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1989 Fiscal Year Final Research Report Summary

Development research of new radiosensitizing agents utilizing melanin-affinity compounds

Research Project

Project/Area Number 63870107
Research Category

Grant-in-Aid for Developmental Scientific Research.

Allocation TypeSingle-year Grants
Research Field 応用薬理学・医療系薬学
Research InstitutionTokyo Medical and Dental University

Principal Investigator

KASUGA Tsutomu  Tokyo Med. Den. Univ., Sch. Med., Professor, 医学部, 教授 (40114748)

Co-Investigator(Kenkyū-buntansha) SUZUKI Soji  Tokyo Med. Den. Univ., Sch. Med., Professor, 医学部, 教授 (80013829)
KITAGAWA Masanobu  Tokyo Med. Den. Univ., Sch. Med., Assistant, 医学部, 助手 (10177834)
YAMADA Ichiro  Tokyo Med. Den. Univ., Sch. Med., Assistant, 医学部, 助手 (90182518)
ITO Shosuke  Fujita-Gakuen Univ., Sch. Hyg., Professor, 衛生学部, 教授 (70121431)
Project Period (FY) 1988 – 1989
KeywordsMalignant melanoma / Melanin precursor / 4-S-cysteaminylphenol / Radiosensitivity / Radiosensitization
Research Abstract

A. The combination effect of 4-S-cysteasinylphenol (4-S-CAP) and radiation was examined. 4-S-CAP decreased the shoulder width of the survival curve of HMV-I melanoma cells. However, the same treatment with 4-S-CAP did not significantly affect the radiation sensitivity of HeLa S3 cells. Many investigators have demonstrated that the large shoulder in the survival curve of melanoma cells may be related to the poor radiation response that has been clinically observed in human melanoma. Thus, 4-S-CAP may be an effective means of overcoming the large shoulder in melanoma cells. 4-S-CAP inhibited the sublethal damage repair in melanoma cells in the split-dose experiment. Further, 4-S-CAP inhibited the potentially lethal damage (PLD) repair in melanoma cells during their plateau phase.
B. The LD^<50> value of 4-S-CAP was 467<plus-minus>32 mg/kg in C57BL/6J male mice (12-16 weeks age). The ip injection of 4-S-CAP (300 mg/kg) for 5 days showed a significant effect on the tumor growth inhibition a … More nd survival interval elongation in B16 melanoma-bearing mice. The combination experiment of 4-S-CAP (300 ig/kg) and radiation (5 Gy) showed no significant potentiating effect of 4- S-CAP on the radiation action in the growth inhibition of B16 melanoma. The lung colony formation experiment showed that 4-S-CAP decreased the colony formation rate significantly, as compared to the untreated controls.
C. We synthesized four new analogues of 4-S-CAP, i.e., N-acetyl-4S-CAP (N-Ac- 4-S-CAP), 4-S-homocysteaminylphenol (4-S-HomoCAP), alpha-methyl-4-S-cysteaminyl- phenol (alpha-Me-4-S-CAP), and N,N-dimethyl-4-S-cysteaminylphenol (N,N-DiMe-4-S- CAP). The depigmenting effect for the hair follicle melanocytes in mice was the most prominent in N-Ac-4-S-CAP (98%), followed by alpha-Me-4-S-CAP (89%) and 4-S-CAP (87%). The effect on the inhibition of the lung colony formation was about 70% in 4-S-CAP and N-Ac-4-S-CAP, respectively. These data suggest that N-Ac-4-S-CAP may be a new antitumor agent in the management of melanomas. Less

  • Research Products

    (30 results)

All Other

All Publications (30 results)

  • [Publications] Yamada,Ichiro: "The cytotoxicity of cysteinylcatechols and related compounds to human melanoma cells in vitro" J.Invest.Dermatol.88. 538-540 (1987)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yamada,Ichiro: "The killing effects of 4-S-cysteinylcatechol and analogues on human melanoma cells" Br.J.Cancer. 58. 776-778 (1988)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yamada,Ichiro: "The effect of L-dopa on the potentiation of radiation damage to human melanoma cells" Br.J.Cancer. (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yamada,Ichiro: "The potentiation of radiation damage by 4-S-cysteaminylphenol,a new melanin precursor,in human melanoma cells" Int.J.Radiat.Biol. (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nakamura,Takuro: "Histologic localization of 4-S-cysteinylphenol in melanoma-bearing mice" Bulletin of Tokyo Madical and Dental University. 34. 93-98 (1987)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nakamura,Takuro: "Specific incorporation of 4-S-cysteaminylphenol into human melanoma cells" J.Invest.Dermatol.90. 725-728 (1988)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nakamura,Takuro: "Transplacental induction of peripheral nervous tumor in the Syrian gold hamster by N-nitroso-N-ethylurea.A new animal model for von Recklinghausen's neurofibromatosis." Amer.J.Pathol.135. 251-259 (1989)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ito,Shosuke: "Mechanism of selective toxicity of 4-S-cysteinylphenol and 4-S-cysteaminylphenol to melanocytes" Biochem.Pharmacol.36. 2007-2011 (1987)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yamada,Kiyoshi: "Selective cytotoxicity of a phenolic melanin precursor,4-S-cysteaminylphenol,on in vitro melanoma cells" Biochem.Pharmacol.38. 2217-2221 (1989)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Pankovich,Jim: "Is melanocytotoxicity of 4-S-cysteaminylphenol related to tyrosinase or monoamine oxidase?" J.Invest.Dermatol.92. 496 (1989)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Inoue,Shigeki: "Mechanism of growth inhibition of melanoma cells by 4-Sーcysteaminylphenol and its analogues" Biochem.Pharmacol. (1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Alena,Frank: "Melanocytotoxicity and antimelanoma effects of phenolic amine compounds in mice in vivo" Canaer Res.(1990)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 山田一郎: "ヒト悪性黒色腫細胞に対する4-S-cysteaminylphenol,ヒトインタ-フェロンーβ及び放射線の併用による制癌効果の検討" 第47回日本癌学会総会記事. 47. 543 (1988)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 山田一郎: "新しいメラミン前駆物質4-S-cysteaminylphenolのB16メラノ-マ・細胞に対する制癌効果ーメラノ-マ特異的抗癌剤の開発研究" 第48回日本癌学会総会記事. 48. 344 (1989)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 北川昌伸: "マウスB16メラノ-マに対する4-S-cysteaminylphenolの制がん作用の検討" 第48回日本癌学会総会記事. 48. 378 (1989)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yamada, I., et al: "The cytotoxicity of cysteinylcatechols and related compounds to human melanoma cells in vitro" J. Invest. Dermatol.88. 538-540 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yamada, I. et al: "The killing effects of 4-S-cysteinylcatechol and analogues on human melanoma cells." Br. J. Cancer. 58. 776-778 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yamada, I., et al: "The effect of L-dopa on the potentiation of radiation damage to human melanoma cells." Br. J. Cancer. (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yamada, I., et al: "The potentiation of radiation damage by 4-S-cysteaminylphenol, a new melanin precursor, in human melanoma cells." Int. J. Radiat. Biol. (1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakamura, T., et al: "Histologic localization of 4-S-cysteinylphenol in melanomabearing mice." Bulletin of Tokyo Medical and Dental University. 34. 93-98 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakamura, T., et al: "T. Specific incorporation of 4-S-cysteinylphenol into human melanoma cells." J. Invest. Dermatol.90. 725-728 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakamura, T., et al: "Transplacental induction of peripheral nervous tumor in the Syrian golden hamster by N-nitroso-N-ethylurea. A new animal model for von Recklinghausen's neurofibromatosis." Amer. J. Pathol.135. 251-259 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ito, S., et al: "Mechanism of selective toxicity of 4-S-cysteinylphenol and 4-S-cysteaminylphenol to melanocytes." Biochem. Pharmacol.36. 2007-2011 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yamada, K., et al: "Selective cytotoxicity of a phenolic melanin precursor, 4-S-cysteaminylphenol, on in vitro melanoma cells." Biochem. Pharmacol.38. 2217-2221 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Pankovich, J., et al: "Is melanocytotoxicity of 4-S-cysteaminylphenol related to tyrosinase or monoamine oxidase?" J. Invest. Dermatol.92. 496 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Inoue, S., et al: "Mechanism of growth inhibition of melanoma cells by 4-S-cysteaminylphenl and its analogues." Biochem. Pharmacol.(1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Alena, F., et al: "Melanocytotoxicity and antimelanoma effects of phenolic amine compounds in mice in vivo." Cancer Res.(1990)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yamada, I., et al: "Oncostatic effects of 4-S-cysteaminylphenol, human interferon-beta and radiation to human malignant melanoma cells." Proceedings of the Japanese Cancer Association. 47. 543 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yamada, I., et al: "Oncostatic effects of 4-S-cysteaminylphenol, a new melanin precursor, on B16 melanoma cells; development of melanoma-specific oncostatic drugs." Proceedings of the Japanese Cancer Association. 48. 344 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kitagawa, M., et al: "In vivo antitumor effect of 4-S-cysteaminylphenol to murine B16 melanoma." Proceedings of the Japanese Cancer Association. 48. 378 (1989)

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

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Published: 1993-03-26  

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