ABSTRACT
The observation that radiation treatment caused the induction of stress response genes in bacteria and yeast provided motivation for the early studies of changes in gene expression in irradiated mammalian cells. The demonstration that radiation induces transcription of the tumor necrosis factor-a (TNF-a) gene was the first evidence for activation of mammalian genes in the response to radiation, and it was subsequently found that radiation treatment is associated with induction of a number of early and late responding genes. These findings demonstrated that ionizing radiation activates nuclear signaling cascades and supported the notion that radiation-inducible genes contribute to the regulation of events such as DNA repair, mutagenesis, apoptosis, tissue repopulation, and the late sequelae of radiation damage, and that the effects of radiation on tumor and normal tissues are mediated in part by autocrine and paracrine responses to a number of secreted factors including TNF-a. As has been described in several of the preceding chapters, ionizing radi-
ation initiates complex intracellular signaling pathways that activate cellcycle checkpoints, DNA repair, and apoptosis. These pathways include the activation of the plasma membrane receptors, ceramide synthesis, modulation of protein kinase cascades, and regulation of transcriptional pathways. This chapter focuses on transcriptional factors induced by ionizing radiation, on the late responding genes that are activated by these factors, and on the gene products that are of extreme importance in shaping the radiation response of the organism. The term ‘‘activation’’ will refer to the conversion of an inert protein to an active form that can stimulate transcription of the gene. Expression of a new transcript or protein as a result of the activation of these transactivation factors is then the product of an induced gene. Much of the information about radiation-induced genes and the impact
these genes produce on the radiation response of the organismwas gathered before the advent of all-inclusive genetic screening methods such as cDNA
microarray technology. The application of these methods has demonstrated that many hundreds of genes are regulated following radiation exposure with the responses being time, dose, and cell-type specific and have also provided support for the conclusions drawn from earlier studies.
