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Updated: May 10, 2026

Evaluating In Vitro DNA Damage Using Comet Assay
Published on: October 11, 2017
Tempol prevents genotoxicity induced by vorinostat: role of oxidative DNA damage
Karem H Alzoubi1, Omar F Khabour, Aya G Jaber
1Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, 22110, Jordan, khalzoubi@just.edu.jo.
Abstract:
Vorinostat is a member of histone deacetylase inhibitors, which represents a new class of anticancer agents for the treatment of solid and hematological malignancies. Studies have shown that these drugs induce DNA damage in blood lymphocytes, which is proposed to be due to the generation of oxidative lesions. The increase in DNA damage is sometimes associated with risk of developing secondary cancer. Thus, finding a treatment that limits DNA damage caused by anticancer drugs would be beneficial. Tempol is a potent antioxidant that was shown to prevent DNA damage induced by radiation. In this study, we aimed to investigate the harmful effects of vorinostat on DNA damage, and the possible protective effects of tempol against this damage. For that, the spontaneous frequency of sister chromatid exchanges (SCEs), chromosomal aberrations (CAs), and 8-hydroxy-2-deoxy guanosine (8-OHdG) levels were measured in cultured human lymphocytes treated with vorinostat and/or tempol. The results showed that vorinostat significantly increases the frequency of SCEs, CAs and 8-OHdG levels in human lymphocytes as compared to control. These increases were normalized by the treatment of cells with tempol. In conclusion, vorinostat is genotoxic to lymphocytes, and this toxicity is reduced by tempol. Such results could set the stage for future studies investigating the possible usefulness of antioxidants co-treatment in preventing the genotoxicity of vorinostat when used as anticancer in human.
Insights
Vorinostat, a histone deacetylase inhibitor, causes DNA damage in lymphocytes. The antioxidant Tempol effectively protected against this genotoxicity, suggesting potential benefits for cancer patients.
Area of Science:
- Oncology
- Genetics
- Pharmacology
Background:
- Vorinostat is a histone deacetylase inhibitor used in cancer therapy.
- Anticancer drugs, including vorinostat, can induce DNA damage via oxidative lesions, potentially increasing secondary cancer risk.
- Antioxidants like Tempol may mitigate drug-induced DNA damage.
Purpose of the Study:
- To investigate the genotoxic effects of vorinostat on human lymphocytes.
- To evaluate the protective potential of Tempol against vorinostat-induced DNA damage.
Main Methods:
- Cultured human lymphocytes were treated with vorinostat and/or Tempol.
- Assessed DNA damage by measuring sister chromatid exchanges (SCEs), chromosomal aberrations (CAs), and 8-hydroxy-2-deoxyguanosine (8-OHdG) levels.
Main Results:
- Vorinostat significantly increased SCEs, CAs, and 8-OHdG levels compared to controls.
- Tempol treatment normalized these elevated DNA damage markers.
- Vorinostat demonstrated genotoxicity in lymphocytes, which was reduced by Tempol.
Conclusions:
- Vorinostat exhibits genotoxic properties in human lymphocytes.
- Tempol can mitigate vorinostat-induced genotoxicity.
- Antioxidant co-treatment warrants further investigation for preventing anticancer drug-related DNA damage.
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