Radiation-Induced Genomic Instability and Radiation Sensitivity

2012 ◽  
Keyword(s):  
Genomic Instability ◽  
Radiation Sensitivity ◽  
Radiation Induced

Radiation-Induced Genomic Instability and Radiation Sensitivity

2013 ◽  
pp. 719-726
Author(s):  
Ning J. Yue ◽  
Kent Lambert ◽  
Jay E. Reiff ◽  
Anthony E. Dragun ◽  
Ning J. Yue ◽  
...  
Keyword(s):  
Genomic Instability ◽  
Radiation Sensitivity ◽  
Radiation Induced

Commentary on radiation-induced bystander effects

2004 ◽  
Vol 23 (2) ◽  
pp. 91-94 ◽  
Author(s):  
Eric G Wright
Keyword(s):  
Free Radical ◽  
Ionizing Radiation ◽  
Genomic Instability ◽  
Inflammatory Responses ◽  
Genetic Alterations ◽  
Bystander Effects ◽  
Intercellular Signalling ◽  
Radiation Induced ◽  
Radical Generation ◽  
In Cells

The paradigm of genetic alterations being restricted to direct DNA damage after exposure to ionizing radiation has been challenged by observations in which effects of ionizing radiation arise in cells that in themselves receive no radiation exposure. These effects are demonstrated in cells that are the descendants of irradiated cells (radiation-induced genomic instability) or in cells that are in contact with irradiated cells or receive certain signals from irradiated cells (radiation-induced bystander effects). Bystander signals may be transmitted either by direct intercellular communication through gap junctions, or by diffusible factors, such as cytokines released from irradiated cells. In both phenomena, the untargeted effects of ionizing radiation appear to be associated with free radical-mediated processes. There is evidence that radiation-induced genomic instability may be a consequence of, and in some cell systems may also produce, bystander interactions involving intercellular signalling, production of cytokines and free radical generation. These processes are also features of inflammatory responses that are known to have the potential for both bystander-mediated and persisting damage as well as for conferring a predisposition to malignancy. Thus, radiation-induced genomic instability and untargeted bystander effects may reflect interrelated aspects of inflammatory type responses to radiation-induced stress and injury and contribute to the variety of the pathological consequences of radiation exposures.

RADIATION-INDUCED GENOMIC INSTABILITY: RADIATION QUALITY AND DOSE RESPONSE

2003 ◽  
Vol 85 (1) ◽  
pp. 23-29 ◽  
Author(s):  
Leslie E. Smith ◽  
Shruti Nagar ◽  
Grace J. Kim ◽  
William F. Morgan
Keyword(s):  
Genomic Instability ◽  
Dose Response ◽  
Radiation Quality ◽  
Radiation Induced

scholarly journals Genomic instability in radiation-induced mouse lymphoma from p53 heterozygous mice

Oncogene ◽  
2005 ◽  
Vol 24 (53) ◽  
pp. 7924-7934 ◽  
Author(s):  
Jiang-Hua Mao ◽  
Jiangzhen Li ◽  
Tao Jiang ◽  
Qian Li ◽  
Di Wu ◽  
...  
Keyword(s):  
Genomic Instability ◽  
Radiation Induced ◽  
Mouse Lymphoma

scholarly journals The dopamine receptor antagonist trifluoperazine prevents phenotype conversion and improves survival in mouse models of glioblastoma

2020 ◽  
Vol 117 (20) ◽  
pp. 11085-11096 ◽  
Author(s):  
Kruttika Bhat ◽  
Mohammad Saki ◽  
Erina Vlashi ◽  
Fei Cheng ◽  
Sara Duhachek-Muggy ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Dopamine Receptor ◽  
Mouse Models ◽  
Radiation Sensitivity ◽  
Adult Brain ◽  
Continuous Treatment ◽  
Cell Phenotype ◽  
Dopamine Receptor Antagonist ◽  
Radiation Induced

Glioblastoma (GBM) is the deadliest adult brain cancer, and all patients ultimately succumb to the disease. Radiation therapy (RT) provides survival benefit of 6 mo over surgery alone, but these results have not improved in decades. We report that radiation induces a glioma-initiating cell phenotype, and we have identified trifluoperazine (TFP) as a compound that interferes with this phenotype conversion. TFP causes loss of radiation-induced Nanog mRNA expression, and activation of GSK3 with consecutive posttranslational reduction in p-Akt, Sox2, and β-catenin protein levels. TFP did not alter the intrinsic radiation sensitivity of glioma-initiating cells (GICs). Continuous treatment with TFP and a single dose of radiation reduced the number of GICs in vivo and prolonged survival in syngeneic and patient-derived orthotopic xenograft (PDOX) mouse models of GBM. Our findings suggest that the combination of a dopamine receptor antagonist with radiation enhances the efficacy of RT in GBM by preventing radiation-induced phenotype conversion of radiosensitive non-GICs into treatment-resistant, induced GICs (iGICs).

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