Combined Radiations: Biological Effects of Mixed Exposures Across the Radiation Spectrum

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Abstract
Combined radiation exposures—pairings of ionizing and non-ionizing radiation—are increasingly relevant in medical, spaceflight, and environmental contexts. This systematic review evaluates their radiobiological effects and therapeutic applications, focusing on synergistic interactions and underlying biological mechanisms. A comprehensive search of PubMed, Google Scholar, Semantic Scholar, bioRxiv, and Europe PMC identified studies published from the 1960s through 2025. Eligible studies assessed biological responses to different radiation types applied either simultaneously or within 24 hours, with minor exceptions. A total of 172 studies were included and categorized into radiobiological, therapeutic, and space radiation domains. Due to the predominance of mechanistic research, no formal risk-of-bias tool was applied; methodological limitations were assessed qualitatively. Findings were synthesized narratively by radiation type and domain. Synergistic and additive effects were frequently observed, with responses influenced by dose, sequence, radiation type, and DNA repair dynamics. Therapeutic combinations often enhanced efficacy, while space radiation studies revealed multifaceted biological damage. This review provides a consolidated reference for advancing research and applications involving combined radiation exposures, emphasizing the need for mechanistic insight and standardized protocols in therapy, radiation protection, and spaceflight. Funded by project 21GRD02 BIOSPHERE (European Partnership on Metrology, Horizon Europe). Reported per PRISMA 2020 guidelines; no protocol registered.

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