Low dose hypersensitivity following in vitro cell irradiation with charged particles: Is the mechanism the same as with X-ray radiation?

Purpose: Among the low dose effects that have been discovered during the past decade, the low dose hypersensitivity (HRS) is of prime importance. This phenomenon, compared to irradiation at higher doses used in conventional radiotherapy, enhances cell killing per unit dose at low doses and is followed by an induced radioresistance (IRR) effect. On survival fraction curves, a deviation from the linear quadratic model can be observed. HRS has mainly been studied after irradiation with sparsely ionizing radiation. Little work has been done to check its actual existence after irradiation with medium and high linear energy transfer (LET) particles. This article reviews recent studies involving HRS following irradiation of rodent and human cells with protons, alpha particles and carbon ions and assesses the applicability of a photon HRS model to charged particles. Conclusion: We propose that the HRS threshold dose and the radiosensitive parameter αs may be LET and deoxyribonucleic acid (DNA) damage-clustering dependent. Combining the use of high-LET particles at low doses and chemotherapy strategies increasing the proportion of HRS-sensitive cells could become a good candidate treatment for radioresistant cancers.