Matsuya Yusuke, Tsutsumi Kaori, Sasaki Kohei, Date Hiroyuki
Graduate School of Health Sciences, Hokkaido University, Kita-12, Nishi-5, Kita-ku, Sapporo 060-0812, Japan.
Faculty of Health Sciences, Hokkaido University, Kita-12, Nishi-5, Kita-ku, Sapporo 060-0812, Japan.
J Radiat Res. 2015 Jan;56(1):90-9. doi: 10.1093/jrr/rru090. Epub 2014 Oct 29.
We have investigated the dose rate effects on cell damage caused by photon-beam irradiation. During a relatively long dose-delivery time with a low dose rate, lesions created in cells may undergo some reactions, such as DNA repair. In order to investigate these reactions quantitatively, we adopted the microdosimetric-kinetic (MK) model and deduced a cell surviving fraction (SF) formula for continuous irradiation. This model enabled us to estimate the SF from dose and dose rate. The parameters in the MK model were determined so as to generate the SF, and we attempted to evaluate the dose rate effects on the SF. To deduce the cell-specific parameters in the SF formula, including the dose rate, we performed a split-dose experiment and a single-dose experiment with a constant dose-delivery time (10 min) (to retain the condition for equivalent behavior of cell lesions) by means of a clonogenic assay. Then, using the MK model parameters, the SFs were reproduced for a variety of dose rates (1.0, 0.31, 0.18, 0.025 and 0.0031 Gy/min) and were compared with reported experimental data. The SF curves predicted by the MK model agreed well with the experimental data, suggesting that the dose rate effects appear in the kinetics of cell lesions during the dose-delivery time. From fitting the analysis of the model formula to the experimental data, it was shown that the MK model could illustrate the characteristics of log-SF in a rectilinear form at a high dose range with a relatively low dose rate.
我们研究了剂量率对光子束辐照引起的细胞损伤的影响。在低剂量率下相对较长的剂量输送时间内，细胞中产生的损伤可能会经历一些反应，如DNA修复。为了定量研究这些反应，我们采用了微剂量动力学（MK）模型，并推导了连续辐照的细胞存活分数（SF）公式。该模型使我们能够根据剂量和剂量率估算SF。确定MK模型中的参数以生成SF，我们试图评估剂量率对SF的影响。为了推导SF公式中包括剂量率在内的细胞特异性参数，我们通过克隆形成试验进行了分割剂量实验和固定剂量输送时间（10分钟）的单剂量实验（以保持细胞损伤等效行为的条件）。然后，使用MK模型参数，针对各种剂量率（1.0、0.31、0.18、0.025和0.0031 Gy/min）重现了SF，并与报道的实验数据进行了比较。MK模型预测的SF曲线与实验数据吻合良好，表明剂量率效应出现在剂量输送时间内细胞损伤的动力学过程中。通过将模型公式的分析拟合到实验数据中，结果表明MK模型能够在相对低剂量率的高剂量范围内以直线形式说明对数SF的特征。
