Radiosensitization by nitric oxide at low radiation doses

Radiat Res. 2007 Apr;167(4):475-84. doi: 10.1667/RR0827.1.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Survival / drug effects*
  • Cell Survival / radiation effects*
  • DNA / drug effects*
  • DNA Damage*
  • Dose-Response Relationship, Drug
  • Dose-Response Relationship, Radiation
  • Nitric Oxide / administration & dosage*
  • Radiation Dosage
  • Radiation Tolerance / drug effects
  • Radiation-Sensitizing Agents / administration & dosage*

Substances

  • Radiation-Sensitizing Agents
  • Nitric Oxide
  • DNA