High-LET Radiation Increases Tumor Progression in a K-Ras-Driven Model of Lung Adenocarcinoma.

Abstract

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.