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



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.



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.



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.
a Centre Jean Perrin , Laboratoire de Radio-Oncologie Expérimentale , Clermont-Ferrand , France ;
Claude
C
Dionet
a Centre Jean Perrin , Laboratoire de Radio-Oncologie Expérimentale , Clermont-Ferrand , France ;|b Clermont Université, Université d'Auvergne, EA7283 CREaT , Clermont-Ferrand , France ;
Melanie
M
Müller-Barthélémy
c Biochimie et Biologie Moléculaire , CHU Clermont-Ferrand, Centre de Biologie , Clermont-Ferrand , France ;
Geoffroy
G
Marceau
d Radiotherapy Department , Cliniques Universitaires Saint Luc-UCL , Bruxelles , Belgique ;|f Université Catholique de Louvain (UCL-IREC-MIRO) , Bruxelles , Belgique ;
Jean-Marc
JM
Denis
e Institut Curie-Recherche, UMR3348 CNRS/IC, Centre Universitaire, Orsay , France ;
Dietrich
D
Averbeck
f Université Catholique de Louvain (UCL-IREC-MIRO) , Bruxelles , Belgique ;
John
J
Gueulette
c Biochimie et Biologie Moléculaire , CHU Clermont-Ferrand, Centre de Biologie , Clermont-Ferrand , France ;
Vincent
V
Sapin
g CHU Clermont-Ferrand, Biostatistics unit (DRCI) , Clermont-Ferrand , France ;
Bruno
B
Pereira
h Cytogénétique médicale, CHU Estaing , Clermont-Ferrand , France.
Andrei
A
Tchirkov
a Centre Jean Perrin , Laboratoire de Radio-Oncologie Expérimentale , Clermont-Ferrand , France ;|b Clermont Université, Université d'Auvergne, EA7283 CREaT , Clermont-Ferrand , France ;
Emmanuel
E
Chautard
a Centre Jean Perrin , Laboratoire de Radio-Oncologie Expérimentale , Clermont-Ferrand , France ;|b Clermont Université, Université d'Auvergne, EA7283 CREaT , Clermont-Ferrand , France ;
Pierre
P
Verrelle
D017209:Apoptosis / Q000528:radiation effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects*; D003198:Computer Simulation; D019583:Dose Fractionation, Radiation; D004307:Dose-Response Relationship, Radiation; D005347:Fibroblasts / Q000473:pathology / Q000528:radiation effects*; D006801:Humans; D008545:Melanoma / Q000473:pathology / Q000532:radiotherapy*; D008954:Models, Biological; D009502:Neutrons; D011836:Radiation Tolerance
ATP; dose rates; fibroblasts; low-dose neutrons; melanoma; radioprotection