Radon induced mitochondrial dysfunction in human bronchial epithelial cells and epithelial-mesenchymal transition with long-term exposure.

Radon is a naturally occurring radionuclide, which has a wide environmental distributed. It emits multiple high linear energy transfer (LET) alpha particles during radiative decay, and has been regarded as a human carcinogen by the International Agency for Research on Cancer. Currently, residential radon exposure is considered as the second highest cause of lung cancer and the leading cause among nonsmokers. Radon exposure leads to genomic instability, which causes the accumulation of multiple genetic changes and leads to cancer development. However, the molecular basis underlying carcinogenesis, especially the radon-induced changes to mitochondria, has not been fully elucidated. The aim of this study was to explore the dynamic changes in mitochondria along with the cell transformations induced by long-term radon exposure. A malignant transformation model of BEAS-2B cells was established with upto 40 times the usual radon exposure (20 000 Bq m-3, 30 min each time every 3 days). Long-term radon exposure induced EMT-like transformation of epithelial cells in our study, evidenced by decrease in epithelial markers and increase in mesenchymal markers, as well as the loss of cell-cell adhesion and alterations to the morphology of cells from compact shape to a spindle shaped, fibroblast-like morphology. Additionally, the proliferation and migration of cells were increased and apoptosis was decreased with long-term radon exposure. Furthermore, mitochondrial function was up-regulated and the levels of oxidative stress were repressed with long-term radon exposure. Our work explored the dynamic changes of mitochondrial in radon induced malignant transformation of lung bronchial epithelial cells, which could partially elucidate the role of mitochondria in radon induced cell malignancy.