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Evaluation of DNA damage induced by norcantharidin in human cultured lymphocytes
Omar F Khabour1,2, Fatima M Enaya1, Karem Alzoubi3
1a Department of Medical Laboratory Sciences , Jordan University of Science and Technology , Irbid , Jordan .
Abstract:
Norcantharidin (NCTD) is currently used in the treatment of several cancers such as leukemia, melanoma and hepatoma. The mechanism of action of NCTD is suggested to involve induction of apoptosis of cancer cells via production of reactive oxygen species. In this study, the genotoxic effect of different concentrations of NCTD (1, 10 and 20 μm) in human lymphocytes was investigated using sister chromatid exchanges (SCEs) and chromosomal aberrations (CAs) assays. The results revealed that NCTD significantly increased the rate of SCEs (p < 0.05) in a dose-dependent manner. In addition, NCTD significantly increased the number of high-frequency cells (SCEs ≥ 8, p < 0.05). However, NCTD did not have any significant effect on the rate of CAs (p > 0.05). In addition, no significant differences were detected in the mitotic index or proliferative index at examined doses (up to 20 μm). In conclusion, NCTD is genotoxic to human cultured lymphocytes as measured by SCE assay.
Insights
Norcantharidin (NCTD) shows genotoxicity in human lymphocytes by increasing sister chromatid exchanges (SCEs) in a dose-dependent manner. However, NCTD did not significantly affect chromosomal aberrations (CAs) or cell proliferation.
Area of Science:
- Toxicology
- Genetics
- Cancer Research
Background:
- Norcantharidin (NCTD) is an anti-cancer agent used for leukemia, melanoma, and hepatoma.
- Its mechanism involves inducing cancer cell apoptosis via reactive oxygen species.
Purpose of the Study:
- To investigate the genotoxic effects of NCTD on human lymphocytes.
- To evaluate NCTD's impact on sister chromatid exchanges (SCEs) and chromosomal aberrations (CAs).
Main Methods:
- Human lymphocytes were treated with varying concentrations of NCTD (1, 10, 20 μm).
- Sister chromatid exchanges (SCEs) and chromosomal aberrations (CAs) assays were performed.
- Mitotic and proliferative indices were also assessed.
Main Results:
- NCTD significantly increased the rate of SCEs in a dose-dependent manner (p < 0.05).
- A significant increase in high-frequency cells with SCEs (≥ 8) was observed (p < 0.05).
- No significant effects were found on CAs, mitotic index, or proliferative index.
Conclusions:
- NCTD demonstrates genotoxicity in human cultured lymphocytes, specifically indicated by increased SCEs.
- The genotoxic effect is dose-dependent.
- NCTD does not appear to induce chromosomal aberrations or affect lymphocyte proliferation at the tested concentrations.
