| First Author | McConnell AM | Year | 2016 |
| Journal | Sci Rep | Volume | 6 |
| Pages | 33455 | PubMed ID | 27659946 |
| Mgi Jnum | J:355057 | Mgi Id | MGI:6223537 |
| Doi | 10.1038/srep33455 | Citation | McConnell AM, et al. (2016) Distal airway epithelial progenitor cells are radiosensitive to High-LET radiation. Sci Rep 6:33455 |
| abstractText | Exposure to high-linear energy transfer (LET) radiation occurs in a variety of situations, including charged particle radiotherapy, radiological accidents, and space travel. However, the extent of normal tissue injury in the lungs following high-LET radiation exposure is unknown. Here we show that exposure to high-LET radiation led to a prolonged loss of in vitro colony forming ability by airway epithelial progenitor cells. Furthermore, exposure to high-LET radiation induced clonal expansion of a subset of progenitor cells in the distal airway epithelium. Clonal expansion following high-LET radiation exposure was correlated with elevated progenitor cell apoptosis, persistent gamma-H2AX foci, and defects in mitotic progression of distal airway progenitors. We discovered that the effects of high-LET radiation exposure on progenitor cells occur in a p53-dependent manner. These data show that high-LET radiation depletes the distal airway progenitor pool by inducing cell death and loss of progenitor function, leading to clonal expansion. Importantly, high-LET radiation induces greater long-term damage to normal lung tissue than the relative equivalent dose of low-LET gamma-rays, which has implications in therapeutic development and risk assessment. |
