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Published on: May 29, 2019
Genotoxicity: damage to DNA and its consequences
David H Phillips1, Volker M Arlt
1Institute of Cancer Research, Sutton, Surrey, United Kingdom. david.phillips@icr.ac.uk
Abstract:
A genotoxin is a chemical or agent that can cause DNA or chromosomal damage. Such damage in a germ cell has the potential to cause a heritable altered trait (germline mutation). DNA damage in a somatic cell may result in a somatic mutation, which may lead to malignant transformation (cancer). Many in vitro and in vivo tests for genotoxicity have been developed that, with a range of endpoints, detect DNA damage or its biological consequences in prokaryotic (e.g. bacterial) or eukaryotic (e.g. mammalian, avian or yeast) cells. These assays are used to evaluate the safety of environmental chemicals and consumer products and to explore the mechanism of action of known or suspected carcinogens. Many chemical carcinogens/mutagens undergo metabolic activation to reactive species that bind covalently to DNA, and the DNA adducts thus formed can be detected in cells and in human tissues by a variety of sensitive techniques. The detection and characterisation of DNA adducts in human tissues provides clues to the aetiology of human cancer. Characterisation of gene mutations in human tumours, in common with the known mutagenic profiles of genotoxins in experimental systems, may provide further insight into the role of environmental mutagens in human cancer.
Insights
Genotoxins damage DNA, potentially causing heritable mutations or cancer. Various tests detect this damage, aiding in safety evaluations and understanding carcinogen mechanisms.
Area of Science:
- Toxicology
- Genetics
- Molecular Biology
Background:
- Genotoxins are agents causing DNA or chromosomal damage.
- Damage in germ cells can lead to heritable mutations, while somatic cell damage may cause cancer.
- Numerous in vitro and in vivo assays detect genotoxicity in various cell types.
Purpose of the Study:
- To review methods for detecting genotoxicity and DNA adducts.
- To highlight the role of genotoxicity testing in safety evaluation of chemicals and products.
- To explore the link between genotoxins, DNA adducts, and human cancer etiology.
Main Methods:
- Utilizing a range of in vitro and in vivo tests to detect DNA damage and its consequences.
- Employing sensitive techniques to detect and characterize DNA adducts in cells and human tissues.
- Analyzing gene mutations in human tumors and comparing them with known genotoxin profiles.
Main Results:
- Genotoxicity assays are crucial for evaluating chemical and product safety.
- Metabolic activation of carcinogens can lead to DNA adducts, detectable in human tissues.
- Characterizing DNA adducts and mutations provides insights into cancer causes.
Conclusions:
- Genotoxicity testing is essential for public health and environmental safety.
- Understanding DNA adducts and mutations aids in identifying environmental mutagens' role in cancer.
- Further research into genotoxin mechanisms can illuminate cancer etiology.
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