Radiosensitization by nitric oxide at low radiation doses
| Autor: | Peter J. Johnston, Lisa K. Folkes, Peter Wardman, Michael Woodcock, Kai Rothkamm |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2007 |
| Předmět: |
Radiosensitizer
Radiation-Sensitizing Agents Radiation Dose-Response Relationship Drug Chemistry DNA damage Cell Survival Radical Radiochemistry Biophysics chemistry.chemical_element Hamster Dose-Response Relationship Radiation DNA Nitric Oxide Radiation Dosage Oxygen Radiation Tolerance In vitro Nitric oxide chemistry.chemical_compound Radiology Nuclear Medicine and imaging Irradiation DNA Damage |
| Zdroj: | Radiation research. 167(4) |
| ISSN: | 1938-5404 0033-7587 |
| Popis: | Nitric oxide was shown to radiosensitize anoxic V79 and CHO hamster cells and MCF7 and UT-SCC-14 human cells, measuring clonogenic survival and/or DNA damage in vitro at low radiation doses (0.1-5 Gy). Radiosensitization was easily detected after 2 Gy in anoxic V79 cells exposed to 40 ppm ( approximately 70 nM) nitric oxide, indicating that nitric oxide is a significantly more efficient radiosensitizer than oxygen. The yield of double-strand breaks (as gamma-H2AX foci) in V79 and MCF7 cells was doubled by irradiation in 1% v/v nitric oxide/N(2), and there was a longer repair time in cells irradiated in nitric oxide than in air or anoxia; single-strand breaks ("comet" assay) also appeared to be enhanced. Potent radiosensitization by nitric oxide is consistent with near diffusion-controlled reaction of nitric oxide with purine and pyrimidine radicals observed by pulse radiolysis, with nitric oxide reacting two to three times faster than oxygen with the 5-hydroxy-uracil-6-yl radical. Stable NO/base adducts were formed with uracil radicals. Effects on the radiosensitivity of cells exposed to as low as 40 ppm v/v nitric oxide after doses of 1-2 Gy suggest that variations in radiosensitivity in individual patients after radiotherapy might include a component reflecting differing levels of nitric oxide in tumors. |
| Databáze: | OpenAIRE |
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