Intensity Modulated Radiation Fields Induce Protective Effects and Reduce Importance of Dose-Rate Effects

Yusuke Matsuya, Stephen J McMahon, Mihaela Ghita, Yuji Yoshii, Tatsuhiko Sato, Hiroyuki Date, Kevin M Prise

Research output: Contribution to journalArticle

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Abstract

In advanced radiotherapy, intensity modulated radiation fields and complex dose-delivery are utilized to prescribe higher doses to tumours. Here, we investigated the impact of modulated radiation fields on radio-sensitivity and cell recovery during dose delivery. We generated experimental survival data after single-dose, split-dose and fractionated irradiation in normal human skin fibroblast cells (AGO1522) and human prostate cancer cells (DU145). The dose was delivered to either 50% of the area of a T25 flask containing the cells (half-field) or 100% of the flask (uniform-field). We also modelled the impact of dose-rate effects and intercellular signalling on cell-killing. Applying the model to the survival data, it is found that (i) in-field cell survival under half-field exposure is higher than uniform-field exposure for the same delivered dose; (ii) the importance of sub-lethal damage repair (SLDR) in AGO1522 cells is reduced under half-field exposure; (iii) the yield of initial DNA lesions measured with half-field exposure is smaller than that with uniform-field exposure. These results suggest that increased cell survival under half-field exposure is predominantly attributed not to rescue effects (increased SLDR) but protective effects (reduced induction of initial DNA lesions). In support of these protective effects, the reduced DNA damage leads to modulation of cell-cycle dynamics, i.e., less G1 arrest 6 h after irradiation. These findings provide a new understanding of the impact of dose-rate effects and protective effects measured after modulated field irradiation.

Original languageEnglish
Pages (from-to)9483
JournalScientific Reports
Volume9
Issue number1
DOIs
Publication statusPublished - 01 Jul 2019

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Radiation
Cell Survival
Intensity-Modulated Radiotherapy
Survival
DNA
Radio
DNA Damage
Prostatic Neoplasms
Cell Cycle
Fibroblasts
Skin
Neoplasms

Cite this

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title = "Intensity Modulated Radiation Fields Induce Protective Effects and Reduce Importance of Dose-Rate Effects",
abstract = "In advanced radiotherapy, intensity modulated radiation fields and complex dose-delivery are utilized to prescribe higher doses to tumours. Here, we investigated the impact of modulated radiation fields on radio-sensitivity and cell recovery during dose delivery. We generated experimental survival data after single-dose, split-dose and fractionated irradiation in normal human skin fibroblast cells (AGO1522) and human prostate cancer cells (DU145). The dose was delivered to either 50{\%} of the area of a T25 flask containing the cells (half-field) or 100{\%} of the flask (uniform-field). We also modelled the impact of dose-rate effects and intercellular signalling on cell-killing. Applying the model to the survival data, it is found that (i) in-field cell survival under half-field exposure is higher than uniform-field exposure for the same delivered dose; (ii) the importance of sub-lethal damage repair (SLDR) in AGO1522 cells is reduced under half-field exposure; (iii) the yield of initial DNA lesions measured with half-field exposure is smaller than that with uniform-field exposure. These results suggest that increased cell survival under half-field exposure is predominantly attributed not to rescue effects (increased SLDR) but protective effects (reduced induction of initial DNA lesions). In support of these protective effects, the reduced DNA damage leads to modulation of cell-cycle dynamics, i.e., less G1 arrest 6 h after irradiation. These findings provide a new understanding of the impact of dose-rate effects and protective effects measured after modulated field irradiation.",
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Intensity Modulated Radiation Fields Induce Protective Effects and Reduce Importance of Dose-Rate Effects. / Matsuya, Yusuke; McMahon, Stephen J; Ghita, Mihaela; Yoshii, Yuji; Sato, Tatsuhiko; Date, Hiroyuki; Prise, Kevin M.

In: Scientific Reports, Vol. 9, No. 1, 01.07.2019, p. 9483.

Research output: Contribution to journalArticle

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AU - Matsuya, Yusuke

AU - McMahon, Stephen J

AU - Ghita, Mihaela

AU - Yoshii, Yuji

AU - Sato, Tatsuhiko

AU - Date, Hiroyuki

AU - Prise, Kevin M

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