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28 July 2017 A Single Exposure to Low- or High-LET Radiation Induces Persistent Genomic Damage in Mouse Epithelial Cells In Vitro and in Lung Tissue
Erica Werner, Ya Wang, Paul W. Doetsch
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Exposures to low- and high-linear energy transfer (LET) radiation induce clustered damage in DNA that is difficult to repair. These lesions are manifested as DNA-associated foci positive for DNA repair proteins and have been shown to persist in vitro and in vivo for days in several cell types and tissues in response to low-LET radiation. Although in some experimental conditions these residual foci have been linked with genomic instability and chromosomal aberrations, it remains poorly understood what type of damage they represent. Because high-LET radiation induces complex DNA lesions more efficiently than low-LET radiation, we compared the efficacy of several heavy ions (oxygen, silicon and iron) in a range (17 , 70 and 175 keV/μm, respectively) of LET and X rays at a 1 Gy dose. Persistent genomic damage was measured by γ-H2AX-53BP1-positive residual foci and micronucleus levels during the first three days and up to a week after in vitro and in vivo irradiation in lung cells and tissue. We demonstrate that in an in vitro irradiated mouse bronchial epithelial cell line, the expression of residual foci is readily detectable at 24 h with levels declining in the following 72 h postirradiation, but still persisting elevated over background at day 7. At this time, foci numbers are low but significant and proportional to the dose and quality of the radiation. The expression of residual foci in vitro was mirrored by increased micronuclei generation measured in cytokinesis-blocked cells, indicating long-term, persistent effects of genomic damage in this cell type. We also tested the expression of residual foci in lung tissue of C57BL/6 mice that received whole-body X-ray or heavy-ion irradiation. We found that at day 7 postirradiation, Clara/Club cells, but not pro-SPC-positive pneumocytes, contained a subpopulation of cells expressing γ-H2AX-53BP1-positive foci in a radiation quality-dependent manner. These findings suggest that in vivo persistent DNA repair foci reflect the initial genotoxic damage induced by radiation and a differential vulnerability among cells in the lung.

©2017 by Radiation Research Society
Erica Werner, Ya Wang, and Paul W. Doetsch "A Single Exposure to Low- or High-LET Radiation Induces Persistent Genomic Damage in Mouse Epithelial Cells In Vitro and in Lung Tissue," Radiation Research 188(4), 373-380, (28 July 2017).
Received: 13 November 2016; Accepted: 1 June 2017; Published: 28 July 2017
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