Radiation protection by a new chemical entity, Ex-Rad™: Efficacy and mechanisms

Sanchita P. Ghosh, Michael W. Perkins, Kevin Hieber, Shilpa Kulkarni, Tzu Cheg Kao, E. Premkumar Reddy, M. V. Ramana Reddy, Manoj Maniar, Thomas Seed, K. Sree Kumar

Research output: Contribution to journalArticle

49 Scopus citations

Abstract

Ex-Rad™ is among a series of small molecule kinase inhibitors developed for modifying cell cycle distribution patterns in cancer cells subjected to radiation therapy, and it has been identified as a potential candidate for radiation protection studies. We have investigated its radioprotective efficacy using mouse and in vitro models. Thirty-day survival studies with C3H/HeN male mice revealed 88% survival when 500 mg/kg of Ex-Rad was injected subcutaneously 24 h and 15 min before γ irradiation with 8.0 Gy. To understand Ex-Rad's mechanism of action, we also studied its radioprotective efficacy in lung fibroblast (HFL-1), skin fibroblast (AG1522) and human umbilical vein endothelial cells (HUVECs). Colony-forming assays indicated that Ex-Rad protected cells from radiation damage after exposure to 60Co γ radiation. A study using single-cell gel electrophoresis (SCGE; also known as the alkaline comet assay) showed that Ex-Rad protected cells from radiation-induced DNA damage. Western blot analyses indicated that the radiation protection provided by Ex-Rad resulted in reduced levels of pro-apoptosis proteins such as p53 as well as its downstream regulators p21, Bax, c-Abl and p73, indicating that Ex-Rad could rescue cells from ionizing radiation-induced p53-dependent apoptosis. In conclusion, it appears that Ex-Rad's radioprotective mechanisms involve prevention of p53-dependent and independent radiation-induced apoptosis.

Original languageEnglish (US)
Pages (from-to)173-179
Number of pages7
JournalRadiation Research
Volume171
Issue number2
DOIs
StatePublished - Feb 1 2009

ASJC Scopus subject areas

  • Biophysics
  • Radiation
  • Radiology Nuclear Medicine and imaging

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    Ghosh, S. P., Perkins, M. W., Hieber, K., Kulkarni, S., Kao, T. C., Premkumar Reddy, E., Ramana Reddy, M. V., Maniar, M., Seed, T., & Sree Kumar, K. (2009). Radiation protection by a new chemical entity, Ex-Rad™: Efficacy and mechanisms. Radiation Research, 171(2), 173-179. https://doi.org/10.1667/RR1367.1