Microarray analysis of the transcriptional response to ionizing radiation in human radiation sensitive cell lines

Abstract

Radiation is a common treatment of cancer. It can be used either as the primary therapy or as an adjuvant treatment. The objective of radiation therapy is to kill the cancer cells, while minimizing the damage on normal tissue. Radiation oncologists have for a long time known that individuals respond differently to radiation. In addition to the variation in tumour response, some patients show severe side effects when exposed to small doses of radiation, while others tolerate larger doses without much complication. Patients that are sensitive to radiation should be protected against the adverse side effects of therapeutic radiation exposure. However, this requires the identification of radiation sensitive patients before initializing the therapy. The aim of this study was to explore the underlying cause of radiation sensitivity in twelve radiation sensitive (RS) patients, by comparing their gene expression profiles with the profiles of four AT (Ataxia Telangiectasia) patients and five normal individuals. The RS patients show an AT phenotype without having mutations in the ATM gene. The RS patients could have different underlying genetic defects, although patients with defects in the same gene were expected to respond similarly in the transcriptional program after radiation. The type of response could point to candidate genes that are defect in the various classes of RS patients. The results showed that the RS samples have a different expression phenotype from both the AT patients and the normal patients, and that six of the RS patients have a distinct expression profile before radiation. This implies that the RS patients are a heterogeneous group, but that six of the patients may have a common cause of radiation sensitivity. These six patients show a highly different expression of genes involved in cell cycle regulation and DNA repair, such as GADD45B, WAF1, and DDB2. Thus, defective genes in these processes, perhaps in the genes mentioned, might be the cause of their radiation sensitivity. These genes may in the future be used to distinguish one group of radiation sensitive patients from patients with normal sensitivity.