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Formation of Covalent DNA Adducts by Enzymatically Activated Carcinogens and Drugs In Vitro and Their Determination by 32P-postlabeling
Published on: March 20, 2018
[Antineoplastic drugs as a potential risk factor in occupational settings: mechanisms of action at the cell level,
Nevenka Kopjar1, Davor Zeljezić, Vilena Kasuba
1Institut za medicinska istrazivanja i medicinu rada, Zagreb, Hrvatska. nkopjar@imi.hr
Abstract:
This article brings an overview of the mechanisms of action of antineoplastic drugs used in the clinical setting. It also describes the genotoxic potentials of the most important classes of antineoplastic drugs involved in standard chemotherapy protocols. Classification of antineoplastic drugs according to the IARC monographs on the evaluation of carcinogenic risks to humans is accompanied by data on their mutagenicity and the most recent updates in the Anatomical Therapeutic Chemical (ATC) Classification System. We report the main findings of biomonitoring studies that were conducted in exposed healthcare workers all over the world between 1980 and 2009 using four biomarkers: sister chromatid exchanges, chromosome aberrations, micronuclei. and the comet assay. The methods are briefly explained and their advantages and disadvantages discussed. Biomarkers provide important information on individual genome sensitivity, which eventually might help to improve current working practices and to manage the risks related with exposure to genotoxic agents. Taking into consideration all known advantages and drawbacks of the existing cytogenetic methods, the micronucleus assay, which is able to detect both clastogenic and aneugenic action, is the most suitable biomarker for assessing harmful effects of antineoplastic drugs currently used in health care.
Insights
This study reviews antineoplastic drugs and their genotoxic risks. The micronucleus assay is identified as the most effective biomarker for assessing chemotherapy drug exposure in healthcare workers.
Area of Science:
- Oncology
- Toxicology
- Genetics
Context:
- Antineoplastic drugs are crucial in cancer treatment but pose genotoxic risks.
- Healthcare workers face occupational exposure to these hazardous agents.
- Understanding drug mechanisms and genotoxicity is vital for safety.
Purpose:
- To provide an overview of antineoplastic drug mechanisms and genotoxic potentials.
- To classify drugs based on IARC monographs and ATC system.
- To review biomonitoring studies on healthcare worker exposure.
Summary:
- Discusses genotoxicity of chemotherapy agents and their classification.
- Analyzes biomonitoring studies (1980-2009) using sister chromatid exchanges, chromosome aberrations, micronuclei, and comet assay.
- Highlights the micronucleus assay as the most suitable biomarker for assessing antineoplastic drug genotoxicity.
Impact:
- Informs risk management for healthcare workers exposed to genotoxic drugs.
- Enhances understanding of individual genome sensitivity to cytotoxic agents.
- Supports improved occupational safety practices in clinical settings.
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