Radiation-induced DNA damage and altered expression of p21, cyclin D1 and Mre11 genes in human fibroblast cell lines with different radiosensitivity
| Autor: | Hosein Azimian, Mahdi Sadat Darbandi, Mohammad-Taghi Bahreyni-Toossi, Navid Zafari, Seyed Hamid Aghaee-Bakhtiari, Mahmoud Mahmoudi |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Cyclin-Dependent Kinase Inhibitor p21
DNA Repair DNA repair Cell Survival Health Toxicology and Mutagenesis Biology Radiation Tolerance Cell Line Cyclin D1 Radioresistance Gene expression Genetics medicine Humans DNA Breaks Double-Stranded Radiosensitivity Fibroblast Molecular Biology Gene MRE11 Homologue Protein X-Rays Dose-Response Relationship Radiation DNA Fibroblasts medicine.anatomical_structure Gene Expression Regulation Cell culture Cancer research |
| Zdroj: | Mutation research. 823 |
| ISSN: | 1873-135X |
| Popis: | Purpose Radiotherapy plays a pivotal role in the treatment of cancer. One of the main challenges in this treatment modality is radiation-induced complications in some patients affected by high radiosensitivity (RS). The differences in RS are determined mainly by genetic factors. Therefore, identifying the genes and mechanisms that affect RS in different cells is essential for evaluating radiotherapy outcomes. In the present study, the ability to repair DNA double-stranded breaks (DSB) is evaluated, followed by examining the expression levels of CDKN1A (p21), cyclinD1, and Mre11 genes in human fibroblasts with different RSs. Materials & methods Cellular RS was measured by survival fraction at 2 Gy (SF2). The γ-H2AX assay was used for assessing DNA repair capacity. Eventually, gene expression levels from each cell line 4 and 24 h after irradiation (at 2, 4, and 8 Gy) were measured by real-time PCR. Results The SF2 values for the cell lines ranged from 0.286 to 0.641, and RS differences of fibroblast cells were identified. Among the studied genes, the expression of Mre11 was the most important. Analysis of the real-time PCR data showed that changes in Mre11 gene expression (4 h after 8 Gy irradiation) were directly correlated with the RS (R2 = 0.905). The difference in the expression of the p21 gene (4 h after 4 Gy irradiation) was also promising. Finally, the flow cytometry analysis showed that the radioresistant cell lines quickly repaired DBS damages. However, the repair process was slow in the radiosensitive cell line, and the residual damage is significantly higher than other cell lines (P Conclusions This study indicates that changes in the expression of p21 and Mre11 genes play an important role in cell response to radiation and thus these genes can be introduced as biomarkers to predict RS in normal cell lines. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|