Analysis of dose-rate effects on cellular responses to chronic low-LET irradiation

Abstract

It is well established that the biological consequences of radiation exposure basically depend on the total dose of irradiation. While many studies on the biological effects of acute irradiation have been conducted, fewer data are available on chronic irradiation studies. In addition, the molecular mechanisms underlying the dose-rate effect on various biological responses to radiation have been remained to be resolved. In this study, in order to better understand the biological effects of chronic radiation exposure and the molecular mechanisms underlying the dose-rate effects, the cellular responses induced by chronic low-LET irradiation at different dose-rates were investigated from different aspects.
Various types of cultured human cell lines, including normal primary diploid fibroblasts, hTERT-immortalized fibroblasts, and a variety of tumor cell lines, were acute irradiated with different doses of ¹³⁷Cs γ-rays at a dose-rate (1.0 Gy/min) or chronically irradiated at different dose-rates (0.007-0.694 mGy/min). The cellular responses to radiation under different irradiation conditions are analyzed using various approaches. The clonogenic survival curves to acute γ-irradiation shown that the analyzed all cell lines had a similar sensitivity to γ-rays. However, significantly different growth inhibitory effects were observed in each cell lines under chronic radiation exposure. Clonogenic assays under chronic conditions demonstrated that there is a dose-rate threshold between reversible and irreversible growth inhibitory effects of radiation. Furthermore, transcriptome analysis by using next-generation sequencing exhibited dose-rate dependent alterations in mRNA expression levels in cells under chronic irradiation conditions. It is noteworthy that the p53 pathways largely contribute to the cellular responses to chronic irradiation in a dose-rate dependent manner.