Modulation of Gene Expression After Exposure to Ionizing Radiation

Regulation of gene expression is one of the fundamental mechanisms by which cells utilize the information in their DNA to obtain diverse characteristics, such as ability of differentiated cells to play specific roles and ability to respond to extracellular stresses including ionizing radiation (IR). The research on transcriptional regulation of genes after exposure to IR has a long history tracing back to early studies in late 1980’s. In those studies, expression of individual genes was separately measured by a classical hybridization method. Recently, however, functional genomics approaches, such as microarray profiling, enable us to simultaneously monitor the expression of thousands of genes, and are now recognized as a firmly established methodology in radiation biosciences. The porpose of investigation of transcriptional gene regulation by IR is primarily to gain an insight into how the human bodies respond to IR and eventually how radiation hazards develop. IR-induced hematopoietic death is an example where proapoptotic gene expression is enhanced in radiosensitive hematopoietic stem cells after exposure to high doses of IR, which causes untolerable loss of peripheral blood cells, ultimately resulting in the individual death. Secondary, the purpose of the reserach on transcriptional gene regulation is to search for biomarkers which indicate the quantitative IR-exposure records. Such biomarkers may help us estimate the exposed dose of public peolpe in the emergency cases. For these purposes, studies have been extensively carried out by lots of researchers, and plenty of insights were obtained. In this review article, some of these studies, including those carried out in our laboratory, will be overviewed with an emphasis on the important roles of a tumor supressor p53 in transcriptional regulation after IR exposure and organ-dependence of transcriptional regulation in vivo. Methodology for the research on transcriptional regulation is also briefly touched. And the future perspectives of the research on transcriptional responses to IR will be discussed.