Kinetics of propagation of bystander effects in human cells cultures exposed to low fluences of high LET radiations

Géraldine Gonon (1, 2) , Sonia M de Toledo (3) , Michel Fromm (2) , Edouard I Azzam (3)

1 UMDNJ - Department of Radiology Division of Radiation Research
2 LCE - Laboratoire Chrono-environnement (UMR 6249)
3 Division of radiation research

We and others have previously shown, in confluent cell cultures exposed to low fluences of a particles, that the proportion of cells that upregulate stress-inducible proteins is much higher that the number of cells irradiated. This phenomenon, called bystander effect, is now well accepted and is thought to impact the health risks of exposure to ionizing radiation. Here, we investigate the kinetics of propagation of signaling events that lead to induction of DNA damage in bystander cells in confluent normal human AG1522 fibroblasts exposed to a mean dose of 0.2 cGy from 3.2 MeV a particles (LET ; 124 keV/lm) or 1 GeV/n iron ions (LET ; 151 keV/lm). We evaluated the formation of 53BP1 foci (p53 binding protein 1), which localizes at sites of DNA double strand breaks, as a function of time after irradiation. The fraction of cells whose nuclei were traversed by an irradiating particle was derived from Poisson statistics and estimates of cell geometry, particle fluence and energy loss. At a mean dose of 0.2 cGy, only 1.4% and 1.2% of the cells are traversed through the nucleus by a particle or iron ion tracks, respectively. The number of 53BP1 foci in control cells was ; 0.61 foci per cell. In a particle-irradiated cell cultures, the mean number of foci per cell was 0.73 (p,0.001) at 15 min; it reached 0.90 by 3h (p,0.001) after irradiation, following which a decrease was observed. The same trend was detected when the fraction of cells with foci was considered: it reached 61% at 3h which is higher than the expected 47.4% of the cells (46% in control + 1.4% traversed). The increase in foci formation over the expected value was eliminated when the cells were incubated with a specific inhibitor of ATM (Ataxia Telangiectasia Mutated protein). Analyses of bystander effects in iron ion-irradiated cell cultures and the effect of partial oxygen tension on the kinetic of 53BP1 foci formation in low fluences alpha particle-irradiated cell populations are in progress.

Domaines: Chimie théorique et/ou physique

Géraldine Gonon, Sonia M de Toledo, Michel Fromm, Edouard I Azzam. Kinetics of propagation of bystander effects in human cells cultures exposed to low fluences of high LET radiations. 56th Annual Meeting Radiation Research Society, Sep 2010, Maui, United States. ⟨hal-00862316⟩