| Project/Area Number |
13557214
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Environmental pharmacy
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| Research Institution | HOKKAIDO UNIVERSITY |
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Principal Investigator |
KAMATAKI Tetsuya (2002) HOKKAIDO Univ., Grad. School of Pharmaceu. Sci., Prof, 大学院・薬学研究科, 教授 (00009177)
藤田 健一 (2001) 北海道大学, 大学院・薬学研究科, 助手 (60281820)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAZAKI Hiroshi HOKKAIDO Univ., Grad. School of Pharmaceu. Sci., Asso. Prof., 大学院・薬学研究科, 助教授 (30191274)
鎌滝 哲也 北海道大学, 大学院・薬学研究科, 教授 (00009177)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2001: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | P450 / COX / fetal toxicity / thalidomide / transgenic mice / humanized mice / animal model / teratogenicity / プロスタグランジンG / H合成酵素 / アフラトキシンB_1 / フェニトイン / チトクロームP450 |
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| Research Abstract |
Most of the human fetal toxicities of xenobiotics are unpredictable, since drug metabolizing enzymes such as cytochrome P450 (CYP), which are present in human fetuses, do not exist in rodent fetuses. In order to establish and animal model to predict human fetal toxicities, we introduced multiple forms of human fetal drug metabolizing enzymes into mice by transgenic technique. Four transgenic lines of mice carrying human fetal enzymes were established. In the 36p line of mice, the expression of human CYP1A1, CYP1B1, CYP3A7, cyclooxygenase (COX)-1 and COX-2 at mRNA levels were detected in the mouse fetuses. Treatment of the 36p female mice with a single dose of thalidomide (100 mg/kg b wt.), a well-known teratogen in humans, on gestational day 9 resulted in the increased deaths or the resorptions of embryos. Thus, these humanized mice may become a suitable model to predict human fetal toxicities of chemicals.
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