Assessment of the Technologies for Molecular Biodosimetry for Human Low-Dose Radiation Exposure Symposium

Exposure to ionizing radiation produces few immediate outwardly-visible clinical signs, yet, depending on dose, can severely damage vital physiological functions within days to weeks and produce long-lasting health consequences among survivors. In the event of a radiological accident, the rapid evaluation of the individual absorbed dose is paramount to discriminate the worried but unharmed from those individuals who must receive medical attention. Physical, clinical and biological dosimetry are usually combined for the best dose assessment. However, because of the practical limits of physical and clinical dosimetry, many attempts have been made to develop a dosimetry system based on changes in biological parameters, including techniques for hematology, biochemistry, immunology, cytogenetics, etc. Lymphocyte counts and chromosome aberrations analyses are among the methods that have been routinely used for estimating radiation dose. However, these assays require several days to a week to be completed and therefore cannot be used to obtain a fast estimate of the dose during the first few days after exposure when the information would be most critical for identifying victims of radiation accidents who could benefit the most by medical intervention. The steadily increasing sophistication in our understanding of the early biochemical responses of irradiated cells and tissues provides the opportunity for developing mechanism-based biosignatures of exposure. Compelling breakthroughs have been made in the technologies for genome-scale analysis of cellular transcriptional and proteomic profiles. There have also been major strides in the mechanistic understanding of the early events in DNA damage and radiation damage products, as well as in the cellular pathways that lead to radiation injury. New research with genomic- and proteomic-wide tools is showing that within minutes to hours after exposure to ionizing radiation protein machines are modified and activated, and large-scale changes occur in the gene expression profile involving a broad variety of cell-process pathways after a wide range of both low ( 10 cGy) exposures. Evaluation of these potential gene and protein biomarkers for early and late diagnostic information will be critical for determining the efficacy of the signatures to both low and high dose IR exposures. Also needed are approaches that enable rapid handling and processing for mass-casualty and population triage scenarios. Development of in vivo model system will be crucial for validating both the biological and the instrumentation for biodosimetry. Such studies will also help further understanding of the molecular mechanisms of the biological effects of radiation and the differences of responses due to individual genetic variation.