Mechanistic biomarkers in genotoxicity testing: A systematic mapping review of their integration with apical endpoints

Resumo original em inglês

O que aconteceu

Genetic toxicology plays a central role in regulatory safety assessment but remains largely dependent on a standardized battery of established genotoxicity assays. Increasing attention has been directed toward the integration of mechanistic information to improve biological interpretation and human relevance. This study presents a systematic mapping review (2020-2025) of biomarkers and methodological developments in genetic toxicology. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, 1478 records were screened, resulting in 120 primary studies. The analysis showed that established genotoxicity assays, particularly the comet and micronucleus tests, remain dominant (91.7%), reflecting their continued role in regulatory hazard identification. However, 65% of the analyzed studies incorporated mechanistic components, indicating enhanced biological resolution. This mechanistic layer was primarily represented by targeted DNA damage response biomarkers (Level II) and systems-level omics-based or computational approaches (Level III), while 35% focused on technical optimization of established assays (Level I), including automation and high-throughput adaptations. Overall, the results indicate a dual structure in current genetic toxicology research, characterized by the sustained predominance of established regulatory assays alongside a heterogeneous integration of mechanistic and computational methodologies. Rather than replacing apical endpoints, these approaches primarily complement and refine the interpretation of genotoxicity data within weight-of-evidence frameworks. Integration of these biomarkers within Integrated Approaches to Testing and Assessment (IATA) may enhance mechanistic resolution in hazard evaluation, although regulatory maturity varies across platforms and application domains.

Resumo publicado sob licença CC BY. A tradução para o português ainda não chegou a este estudo.