QUANTIFICATION OF BIOLOGICAL RESPONSE TO LOW DOSE IONIZING RADIATION: A DOSE-RESPONSE MODELING APPROACH

Abstract

This dissertation explores the biological effects of low-dose ionizing radiation (LDIR). It investigates the mechanisms underlying adaptive responses that challenge traditional radiation risk models, particularly the linear no-threshold (LNT) model. The research aims to refine the dose-response framework by examining molecular, cellular, and epidemiological evidence, specifically focusing on DNA damage response (DDR), DNA repair pathways, immune response, and apoptosis. The study identifies key biomarkers involved in radiation-induced adaptive responses, including DNA repair proteins encoded by the protein kinase, DNA-activated, catalytic subunit gene (PRKDC) and antioxidant enzymes like superoxide dismutase (SOD) and catalase (CAT). Experimental findings demonstrate that LDIR activates defense mechanisms, with the most pronounced effects observed in the 1 – 5 mSv dose range. These findings suggest a potential threshold for adaptive responses below which radiation exposure may enhance cellular resistance to subsequent damage. Epidemiological data further support the notion that low-dose environmental and occupational radiation exposures do not consistently correlate with increased cancer risks, further substantiating the concept of radiation hormesis. However, at doses exceeding 20 mSv, a transition to LNT behavior is observed, aligning with the traditional understanding of radiation risk at higher doses. These results have implications for radiation protection and therapeutic strategies. Identifying biomarkers involved in the adaptive response enables the development of personalized radiation risk assessments and more effective radioprotective interventions. The study also suggests the need to revise current radiation safety standards, taking into account the potential for beneficial adaptive effects at low doses. In conclusion, this dissertation contributes to advancing our understanding of the biological effects of LDIR and adopts a model of radiation risk that incorporates adaptive responses. The findings provide a foundation for future research in radiation biology, policy development, and therapeutic applications, with a focus on personalized approaches to radiation safety and the potential for long-term adaptive effects.