| Project/Area Number |
59440087
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| Research Category |
Grant-in-Aid for General Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
応用薬理学・医療系薬学
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| Research Institution | Chiba University |
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Principal Investigator |
KITAGAWA Haruo Fac. of Pharmaceut. Sci., Chiba Univ., Professor, 薬学部, 教授 (60009157)
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| Co-Investigator(Kenkyū-buntansha) |
OHMORI Shigeru Fac. of Pharmaceut. Sci., Chiba Univ., Research Assistant, 薬学部, 教務職員 (70169069)
IGARASHI Takashi Fac. of Pharmaceut. Sci., Chiba Univ., Assistant, 薬学部, 助手 (60104692)
UENO Koichi Fac. of Pharmaceut. Sci., Chiba Univ., Lecturer, 薬学部, 講師 (60125903)
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| Project Period (FY) |
1984 – 1986
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| Project Status |
Completed (Fiscal Year 1986)
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| Budget Amount *help |
¥26,000,000 (Direct Cost: ¥26,000,000)
Fiscal Year 1986: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1985: ¥6,500,000 (Direct Cost: ¥6,500,000)
Fiscal Year 1984: ¥18,000,000 (Direct Cost: ¥18,000,000)
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| Keywords | Whole embryo culture / Chemicals / Developmental toxicity / Teratogenicity / Drug metabolism / Experimantal animals / P-450 / GST / Isozyme / サル / 種差 / 性差 / P-450 / グルタチオンS-トランスフェラーゼ / アイソザイム / 8-GTP / 代替法 / 胎仔培養 / invitro毒科学 |
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| Research Abstract |
To investigate clearly the mechanism of developmental toxicity induced by chemical substances, the whole embryo culture system using day 10.5 to 12.5 rat embryos of gestation was confirmed. Aspirin, salicylic acid and aminopyrine produced malformations in cultured rat embryos at day 11.5 of gestation. Caffeine caused malformation in cultured 12.5 day old rat embryo. Similar effect of caffeine was observed with 11.5 day old embryos, but in lower quantity. The embryotoxicity of cyclophosphamide and DMSO were evaluated in cultured 10.5 day old rat embryos. The whole embryo culture system was utilized in order to avoid potentially confounding meternal factors. Phenobarbital pretreated rat lever S-9 fraction singificantly increased the embryotoxicity and malformations of aminopyrine. And then teratological potency of 4-aminoantipyrine or 4-acetoamidoantipyrine was less than that of aminopyrine on cultured rat embryos. These results suggest that intrinsic teratogenicity, true active compound, of aminopyrine would be 3-position hydroxy metabolites rather than aminopyrine itself or 4-position N-demethyl metabolites. The increase of gamma-glutamyltranspeptidase activity in rat liver during perinatal period was observed in agreement with the elevation of cysteine consunption in fetus and the reduction of conversion from methionine to cysteine in this period. Sex and species differences of hepatic glutathione S-transferase and cytochrome P-450 in experimantal animals including monkey were investigated.
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