The ozone layer in the Earth’s atmosphere filters solar radiation and limits the unwanted effects on humans. A depletion of this ozone shield would permit hazardous levels of UV solar radiation, especially in the UVB range, to bombard Earth’s surface, resulting in potentially significant effects on human health. The concern for these adverse effects intensifies if we consider that the UVB solar radiation is combined with secondary cosmic radiation (SCR) components, such as protons and muons, as well as terrestrial gamma rays. This research aims to delve into the intricate interplay between cosmic and solar radiation on earth at the cellular level, focusing on their synergistic effects on human cell biology. Through a multidisciplinary approach integrating radiobiology and physics, we aim to explore key aspects of biological responses, including cell viability, DNA damage, stress gene expression, and finally, genomic instability. To assess the impact of the combined exposure, normal i.e., non-malignant human cells (skin fibroblasts, keratinocytes, monocytes, and lymphocytes) were exposed to high-energy protons or gamma rays in combination with UVB. Cellular molecular and cytogenetic biomarkers of radiation exposure, such as DNA damage (γH2AΧ histone protein and dicentric chromosomes), as well as the expression pattern of various stress genes, were analyzed. In parallel, the MTS reduction and lactate dehydrogenase assays were used as indicators of cell viability, proliferation, and cytotoxicity. Results reveal remaining DNA damage for the co-exposed samples compared to samples exposed to only one type of radiation in all types of cells, accompanied by increased genomic instability and distinct stress gene expression patterns detected at 24–48 h post-exposure. Understanding the impact of combined radiation exposures is crucial for assessing the health risks posed to humans if the ozone layer is partially depleted, with structural and functional damages inflicted by combined cosmic and UVB exposure.

Radiotherapy (RT) is a major part of cancer treatment. The reported variability in patient response to this modality can interfere with the continuation of best-possible care, promote side effects, and lead to long-term morbidity. Tools to predict a patient’s response to radiation could be highly useful in improving therapeutic outcomes while minimizing unnecessary and toxic exposure to radiation. This study investigates the potential of using molecular biomarkers as predictors of radiosensitivity in clinical practice. We review relative studies researching the positive correlation between various molecular biomarkers and patient radiosensitivity, including DNA damage response and repair proteins, inflammation and apoptosis markers, cell cycle regulators, and other biological markers. The clinical perspectives and applicability of these biomarkers in the prediction of radiosensitivity are also critically discussed. Conclusively, we underline the dynamics of molecular biomarkers to improve the efficacy and safety of radiotherapy in clinical practice and highlight the need for further research in this field. Identification of the most prominent markers is crucial for the personalization of therapies entailing ionizing radiation.

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 h, 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. This study was funded by project 21GRD02 BIOSPHERE (European Partnership on Metrology, Horizon Europe) and reported per PRISMA 2020 guidelines; no protocol was registered.

Replication stress (RS) is a hallmark of cancer, largely driven by oncogene activation. Due to high levels of RS, cancer cells depend heavily on the RS response mechanisms to avoid DNA damage. This dependency creates a therapeutic opportunity that can be exploited for more effective cancer treatment. This review synthesizes current mechanistic understanding of RS and RS response and further describes how targeted disruption of RS response proteins (ATR, Chk1, Wee1, PARP, RPA) has been used in preclinical and clinical studies. We summarize preclinical and emerging clinical evidence for exploiting RS for radiosensitization, and outline candidate biomarkers and functional assays for patient selection. We also highlight the links between RS, therapy-induced senescence and innate immune activation via the cGAS–STING (cyclic GMP-AMP synthase—Stimulator of Interferon Genes) pathway, and address current challenges and future directions.

Exposure to ionizing and non-ionizing radiation from environmental and clinical settings can significantly threaten genomic stability, especially when combined. This ex vivo study investigates the potential combined effects of gamma radiation and ultraviolet B (UVB) exposure on human peripheral blood mononuclear cells (PBMCs) from healthy donors by exposing whole blood and isolated PBMCs to 1 Gy of gamma rays, to an absolute dose of approximately 100 J/m² of UVB, or to their combination. Combined exposure resulted in significantly elevated γH2AX foci formation and chromosomal aberrations relative to individual stressors, with the most pronounced effects observed in isolated PBMCs. Notably, lymphocytes from some donors failed to proliferate after UVB or co-exposure. Based on our results, a predictive biophysical model derived from dicentric yield was developed to estimate the gamma-ray equivalent dose from co-exposure, indicating up to ~9% increase in lifetime cancer risk. Although this proof-of-concept study included only a small number of donors and focused on two endpoints (γH2AX and dicentric assays), it provides a controlled framework for investigating mechanisms of radiation-induced genomic instability. The results emphasize the importance of accounting for mixed radiation exposures in genotoxic risk assessment and radiation protection.

The production, attenuation, and absorption of secondary cosmic rays (SCR) are influenced by atmospheric parameters such as air pressure and temperature. To reliably correlate SCR flux measurements with atmospheric ionization driven by energetic particle precipitation, these dependencies must be quantified. Monte Carlo simulations enable detailed modeling of stochastic interactions between cosmic radiation and atmospheric components, providing a robust framework for analyzing underlying physical processes and predicting SCR flux under varying atmospheric conditions. This study introduces a simulation model based on the Monte Carlo N‐Particle (MCNP) code, integrating atmospheric profiles from radiosonde data to model the production, absorption, and attenuation of SCR. The model's accuracy was validated through comparisons with the PHITS (Particle and Heavy Ion Transport code System)‐based Analytical Radiation Model in the Atmosphere (PARMA) and experimental ground‐based muon count measurements. It was subsequently used to investigate the dependence of muon flux on atmospheric pressure and temperature up to 20 km altitude. Results reveal a complex relationship between muon flux and atmospheric variables, particularly in the troposphere and lower stratosphere, where pressure correlations and barometric coefficients exhibit both positive and negative values depending on altitude. The model provides a valuable tool for investigating interactions between SCR and climate variables such as humidity and cloud coverage. Furthermore, the model can be coupled with dosimetry models to assess the biological effects of SCR, including deoxyribonucleic acid (DNA) damage, genomic instability, cellular dysfunction, and long‐term health risks such as cancer.