Gene expression profiling after irradiation: clues to understanding acute and persistent responses?
Ionizing radiation (IR) is an ever-present hazard to humans primarily due to its mutagenic, carcinogenic, and cell killing ability. In addition to causing DNA damage, irradiation initiates a plethora of signal transduction cascades responsible for maintaining cellular homeostasis and promoting interactions with neighboring cells. Large-scale changes in gene expression have also been found after irradiation, and microarrays have helped discern these subsequent transcriptional alterations. While some studies have focused on low dose-rate experiments, others have analyzed the gene expression response of IR compared to other DNA damaging agents. Very few genes have been found to be consistently up-regulated by IR, but that set includes GADD45, CDKN1A, and genes associated with the nucleotide excision repair pathway. Overall, the immediate transcriptional responses to IR have implications for DNA repair, cell cycle arrest, growth control, and cell signaling. Additionally, there is a substantial p53-independent component to the transcriptional profile that could be exploited to increase the effectiveness of radiotherapy. Initial characterizations of the persistent responses to IR yielded a completely different profile than observed immediately after exposure. This profile is ephemeral, shifting even over the course of one set of experiments. Microarray analysis of radiation responses has also been applied to clinical response to radiotherapy, identifying genes linked to radio-sensitivity and resistance in B-cell chronic lymphoid leukemia and cervical cancer. Overall, these large-scale gene expression studies have added to the understanding of the complicated biological responses to IR, and when combined with other data sets will yield a complete picture of the short and long-term consequences of radiation.
Snyder
Andrew R
AR
Molecular and Cell Biology Graduate Program, Radiation Oncology Research Laboratory, University of Maryland, Baltimore, USA. asnyd002@umaryland.edu
Morgan
William F
WF
D000818:Animals; D004249:DNA Damage / Q000235:genetics / Q000528:radiation effects; D015870:Gene Expression / Q000528:radiation effects*; D020869:Gene Expression Profiling; D023281:Genomics; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000532:radiotherapy; D011839:Radiation, Ionizing