Radiosensitization by nitric oxide at low radiation doses
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Radiosensitization by nitric oxide at low radiation doses. / Wardman, Peter; Rothkamm, Kai; Folkes, Lisa K; Woodcock, Michael; Johnston, Peter J.
In: RADIAT RES, Vol. 167, No. 4, 04.2007, p. 475-84.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Radiosensitization by nitric oxide at low radiation doses
AU - Wardman, Peter
AU - Rothkamm, Kai
AU - Folkes, Lisa K
AU - Woodcock, Michael
AU - Johnston, Peter J
PY - 2007/4
Y1 - 2007/4
N2 - 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.
AB - 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.
KW - Cell Survival/drug effects
KW - DNA/drug effects
KW - DNA Damage
KW - Dose-Response Relationship, Drug
KW - Dose-Response Relationship, Radiation
KW - Nitric Oxide/administration & dosage
KW - Radiation Dosage
KW - Radiation Tolerance/drug effects
KW - Radiation-Sensitizing Agents/administration & dosage
U2 - 10.1667/RR0827.1
DO - 10.1667/RR0827.1
M3 - SCORING: Journal article
C2 - 17388699
VL - 167
SP - 475
EP - 484
IS - 4
ER -