| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Outline of Final Research Achievements |
We investigated cellular responses to a high-dose-per-fraction radiotherapy compared with a conventionally fractionated radiotherapy. Based on an analysis using biomathematical models, underlying mechanisms of radiosensitizing effects were classified into three factors: 1) Increase of initial DNA damages, 2) Inhibition of DNA double-strand break (DNA-DSB) repairs, and 3) Increased chromosomal translocations mediated by non-homologous end joining. Since a probability of chromosomal translocations is proportional to a square dose, the third mechanism enhanced radiosensitivity in the high dose range to a greater extent than the second mechanism. Through the third mechanism, the altered selection of DNA-DSB repair pathways impacted on radiosensitivity without any changes in the total amount of the initial DNA damage and its repair. The pathway choice of the DNA-DSB repair can be a potential molecular target for hypofractionated high-precision radiotherapy.
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