Dual Modulation of Radiation Response by Natural Compounds: Mechanisms and Translational Applications

Dear Colleagues,

Ionizing radiation is widely used in cancer diagnosis and therapy, but its clinical application is constrained by the balance between tumor cell radiosensitization and the protection of surrounding healthy tissue. Natural compounds—including polyphenols, flavonoids, and phenolic diterpenes such as rosmarinic acid, carnosic acid, and grape seed procyanidins—have emerged as promising candidates for dual modulation of the radiation response: exerting radioprotective effects in normal cells while, paradoxically, sensitizing certain tumor cell lines to radiation-induced damage. Characterizing this dual behavior across tumor and normal cell models is central to the scope of this Special Issue.

Understanding the cellular and molecular mechanisms underlying this dual modulation—including cell cycle arrest, apoptosis induction, DNA damage markers (e.g., γ-H2AX, caspases), and antioxidant system modulation—is essential for the rational design of radiotherapy-adjuvant strategies that maximize tumor control while minimizing normal tissue toxicity.

Beyond its mechanistic focus, this Special Issue places particular emphasis on the translational and applied dimensions of this research field, in line with the applied-science orientation of this journal. We specifically encourage submissions that connect basic mechanistic findings with concrete clinical or technological applications, such as the use of natural radioprotectors as adjuvants in oncological radiotherapy, strategies for normal tissue protection during radiodiagnostic and nuclear medicine procedures, biodosimetric tools for monitoring radiation exposure in clinical and occupational settings, and the development of protocols or formulations with potential for preclinical-to-clinical translation. Purely descriptive mechanistic studies are welcome but should, whenever possible, discuss their applied or translational implications.

This Special Issue aims to bring together original research and review articles addressing, in tumor versus normal tissue models:

• Radioprotective and radiosensitizing effects of natural antioxidant compounds (polyphenols, flavonoids, diterpenes, vitamins, and related substances) in cells exposed to ionizing radiation.
• Cellular and molecular mechanisms of radiosensitivity and radioresistance in cancer cell models (e.g., melanoma, prostate, and other tumor types) compared with normal cell counterparts.
• Cell cycle regulation, apoptosis pathways, and DNA damage response following irradiation, with or without co-treatment with natural compounds.
• Comparative studies across tumor and normal cell lines evaluating differential radiation responses and their biological determinants.
• Cytogenetic and biodosimetric approaches (e.g., micronucleus assay, chromosomal aberrations) applied to the assessment of radioprotective efficacy.
• Physical and dosimetric modeling approaches (e.g., dose–response curve fitting, Bayesian or Poisson-based statistical models, calibration curves) supporting the quantitative assessment of radioprotective and radiosensitizing effects in tumor and normal tissue models.
• Translational and preclinical studies exploring the potential of natural compounds as radiotherapy adjuvants or normal tissue protectants, including clinical and occupational applications in radiodiagnostic and nuclear medicine settings.

We welcome contributions from radiobiology, oncology, molecular and cellular biology, medical physics, and pharmacology, spanning in vitro, in vivo, and translational research.

Prof. Dr. Miguel Alcaraz Baños
Guest Editor

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• radioprotection
• radiosensitivity
• dual modulation
• natural antioxidants
• rosmarinic acid
• carnosic acid
• polyphenols
• ionizing radiation
• cell cycle
• apoptosis
• DNA damage
• melanoma
• cancer cell models
• cytogenetic biodosimetry
• micronucleus assay
• translational radiotherapy