In vitro study of the influence of alpha particles irradiation on the pre-neoplastic transformation of rat trachea epithelial cells

Intern contamination by actinide oxide inhalation is potentially one health hazard during the nuclear fuel fabrication process. The aerosol particles can induce pulmonary lesions, such as epithelial cancers in particular. Their toxicity is mainly due to radiotoxicity of α irradiation. The aim of this work was to contribute, by an in vitro model, to the study of the apparition of pre-neoplastic states on epithelial cells after high LET irradiation. Primary cultures of rat tracheal epithelial cells were used. Two rat strain cells, SD TR for Sprague Dawley rats and WF TR for Wistar Furth I Fischer F344 rats, were compared after exposure to a dose range from 0 to 5 Gy. Reproductive cell death, i.e. senescent death, seems to be the main lethal way induced by α and γ irradiations. The nuclear volume of WF TR cells is higher than that of SD TR ones, explaining the higher α radiation-induced lethality of these cells. These WF TR cells are also much sensitive to dose rate and α particles energy. In the same manner, pre-neoplastic transformation rate of the cells seems to depend on the physical parameters of irradiation. But, it mainly varies as a function of cell radiosensitivity, that means cell death. In fact, the transformation rate of sensitive WF TR cells is lower than that of SD TR ones. In term of transformation for SD TR cells, dose-effect relationship fits to a linear and infra linear function after α irradiation, whereas the curve fits to linear and quadratic function after γ irradiation. The Relative Biological Efficiency (RBE) of α particles for lethality and pre-neoplastic transformation were determined for several levels of dose. A constant value of about 3 was found for RBE of lethality whatever the α dose. By contrast, the RBE of transformation has a value of about 10 up to 0.5 Gy and gradually decreases at higher doses to reach a value of 1 at 5 Gy. Similar shapes of dose-effect relationship can be observed for malignant lung tumour induction after inhalation of actinide oxide aerosols. Physical characteristics of irradiation, intrinsic cell population properties and different radio-induced effect might be taken into account to better estimate in vitro pre-neoplastic transformation and in vivo cancer induction. (author)