Modeling cell survival and change in amount of DNA during protracted irradiation

• Published in: Journal of radiation research Vol. 58; no. 3; pp. 302 - 312
• Main Authors: Matsuya, Yusuke, Tsutsumi, Kaori, Sasaki, Kohei, Yoshii, Yuji, Kimura, Takaaki, Date, Hiroyuki
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.05.2017
• Subjects: Animals; Biology; Cell Cycle - radiation effects; Cell Nucleus - metabolism; Cell Nucleus - radiation effects; Cell Survival - radiation effects; CHO Cells; Clone Cells; Cricetinae; Cricetulus; DNA - metabolism; DNA - radiation effects; Dose-Response Relationship, Radiation; Kinetics; Models, Biological; Probability; Radiation; Reproducibility of Results; X-Rays; dose-rate effects; surviving fraction; microdosimetric-kinetic model; protracted irradiation; amount of DNA; accumulation of cells in G; accumulation of cells in G2
• ISSN: 0449-3060; 1349-9157
• DOI: 10.1093/jrr/rrw110

Abstract Hyper-radiosensitivity (HRS) is a well-known bioresponse under low-dose or low-dose-rate exposures. Although disorder of the DNA repair function, non-targeted effects and accumulation of cells in G2 have been experimentally observed, the mechanism for inducing HRS by long-term irradiation is still unclear. On the basis of biological experiments and a theoretical study, we have shown that change in the amount of DNA associated with accumulation of cells in G2 enhances radiosensitivity. To demonstrate continuous irradiation with 250 kVp X-rays, we adopted a fractionated regimen of 0.186 or 1.00 Gy per fraction at intervals of 1 h (i.e. 0.186 Gy/h, 1.00 Gy/h on average) to Chinese Hamster Ovary (CHO)-K1 cells. The change in the amount of DNA during irradiation was quantified by flow cytometric analysis with propidium iodide (PI). Concurrently, we attempted a theoretical evaluation of the DNA damage by using a microdosimetric-kinetic (MK) model that was modified to incorporate the change in the amount of DNA. Our experimental results showed that the fraction of the cells in G2/M phase increased by 6.7% with 0.186 Gy/h and by 22.1% with 1.00 Gy/h after the 12th irradiation. The MK model considering the change in amount of DNA during the irradiation exhibited a higher radiosensitivity at a high dose range, which could account for the experimental clonogenic survival. The theoretical results suggest that HRS in the high dose range is associated with an increase in the total amount of DNA during irradiation.