O-316 the Potential Application of Gene Expression Profiles to Predict Biological Effects of Low Dose Ionizing Radiation Exposure: Are Biomarkers in Human Blood Cells Reliable for the Carcinogenic Risk Assessment?

Introduction Low dose ionizing radiation (LDIR, dose<100mGy) could increase the risk of occurrence of stochastic effects (e.g., cancer induction) in irradiated cells, but also in nearby or distant cells not directly irradiated (bystander effect). The probability of LDIR harmful effects is currently evaluated using the linear no-threshold model for preventive radiation protection purposes. Potential biological dosimeters include several classes of biomarkers: cytogenetic, gene mutation related, nucleotide pool and DNA damage related, and transcriptional and translational changes related. Methods Since LDIR can trigger biological mechanisms which alter genome, epigenome, transcriptome and/or proteome before modifying cell differentiation and phenotype, the study of gene expression profiles can improve biodosimetry-based assessment. Results The ideal biomarker for occupational radioprotection should differentiate acute from chronic exposure; estimate dose received; identify early and long-term health effects; assess increased susceptibility both during and after exposure in terms of carcinogenic risk. Changes in gene expression may be an early indicator of cellular responses to LDIR, with some genes dose-dependent and others dose-independent. Gene expression profiles derived from microarray technology are used on blood cells for IR doses (between 0.5-10Gy for 4-24 hours). Discussion According to the results of in-vivo and ex-vivo studies on human blood cells, IR-specific mRNA transcript profiles have been shown to be as reliable as the gold standard of biodosimetry (Dicentric Chromosome Assay), even among laboratories using different protocols. Conclusion Additional research on the individual IR gene signature and possible confounders is required to estimate the true harmful dose and duration, and create a customized radiation protection model for LDIR-exposed workers.