Studies on the Effects of Carcinogenic Synthetic Estrogens on Microtubules
| Project/Area Number |
61571064
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Biological pharmacy
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| Research Institution | Kyoritsu College of Pharmacy |
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Principal Investigator |
SATO Yoshihiro Kyoritsu College of Pharmacy, 薬学部生化学教室, 教授 (20050726)
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| Co-Investigator(Kenkyū-buntansha) |
榊原 由美子 共立薬科大学, 薬学部生化学教室, 助手
ODA Taiko Kyoritsu College of Pharmacy, 薬学部生化学教室, 講師 (20050750)
SAKAKIBARA Yumiko Kyoritsu College of Pharmacy
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| Project Period (FY) |
1986 – 1988
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| Project Status |
Completed (Fiscal Year 1988)
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| Budget Amount *help |
¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1988: ¥100,000 (Direct Cost: ¥100,000)
Fiscal Year 1987: ¥200,000 (Direct Cost: ¥200,000)
Fiscal Year 1986: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | Synthetic estrogen / diethylstilbestrol / microtubules / PC-tubulin / microtubule proteins / turbidity measurement / electron microscopy / meso-Hexestrol / S-tubulin / trans-DES-epoxide / 4-Hydroxy-meso-hexestral |
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| Research Abstract |
A synthetic estrogen, diethylstilbestrol(DES), is not only chinically effective in chemotherapy but also carcinogenic in humans. We have proved that DES is active to inhibit in vitro microtubule polymerization. Microtubules are the cytoskelton in eucaryotes and also the important component of spindles. Consequently, vincristine, the compound which disrupts microtubules, is known as an anticarcinogenic agent. Present investigation was performed to clarify the mechanism of DES carcinognenesis using des derivatives by analyzing their effects on microtubule assembly and Chinese hamster V79 cells.
DES and meso-hexestrol were starting meterials for the synthesis of DES derivatives. From microtubule proteins of porcine brains, PC-tubulin, S-tubulin, MAP2 and tau were obtained. The effects of the synthetic estrogens on reconstituted systems were analyzed by turbidity mesurement and electron microscopy. The results indicated that meso-hexestrol and E,E-dienestrol have activities to induce ribbon structures from microtubule proteins. The stereoisomers, dl-, (+)- and (-)-hexestrols showed some differences in their activity. Further, effects on plating efficiency and chromosomes of Chinese hamster V79 cells were examined by some DES derivatives, demonstrating the structure-activity relationship.
Recently, it was indicated that peroxidative metabolism of DES might be the bases of DES induced cell transformation. Our present investigation would make an another important breakthough to solve DES carcinogenesis.
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Report
(3 results)
Research Products
(12 results)
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[Publications] Sakakibara, Y.; Hasegawa, K.; Oda, T.; Saito, H.; Kodama, M.; Hirata, A.; Matsuhashi, M.; Sato, Y.: "Effects of Synthetic Estrogens, (+)-, (-)-, dl- and meso-Hexestrol Stereoisomers on Microtubule Assembly" Biochem. Pharmacol.Submitted.
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「研究成果報告書概要(欧文)」より
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