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Abstract
The use of radioactive materials in medicine, agriculture, nuclear power production, and weapons development has long stimulated interest in the effects of prolonged exposure to low doses of ionizing radiation (IR). IR can break DNA strands by direct action and indirectly can result in protein oxidation, lipid peroxidation, and the inactivation of enzymes as a result of the formation of reactive oxygen species. While the effects of exposure to high doses of IR (1 Gy) are well documented, one of the biggest challenges in radiobiology is to understand if, at low doses of IR exposure, the consequences to an organism behave in a linear or non-linear manner. Currently, the health risks of low dose IR are extrapolated from higher dose studies, and as a result, the risks are based on predictions rather than on verifiable scientific evidence. The relation between chronic exposure to low dose IR and the increased risk of development of certain diseases has been suggested, but the mechanisms of that relationship are not clear. There is a clear need to understand how an organism responds to chronic exposure of low dose IR. This in turn will help to establish safety limits that are based in documented evidence rather than on extrapolation. Our goal was to begin to bridge the knowledge gap on this topic. To accomplish this, we first developed protocols from fish acutely exposed to IR to validate our experimental approach. Using the methods developed, we then investigated how the accumulation of environmentally relevant levels of IR impacts the expression of proteins and N-glycans in Medaka (Oryzias latipies), by performing a comparative proteomic-glycomic study. We observed that N-glycans containing fucose and/or sialic acid are the most responsive to low dose IR exposure. We found changes at the protein level that impact lipid, glycan, and protein metabolism, and these can be related to the phenotypes detected. The semi-quantitative glycoproteomic results revealed several potential biomarkers for chronic exposure to environmentally relevant levels of IR. Further research will establish their applicability in fields including radiation protection and safety, ecotoxicology, epidemiology, molecular medicine, and nuclear energy.