Nontargeted stressful effects in normal human fibroblast cultures exposed to low fluences of high charge, high energy (HZE) particles: kinetics of biologic responses and significance of secondary radiations.
Fiche publication
Date publication
avril 2013
Auteurs
Membres identifiés du Cancéropôle Est :
Pr FROMM Michel, Dr GROETZ Jean-Emmanuel
Tous les auteurs :
Gonon G, Groetz JE, de Toledo SM, Howell RW, Fromm M, Azzam EI
Lien Pubmed
Résumé
The induction of nontargeted stressful effects in cell populations exposed to low fluences of high charge (Z) and high energy (E) particles is relevant to estimates of the health risks of space radiation. We investigated the up-regulation of stress markers in confluent normal human fibroblast cultures exposed to 1,000 MeV/u iron ions [linear energy transfer (LET) approximately 151 keV/mum] or 600 MeV/u silicon ions (LET approximately 50 keV/mum) at mean absorbed doses as low as 0.2 cGy, wherein 1-3% of the cells were targeted through the nucleus by a primary particle. Within 24 h postirradiation, significant increases in the levels of phospho-TP53 (serine 15), p21(Waf1) (CDKN1A), HDM2, phospho-ERK1/2, protein carbonylation and lipid peroxidation were detected, which suggested participation in the stress response of cells not targeted by primary particles. This was supported by in situ studies that indicated greater increases in 53BP1 foci formation, a marker of DNA damage. than expected from the number of primary particle traversals. The effect was expressed as early as 15 min after exposure, peaked at 1 h and decreased by 24 h. A similar tendency occurred after exposure of the cell cultures to 0.2 cGy of 3.7 MeV alpha particles (LET approximately 109 keV/mum) that targets approximately 1.6% of nuclei, but not after 0.2 cGy from 290 MeV/u carbon ions (LET approximately 13 keV/mum) by which, on average, approximately 13% of the nuclei were hit, which highlights the importance of radiation quality in the induced effect. Simulations with the FLUKA multi-particle transport code revealed that fragmentation products, other than electrons, in cell cultures exposed to HZE particles comprise
Référence
Radiat Res. 2013 Apr;179(4):444-57