Delineation of the chemical pathways underlying nitric oxide-induced homologous recombination in mammalian cells

Chem Biol. 2005 Mar;12(3):357-69. doi: 10.1016/j.chembiol.2004.12.011.


Inflammation is an important risk factor for cancer. During inflammation, macrophages secrete nitric oxide (NO*), which reacts with superoxide or oxygen to create ONOO- or N2O3, respectively. Although homologous recombination causes DNA sequence rearrangements that promote cancer, little was known about the ability of ONOO- and N2O3 to induce recombination in mammalian cells. Here, we show that ONOO- is a potent inducer of homologous recombination at an integrated direct repeat substrate, whereas N2O3 is relatively weakly recombinogenic. Furthermore, on a per lesion basis, ONOO(-)-induced oxidative base lesions and single-strand breaks are significantly more recombinogenic than N2O3-induced base deamination products, which did not induce detectable recombination between plasmids. Similar results were observed in mammalian cells from two different species. These results suggest that ONOO(-)-induced recombination may be an important mechanism underlying inflammation-induced cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • COS Cells
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • Chlorocebus aethiops
  • DNA / genetics
  • Mice
  • Nitric Oxide / pharmacology*
  • Nitric Oxide / physiology
  • Plasmids
  • Recombination, Genetic / drug effects*
  • Recombination, Genetic / physiology
  • Repetitive Sequences, Nucleic Acid
  • Signal Transduction / drug effects*
  • Signal Transduction / physiology


  • Nitric Oxide
  • DNA