Document Detail


Spatially fractionated radiation induces cytotoxicity and changes in gene expression in bystander and radiation adjacent murine carcinoma cells.
MedLine Citation:
PMID:  22559204     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Radiation-induced bystander effects have been extensively studied at low doses, since evidence of bystander induced cell killing and other effects on unirradiated cells were found to be predominant at doses up to 0.5 Gy. Therefore, few studies have examined bystander effects induced by exposure to higher doses of radiation, such as spatially fractionated radiation (GRID) treatment. In the present study, we evaluate the ability of GRID treatment to induce changes in GRID adjacent (bystander) regions, in two different murine carcinoma cell lines following exposure to a single irradiation dose of 10 Gy. Murine SCK mammary carcinoma cells and SCCVII squamous carcinoma cells were irradiated using a brass collimator to create a GRID pattern of nine circular fields 12 mm in diameter with a center-to-center distance of 18 mm. Similar to the typical clinical implementation of GRID, this is approximately a 50:50 ratio of direct and bystander exposure. We also performed experiments by irradiating separate cultures and transferring the medium to unirradiated bystander cultures. Clonogenic survival was evaluated in both cell lines to determine the occurrence of radiation-induced bystander effects. For the purpose of our study, we have defined bystander cells as GRID adjacent cells that received approximately 1 Gy scatter dose or unirradiated cells receiving conditioned medium from irradiated cells. We observed significant bystander killing of cells adjacent to the GRID irradiated regions compared to sham treated controls. We also observed bystander killing of SCK and SCCVII cells cultured in conditioned medium obtained from cells irradiated with 10 Gy. Therefore, our results confirm the occurrence of bystander effects following exposure to a high-dose of radiation and suggest that cell-to-cell contact is not required for these effects. In addition, the gene expression profile for DNA damage and cellular stress response signaling in SCCVII cells after GRID exposure was studied. The occurrence of GRID-induced bystander gene expression changes in significant numbers of DNA damage and cellular stress response signaling genes, providing molecular evidence for possible mechanisms of bystander cell killing.
Authors:
Rajalakshmi S Asur; Sunil Sharma; Ching-Wei Chang; Jose Penagaricano; Indira M Kommuru; Eduardo G Moros; Peter M Corry; Robert J Griffin
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-05-04
Journal Detail:
Title:  Radiation research     Volume:  177     ISSN:  1938-5404     ISO Abbreviation:  Radiat. Res.     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-06-29     Completed Date:  2012-09-05     Revised Date:  2013-06-25    
Medline Journal Info:
Nlm Unique ID:  0401245     Medline TA:  Radiat Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  751-65     Citation Subset:  IM; S    
Affiliation:
Department of Radiation Oncology, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Bystander Effect / genetics,  radiation effects*
Carcinoma, Squamous Cell / genetics*,  pathology*
Cell Line, Tumor
Cell Survival / radiation effects
DNA Damage
Dose Fractionation*
Dose-Response Relationship, Radiation
Film Dosimetry
Gene Expression Regulation, Neoplastic / radiation effects*
Mammary Neoplasms, Experimental / genetics*,  pathology*
Mice
Oxidative Stress / radiation effects
Signal Transduction / radiation effects
Grant Support
ID/Acronym/Agency:
CA44114/CA/NCI NIH HHS; R01 CA107160/CA/NCI NIH HHS
Comments/Corrections

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