Hypoxia and Cellular Localization Influence the Radiosensitizing Effect of Gold Nanoparticles (AuNPs) in Breast Cancer Cells
| Autor: | Gaetano Zafarana, Robert G. Bristow, Lei Cui, Christine Allen, Payam Zahedi, Kenneth Chor Kin Tse, Shane M. Harding, David A. Jaffray |
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| Rok vydání: | 2014 |
| Předmět: |
Radiation-Sensitizing Agents
Biophysics RAD51 Metal Nanoparticles Breast Neoplasms Biology Cell Line Tumor Radioresistance medicine Humans DNA Breaks Double-Stranded Radiology Nuclear Medicine and imaging Radiosensitivity Cell synchronization Cellular localization Genetics Radiation Cell Cycle Hypoxia (medical) Cell cycle Cell Hypoxia Cell culture Cancer research Female Gold Rad51 Recombinase medicine.symptom Reactive Oxygen Species |
| Zdroj: | Radiation Research. 182:475-488 |
| ISSN: | 1938-5404 0033-7587 |
| DOI: | 10.1667/rr13642.1 |
| Popis: | Hypoxia exists in all solid tumors and leads to clinical radioresistance and adverse prognosis. We hypothesized that hypoxia and cellular localization of gold nanoparticles (AuNPs) could be modifiers of AuNP-mediated radiosensitization. The possible mechanistic effect of AuNPs on cell cycle distribution and DNA double-strand break (DSB) repair postirradiation were also studied. Clonogenic survival data revealed that internalized and extracellular AuNPs at 0.5 mg/mL resulted in dose enhancement factors of 1.39 ± 0.07 and 1.09 ± 0.01, respectively. Radiosensitization by AuNPs was greatest in cells under oxia, followed by chronic and then acute hypoxia. The presence of AuNPs inhibited postirradiation DNA DSB repair, but did not lead to cell cycle synchronization. The relative radiosensitivity of chronic hypoxic cells is attributed to defective DSB repair (homologous recombination) due to decreased (RAD51)-associated protein expression. Our results support the need for further study of AuNPs for clinical development in cancer therapy since their efficacy is not limited in chronic hypoxic cells. |
| Databáze: | OpenAIRE |
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