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

Nitrates act as donors of nitric oxide (NO), a molecule with a recognized p otential for genotoxicity. In order to assess whether chronic long-term nit rate therapy may increase genotoxicity, we evaluated chromosomal damage in peripheral lymphocytes of 27 ischaemic patients undergoing chronic nitrate treatment for box with greater than or equal to4 years (7.9 +/- 3.1, mean /- SD) and 18 age- and sex-matched subjects without any previous nitrate tr eatment. At the same time, after treatment in vitro with 0-20 muM sodium ni troprusside 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 sig nificantly higher in the drug-treated group than the control [2.1 +/- 1.4 v ersus 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 inc reasing SNP concentrations. Cytotoxicity and cell cycle delay, with a stati stically significant difference with respect to control culture, were also observed. Our results suggest a possible genotoxic activity of nitrate ther apy. Further studies focusing on the possible link between nitrate therapy and genotoxicity are warranted at this point.