Low dose irradiation profoundly affects transcriptome and microRNAme in rat mammary gland tissues

Abstract

Ionizing radiation has been successfully used in medical tests and treatment therapies for a variety of medical conditions. However, patients and health-care workers are greatly concerned about overexposure to medical ionizing radiation and possible cancer induction due to frequent mammographies and/or CT scans. Diagnostic imaging involves the use of low doses of ionizing radiation, and its potential carcinogenic role creates a cancer risk concern for exposed individuals. In this study, the effects of X-ray exposure of different doses on the gene expression patterns and the micro-RNA expression patterns in normal breast tissue were investigated in rats. Our results revealed the activation of immune response pathways upon low dose of radiation exposure. These included natural killer mediated cytotoxicity pathways, antigen processing and presentation pathways, chemokine signaling pathways, and T- and B-cell receptor signaling pathways. Both high and low doses of radiation led to miRNA expression alterations. Increased expression of miR-34a may be linked to cell cycle arrest and apoptosis. Up-regulation of miR-34a was correlated with down-regulation of its target E2F3 and up-regulation of p53. This data suggests that ionizing radiation at specific high and low doses leads to cell cycle arrest and a possible initiation of apoptosis.