Different dose rate-dependent responses of human melanoma cells and fibroblasts to low dose fast neutrons

Abstract

Purpose: To analyze the dose rate influence in hyper-radiosensitivity (HRS) of human melanoma cells to very low doses of fast neutrons and to compare to the behaviour of normal human skin fibroblasts.

Materials and methods: We explored different neutron dose rates as well as possible implication of DNA double-strand breaks (DSB), apoptosis, and energy-provider adenosine-triphosphate (ATP) levels during HRS.

Results: HRS in melanoma cells appears only at a very low dose rate (VLDR), while a high dose rate (HDR) induces an initial cell-radioresistance (ICRR). HRS does not seem to be due either to DSB or to apoptosis. Both phenomena (HRS and ICRR) appear to be related to ATP availability for triggering cell repair. Fibroblast survival after neutron irradiation is also dose rate-dependent but without HRS.

Conclusions: Melanoma cells or fibroblasts exert their own survival behaviour at very low doses of neutrons, suggesting that in some cases there is a differential between cancer and normal cells radiation responses. Only the survival of fibroblasts at HDR fits the linear no-threshold model. This new insight into human cell responses to very low doses of neutrons, concerns natural radiations, surroundings of accelerators, proton-therapy devices, flights at high altitude. Furthermore, ATP inhibitors could increase HRS during high-linear energy transfer (high-LET) irradiation.

Keywords:

• ATP
• dose rates
• low-dose neutrons
• fibroblasts
• melanoma
• radioprotection

Acknowledgements

This work was supported by a grant of Scientific Comity of Electricité De France (Grant No. RB-2014-11). The authors are indebted to Pr Vincent Grégoire, leader of Research team at UCL. They express their thanks to the physicist staff for efficiently running the cyclotron, to Véronique Dedieu (Cancer Center Jean Perrin France) for autofeeder preparation, to Imagerie Confocale plateform (GReD, France), to Pr David Payne for his critical reading of this manuscript and to Pr Schneider (UCL, Louvain la Neuve).

Authors’ contributions

C.D. supervised the project and designed the experiments. G.M., V.S., M.M-B., E.C., and C.D. made the experiments and analysed the data. J-M. D. performed the radiation experiments B.P. performed statistical analysis. C.D., M.M-B., J.G., D.A., A.T., E.C., and P.V. wrote the manuscript.

Disclosure statement

The authors report no conflicts of interest. The authors alone are response for the content and writing of the paper.