D006842:Hydrocarbons, Brominated; D010575:Pesticides; D010647:Phenyl Ethers; D011960:Receptors, Estrogen; D011988:Receptors, Thyroid Hormone; D014284:Triiodothyronine; C065775:4,4'-diiodobiphenyl; C089796:hexabromocyclododecane; D008156:Luciferases; C007350:nitrofen