Radiation biomarkers: novel insights from transcriptional studies

Every human living on Earth is constantly exposed to very low levels of natural ionizing radiation, which are harmless. Occasionally, though, individuals are exposed to radiation doses exceeding the natural background levels, often as a result of medical diagnostic tests and treatments but sometimes through the accidental or deliberate release of radioactivity. Identification of robust and reliable radiation biomarkers of exposure, which can be used as biological dosimeters following a large-scale nuclear accident or a terroristic attack are of pivotal importance for radiobiological research. At the same time, specific biomarkers of individual radiosensitivity would be of great value for improving radiotherapy treatment or for the selection of crews for long-term Space missions. As the model for our study we chose human blood cells. In the first step of our study we identified transcriptional biomarkers (genes and exons) of exposure to radiation with increased sensitivity to low-dose exposures. Our analysis also showed that several genes, especially those that were differentially expressed, are alternatively transcribed and spliced in response to irradiation. In the next step we designed a customized qRT-PCR array suitable for accurate prediction of both dose and time following radiation exposure, which allowed us to validate our approach using a system applicable to large-scale radiological accidents. In the last step of this study we compared the transcriptional response and DNA repair kinetics of human blood cells after exposure to X-rays, carbon and iron ions. With an eye to possible long-term Space flights we also showed the high potential of genes responsive to iron ions exposure to serve as an indicator of varied DNA repair capacity of healthy astronauts, which are expected to be selected for a similar mission.