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.

Cytotechnology
|June 14, 2013
PubMed

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.

Related Concept Videos

DNA Damage can Stall the Cell Cycle02:36

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
DNA Damage Can Stall the Cell Cycle02:36

DNA Damage Can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
Mutagenicity and Carcinogenicity01:25

Mutagenicity and Carcinogenicity

Mutagenicity and carcinogenicity refer to the ability of drugs to cause genetic defects and induce cancer, respectively. The International Agency for Research on Cancer (IARC) classifies agents into four groups based on their carcinogenic potential. Group 1 agents are known human carcinogens; group 2A agents are probably carcinogenic to humans; group 3 agents lack data to support their role in carcinogenesis; and group 4 includes agents for which data support that they are not likely to be...
In vitro Mutagenesis01:16

In vitro Mutagenesis

To learn more about the function of a gene, researchers can observe what happens when the gene is inactivated or “knocked out,” by creating genetically engineered knockout animals. Knockout mice have been particularly useful as models for human diseases such as cancer, Parkinson’s disease, and diabetes.
In-vitro Mutagenesis01:16

In-vitro Mutagenesis

To learn more about the function of a gene, researchers can observe what happens when the gene is inactivated or “knocked out,” by creating genetically engineered knockout animals. Knockout mice have been particularly useful as models for human diseases such as cancer, Parkinson’s disease, and diabetes.
Mutations01:35

Mutations

Mutations are changes in the sequence of DNA. These changes can occur spontaneously or they can be induced by exposure to environmental factors. Mutations can be characterized in a number of different ways: whether and how they alter the amino acid sequence of the protein, whether they occur over a small or large area of DNA, and whether they occur in somatic cells or germline cells.
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...