Oxygen and Silicon Ion Particles Induce Neoplastic Transformation in Human Colonic Epithelial Cells

ABSTRACT High charge (Z) and energy (E) (HZE) particles in deep space have significantly contributed to the biological effects of space radiation, although they only account for less than 1% of the galactic cosmic rays (GCR) particle fluxes. Previously we have shown that combined radiation exposure of 2-Gy proton (1H) followed by 0.5-Gy iron (56Fe) ion particles increase transformation in human colonic epithelial cells (HCEC CT7). The present study was undertaken to characterize if additional HZE ions, such as oxygen (16O) and silicon (28Si) particles, also result in increased cell transformation. HCEC CT7 cells irradiated with 1-Gy 16O (250 MeV/nucleon), followed 24 hours later by 1-Gy 28Si particle (300 MeV/nucleon), showed an increase in proliferation, anchorage-independent growth, migration, and invasion abilities compared to unirradiated controls. In addition, we found that the β-catenin pathway was activated and that subsets of DNA repair genes were under-expressed in these transformed cells. Pretreatment with the radioprotector, CDDO-Me, 18 hours before and during irradiation prevented the HZE-induced transformation. These results can be interpreted to suggest that the mixed radiation exposure of 16O followed by 28Si has carcinogenic potential. Importantly, this transformation can be protected by CDDO-Me pre-treatment.