Abstract
Background and purposeHydralazine (HDZ) is a cardiovascular drug that is widely used to treat hypertension. The present study was done to assess the cytogenetic effects of HDZ on Chinese hamster ovary (CHO) cells. Materials and methodsMethylthiazol tetrazolium (MTT) assay was carried out to determine the half maximal inhibitory concentration (IC50) of the drug. The IC50 value for HDZ was 243.3±16.9μg/ml. To investigate the clastogenic effects of the drug, chromatid breaks and polyploidy in metaphases were analyzed. CHO cells were exposed to different concentrations of HDZ (20 and 40μg/ml) for 24h. The experiments were carried out in the presence and absence of metabolic activation system (S9 mix; 1ml S9 mix contained: 0.3ml phosphate solutions, 0.2ml KCl, 0.2ml MgCl2, 0.1ml S9 fraction, 0.1ml G-6-P and 0.1ml NADP), because HDZ is metabolized in the liver. Mitomycin-C and sodium arsenite were used as positive controls. ResultsIn the absence of S9 fraction, the level of chromatid breaks statistically increased (P=0.011) and mitotic index significantly decreased (P<0.001) in CHO cells treated with HDZ. There was no significant difference between treated and untreated CHO cells with HDZ for the level of polyploidy (F=0.05; df=2, 6; P=0.945). In the presence of S9 fraction, although the mitotic index elevated, still there was a significant difference between control and treated cells (F=50.53; df=2, 6; P<0.001). There was no significant difference between 20μg/ml of HDZ (+S9) and untreated cells for frequency of chromatid breaks. However, at the 40μg/ml concentration of HDZ (+S9), there was a significant difference between treated and untreated cells. ConclusionHDZ have genotoxic effects on CHO cells in their non-toxic dose, but S9 mix addition decreased these effects.
Published Version
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