Atmospheric fine particulate matter and epithelial mesenchymal transition in pulmonary cells: state of the art and critical review of the in vitro studies.

Exposure to fine particulate matter (PM2.5) has been associated with several diseases including asthma, chronic obstructive pulmonary disease (COPD) and lung cancer. Mechanisms such as oxidative stress and inflammation are well-documented and are considered as the starting point of some of the pathological responses. However, a number of studies also focused on epithelial-mesenchymal transition (EMT), which is a biological process involved in fibrotic diseases and cancer progression notably via metastasis induction. Up until now, EMT was widely reported in vivo and in vitro in various cell types but investigations dealing with in vitro studies of PM2.5 induced EMT in pulmonary cells are limited. Further, few investigations combined the necessary endpoints for validation of the EMT state in cells: such as expression of several surface, cytoskeleton or extracellular matrix biomarkers and activation of transcription markers and epigenetic factors. Studies explored various cell types, cultured under differing conditions and exposed for various durations to different doses. Such unharmonized protocols (1) might introduce bias, (2) make difficult comparison of results and (3) preclude reaching a definitive conclusion regarding the ability of airborne PM2.5 to induce EMT in pulmonary cells. Some questions remain, in particular the specific PM2.5 components responsible for EMT triggering. The aim of this review is to examine the available PM2.5 induced EMT in vitro studies on pulmonary cells with special emphasis on the critical parameters considered to carry out future research in this field. This clarification appears necessary for production of reliable and comparable results.

Co-exposure to internal and external radiation alters cesium biokinetics and retention in mice.

Exposures in post-accidental situations are complex and include both external exposure and internal contamination with several radionuclides. However, in vivo and in vitro studies generally use simplified exposures, while a recent study suggested that combined external irradiation and internal contamination may induce more severe biological effects compared to single exposures. In an attempt to test the hypothesis of potential non-additive effects of multiple radiological exposures, we used a mouse model of combined external x-ray irradiation at 1 and 5 Gy and internal contamination with injection of 20 KBq 137Cs. The results showed differential kinetics of 137Cs elimination in irradiated animals compared to sham-irradiated, 137Cs injected animals. Moreover, changes in plasma potassium and in relative testis weight were observed 38 days after irradiation and injection in co-exposed animals compared to 137Cs injection alone. These results demonstrate that an external exposure combined with an internal contamination may lead to unexpected changes in biokinetics of radionuclides and biological effects compared to single exposures.