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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
Mutagenic and carcinogenic structural alerts and their mechanisms of action
Abstract:
Knowing the mutagenic and carcinogenic properties of chemicals is very important for their hazard (and risk) assessment. One of the crucial events that trigger genotoxic and sometimes carcinogenic effects is the forming of adducts between chemical compounds and nucleic acids and histones. This review takes a look at the mechanisms related to specific functional groups (structural alerts or toxicophores) that may trigger genotoxic or epigenetic effects in the cells. We present up-to-date information about defined structural alerts with their mechanisms and the software based on this knowledge (QSAR models and classification schemes).
Insights
Understanding chemical mutagenicity and carcinogenicity is vital for hazard assessment. This review details how specific chemical structures (structural alerts) form adducts, triggering genotoxic and epigenetic effects, and discusses related predictive software.
Area of Science:
- Toxicology
- Molecular Biology
- Computational Chemistry
Background:
- Chemicals can cause mutagenic and carcinogenic effects, impacting hazard and risk assessment.
- Adduct formation between chemicals and nucleic acids/histones is a key event triggering genotoxicity and carcinogenicity.
- Identifying specific chemical functional groups (structural alerts) is crucial for understanding these effects.
Purpose of the Study:
- To review the mechanisms by which structural alerts induce genotoxic and epigenetic effects.
- To present current knowledge on defined structural alerts and their modes of action.
- To discuss software tools, including Quantitative Structure-Activity Relationship (QSAR) models and classification schemes, that utilize this knowledge.
Main Methods:
- Literature review of genotoxicity and carcinogenicity mechanisms.
- Analysis of structure-activity relationships for chemical functional groups.
- Compilation of information on predictive toxicology software.
Main Results:
- Detailed mechanisms for various structural alerts linked to DNA and histone adduct formation.
- Updated information on established structural alerts and their associated toxicological endpoints.
- Overview of QSAR models and classification systems for predicting genotoxic and epigenetic potential.
Conclusions:
- Structural alerts are key indicators of potential genotoxic and epigenetic hazards.
- Understanding these mechanisms aids in chemical safety assessment and regulatory evaluation.
- Predictive software based on structural alerts can support early-stage risk assessment.
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