title: Modeling cell survival and change in amount of DNA during protracted irradiation.
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.
authors.affiliation: Graduate School of Health Sciences, Hokkaido University, Kita-12, Nishi-5, Kita-ku, Sapporo 060-0812, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Matsuya
authors.affiliation: Faculty of Health Sciences, Hokkaido University, Kita-12, Nishi-5, Kita-ku, Sapporo 060-0812, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Tsutsumi
authors.affiliation: Faculty of Health Sciences, Hokkaido University of Science, Maeda 7-15, Teine-ku, Sapporo 006-8585, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Sasaki
authors.affiliation: Biological Research, Education and Instrumentation Center, Sapporo Medical University, Minami-1, Nichi-17, Chuo-ku, Sapporo 060-8556, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Yoshii
authors.affiliation: Graduate School of Health Sciences, Hokkaido University, Kita-12, Nishi-5, Kita-ku, Sapporo 060-0812, Japan.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Kimura
authors.affiliation: Faculty of Health Sciences, Hokkaido University, Kita-12, Nishi-5, Kita-ku, Sapporo 060-0812, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Date
mesh_terms: D000818:Animals; D016466:CHO Cells; D002453:Cell Cycle / Q000528:radiation effects; D002467:Cell Nucleus / Q000378:metabolism / Q000528:radiation effects; D002470:Cell Survival / Q000528:radiation effects; D002999:Clone Cells; D006224:Cricetinae; D003412:Cricetulus; D004247:DNA / Q000378:metabolism* / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D007700:Kinetics; D008954:Models, Biological; D011336:Probability; D011827:Radiation; D015203:Reproducibility of Results; D014965:X-Rays
chemical_list: D004247:DNA
keywords: accumulation of cells in G2; amount of DNA; dose-rate effects; microdosimetric-kinetic model; protracted irradiation; surviving fraction