Development of radiation-responsive bioassays for biodosimetry applications.

The present proposal aims at developing and evaluating bioassays to assess radiation dose rapidly in case of mass-casualty, and population-monitoring and space exploration scenarios. The project includes an evaluation of potential biomarkers (molecular and proteic) that could provide early information after exposure and will be a collaboration between the China Institute for Radiation Protection (CIRP, China) and the Belgian Nuclear Research Center (SCK?CEN, Belgium), and the University of Namur (FUNDP-Namur, Belgium)..

The project will include an evaluation of potential biomarkers (molecular and proteic) that could provide early information after exposure to X-rays and protons.

Using an ex vivo model system of human peripheral lymphocytes, we will study molecular biomarkers (e.g., gene expression, protein level) of DNA damage and repair key-players as well as immunological markers present in the serum. Blood from donors will be collected and submitted to doses of X-irradiation and proton-irradiation between 0 and 6 Gy (including many sub-Gy doses). The proteins that would be studied are among others ras-p21, raf-1, p21Waf1Cip, GADD45, IL-6 and also others from the literature. The expression level of those biomarkers will be followed at various times (up to 48 hours) after X-irradiation by using the genomic platform and the Luminex technologies available at SCK?CEN and by using premature chromosome condensation coupled with fluorescent in situ hybridization as well as HPRT mutations availale at CIRP.

At FUNDP, The experiment protocol for irradiating HPBL cells will consist of exposing the cells to proton beam of various dose rates (1µGy/min (1 proton/s) to 1 Gy/min) and energies (1 to 2.8 MeV) under sterile conditions.
The irradiation will be performed on our Tandem accelerator equipped with a special irradiation station devoted to radiobiological irradiation. The proton beam is accelerated at various energies and fluences and irradiates a thin layer of liquid (blood) or cell separated from vacuum by a 8 µm kapton foil. Broad beam configuration (1 cm2) ensure good exposure uniformity. Fluences and dose rates are assessed by a special proton particle detector dedicated for this purpose. All irradiation will be performed in sterile conditions.