Related Experiment Video

Updated: Oct 15, 2026

Simple and Fast Rolling Circle Amplification-Based Detection of Topoisomerase 1 Activity in Crude Biological Samples
10:13

Simple and Fast Rolling Circle Amplification-Based Detection of Topoisomerase 1 Activity in Crude Biological Samples

Published on: December 2, 2022

Genotoxicity of several clinically used topoisomerase II inhibitors

G Boos1, H Stopper

  • 1Department of Toxicology, University of Würzburg, Germany.

Toxicology Letters
|July 25, 2000
PubMed

Insights

This study assessed the genotoxicity and mutagenicity of six DNA topoisomerase II inhibitors. Most inhibitors caused DNA damage and mutations, aligning with their known mechanisms of action.

Area of Science:

  • Molecular Biology
  • Genetics
  • Pharmacology

Background:

  • DNA topoisomerase II is crucial for DNA topology regulation during replication and segregation.
  • Inhibition of DNA topoisomerase II is a key mechanism for antitumor drugs and antibiotics.
  • Drug interactions with topoisomerase II present targets for therapeutic intervention and potential toxicity.

Purpose of the Study:

  • To investigate and compare the genotoxicity and mutagenicity of six mechanistically distinct DNA topoisomerase II inhibitors.
  • To evaluate the in vitro genotoxic and mutagenic profiles of m-amsacrine, mitoxantrone, etoposide, genistein, ICRF 193, and berenil.
  • To correlate the observed toxicities with the proposed mechanisms of topoisomerase II inhibition.

Main Methods:

  • Utilized the in vitro micronucleus test to assess chromosomal damage.
  • Employed the single-cell gel electrophoresis (comet assay) to detect DNA strand breaks.
  • Applied the mutation assay at the tk-locus in L5178Y mouse lymphoma cells to determine mutagenicity.

Main Results:

  • All six compounds induced micronuclei, indicating chromosomal damage.
  • Five of the six compounds (all except berenil) were found to be mutagenic.
  • M-amsacrine, mitoxantrone, etoposide, and genistein induced significant DNA migration in the comet assay, suggesting DNA strand breaks. ICRF 193 showed weak positive results, and berenil was negative.
  • The observed genotoxicity and mutagenicity results were consistent with the known mechanisms of action for each topoisomerase II inhibitor.

Conclusions:

  • The study successfully characterized the genotoxic and mutagenic potential of diverse DNA topoisomerase II inhibitors.
  • The findings support the hypothesis that interactions with DNA topoisomerase II can lead to various forms of genetic toxicity.
  • This research provides valuable data for understanding the safety profiles of topoisomerase II-targeting agents and informs drug development strategies.

More Related Videos

Quantitative Detection of DNA-Protein Crosslinks and Their Post-Translational Modifications10:12

Quantitative Detection of DNA-Protein Crosslinks and Their Post-Translational Modifications

Published on: April 21, 2023

Related Concept Videos

DNA Topoisomerases02:02

DNA Topoisomerases

Topoisomerases are enzymes that relax overwound DNA molecules during various cell processes, including DNA replication and transcription. These enzymes regulate positive and negative DNA supercoiling without changing the nucleotide sequence. DNA overwinding in a clockwise direction results in positively supercoiled DNA, whereas underwinding in a counterclockwise direction produces negatively supercoiled DNA.
Types and Mechanism of action
Topoisomerases are divided into two main types.  Type I...
Inhibitors of Bacterial DNA Synthesis01:28

Inhibitors of Bacterial DNA Synthesis

Bacterial pathogens depend on precise and efficient DNA replication to sustain infection. Two type II topoisomerases—DNA gyrase and topoisomerase IV—are critical to this process, as they resolve DNA supercoiling and unlink chromosomes during replication. Fluoroquinolones, synthetic derivatives of quinolones, exploit this mechanism by stabilizing the transient DNA–enzyme cleavage complex, preventing strand religation, and causing lethal double-strand breaks. These antibiotics are selectively...
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...
Teratogenicity01:07

Teratogenicity

The ability of a drug to produce structural deformations and functional abnormalities in the developing embryo or the fetus is called teratogenicity, and the drug producing this effect is known as a teratogen. Teratogenic effects include stillbirth, miscarriage, intrauterine growth restriction, and neurocognitive delay. A teratogen may affect the embryo at different stages of development, which is important in determining the type and extent of the damage. During blastocyst formation, the early...
In vitro Mutagenesis02:29

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.
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...