Heavy ion radiation exposure triggered higher intestinal tumor frequency and greater β-catenin activation than γ radiation in APC(Min/+) mice.
Heavy ion radiation exposure triggered higher intestinal tumor frequency and greater β-catenin activation than γ radiation in APC(Min/+) mice.
复制标题
DOI：
10.1371/journal.pone.0059295
复制
发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Fornace AJ Jr
中科院分区：
文献类型：
--
作者：
Datta K;Suman S;Kallakury BV;Fornace AJ Jr
对原子弹爆炸幸存者的研究强调了暴露于γ射线等低线性能量转移（low-LET）辐射后发生结直肠癌（CRC）的风险。相反，由于体内数据的稀缺，高LET宇宙重离子辐射暴露后的CRC风险预测受到阻碍。因此，在APCMin/+小鼠中研究了肠肿瘤的频率、大小、簇和等级（每组n = 20; 6 ~ 8周龄;雌性）100 - 110天，并与2或戈伊γ辐射剂量进行比较，这两种剂量分别与1.6和戈伊56 Fe的毒性相等。由于较低剂量与放射治疗分次和空间探索的相关性，我们跟踪了2戈伊γ和等毒性1.6戈伊56 Fe，使用免疫印迹和免疫组织化学比较分析两种辐射类型之间的肠上皮细胞（IEC）增殖、分化和β-连环蛋白信号通路改变。相对于对照组和γ射线，56 Fe辐射后肠道肿瘤的发生率和分级显著升高。此外，相对于γ辐射，56 Fe辐射后每单位辐射（每cGy）的肿瘤发生率也更高。与γ射线照射的样品相比，56 Fe中磷酸化组蛋白H3的染色（指示IEC增殖）更多，而阿辛蓝染色（指示IEC分化）较少。β-catenin在56 Fe照射的无瘤区和荷瘤区的肠组织中活化更多。当考虑到沿着较高水平的细胞周期蛋白D1时，我们推断相对于γ辐射暴露，56 Fe辐射诱导IEC分化显著降低，增殖指数增加，导致更大尺寸和等级的肠肿瘤增加，这是由于β-连环蛋白及其下游效应物的优先更大活化。
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.
登录
查看更多内容
影响因子：
3.4
作者：
Ding, LH;Shingyoji, M;Chen, DJ
通讯作者：
Chen, DJ
DOI：
10.1038/ncpgasthep0256
发表时间：
2005-09-01
期刊：
NATURE CLINICAL PRACTICE GASTROENTEROLOGY & HEPATOLOGY
影响因子：
--
作者：
Adler, DG
通讯作者：
Adler, DG
影响因子：
11.4
作者：
Aberle, H;Bauer, A;Kemler, R
通讯作者：
Kemler, R
影响因子：
3.4
作者：
Ding, LH;Shingyoji, M;Chen, DJ
通讯作者：
Chen, DJ
DOI：
10.1073/pnas.91.19.8969
发表时间：
1994-09-13
影响因子：
11.1
作者：
FODDE, R;EDELMANN, W;KUCHERLAPATI, R
通讯作者：
KUCHERLAPATI, R