Induction of gene expression as a monitor of exposure to ionizing radiation

The complex molecular responses to genotoxic stress are mediated by a varie ty of regulatory pathways. The transcription factor TP53 plays a central ro le in the cellular response to DNA-damaging agents such as ionizing radiati on, but other pathways also play important roles. In addition, differences in radiation quality, such as the exposure to high-LET radiation that occur s during space travel, may influence the pattern of responses. The premise is developed that stress gene responses can be employed as molecular marker s for radiation exposure using a combination of informatics and functional genomics approaches. Published studies from our laboratory have already dem onstrated such transcriptional responses with doses of gamma rays as low as 2 cGy, and in peripheral blood lymphocytes (PBLs) irradiated ex vivo with doses as low as 20 cGy. We have also found several genes elevated in vivo 2 4 h after whole-body irradiation of mice with 20 cGy. Such studies should p rovide insight into the molecular responses to physiologically relevant dos es, which cannot necessarily be extrapolated from high-dose studies. In add ition, ongoing experiments are identifying large numbers of potential bioma rkers using microarray hybridization and various irradiation protocols incl uding expression at different times after exposure to low- and high-LET rad iation. Computation-intensive informatics analysis methods are also being d eveloped for management of the complex gene expression profiles resulting f rom these experiments. With further development of these approaches, it may be feasible to monitor changes in gene expression after low-dose radiation exposure and other physiological stresses that may be encountered during m anned space flight, such as the planned mission to Mars. (C) 2001 by Radiat ion Research Society.