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

Claude Dionet (1) , Mélanie Müller-Barthélémy (1, 2) , Geoffroy Marceau (3) , Jean-Marc Denis (4, 5) , Dietrich Averbeck (6) , John Gueulette (5) , Vincent Sapin (3) , Bruno Pereira (7) , Andrei Tchirkov (8) , E. Chautard (2, 1) , Pierre Verrelle (1, 2)

1 UNICANCER/CJP - Centre Jean Perrin [Clermont-Ferrand]
2 CREaT - Cancer Resistance Exploring and Targeting
3 CHU Clermont-Ferrand
4 Cliniques Universitaires Saint-Luc [Bruxelles]
5 UCL - Université Catholique de Louvain = Catholic University of Louvain
6 Stress génotoxiques et cancer
7 DRCI - Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand]
8 CHU Estaing [Clermont-Ferrand]

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.

Mots clés: dose rates; ATP; radioprotection; fibroblasts; low-dose neutrons; melanoma

Domaines: Cancer

Claude Dionet, Mélanie Müller-Barthélémy, Geoffroy Marceau, Jean-Marc Denis, Dietrich Averbeck, et al.. Different dose rate-dependent responses of human melanoma cells and fibroblasts to low dose fast neutrons. International Journal of Radiation Biology, 2016, 92 (9), pp.527-35. ⟨10.1080/09553002.2016.1186300⟩. ⟨hal-01643046⟩