Heavy Ion Radiation Exposure Triggered Higher Intestinal Tumor Frequency and Greater β-Catenin Activation than γ Radiation in APCMin/+ Mice
Open Access
- 21 March 2013
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 8 (3), e59295
- https://doi.org/10.1371/journal.pone.0059295
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 APCMin/+ 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 56Fe 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 56Fe respectively. Due to relevance of lower doses to radiotherapy treatment fractions and space exploration, we followed 2 Gy γ and equitoxic 1.6 Gy 56Fe 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 56Fe radiation. Additionally, tumor incidence per unit of radiation (per cGy) was also higher after 56Fe 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 56Fe than γ irradiated samples. Activation of β-catenin was more in 56Fe-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 56Fe 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.Keywords
This publication has 66 references indexed in Scilit:
- Sex-dependent Differences in Intestinal Tumorigenesis Induced in Apc1638N/+ Mice by Exposure to γ RaysInternational Journal of Radiation Oncology*Biology*Physics, 2013
- Accelerated hematopoietic toxicity by high energy56Fe radiationInternational Journal of Radiation Biology, 2011
- Whole mouse blood microRNA as biomarkers for exposure to 𝛄-rays and56Fe ionsInternational Journal of Radiation Biology, 2011
- Enhanced intestinal tumor multiplicity and grade in vivo after HZE exposure: mouse models for space radiation risk estimatesRadiation and Environmental Biophysics, 2010
- Stem Cells, Self-Renewal, and Differentiation in the Intestinal EpitheliumAnnual Review of Physiology, 2009
- Genomic and Epigenetic Instability in Colorectal Cancer PathogenesisGastroenterology, 2008
- THE WNT SIGNALING PATHWAY IN DEVELOPMENT AND DISEASEAnnual Review of Cell and Developmental Biology, 2004
- Cancer genes and the pathways they controlNature Medicine, 2004
- Heavy ion mutagenesis: Linear energy transfer effects and genetic linkageRadiation and Environmental Biophysics, 1995
- Radiation-induced Genomic InstabilityInternational Journal of Radiation Biology, 1994