Non-targeted and Delayed Effects of Exposure to Ionizing Radiation: I. Radiation-Induced Genomic Instability and Bystander EffectsIn Vitro

2012 ◽  
Vol 178 (2) ◽  
pp. AV223-AV236 ◽  
Author(s):  
William F. Morgan
Keyword(s):  
Ionizing Radiation ◽  
Genomic Instability ◽  
Delayed Effects ◽  
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.

Ionizing Radiation-Induced Genomic Instability in CHO cells Is Followed by Selection of Radioresistant Cell Clones

2009 ◽  
Vol 147 (5) ◽  
pp. 596-598 ◽  
Author(s):  
D. V. Guryev ◽  
A. N. Osipov ◽  
E. Yu. Lizunova ◽  
N. Yu. Vorobyeva ◽  
O. V. Boeva
Keyword(s):  
Ionizing Radiation ◽  
Genomic Instability ◽  
Cho Cells ◽  
Cell Clones ◽  
Radiation Induced ◽  
Selection Of

scholarly journals Replication stress and FOXM1 drive radiation induced genomic instability and cell transformation

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0235998
Author(s):  
Zhentian Li ◽  
David S. Yu ◽  
Paul W. Doetsch ◽  
Erica Werner
Keyword(s):  
Cell Line ◽  
Genomic Instability ◽  
Cell Transformation ◽  
Replication Stress ◽  
Bronchial Epithelial Cell ◽  
Epithelial Cell Line ◽  
Osteosarcoma Cell ◽  
Functional Protein ◽  
Delayed Effects ◽  
Radiation Induced

In contrast to the vast majority of research that has focused on the immediate effects of ionizing radiation, this work concentrates on the molecular mechanism driving delayed effects that emerge in the progeny of the exposed cells. We employed functional protein arrays to identify molecular changes induced in a human bronchial epithelial cell line (HBEC3-KT) and osteosarcoma cell line (U2OS) and evaluated their impact on outcomes associated with radiation induced genomic instability (RIGI) at day 5 and 7 post-exposure to a 2Gy X-ray dose, which revealed replication stress in the context of increased FOXM1b expression. Irradiated cells had reduced DNA replication rate detected by the DNA fiber assay and increased DNA resection detected by RPA foci and phosphorylation. Irradiated cells increased utilization of homologous recombination-dependent repair detected by a gene conversion assay and DNA damage at mitosis reflected by RPA positive chromosomal bridges, micronuclei formation and 53BP1 positive bodies in G1, all known outcomes of replication stress. Interference with the function of FOXM1, a transcription factor widely expressed in cancer, employing an aptamer, decreased radiation-induced micronuclei formation and cell transformation while plasmid-driven overexpression of FOXM1b was sufficient to induce replication stress, micronuclei formation and cell transformation.

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