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Cited by 75Effects of Radiation ExposureRadiation Therapy and DosimetryCarcinogens and Genotoxicity Assessment

Heavy Ion Radiation Exposure Triggered Higher Intestinal Tumor Frequency and Greater β-Catenin Activation than γ Radiation in APCMin/+ Mice

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Datta, Kamal, Suman, Shubhankar, Kallakury, Bhaskar V. S., Fornace, Albert J.·2013·PLoS ONE
DOI 10.1371/journal.pone.0059295PMC PMC3605451
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Abstract

Risk of colorectal cancer (CRC) after exposure to low linear energy transfer (low-LET) radiation such as γ-ray is highlighted by the studies in atom bomb survivors. On the contrary, CRC risk prediction after exposure to high-LET cosmic heavy ion radiation exposure is hindered due to scarcity of in vivo data. Therefore, intestinal tumor frequency, size, cluster, and grade were studied in APC(Min/+) mice (n = 20 per group; 6 to 8 wks old; female) 100 to 110 days after exposure to 1.6 or 4 Gy of heavy ion (56)Fe radiation (energy: 1000 MeV/nucleon) and results were compared to γ radiation doses of 2 or 5 Gy, which are equitoxic to 1.6 and 4 Gy (56)Fe respectively. Due to relevance of lower doses to radiotherapy treatment fractions and space exploration, we followed 2 Gy γ and equitoxic 1.6 Gy (56)Fe for comparative analysis of intestinal epithelial cell (IEC) proliferation, differentiation, and β-catenin signaling pathway alterations between the two radiation types using immunoblot, and immunohistochemistry. Relative to controls and γ-ray, intestinal tumor frequency and grade was significantly higher after (56)Fe radiation. Additionally, tumor incidence per unit of radiation (per cGy) was also higher after (56)Fe radiation relative to γ radiation. Staining for phospho-histone H3, indicative of IEC proliferation, was more and alcian blue staining, indicative of IEC differentiation, was less in (56)Fe than γ irradiated samples. Activation of β-catenin was more in (56)Fe-irradiated tumor-free and tumor-bearing areas of the intestinal tissues. When considered along with higher levels of cyclin D1, we infer that relative to γ radiation exposure to (56)Fe radiation induced markedly reduced differentiation, and increased proliferative index in IEC resulting in increased intestinal tumors of larger size and grade due to preferentially greater activation of β-catenin and its downstream effectors.

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  • In intestinal tumors in APC Min/+ mice, heavy ions increased tumor multiplicity and grade compared to protons or γ-rays.

    “Intestinal tumors in APC Min/+ mice (Datta et al., 2013) Heavy ions increased tumor multiplicity and grade compared to protons or γ-rays.”

    From A proposed change to astronaut exposures limits is a giant leap backwards for radiation protection (2021) · cites this paper as Datta et al., 2013

    The Results sections on intestinal tumorigenesis and higher-grade tumors (page unavailable) report more tumors and a higher proportion of invasive adenocarcinomas after heavy-ion ⁵⁶Fe exposure than after equitoxic γ-ray exposure in APCMin/+ mice. The paper does not report a comparison with protons, so that comparator is unsupported. (LLM, conf=0.91)

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References 67 · Cited by 75

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Authors
Datta, K., Suman, S., Kallakury, B. V. S., & Fornace, A. J.
Affiliations
  • Georgetown University (US)
  • Georgetown University Medical Center (US)
Corresponding author
  • Datta, Kamal
  • Fornace, Albert J.
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2013-03-21
Volume
8
Issue
3
Pages
e59295
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0059295
PMC
PMC3605451
OpenAlex
W2041600512
Cited by
75
References
67
Citations by year
2026: 3 · 2025: 5 · 2024: 10 · 2023: 3 · 2022: 3 · 2021: 8 · 2020: 8 · 2019: 6 · 2018: 2 · 2017: 4 · 2016: 2 · 2015: 10 · 2014: 8 · 2013: 3
FWCI
5.95
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • National Aeronautics and Space Administration (NNX07AH70G, NNX09AU95G)
  • Brookhaven National Laboratory
Topics
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Radiation Therapy and Dosimetry
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
Keywords
heavy ion irradiation, iron-56, gamma radiation, colorectal cancer, intestinal tumors, β-catenin signaling, ApcMin/+ mice, intestinal epithelial cell proliferation, intestinal epithelial differentiation, cyclin D1, low linear energy transfer, cosmic rays, space radiation, tumor grade
MeSH terms
Animals, Cell Differentiation, Dose-Response Relationship, Radiation, Epithelial Cells, Female, Gamma Rays, Intestinal Neoplasms, Intestines, Iron, Mice, Transgenic, Signal Transduction, Gene Expression Regulation, Neoplastic, Linear Energy Transfer, Heavy Ions, Cell Proliferation, beta Catenin, Mice

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