This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.įunding: This study was supported by the National Aeronautics and Space Administration (NASA) grants NNX07AH70G and NNX09AU95G. Received: OctoAccepted: FebruPublished: March 21, 2013Ĭopyright: © 2013 Datta et al. 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.Ĭitation: Datta K, Suman S, Kallakury BVS, Fornace AJ Jr (2013) Heavy Ion Radiation Exposure Triggered Higher Intestinal Tumor Frequency and Greater β-Catenin Activation than γ Radiation in APC Min/+ Mice. Activation of β-catenin was more in 56Fe-irradiated tumor-free and tumor-bearing areas of the intestinal tissues. 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. Additionally, tumor incidence per unit of radiation (per cGy) was also higher after 56Fe radiation relative to γ radiation.
Relative to controls and γ-ray, intestinal tumor frequency and grade was significantly higher after 56Fe radiation. 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. 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 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. 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. 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.
0 kommentar(er)
