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Impaired cytogenetic damage repair and cell cycle regulation in response to ionizing radiation in human fibroblast cells with individual knock-down of 25 genes
| Content Provider | NASA Technical Reports Server (NTRS) |
|---|---|
| Author | Hammond, Dianne Pierson, Duane Jeevarajan, Antony Zhang, Ye Rohde, Larry Casey, Rachael Wu, Honglu Emami, Kamal Mehta, Satish |
| Copyright Year | 2008 |
| Description | Changes of gene expression profile are one of the most important biological responses in living cells after ionizing radiation (IR) exposure. Although some studies have demonstrated that genes with upregulated expression induced by IR may play important roles in DNA damage sensing, cell cycle checkpoint and chromosomal repair, the relationship between the regulation of gene expression by IR and its impact on cytogenetic responses to ionizing radiation has not been systematically studied. In our present study, the expression of 25 genes selected based on their transcriptional changes in response to IR or from their known DNA repair roles were individually knocked down by siRNA transfection in human fibroblast cells. Chromosome aberrations (CA) and micronuclei (MN) formation were measured as the cytogenetic endpoints. Our results showed that the yield of MN and/or CA formation were significantly increased by suppressed expression of 5 genes that included Ku70 in the DSB repair pathway; XPA in the NER pathway; RPA1 in the MMR pathway; RAD17 and RBBP8 in cell cycle control. Knocked-down expression of 4 genes including MRE11A, RAD51 in the DSB pathway, and SESN1 and SUMO1 showed significant inhibition of cell cycle progression, possibly because of severe impairment of DNA damage repair. Furthermore, loss of XPA, p21 and MLH1 expression resulted in both enhanced cell cycle progression and significantly higher yield of cytogenetic damage, indicating the involvement of these gene products in both cell cycle control and DNA damage repair. Of these 11 genes that affected the cytogenetic response, 9 were up-regulated in the cells exposed to gamma radiation, suggesting that genes transcriptionally modulated by IR were critical to regulating the biological consequences after IR. Failure to express these IR-responsive genes, such as by gene mutation, could seriously change the outcome of the post IR scenario and lead to carcinogenesis. |
| File Size | 181093 |
| Page Count | 32 |
| File Format | |
| Alternate Webpage(s) | http://archive.org/details/NASA_NTRS_Archive_20080013375 |
| Archival Resource Key | ark:/13960/t29936p57 |
| Language | English |
| Publisher Date | 2008-01-01 |
| Access Restriction | Open |
| Subject Keyword | Aerospace Medicine Radiation Effects Mutations Pathological Effects Genes Gene Expression Regulation Physiological Responses Gamma Rays Ionizing Radiation Biological Effects Mutagens Cells Biology Deoxyribonucleic Acid Fibroblasts Chromosomes Chromosome Aberrations Ntrs Nasa Technical Reports Server (ntrs) Nasa Technical Reports Server Aerodynamics Aircraft Aerospace Engineering Aerospace Aeronautic Space Science |
| Content Type | Text |
| Resource Type | Article |
