Chemical Studies on the Screening of Radioprotectors
| Project/Area Number |
62470131
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Radiation science
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| Research Institution | Kyoto University |
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Principal Investigator |
KAGIYA Tsutomu Kyoto University, Hydrocarbon Chemistry, Professor, 工学部, 教授 (00025826)
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| Co-Investigator(Kenkyū-buntansha) |
OHOTANI Bunsho Kyoto University, Hydrocarbon Chemistry, Assistant, 工学部, 助手 (80176924)
NISHIMOTO Sei-ichi Kyoto University, Hydrocarbon Chemistry, Associate Professor, 工学部, 助教授 (10115909)
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| Project Period (FY) |
1987 – 1989
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| Project Status |
Completed (Fiscal Year 1989)
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| Budget Amount *help |
¥6,100,000 (Direct Cost: ¥6,100,000)
Fiscal Year 1989: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1988: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1987: ¥3,300,000 (Direct Cost: ¥3,300,000)
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| Keywords | Radioprotector / DNA / Nnucleic acid base / Radiolytic Hydroxylation / Thiol Derivatives / Liphoamide Derivatives / Pharmacokinetics / 酸素増感比 / トリアゾール環 / 含硫黄化合物 / 培養細胞 / チオアミド / チオール / ヒドロキシル化 / オリゴチミジル酸 / γ線照射 / G値 / 水酸ラジカル |
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| Research Abstract |
Relationship between the activities of radioprotectors in the radiation chemical reaction of DNA and its base components and in the incubated cellular system was investigated in order to develop new types of radioprotectors for clinical and industrial uses. The followings are the summary of results obtained in this research project:
(1) Aqueous thymine solution containing various radioprotectors was gamma-irradiated to determine the G-value of thymine glycol as a characteristic product due to radiolytic hydroxylation of thymine, from which radiation chemical activity of radioprotectors were evaluated.
(2) Influences of alcohols and thiols as additives on the radiolysis of aqueous thymine solution and the thymine glycol formation were investigated to clarify the reactivities of primary active species generated in the radiolysis and the reaction mechanism of radioprotection.
(3) Various kinds of liphoamide derivatives were synthesized to evaluate their radioprotecting activity in the radiation chemical assay system.
(4) The radioprotecting activity of various compounds for EMT6 single cell was correlated to the extent of depression of thymine glycol formation in the radiation chemical reaction system.
(5) Pharmacokinetic behavior of an N_1-substituted 1,2,4-triazole derivative bearing thioamide grope in the side-chain was investigated. This compound was quite stable in plasma to keep constant in its concentration for long period.
In conclusion, we could establish a conventional screening method using radiation chemical and incubated cellular systems. It is further necessary to evaluate the radioprotecting activity of various types of compounds in vivo using animals.
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Report
(4 results)
Research Products
(14 results)
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[Publications] Y. Shibamoto, S. Nishimoto, K. Shimokawa, Y. Hisanaga, L. Zhou, J. Wang, K. Sasai, M. Takahashi, M. Abe, and T. Kagiya: "Characteristics of Fluorinated Nitroazoles as Hypoxic Cell Radiosensitizers." Int. J. Radiat. Oncol. Biol. Phys., 16, 1045 (1989).
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[Publications] K. Sasai, Y. Shibamoto, M. Takahashi, M. Abe, J. Wang, L. Zhou, S. Nishimoto, and T. Kagiya: "A New, Potent 2-Nitroimidazole Nucleoside Hypoxic Cell Radiosensitizer, RP170." Jpn. J. Cancer Res., 80, 1113 (1989).
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