| Project/Area Number |
14104020
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| Research Category |
Grant-in-Aid for Scientific Research (S)
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| Allocation Type | Single-year Grants |
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| Research Field |
環境影響評価(含放射線生物学)
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| Research Institution | The University of Tokyo |
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Principal Investigator |
YOSHIKAWA Yasuhiro The University of Tokyo, Graduate School of Agricultural and Life Sciences, Professor, 大学院農学生命科学研究科, 教授 (80109975)
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| Co-Investigator(Kenkyū-buntansha) |
KYUWA Shigeru The University of Tokyo, Graduate School of Agricultural and Life Sciences, Associate Professor, 大学院農学生命科学研究科, 助教授 (30177943)
NAKAYAMA Hiroyuki The University of Tokyo, Graduate School of Agricultural and Life Sciences, Professor, 大学院農学生命科学研究科, 教授 (40155891)
TSUBONE Hirokazu The University of Tokyo, Graduate School of Agricultural and Life Sciences, Professor, 大学院農学生命科学研究科, 教授 (30142095)
NISHIHARA Msugi The University of Tokyo, Graduate School of Agricultural and Life Sciences, Professor, 大学院農学生命科学研究科, 教授 (90145673)
TERAO Keiji National Institute of Infectious Diseases, Tsukuba Primate Center, Direcor, 筑波霊長類センター, センター長 (30109920)
土井 邦雄 東京大学, 大学院農学生命科学研究科, 教授 (70155612)
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| Project Period (FY) |
2002 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥113,620,000 (Direct Cost: ¥87,400,000、Indirect Cost: ¥26,220,000)
Fiscal Year 2006: ¥14,560,000 (Direct Cost: ¥11,200,000、Indirect Cost: ¥3,360,000)
Fiscal Year 2005: ¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000)
Fiscal Year 2004: ¥24,570,000 (Direct Cost: ¥18,900,000、Indirect Cost: ¥5,670,000)
Fiscal Year 2003: ¥26,780,000 (Direct Cost: ¥20,600,000、Indirect Cost: ¥6,180,000)
Fiscal Year 2002: ¥29,770,000 (Direct Cost: ¥22,900,000、Indirect Cost: ¥6,870,000)
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| Keywords | endocrine disrupting chemicals / neural development / behavioral assessment / rat / cynomolgus monkey / thyroid hormone / PCB / Bisphenol A / 内分泌撹乱化学物質 / 胎盤移行 / ダイオキシン / TCDD / 妊娠 / サル類ES細胞 / 神経細胞 / 行動 |
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| Research Abstract |
Purpose : Study of endocrine disrupting chemicals (EDCs) on neural development in higher animals is new research field. There are few reports on effect of EDCs on neural systems at the level of certain gene or animals. In this study, rat, monkey and chimpanzees were used for risk assessment of EDCs on nueral development to extrapolate for humans. Fetuses of rat, monkey, and primary neural cultures of primate and rodents, and ES cells were used as models for human risk assessments. Veterinary researchers being good at whole body animals are collaborate each other to get an answer whether adverse effect of EDCs on neural developments in higher animal species.
Research results : Using rat as a model, effects of estrogen like EDCs, such as BPA, NP or thyroid hormone like EDCs such as PCB and positive control drugs i.e., amiodarone, thiamasole, PTU on neural development of rat fetuses were validated by administrating the materials to the pregnant mothers. Nurobehavioral tests were conducted
… More
and the results suggested that estrogen like EDCs induced nervous offspring and thyroid hormone disturbing drugs induced ADHD like behaviors. These results were published in the international journals.
Non human primate fetuses were also used for comparison of the difference of rodents and primate including human being. The results suggested that 1) rodent fetus are born with immature neural development but primate fetus are born with matured neural development at birth stage. 2) Metabolism and exclusion of EDCs such as BPA and thyroid hormone are completely different between rodents and primates. 3) During the stage of pregnancy, ratio of the maternal transfer of BPA to fetus is different and the fetus uptake ratio especially in the CNS was rapidly increased in the later stage of pregnancy. These results suggested that simple extrapolation of rat data to human is relatively risky.
Using monkey fetus as a model, TCDD administration to the pregnant mother induced abnormal social behaviors in offspring but these abnormalities were diminished during the development of the infants. On the contrary, BPA exposure of the pregnant mothers resulted in sever sex-identification disorders to only male offspring and its abnormality is continued after developmental stages of the infants. Preliminary studies on offspring delivered from high dose PCB exposed mothers showed relatively retardation to the high cognitive tests (four step finger maze tests) and thyroid hormone blocker (thiamasole) treatments resulted in poor development of the CNS in the monkey fetuses.
All these new results were obtained by this projects and it is important clearing mechanism and threshold of EDCs on development of the primate neural systems. The next objectives are how we can find maker proteins of these abnormalities for early diagnosis and how we may be able to avoid the risk and find suitable treatment of the suffering children. Less
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