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Published on: June 2, 2022
Evaluation of chromosome aberrations induced by digoxin in Chinese hamster ovary cells
Mozhgan Sedigh-Ardekani1, Iraj Saadat1, Mostafa Saadat1
1Department of Biology, College of Sciences, Shiraz University, Shiraz 71454, Iran and Institute of Biotechnology, Shiraz University, Shiraz, Iran.
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.
Insights
Digoxin exposure caused significant chromosomal damage in Chinese Hamster Ovary cells, including chromatid breaks and polyploidy. These effects occurred at cytotoxic concentrations, much higher than typical patient serum levels.
Area of Science:
- Cytogenetics
- Pharmacology
- Toxicology
Background:
- Digoxin, a cardiac glycoside, exhibits anti-tumor properties in vitro.
- The cytogenetic effects of digoxin on mammalian cells require further investigation.
Purpose of the Study:
- To assess the clastogenic and cytotoxic effects of digoxin on Chinese Hamster Ovary (CHO) cells.
- To determine the relationship between digoxin concentration and chromosomal aberrations.
Main Methods:
- Chinese Hamster Ovary (CHO) cells were exposed to varying concentrations of digoxin (5-20 µg/ml) for 24 hours.
- Chromosomal aberrations, including chromatid breaks and polyploidy, were analyzed in metaphase cells.
- Mitotic index was evaluated, and positive controls (Mitomycin-C, sodium arsenite) were used.
Main Results:
- Digoxin significantly increased the frequency of chromosomal aberrations (chromatid breaks, polyploidy) and aberrant cells in a dose-dependent manner.
- The mitotic index showed a significant negative correlation with digoxin concentration.
- Observed chromosomal aberrations occurred within the cytotoxic concentration range of digoxin.
Conclusions:
- Digoxin induces significant clastogenic effects in CHO cells at cytotoxic concentrations.
- Therapeutic digoxin serum concentrations are substantially lower than those causing observed genotoxicity in vitro.
- Further in vivo studies on patients receiving digoxin are recommended to evaluate genotoxic risks.
