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1994 Fiscal Year Final Research Report Summary

Study of Photosensitizers for Effective Photodynamic Theraphy of Cancer

Research Project

Project/Area Number 04555193
Research Category

Grant-in-Aid for Developmental Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field 工業物理化学・複合材料
Research InstitutionThe University of Tokyo

Principal Investigator

KOMIYAMA Makoto  Faculty of Engineering, University of Tokyo : Profess, 工学部, 教授 (50133096)

Co-Investigator(Kenkyū-buntansha) NAKAZATO Masataka  SLT JAPAN Co.Ltd : Main-researcher, 技術課, 主任研究員
DAIKUZONO Norio  SLT JAPAN Co.Ltd : Director, 開発部門, 研究担当取締役
KOBAYASHI Masami  Faculty of Engineering, University of Tokyo : Assist, 工学部, 助手 (70234846)
Project Period (FY) 1992 – 1994
KeywordsPDT for Concer / Photosensitizer / Chlorophll / Porphyrin / Nucleic Acid / DNA / RNA / PDT
Research Abstract

Plasmid DNA has been efficiently photocleaved by pheophorbides (Phdes) a and b. Irrespective of the presence of oxygen, Phde b has photocleaved DNA more effectively than phde a.
Photocleavage efficiency of Phde b in the presence of oxygen is higher than in the absence of oxygen. In contrast, the efficiency of Phde a in the presence of oxygen is lower than in the absence of oxygen.
The quantum yields of singlet oxygen (^1O_2) production are obtained by using a very reactive ^1O_2 acceptor, tetramethylene or furluryl alcohol. Singlet oxygen production sensitized by Phdes a or b can not be observed in the aqueous media (Tris-HC1/EDTA butter, pH7.4-7.9 or phosphate butter, pH7.4). Thus, the increase of photocleavege by Phde b in the presence of oxygen is not due to the formation of singlet oxygen. In organic solvents, however, Phde a shows the high quantum yields for ^1O_2 production : 0.61 in methanol and 0.85 in toluene.
Fluorescence microscopic observation has shown a rapid incorporation of pheophorbide a into nuclei, mitochondria and lysosome of human oral mucosa cells. A long time irradiation produces a color change of folrescence from red to orange, indicating that some photochemical reactions take place in the above orangelle.
Uptake of Phde a by tumor cells is also observed, although it is not clear where Phde a is located in the cells.
These results suggest that Phde a is likely to scissors DNA,probably in mitochondria, in photodynamic therapy, and higher therapeutic effect can be expected by use of Phde b in place of Phde a.

  • Research Products

    (8 results)

All Other

All Publications (8 results)

  • [Publications] Masami Kobayashi: "Oxygen-independent photocleavage 0f DNA, and uptake of chlorophyll derivatives by cellular nuclei and mitochondria" J.Clinic.Med.Surg.12. 133-138 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Charles Tanielian: "Pheophorbides as photosensitizors for the photodynamic theraphy" SPIE. 2325. 416-424 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Masami Kobayashi: "Photocleavage of DNA by chlorophyll-derivatives and porphyrin-derivatives" Photomed.Photobiol.(印刷中). (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Motoki Watanabe: "Introduction of fluorescein-labeledoligonucleotides into cultured human keratinocytes and detection of their attinity sites in the all" Photomed.Photobiol.(印刷中). (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Masami Kobayashi: "Oxygen-idependent photocleavage of DNA,and uptake of chlorophyll derivatives by cellular nuclei and mitochondria" J.Clinic.Med.Surg.12. 133-138 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Charles Tanielian: "Pheophorbides as phosensitizers for the photodynamic theraphy" SPIE. 2325. 416-424 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Masami Kobayashi: "Photocleavage of DNA by chlorophll-derivatives and porphyrin-derivatives" Photomed.Photobiol.in press. (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Motoki Watanabe: "Introduction of fluorescein-labeled oligonucleotides into cultured human keratinocytes and detection of their affinity sites in the cells" Photomed.Photobiol.in press. (1995)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1996-04-15  

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