Evaluation of chromosomal aberrations induced by hydralazine in Chinese hamster ovary cells

Background and purpose: Hydralazine (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 methods: Methylthiazol 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 ± 16.9 μg/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 40 μg/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,0.2 ml 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. Results: In the absence of S9 fraction,the level of chromatid breaks statistically increased (P= 0.011) and mitotic index significantly decreased (P lt; 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 lt; 0.001). There was no significant difference between 20. μg/ml of HDZ (+S9) and untreated cells for frequency of chromatid breaks. However,at the 40. μg/ml concentration of HDZ (+S9),there was a significant difference between treated and untreated cells. Conclusion: HDZ have genotoxic effects on CHO cells in their non-toxic dose,but S9 mix addition decreased these effects. © 2014.