Chronic long-term nitrate therapy: possible cytogenetic effect in humans?

Mutagenesis. 2001 Nov;16(6):517-21. doi: 10.1093/mutage/16.6.517.


Nitrates act as donors of nitric oxide (NO), a molecule with a recognized potential for genotoxicity. In order to assess whether chronic long-term nitrate therapy may increase genotoxicity, we evaluated chromosomal damage in peripheral lymphocytes of 27 ischaemic patients undergoing chronic nitrate treatment for vertical line4 years (7.9 +/- 3.1, mean +/- SD) and 18 age- and sex-matched subjects without any previous nitrate treatment. At the same time, after treatment in vitro with 0-20 microM sodium nitroprusside as NO donor, micronucleus induction and cell proliferation were also evaluated using blood from six different healthy donors. The results showed that the frequency of structural chromosomal aberrations was not significantly higher in the drug-treated group than the control [2.1 +/- 1.4 versus 1.6 +/- 1.2 (mean +/- SD); P = 0.23]. The frequency of micronucleated lymphocytes was higher in the nitrate group than in the control group (6.5 +/- 4.6 versus 3.5 +/- 2.9, P=0.01). In vitro treatment indicated a dose-dependent increase in the frequency of micronucleated lymphocytes with increasing SNP concentrations. Cytotoxicity and cell cycle delay, with a statistically significant difference with respect to control culture, were also observed. Our results suggest a possible genotoxic activity of nitrate therapy. Further studies focusing on the possible link between nitrate therapy and genotoxicity are warranted at this point.

MeSH terms

  • Case-Control Studies
  • Chromosome Aberrations / drug effects*
  • Cytogenetic Analysis
  • DNA Damage / drug effects*
  • DNA Damage / genetics
  • Female
  • Humans
  • Isosorbide Dinitrate / adverse effects*
  • Isosorbide Dinitrate / analogs & derivatives*
  • Isosorbide Dinitrate / therapeutic use*
  • Lymphocytes / drug effects
  • Lymphocytes / metabolism
  • Male
  • Micronuclei, Chromosome-Defective / drug effects
  • Micronuclei, Chromosome-Defective / genetics
  • Middle Aged
  • Nitroprusside / adverse effects
  • Nitroprusside / therapeutic use
  • Polymorphism, Single Nucleotide / drug effects
  • Polymorphism, Single Nucleotide / genetics
  • Vasodilator Agents / adverse effects
  • Vasodilator Agents / therapeutic use


  • Vasodilator Agents
  • Nitroprusside
  • Isosorbide Dinitrate
  • isosorbide-5-mononitrate