科研之友
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摘要
Risk of colorectal cancer (CRC) after exposure to low linear energy transfer (low-LET) radiation such as c-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 Fe-56 radiation (energy: 1000 MeV/nucleon) and results were compared to gamma radiation doses of 2 or 5 Gy, which are equitoxic to 1.6 and 4 Gy Fe-56 respectively. Due to relevance of lower doses to radiotherapy treatment fractions and space exploration, we followed 2 Gy gamma and equitoxic 1.6 Gy Fe-56 for comparative analysis of intestinal epithelial cell (IEC) proliferation, differentiation, and beta-catenin signaling pathway alterations between the two radiation types using immunoblot, and immunohistochemistry. Relative to controls and gamma-ray, intestinal tumor frequency and grade was significantly higher after Fe-56 radiation. Additionally, tumor incidence per unit of radiation (per cGy) was also higher after Fe-56 radiation relative to gamma radiation. Staining for phospho-histone H3, indicative of IEC proliferation, was more and alcian blue staining, indicative of IEC differentiation, was less in Fe-56 than gamma irradiated samples. Activation of beta-catenin was more in Fe-56-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 gamma radiation exposure to Fe-56 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 beta-catenin and its downstream effectors.
- 出版日期2013-3-21
