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1 February 2009 Radiation Protection by a New Chemical Entity, Ex-Rad™: Efficacy and Mechanisms
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Abstract

Ghosh, S. P., Perkins, M. W., Hieber, K., Kulkarni, S., Kao, T-C., Reddy, E. P., Reddy, M. V. R., Maniar, M., Seed, T. and Kumar, K. S. Radiation Protection by a New Chemical Entity, Ex-RadTM : Efficacy and Mechanisms. Radiat. Res. 171, 173–179 (2009).

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.

Sanchita P. Ghosh, Michael W. Perkins, Kevin Hieber, Shilpa Kulkarni, Tzu-Cheg Kao, E. Premkumar Reddy, M. V Ramana Reddy, Manoj Maniar, Thomas Seed, and K. Sree Kumar "Radiation Protection by a New Chemical Entity, Ex-Rad™: Efficacy and Mechanisms," Radiation Research 171(2), 173-179, (1 February 2009). https://doi.org/10.1667/RR1367.1
Received: 13 February 2008; Accepted: 1 September 2008; Published: 1 February 2009
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