| Project/Area Number |
14570303
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hygiene
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| Research Institution | Yokohama City University |
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Principal Investigator |
OKABE Toshiko Yokohama City University, School of Medicine, Associate Professor, 医学部, 助教授 (20152564)
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| Co-Investigator(Kenkyū-buntansha) |
KASHIMA Yuji Yokohama City University, School of Medicine, Assistant Professor, 医学部, 助手 (50233705)
SAKAI Haruya Yokohama City University, School of Medicine, Assistant Professor, 医学部, 助手 (20303555)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2004: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2003: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2002: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | thyroid hormone / thyroid hormone receptor / organohalogen compounds / endocrine disrupters / reporter assay / estrogen receptor / thyroid hormone response element / 有機ハロゲン態ハロゲン化合物 / 環境汚染物質 / DNAマイクロアレー / 農薬 / 臭素化難燃剤 / 4-1BB / 内分泌攪乱物質 / 難燃剤 |
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| Research Abstract |
It had been reported that reproductive and immune systems were affected in wildlife containing high concentrations of dioxins and/or polychlorinated biphenyls (PCBs). Recently the organohalogen compounds which have structural similarities with thyroid hormone have been used widely as flame retardants and some of them are detected in environmental samples. From these facts, it has been suspected that these organohalogen compounds may affect on wildlife as well as human beings as environmental contaminants. In this work, we constructed the bioassay system using transcriptional activation by thyroid hormone receptor as biomarkers. First, we established human cell line in which thyroid hormone receptor α gene was stable transfected and designated HeLaTR cells. Then DR4-SV-Luc plasmid in which thyroid hormone response element (DR4) was inserted upstream of luciferase gene was transfected into HeLaTR cells transiently in the presence or absence of T3. Luciferase activities were determined us
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ing cell lysate and it was found that T3 increased luciferase activity four to five fold. After addition of various organohalogen compounds such as environmental contaminants to this bioassay system, luciferase activities in each cell lysates were determined to evaluate the effects on thyroid hormone system by organohalogen compounds. One hydroxylated PCB, which was the metabolite of PCB turned to reduce the luciferase activity which was induced by T3 in HeLaTR cells. In contrast, dioxin, hexacyclododecane which is used for flame retardant, and nitrofen which had been used for pesticide augmented the luciferase activities induced by T3. Diiodobiphenyl (DIB) which is used for photoconductor of cellular phone could induce luciferase activity and augment the T3 action. Furthermore, DIB could augment the transcriptional activation by estrogen receptor through estrogen response element. We also determined the gene expression profile after addition of T3 into HeLaTR cells by DNA microarray, and showed that apoptosis signal through 4-1BB was activated after addition of T3. Less
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