Models for the Development of Radiation Countermeasures

Appropriate models are essential for making the transition from scientific discoveries to meaningful applications of the knowledge for human use. Acute as well as delayed effects of ionising radiation to the biological systems develop hierarchically starting from damage to the vital macromolecules up to the disturbances caused at the whole organism level. In vitro models like bacteria, yeast, various mammalian cells cultured as monolayers (2-D) and spheroids (3-D) as well as cells with specific genetic alterations have provided insight into the complex relationships between damage induction and various signal transduction pathways, allowing identification of molecular and sub-cellular targets vital to the fate of irradiated cells. On the other hand, in vivo models (multicellular whole organisms), ranging from simple worms to non-human primates, have been gainfully employed to evaluate efficacy as well as toxicity of potential countermeasure agents (molecules, combinations and formulated preparations) facilitating their deployment in human subjects. This review provides a brief account of the efforts with various in vitro and in vivo models for understanding the biological basis of radiation damage as well as the development of radiation countermeasures, viz., protectors, mitigators and therapeutics. [PUBLICATION ABSTRACT]