| Autor: |
West, Natalie, Marinello, Poliana C., Manandhar, Mandira, Bright, Scott, Flint, David, Martinus, David, Kacem, Mariam Ben, Su, Tingshi, Piscitello, Desiree, Ranzani, Marco, Shaitelman, Simona F., Sawakuchi, Gabriel O. |
| Rok vydání: |
2023 |
| DOI: |
10.6084/m9.figshare.23689179 |
| Popis: |
DNA polymerase theta (Polθ) is an enzyme essential to microhomology-mediated end joining. Here we analyze the radiosensitization of human fibrosarcoma (HT1080) cells in conjunction with photon radiation of a Polθ inhibitor. We used wild type (HT1080-WT53BP1) and homologous recombination-deficient (HT1080-RAD51KD) cells. We treated HT1080 cells with 400 µg/mL of a G418 antibiotic to produce homologous recombination-deficient cells with a Rad51 knockdown. Half of these cells were treated with the Polθ inhibitor 1-2 hours prior to radiation and all cells were then treated with 6 MV x-rays. We then stained the plates with a crystal violet solution and performed a clonogenic cell survival assay. While the dose required to reach 10% cell survival was unchanged in the wild type cells, the dose decreased by 2 Gy for the HR-deficient cells treated with the Polθ inhibitor. Similarly, the sensitization enhancement ratio (SER) increased for the Polθ inhibitor in HR-deficient cells. The survival fraction at 2 Gy was decreased for the HR-deficient cells and increased for the WT cells when treated with the Polθ inhibitor. The SER for the survival fraction at 2 Gy remained approximately the same for the WT cells while it increased for HR-deficient cells when treated with the Polθ inhibitor. Preliminary data analysis shows that the Polθ inhibitor affects the HR-deficient cells and does not affect the wild type cells when exposed to photon radiation. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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