Jean-Emmanuel Groetz

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.

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) ∼151 keV/μm] or 600 MeV/u silicon ions (LET ∼50 keV/μm) 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), p21Waf1 (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 α particles (LET ∼109 keV/μm) that targets ∼1.6% of nuclei, but not after 0.2 cGy from 290 MeV/u carbon ions (LET ∼13 keV/μm) by which, on average, ∼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 <1% of the absorbed dose. Further, the radial spread of dose due to secondary heavy ion fragments is confined to approximately 10–20 μm. Thus, the latter are unlikely to significantly contribute to stressful effects in cells not targeted by primary HZE particles.

COHERENT LIGHT SCATTERING BY NUCLEAR ETCHED TRACKS IN THE PADC (A FORM OF CR-39)

Abstract A new kind of measurement has been proposed to improve the reading of the Solid State Nuclear Track Detector CR-39. This method is based on coherent light scattering (He–Ne laser) by etched proton tracks, and is complementary to observation under an optical microscope and reading by optical density of the CR-39. The irradiated and chemically etched CR-39 sample is illuminated by a laser beam under a normal incidence angle. The light intensity diffracted by the tracks beyond the sample – defined with the bi-directional transmissive distribution functions – is measured with a photodiode. Thus, the bi-directional transmissive distribution functions depend on the characteristics of the irradiation, namely the track density, track sizes and orientations. We have performed a track light diffraction model calculation through the use of the Fraunhofer diffraction, Babinets principle and the spatial coherence and incoherence. We compared calculations and experimental results for the different shapes of tracks: conical, oblique and spherical-shaped.

Conception and realization of a parallel-plate free-air ionization chamber for the absolute dosimetry of an ultrasoft X-ray beam

We report the design of a millimeter-sized parallel plate free-air ionization chamber (IC) aimed at determining the absolute air kerma rate of an ultra-soft X-ray beam (E = 1.5 keV). The size of the IC was determined so that the measurement volume satisfies the condition of charged-particle equilibrium. The correction factors necessary to properly measure the absolute kerma using the IC have been established. Particular attention was given to the determination of the effective mean energy for the 1.5 keV photons using the PENELOPE code. Other correction factors were determined by means of computer simulation (COMSOL™ and FLUKA). Measurements of air kerma rates under specific operating parameters of the lab-bench X-ray source have been performed at various distances from that source and compared to Monte Carlo calculations. We show that the developed ionization chamber makes it possible to determine accurate photon fluence rates in routine work and will constitute substantial time-savings for future radiobiological experiments based on the use of ultra-soft X-rays.

Simulation of processes in a SSNTD exposed by monoenergetic neutrons

Abstract The nuclear track technique is based on the registering of latent track ions in a solid state dielectric material (Solid State Nuclear Track Detector) which will be chemically etched in order to be observed and analysed using microscopic analysis tools. The purpose of this study is to observe how a polymeric detector irradiated by a neutron fluence can explain the intensity of ionizing radiations to which structures, electronic components or living organism are exposed. To do this, it is necessary to take into account on the one hand the production of ionizing particles in the detector, and on the other hand the efficacy of their detection. The model we propose must be able to link the number of etched tracks and their parameters to the neutron fluence. The use of both a Monte Carlo code which determines the number of recoil nuclei and a computed model of etched track parameters calculations is needed. The Monte Carlo code performs a simulation of neutron-nucleus elastic collision in the detector. We compute the number of recoil nuclei produced between the surface and a depth of 20 μm in the detector. The computer code assigns six pseudo-random numbers ( x E , z E , a , b , c , α) to each neutron having an energy E N and an angle of incidence and give the results of calculations. We used statistical tests (the moments of the origin of order n and of the average of order n , the χ 2 test, the gap test, the Pearson test, the run-up run-down test and the serial test) to check the quality of our pseudo-random number generator. Finally, we will compare the calculated results of the response of the SSNTD (tracks cm −2 ) with the experimental ones to validate the simulation.

Comparable Senescence Induction in Three-dimensional Human Cartilage Model by Exposure to Therapeutic Doses of X-rays or C-ions

PURPOSE Particle therapy using carbon ions (C-ions) has been successfully used in the treatment of tumors resistant to conventional radiation therapy. However, the potential side effects to healthy cartilage exposed to lower linear energy transfer (LET) ions in the beam track before the tumor have not been evaluated. The aim of the present study was to assess the extent of damage after C-ion irradiation in a 3-dimensional (3D) cartilage model close to human homeostasis. METHODS AND MATERIALS Primary human articular chondrocytes from a healthy donor were cultured in a collagen scaffold to construct a physioxic 3D cartilage model. A 2-dimensional (2D) culture was used as a reference. The cells were irradiated with a single dose of a monoenergetic C-ion beam with a LET of approximatively 30 keV/μm. This LET corresponds to the entrance channel of C-ions in the shallow healthy tissues before the spread-out Bragg peak (∼100 keV/μm) during hadron therapy protocols. The same dose of X-rays was used as a reference. Survival, cell death, and senescence assays were performed. RESULTS As expected, in the 2D culture, C-ions were more efficient than X-rays in reducing cell survival with a relative biological effectiveness of 2.6. This correlated with stronger radiation-induced senescence (two-fold) but not with higher cell death induction. This differential effect was not reflected in the 3D culture. Both ionizing radiation types induced a comparable rate of senescence induction in the 3D model. CONCLUSIONS The greater biological effectiveness of C-ions compared with low LET radiation when evaluated in treatment planning systems might be misevaluated using 2D culture experiments. Radiation-induced senescence is an important factor of potential cartilage attrition. The present data should encourage the scientific community to use relevant models and beams to improve the use of charged particles with better safety for patients.