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

Abstract EN

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 lg / 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 lg / ml) for 24 h.

The experiments were carried out in the presence and absence of metabolic activation system (S9 mix; 1 ml S9 mix contained : 0.3 ml phosphate solutions, 0.2 ml KCl, 0.2 ml MgCl2, 0.1 ml S9 fraction, 0.1 ml G-6-P and 0.1 ml 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 < 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 20 lg / ml of HDZ (+S9) and untreated cells for frequency of chromatid breaks.

However, at the 40 lg / 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.