REVISITING LOW DOSE RADIOBIOLOGY: MECHANISTIC INSIGHTS AND FUTURE DIRECTIONS
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Abstract
Low-dose radiobiology focuses on the biological effects of ionizing radiation at absorbed doses that are less than about 100 mGy or low dose rates (less than 10 mGy/h -1). These exposures are common, and they include the diagnostic imaging, nuclear medicine, radiotherapy scatter, occupational and environmental exposures, radon exposures and space travel. Although widespread, the biological effects of low dose radiation (LDR) have not been fully defined and they persistently troubles the current radiation risk assessment systems. Linear no-threshold (LNT) radiation protection has been the basis upon which radiation protection has depended over decades, wherein a proportional relationship exists between dose and stochastic risk and there exists no safe dose. Despite the fact that LNT has offered a conservative and practical regulatory foundation, increasing experimental and mechanistic information suggests that it is not sufficiently comprehensive of biological responses in the low-dose area. Recent developments in the field of molecular biology, epigenetics, microdosimetry, and systems biology show that LDR can trigger adaptive signaling, non-targeted, and long-lasting epigenetic reprogramming without causing a corresponding DNA damage. The responses tend to be qualitative as opposed to high-dose effects being extended in a linear manner. This is a critical review of the empirical and biological basis of the LNT paradigm against modern mechanistic data, a comparison with currently evolving non-linear dose response models, and epigenetic regulation as the key determinant of low dose effects. Combining historical information with the current experimental and clinical data, we will seek to answer the current controversies, and provide a way forward in terms of biologically informed but pragmatically feasible models of low-dose radiation risk assessment.
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