Document Detail


Radiation induced non-targeted response: mechanism and potential clinical implications.
MedLine Citation:
PMID:  21143185     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Generations of students in radiation biology have been taught that heritable biological effects require direct damage to DNA. Radiation-induced non-targeted/bystander effects represent a paradigm shift in our understanding of the radiobiological effects of ionizing radiation in that extranuclear and extracellular effects may also contribute to the biological consequences of exposure to low doses of radiation. Although radiation induced bystander effects have been well documented in a variety of biological systems, including 3D human tissue samples and whole organisms, the mechanism is not known. There is recent evidence that the NF-κB-dependent gene expression of interleukin 8, interleukin 6, cyclooxygenase-2, tumor necrosis factor and interleukin 33 in directly irradiated cells produced the cytokines and prostaglandin E2 with autocrine/paracrine functions, which further activated signaling pathways and induced NF-κB-dependent gene expression in bystander cells. The observations that heritable DNA alterations can be propagated to cells many generations after radiation exposure and that bystander cells exhibit genomic instability in ways similar to directly hit cells indicate that the low dose radiation response is a complex interplay of various modulating factors. The potential implication of the non-targeted response in radiation induced secondary cancer is discussed. A better understanding of the mechanism of the non-targeted effects will be invaluable to assess its clinical relevance and ways in which the bystander phenomenon can be manipulated to increase therapeutic gain in radiotherapy.
Authors:
Tom K Hei; Hongning Zhou; Yunfei Chai; Brian Ponnaiya; Vladimir N Ivanov
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Review    
Journal Detail:
Title:  Current molecular pharmacology     Volume:  4     ISSN:  1874-4702     ISO Abbreviation:  Curr Mol Pharmacol     Publication Date:  2011 Jun 
Date Detail:
Created Date:  2011-06-15     Completed Date:  2011-09-30     Revised Date:  2012-05-22    
Medline Journal Info:
Nlm Unique ID:  101467997     Medline TA:  Curr Mol Pharmacol     Country:  United Arab Emirates    
Other Details:
Languages:  eng     Pagination:  96-105     Citation Subset:  IM    
Affiliation:
Center for Radiological Research, Department of Radiation Oncology, Columbia University Medical Center, Vanderbilt Clinic, New York, USA. tkh1@columbia.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis / radiation effects
Bystander Effect / radiation effects*
DNA / radiation effects
DNA Damage
Gap Junctions / metabolism
Gene Expression / radiation effects
Humans
Intercellular Signaling Peptides and Proteins / metabolism
MAP Kinase Signaling System / radiation effects
NF-kappa B / metabolism
Radiation, Ionizing*
Radiobiology
Receptors, Growth Factor / metabolism
Grant Support
ID/Acronym/Agency:
EB-002033/EB/NIBIB NIH HHS; ES09089/ES/NIEHS NIH HHS; P01-CA 49062/CA/NCI NIH HHS; P41 EB002033/EB/NIBIB NIH HHS; R01-ES 012888/ES/NIEHS NIH HHS
Chemical
Reg. No./Substance:
0/Intercellular Signaling Peptides and Proteins; 0/NF-kappa B; 0/Receptors, Growth Factor; 9007-49-2/DNA

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