title: Evaluation of chromosome aberrations induced by digoxin in Chinese hamster ovary cells.
abstract: Digoxin is a cardiac glycoside that has been reported to inhibit growth of multiple tumor cell types in vitro. The present study was assessing the cytogenetic effects of this drug on Chinese Hamster Ovary (CHO) cells. All experiments were performed in triplicate. The IC50 was 22.5 ± 0.8 µg/ml. To investigate the clastogenic effects of drug, chromosomal aberration in metaphase cells were analyzed. Chromatid breaks and polyploidy were the main types of aberration. Mitomycin-C and sodium arsenite were used as positive controls. CHO cells were exposed to different concentration of drug (5, 10, 15, 20 µg/ml) in 24 hours. All of the study aberrations and frequency of aberrant cells significantly increased as a function of digoxin concentration (for chromatid breaks: r = 0.881, df = 13, P < 0.001; for polyploidy: r = 0.777, df = 13, P = 0.001; for cells with aberrations: r = 0.926, df = 13, P < 0.001). The mitotic index negatively correlated with the concentration of digoxin (r = -0.978, df = 13, P < 0.001). All concentrations that cause chromosomal aberrations are in the cytotoxic range of the drug. The peak serum digoxin concentration (5 - 20 ng/ml) was very lower than concentrations we used in the present experiments. Further studies on valuation of chromatid breaks, micronuclei, and sister chromatid exchange in lymphocytes of patients who received digoxin, were recommended.
authors.affiliation: Department of Biology, College of Sciences, Shiraz University, Shiraz 71454, Iran and Institute of Biotechnology, Shiraz University, Shiraz, Iran.
authors.forename: Mozhgan
authors.initials: M
authors.lastname: Sedigh-Ardekani
authors.affiliation: Department of Biology, College of Sciences, Shiraz University, Shiraz 71454, Iran and Institute of Biotechnology, Shiraz University, Shiraz, Iran.
authors.forename: Iraj
authors.initials: I
authors.lastname: Saadat
authors.affiliation: Department of Biology, College of Sciences, Shiraz University, Shiraz 71454, Iran and Institute of Biotechnology, Shiraz University, Shiraz, Iran.
authors.forename: Mostafa
authors.initials: M
authors.lastname: Saadat
keywords: chromatid breakage; digoxin; mitotic index; polyploidy