Asselin-Labat Marie-Liesse, Rampersad Rishi, Xu Xia, Ritchie Matthew E, Michalski Jacob, Huang Lingling, Onaitis Mark W
a University California San Diego, Moores Cancer Center, La Jolla, California.
b ACRF Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
Radiat Res. 2017 Nov;188(5):562-570. doi: 10.1667/RR14794.1. Epub 2017 Sep 27.
High-linear energy transfer (LET) radiation encountered by astronauts in space generates clustered DNA damage that is potentially oncogenic. Analysis of the impact of exposure to space radiation on cancer formation is necessary to determine the best ways to prepare astronauts for space travel so they are protected for the duration of the space mission. A mouse model of lung adenocarcinoma driven by oncogenic K-Ras was used to ascertain the effect of low- and high-LET radiation on tumor formation. We observed increased tumor progression and tumor cell proliferation after single dose or fractionated high-LET doses, which was not observed in mice exposed to low-LET radiation. Location of the tumor nodules was not affected by radiation, indicating that the cell of origin of K-Ras-driven tumors was the same in irradiated or nonirradiated mice. Gene expression analysis revealed an upregulation of genes involved in cell proliferation and DNA damage repair. This study provides evidence that exposure to a single dose or fractionated doses of high-LET radiation induces molecular and cellular changes that accelerate lung tumor growth.
宇航员在太空中遇到的高线性能量转移（LET）辐射会产生具有潜在致癌性的簇状DNA损伤。分析太空辐射暴露对癌症形成的影响，对于确定让宇航员为太空旅行做好准备的最佳方式至关重要，这样他们在太空任务期间就能得到保护。利用一种由致癌性K-Ras驱动的肺腺癌小鼠模型，来确定低LET和高LET辐射对肿瘤形成的影响。我们观察到，在单次剂量或分次高LET剂量照射后，肿瘤进展和肿瘤细胞增殖增加，而在接受低LET辐射的小鼠中未观察到这种情况。肿瘤结节的位置不受辐射影响，这表明在接受辐射或未接受辐射的小鼠中，K-Ras驱动的肿瘤的起源细胞是相同的。基因表达分析显示，参与细胞增殖和DNA损伤修复的基因上调。这项研究提供了证据，即暴露于单次剂量或分次剂量的高LET辐射会诱导分子和细胞变化，从而加速肺肿瘤生长。
