Related Experiment Videos
Biological relevance and consequences of chemical- or metal-induced DNA cross-linking
D J Paustenbach1, B L Finley, S Kacew
1Department of Pharmacology, University of Ottawa, Ontario, Canada.
Abstract:
A vast number of chemicals are known to induce mutagenesis and/or carcinogenesis in mammals. Although disruption of cellular nuclear material resulting ultimately in mutagenesis/carcinogenesis can be accomplished by various mechanisms, the search for biomarkers of chemical-induced toxicity continues. This review focuses on the ability of certain metals or chemicals to bind to DNA in a cross-link fashion in whole animal as well as under in vitro conditions. The methodologies currently used to determine DNA cross-linking are described. The biological relevance of the presence of chemical- or metal-induced DNA cross-linking as a measure of carcinogenesis in humans is still under debate, as there is no clear correlation between the disease and the DNA cross-link reaction.
Insights
Certain chemicals and metals can bind to DNA, forming cross-links. While this DNA cross-linking is studied as a biomarker for chemical toxicity and carcinogenesis, its direct link to human cancer remains unclear.
Area of Science:
- Toxicology
- Molecular Biology
- Carcinogenesis
Background:
- Chemicals and metals are known mutagens and carcinogens.
- Disruption of nuclear material can lead to mutagenesis/carcinogenesis.
- Biomarkers for chemical-induced toxicity are actively sought.
Purpose of the Study:
- To review the ability of chemicals/metals to induce DNA cross-linking.
- To describe methodologies for determining DNA cross-linking.
- To discuss the biological relevance of DNA cross-linking in human carcinogenesis.
Main Methods:
- Review of existing literature on chemical/metal-induced DNA cross-linking.
- Description of current methodologies for DNA cross-linking assessment.
- Analysis of in vivo and in vitro study conditions.
Main Results:
- Certain metals and chemicals can bind to DNA, forming cross-links.
- Various methodologies exist for detecting DNA cross-linking.
- The direct correlation between DNA cross-linking and human carcinogenesis is debated.
Conclusions:
- DNA cross-linking by chemicals/metals is a potential biomarker for toxicity.
- The biological relevance of DNA cross-linking as a predictor of human cancer requires further investigation.
- A clear correlation between DNA cross-links and human carcinogenesis is not yet established.