The radiation bystander effect and its potential implications for human health

TitleThe radiation bystander effect and its potential implications for human health
Publication TypeArticolo su Rivista peer-reviewed
Year of Publication2012
AuthorsMancuso, Mariateresa, Pasquali Emanuela, Giardullo Paola, Leonardi Simona, Tanori Mirella, Di Majo V., Pazzaglia Simonetta, and Saran Anna
JournalCurrent Molecular Medicine
Keywordsalpha radiation, Animals, Apoptosis, Arabidopsis, article, ATM protein, ATR protein, Breast cancer, Bystander Effect, cancer chemotherapy, cancer gene therapy, cancer radiotherapy, cancer risk, cancer stem cell, carcinogenesis, cell communication, cell culture, cell cycle G0 phase, cell cycle regulation, cell damage, cell density, cell differentiation, cell nucleus DNA, cell proliferation, Cell Survival, Chromosome aberration, chromosome damage, clonogenesis, connexin 43, cyclin dependent kinase inhibitor 1, Cytotoxicity, DNA damage, DNA Methylation, DNA strand breakage, dose response, environmental exposure, epithelium cell, fibroblast, gamma irradiation, gap junction, glutathione, human, Humans, hypoxic cell, in vitro study, in vivo study, intensity modulated radiation therapy, interleukin 1, Ionizing, Ionizing radiation, low energy radiation, lung cancer, medulloblastoma, mutagenicity, Neoplasms, nonhuman, occupational exposure, oncogene c myc, protein p53, protein Patched, Radiation, radiation dose, Radiation exposure, radiation injury, radiation pneumonia, radiation response, radiosensitivity, reactive oxygen metabolite, reoxygenation, T lymphocyte, tomotherapy, transcription regulation, Tumor Necrosis Factor

A long-held dogma in radiation biology has been that the biological effects of exposure to ionizing radiation occur as a result of damage in directly irradiated cells and that no effect would occur in neighboring unirradiated cells. This paradigm has been frequently challenged by reports of radiation effects in unirradiated or 'bystander' cells receiving signals from directly irradiated cells, an issue that may have substantial impact on radiation risk assessment and development of radiation-based therapies. Radiation-induced bystander effects have been shown in single-cell systems in vitro for an array of cancer relevant endpoints, and may trigger damage in more complex 3-D tissue systems. They may be mediated by soluble factors released by irradiated cells into the extracellular environment and/or by the passage of mediator molecules through gap-junction intercellular communication. To date, evidence that radiation-associated bystander or abscopal responses are effectual in vivo has been limited, but new data suggest that they may significantly affect tumor development in susceptible mouse models. Further understanding of how the signal/s is transmitted to unirradiated cells and tissues and how it provokes long-range and significant responses is crucial. By summarizing the existing evidence of radiation induced bystander-like effects in various systems with emphasis on in vivo findings, we will discuss the potential mechanisms involved in these observations and how effects in bystander cells contribute to uncertainties in assessing cancer risks associated with radiation exposure. © 2012 Bentham Science Publishers.


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