Genotoxicity Assessment in Mammalian Systems

Genotoxicity assessment in mammalian systems encompasses a suite of in vitro and in vivo assays designed to detect DNA damage, gene mutations and chromosomal aberrations induced by chemical and physical agents. Core methodologies include the comet assay for strand-break detection, micronucleus and chromosome aberration tests for clastogenic and aneugenic effects, and gene mutation assays such as the PIG-A or transgenic rodent mutation (TGR) assays. Recent emphasis has shifted from purely qualitative hazard identification towards quantitative dose–response analysis, employing benchmark dose metrics and margin of exposure calculations to inform risk-based decision making. Advances in three-dimensional tissue models and humanised cell lines are enhancing physiological relevance, while high-throughput and flow cytometric platforms are increasing sensitivity and throughput. Integration of mechanistic endpoints, such as DNA repair kinetics and cell-cycle perturbations, alongside traditional genotoxicity readouts, is refining mode-of-action understanding. Collectively, these developments bolster the global regulatory framework by improving the accuracy of human risk assessment and reducing reliance on animal studies through the adoption of alternative and integrated testing strategies.

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Genotoxicity Assessment in Mammalian Systems publication trend

The graph below shows the total number of articles in genotoxicity assessment in mammalian systems across all publications each year (not limited to Nature Index journals).

Technical terms

Benchmark dose (BMD): A dose level derived from a statistical model of the dose–response curve corresponding to a predefined change in effect, used as a point of departure for risk assessment.

Margin of exposure (MOE): The ratio between a reference point (e.g., BMD) and estimated human exposure, applied to characterise risk and prioritise substances.

Comet assay: A sensitive gel electrophoresis method for detecting DNA strand breaks and alkali-labile sites in single cells.

PIG-A assay: An in vitro or in vivo mutation test measuring loss of glycosylphosphatidylinositol anchor synthesis due to mutations in the PIG-A gene, indicative of gene-inactivating events.

References

1. Genotoxicity assessment: opportunities, challenges and perspectives for quantitative evaluations of dose–response data. Archives of Toxicology (2023).
2. Reconstructed human intestinal comet assay, a possible alternative in vitro model for genotoxicity assessment. Mutagenesis (2023).
3. Assessment of the In Vitro Phosphatidylinositol Glycan Class A (PIG-A) Gene Mutation Assay Using Human TK6 and Mouse Hepa1c1c7 Cell Lines. Journal of Xenobiotics (2024).