Beneficial effects of low dose radiation in response to the oncogenic KRAS induced cellular transformation

Sci Rep. 2015 Oct 30:5:15809. doi: 10.1038/srep15809.

Abstract

Recently low dose irradiation has gained attention in the field of radiotherapy. For lack of understanding of the molecular consequences of low dose irradiation, there is much doubt concerning its risks on human beings. In this article, we report that low dose irradiation is capable of blocking the oncogenic KRAS-induced malignant transformation. To address this hypothesis, we showed that low dose irradiation, at doses of 0.1 Gray (Gy); predominantly provide defensive response against oncogenic KRAS -induced malignant transformation in human cells through the induction of antioxidants without causing cell death and acts as a critical regulator for the attenuation of reactive oxygen species (ROS). Importantly, we elucidated that knockdown of antioxidants significantly enhanced ROS generation, invasive and migratory properties and abnormal acini formation in KRAS transformed normal as well as cancer cells. Taken together, this study demonstrates that low dose irradiation reduces the KRAS induced malignant cellular transformation through diminution of ROS. This interesting phenomenon illuminates the beneficial effects of low dose irradiation, suggesting one of contributory mechanisms for reducing the oncogene induced carcinogenesis that intensify the potential use of low dose irradiation as a standard regimen.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / radiation effects
  • Catalase / antagonists & inhibitors
  • Catalase / genetics
  • Catalase / metabolism
  • Cell Line
  • Cell Movement / radiation effects
  • Cell Transformation, Neoplastic / radiation effects*
  • Dose-Response Relationship, Radiation
  • Epithelial-Mesenchymal Transition
  • Gamma Rays*
  • Glutathione Peroxidase / antagonists & inhibitors
  • Glutathione Peroxidase / genetics
  • Glutathione Peroxidase / metabolism
  • Humans
  • MCF-7 Cells
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Reactive Oxygen Species / metabolism
  • ras Proteins / genetics*
  • ras Proteins / metabolism

Substances

  • RNA, Small Interfering
  • Reactive Oxygen Species
  • Catalase
  • Glutathione Peroxidase
  • ras Proteins