Evaluation of the In vivo Radiosensitizing Activity of Etanidazole Using Tumor-bearing Chick Embryo

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  • ABE Chiaki
    Department of Life System, Institute of Technology and Science, Graduate School, The University of Tokushima
  • UTO Yoshihiro
    Department of Life System, Institute of Technology and Science, Graduate School, The University of Tokushima
  • NAKAE Takashi
    Department of Life System, Institute of Technology and Science, Graduate School, The University of Tokushima
  • SHINMOTO Yuuya
    Department of Life System, Institute of Technology and Science, Graduate School, The University of Tokushima
  • SANO Keiichiro
    Department of Life System, Institute of Technology and Science, Graduate School, The University of Tokushima
  • NAKATA Hiroko
    Department of Life System, Institute of Technology and Science, Graduate School, The University of Tokushima
  • TERAOKA Mizue
    Department of Life System, Institute of Technology and Science, Graduate School, The University of Tokushima
  • ENDO Yoshio
    Central Research Resource Branch, Cancer Research Institute, Kanazawa University
  • MAEZAWA Hiroshi
    Institute of Health Biosciences, Graduate School, The University of Tokushima
  • MASUNAGA Shin-ichiro
    Particle Radiation Oncology Research Center, Research Reactor Institute, Kyoto University
  • NAKATA Eiji
    Department of Life System, Institute of Technology and Science, Graduate School, The University of Tokushima
  • HORI Hitoshi
    Department of Life System, Institute of Technology and Science, Graduate School, The University of Tokushima

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Abstract

Chick embryos have been used as alternative experimental animals in various research fields, including virology, immunology, toxicology, oncology, and embryology. Until now, there have been no in vivo models using chick embryo to evaluate radiosensitizing activity. Here, the in vivo radiosensitizing activity of etanidazole, a well-known hypoxic cell radiosensitizer, was evaluated using tumor-bearing chick embryo. On the basis of tumor growth, drug administration and X-ray irradiation were performed on day 15 chick embryo, with the endpoint being day 18 chick embryo. In day 15 chick embryo, an X-ray irradiation dose of equal or less than 10 Gy did not cause significant tumor growth suppression. Intravenous administration of equal or less than 1.0 mg of etanidazole did not cause tumor growth suppression. Neither doses of equal or less than 8 Gy of irradiation nor 1.0 mg of etanidazole caused fatality of the chick embryo. On the basis of these results, we evaluated the radiosensitizing effect of a combination treatment with 8 Gy of irradiation and 1.0 mg of etanidazole. As noted above, 1.0 mg of etanidazole alone and 8 Gy of irradiation alone did not show tumor growth suppression. In contrast, a combination treatment with 8 Gy of irradiation and 1.0 mg of etanidazole showed 35% of significant tumor growth suppression. Thus, we succeeded in evaluating the in vivo radiosensitizing activity of etanidazole using tumor-bearing chick embryo. These results suggest that the use of tumor-bearing chick embryo may be part of a promising system for evaluating radiosensitizing activity.

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