Radiation-Induced Bystander Effects in Cellular Systems
Summary
Ionising radiation can provoke biological responses not only in directly irradiated cells but also in neighbouring or distant non-irradiated cells, a phenomenon known as the radiation-induced bystander effect. These non-targeted effects arise through intercellular communication pathways that include gap-junction intercellular communication, soluble mediators such as cytokines and free radicals, and the release of extracellular vesicles carrying nucleic acids and proteins. Mitochondria occupy a central role by regulating reactive oxygen species production, energy metabolism and epigenetic modifications, thereby influencing both the generation of bystander signals and the recipient cell response. Low-dose exposures often trigger adaptive responses, genomic instability or hypersensitivity via bystander signalling, whereas high-linear energy transfer radiations may induce both local bystander effects and distant abscopal responses with potential therapeutic benefit. The magnitude and polarity of these effects depend on radiation quality, dose, cell type, oxygenation status and the composition of the extracellular milieu. A detailed understanding of the underlying molecular mechanisms offers routes to optimise radiotherapy efficacy, minimise normal tissue injury and refine radiological protection models, highlighting the global significance of bystander phenomena in carcinogenesis, tissue homeostasis and risk assessment.
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Radiation-Induced Bystander Effects in Cellular Systems publication trend
The graph below shows the total number of articles in radiation-induced bystander effects in cellular systems across all publications each year (not limited to Nature Index journals).
Technical terms
Bystander effect: Radiation-induced biological responses in non-irradiated cells adjacent to or distant from directly irradiated cells.
Abscopal effect: Systemic responses at sites remote from the irradiated volume, mediated by immune or soluble factors.
Reactive oxygen species (ROS): Chemically reactive molecules derived from oxygen that act as signalling mediators or cause macromolecular damage.
Gap-junction intercellular communication (GJIC): Direct cytoplasmic connections between adjacent cells permitting small molecules and ions to pass.
Extracellular vesicles (exosomes): Membrane-bound nanoparticles released by cells that transport proteins, lipids and nucleic acids to recipient cells.
References
- Low-Dose Non-Targeted Effects and Mitochondrial Control. International Journal of Molecular Sciences (2023).
- X-rays-Induced Bystander Effect Consists in the Formation of DNA Breaks in a Calcium-Dependent Manner: Influence of the Experimental Procedure and the Individual Factor. Biomolecules (2023).
- Primary and Secondary Bystander Effects of Proton Microbeam Irradiation on Human Lung Cancer Cells under Hypoxic Conditions. Biology (2023).
- Role of Mitochondria in Radiation Responses: Epigenetic, Metabolic, and Signaling Impacts. International Journal of Molecular Sciences (2021).
- Emerging role of radiation induced bystander effects: Cell communications and carcinogenesis. Genome Integrity (2010).
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