Project/Area Number |
12660288
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Applied veterinary science
|
Research Institution | School of Veterinary Medicine, Rakuno Gakuen University |
Principal Investigator |
HIRAGA Takeo School of Veterinary Medicine, Rakuno Gakuen University, Professor, 獣医学部, 教授 (30112577)
|
Co-Investigator(Kenkyū-buntansha) |
TERAOKA Hiroki School of Veterinary Medicine, Rakuno Gakuen University, Assistant Professor, 獣医学部, 講師 (50222146)
|
Project Period (FY) |
2000 – 2001
|
Project Status |
Completed (Fiscal Year 2001)
|
Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2001: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2000: ¥2,500,000 (Direct Cost: ¥2,500,000)
|
Keywords | endocrine disrupter / developmental toxicity / zebra fish / dioxin / AhR / apoptosis / hypoplasia of jaw / tributyl tin / 脳のアポトーシス / 動物実験モデル / スズ / エストロゲン / 分子生物学 |
Research Abstract |
The effects of 2, 3, 7,8-tetxachbrodibenzovrdbxin (TCDD) and tributyl tin (TBT) exposure on central nervous system, lower jaw development and edema were investigated in early zebrafish (Danio rerio) embryos. The results are summarized as follow : 1.TCDD exposure induced the occurrence of apoptotic cell death during the early stage of development in the dorsal midbrain of zebrafish. Some experiments showed that TCDD induced apoptosis could be related to aryl hydrocarbon receptor (AHR) activation, induction of cytochrome P450 1A (CYP1A) and oxidative stress. Moreover, we determined the complete CDNA sequence of a CYP1A open reading frame with both 5'- and 3'-ends in zebrafish 2.TCDD retarded lower jaw development in a concentration-dependent manner. Initially, TCDD may act directly on the lower jaw development. Reductions in hypobranchial blood flow occurred after the initial retardation in lower jaw development had com apparent, and may contribute further to the effect. From the whole-mount in situ hybridization and immunohistochemical method, sonic hedgehog protein and its receptors are strongly suggested to be involved in a jaw development. 3.TBT exposure induced general edema caused by circulation failure in zebrafish embryos. These results suggest that the zebrafish have many advantages as a useful vertebrate model to detect the toxicity of endocrine disrupters.
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