| Project/Area Number |
62570994
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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 | University of Shizuoka |
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Principal Investigator |
IWAMOTO Yoshihisa School of Pharmaceutical Science, University of Shizuoka, 薬学部, 講師 (60046290)
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| Project Period (FY) |
1987 – 1988
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| Project Status |
Completed (Fiscal Year 1988)
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| Budget Amount *help |
¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1988: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1987: ¥800,000 (Direct Cost: ¥800,000)
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| Keywords | Photodynamic therapy / Photosensitizer / Yeast cell inactivation / Mitochondrial mutation / Plasmid DNA / Single strand break / DNA一本鎖切断 / 光溶血活性 / プラスミドYRp7 / 変異誘発 / 一本鎖切断 / 一重項酸素 / 活性酸素消去剤 / アクリジン色素 / 酵母 / 細胞致死作用 |
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| Research Abstract |
In order to develop useful photosensitizers effective on photodynamic therapy several investigations were performed ; 1) How convenient and effective screening system for photosensitizers can be established? 2) What cell components each photosensitizer interact to? 3) What biological damages are induced after photoirradiation? 4) What photosensitizing mechanisms might be involved?
Variety of biological damages were induced by photodynamic action of drugs. Photodynamic treatment of Acriflavine (AF) induced "Cell Inactivation", "Mitochondrial Mutations" such as petite induction and "Nuclear Mutation" such as reversion from Trp- to Trp+ in yeast, Saccharomyces cerevisiae. "Single Strand Breaks(SSB)" of nuclear DNA in yeast, chromosomal DNA and plasmid (YRp7) DNA were also induced by AF-photosensitization. Hematoporphyrin, ketoprofen and afloqualone showed photohemolytic activities of HRBC. Correlation between the photohemolytic activities and lipid peroxidation was observed.
Many photosensitizers induced both the cell inactivation of yeast and the induction of SSB of plasmid DNA. The latter experimental system suuggested to work useful screening system for photosensitizers. SSBs by the photodynamic action of euflavine were remarkably inhibited by NaN_3 ( a singlet oxygen scavenger) but not by catalase (H_2O_2 scavenger). SSB by chlortetracycline were inhibited by D-mannitol (hydroxyl radical scavenger) and catalase but not by superoxide dismutase (SOD)(superoxide anion scavenger). Those by protoporphyrin were extensively inhibited by NaN_3, catalase, D-mannitol and SOD, respectively. These results suggested different active oxygen(s) might be involved in the photosensitization by different drugs.
It must be fruitful to search potent photosensitizers and to clarify what kind of active oxygen(s) may be involved in each drug-photosensitization using established screening system for the development of effective photosensitizer.
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