Distal airway epithelial progenitor cells are radiosensitive to High-LET radiation.

Journal Article (Journal Article)

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 γ-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 γ-rays, which has implications in therapeutic development and risk assessment.

Full Text

Duke Authors

Cited Authors

  • McConnell, AM; Konda, B; Kirsch, DG; Stripp, BR

Published Date

  • September 23, 2016

Published In

Volume / Issue

  • 6 /

Start / End Page

  • 33455 -

PubMed ID

  • 27659946

Pubmed Central ID

  • PMC5034250

Electronic International Standard Serial Number (EISSN)

  • 2045-2322

Digital Object Identifier (DOI)

  • 10.1038/srep33455

Language

  • eng

Conference Location

  • England