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Apoptosis and expression of apoptosis-related genes in mouse intestinal tissue after whole-body proton exposure

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Abstract

Energetic protons are the most abundant particle type in space and can pose serious health risks to astronauts during long-duration missions. The health effects of proton exposure are also a concern for cancer patients undergoing radiation treatment with accelerated protons. To investigate the damage induced by energetic protons in vivo to radiosensitive organs, 6-week-old BALB/c male mice were subjected to 250 MeV proton radiation at whole-body doses of 0.1, 1, and 2 Gy. The gastrointestinal (GI) tract of each exposed animal was dissected 4 h post-irradiation, and the isolated small intestinal tissue was analyzed for histopathological and gene expression changes. Histopathologic observation of the tissue using standard hematoxylin and eosin (H&E) staining methods to screen for morphologic changes showed a marked increase in apoptotic lesions for even the lowest dose of 0.1 Gy, similar to X- or γ rays. The percentage of apoptotic cells increased dose-dependently, but the dose response appeared supralinear, indicating hypersensitivity at low doses. A significant decrease in surviving crypts and mucosal surface area, as well as in cell proliferation, was also observed in irradiated mice. Gene expression analysis of 84 genes involved in the apoptotic process showed that most of the genes affected by protons were common between the low (0.1 Gy) and high (1 and 2 Gy) doses. However, the genes that were distinctively responsive to the low or high doses suggest that high doses of protons may cause apoptosis in the small intestine by direct damage to the DNA, whereas low doses of protons may trigger apoptosis through a different stress response mechanism.

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Acknowledgements

The first author (AP) wishes to dedicate this work to the memory of Michael Gilles Purgason. This work was supported by the US Department of Energy Low Dose Radiation Program and the NASA Human Research Program. AP was supported in part by the NASA Graduate Student Research Program. MMV was supported by German Research Foundation (DFG).

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Authors and Affiliations

  1. University of Texas at Arlington, Arlington, TX, USA

    Ashley Purgason

  2. NASA Kennedy Space Center, Cape Canaveral, FL, USA

    Ye Zhang

  3. University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Stanley R. Hamilton

  4. Loma Linda University Medical Center, Loma Linda, CA, USA

    Daila S. Gridley

  5. Texas Southern University, Houston, TX, USA

    Ayodotun Sodipe

  6. Long Star College-Kingwood, Kingwood, TX, USA

    Olufisayo Jejelowo

  7. Norfolk State University, Norfolk, VA, USA

    Govindarajan T. Ramesh

  8. NASA Johnson Space Center, SK: Bldg. 37:1100D, 2101 NASA Pkwy, Houston, TX, 77058, USA

    Maria Moreno-Villanueva & Honglu Wu

  9. University of Konstanz, Constance, Germany

    Maria Moreno-Villanueva

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  1. Ashley Purgason
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Purgason, A., Zhang, Y., Hamilton, S.R. et al. Apoptosis and expression of apoptosis-related genes in mouse intestinal tissue after whole-body proton exposure. Mol Cell Biochem 442, 155–168 (2018). https://doi.org/10.1007/s11010-017-3200-0

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