Low dose hyper-radiosensitivity in normal human cells

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Cells usually have different sensitivity to ionising radiation depending on their phase during the cell cycle, particularly at low-LET radiation. The most sensitive phases in the cell cycle are the M- and G2 phases, where S and G1 are the resistant phases. Low doses of radiation can induce various delayed and non-targeted effects, including bystanders (BE) and hyper-radiosensitivity (HRS), in vitro and in vivo. The region of HRS is thought to be formed by an excessive induction of DNA DSBs, which consequently led to a hyper-activation of the DNA repair mechanisms. Such phenomena result in a modification to the Linear Quadratic (LQ) model to include the out-of-fit dose points. At low doses below 1 Gy of radiation, most mammalian cells have shown HRS, which is frequently followed by an Induced-radioresistance (IRR) phenomenon. To confirm the observations of the HRS and IRR effects and identify their start- and endpoints at low doses of X-ray irradiations, the AG1522 normal human fibroblasts cells were irradiated with a range of selected high- and low doses of 0.2, 0.4, 0.6, 1, 2, 3, 4 and 5 Gy with a specific interest at the doses below 1 Gy. The HRS is pronounced at the dose of 0.2 Gy of X-ray irradiation, followed by the IRR phenomenon as the dose increases up to 0.6 Gy. In the context of radiation protection, these results need to be considered during radiotherapy treatment. The presence of the HRS in the survival curves of normal AG1522 cells after X-irradiation maximises the possible advantage of using such low doses to improve clinical outcomes. These data provide further insight into the radiobiological parameters, highlighting the need to refine existing radiobiological parameters to incorporate such effects and modulate dose distributions.