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Altered Gene Expressions and Cytogenetic Repair Efficiency in Cells with Suppressed Expression of XPA after Proton ExposureCellular responses to damages from ionizing radiation (IR) exposure are influenced not only by the genes involved in DNA double strand break (DSB) repair, but also by non- DSB repair genes. We demonstrated previously that suppressed expression of several non-DSB repair genes, such as XPA, elevated IR-induced cytogenetic damages. In the present study, we exposed human fibroblasts that were treated with control or XPA targeting siRNA to 250 MeV protons (0 to 4 Gy), and analyzed chromosome aberrations and expressions of genes involved in DNA repair. As expected, after proton irradiation, cells with suppressed expression of XPA showed a significantly elevated frequency of chromosome aberrations compared with control siRNA treated (CS) cells. Protons caused more severe DNA damages in XPA knock-down cells, as 36% cells contained multiple aberrations compared to 25% in CS cells after 4Gy proton irradiation. Comparison of gene expressions using the real-time PCR array technique revealed that expressions of p53 and its regulated genes in irradiated XPA suppressed cells were altered similarly as in CS cells, suggesting that the impairment of IR induced DNA repair in XPA suppressed cells is p53-independent. Except for XPA, which was more than 2 fold down regulated in XPA suppressed cells, several other DNA damage sensing and repair genes (GTSE1, RBBP8, RAD51, UNG and XRCC2) were shown a more than 1.5 fold difference between XPA knock-down cells and CS cells after proton exposure. The possible involvement of these genes in the impairment of DNA repair in XPA suppressed cells will be further investigated.
Document ID
20090014107
Document Type
Conference Paper
Authors
Zhang, Ye (NASA Johnson Space Center Houston, TX, United States)
Rohde, Larry H. (Houston Univ.-Clear Lake Houston, TX, United States)
Gridley, Daila S. (Loma Linda Univ. CA, United States)
Mehta, Satish K. (NASA Johnson Space Center Houston, TX, United States)
Pierson, Duane L. (NASA Johnson Space Center Houston, TX, United States)
Wu, Honglu (NASA Johnson Space Center Houston, TX, United States)
Date Acquired
August 24, 2013
Publication Date
January 1, 2009
Subject Category
Life Sciences (General)
Report/Patent Number
JSC-CN-18097
JSC-CN-18117
Meeting Information
55th Annual Meeting of the Radiation Research Society(Savannah, GA)
Distribution Limits
Public
Copyright
Other