Genotoxicity and Genomic Instability Induced by Micro- and Nanoplastics: A Comprehensive Multi-Taxa Mechanistic Review.

Micro- and nanoplastics (MNPs) are pervasive contaminants increasingly implicated in DNA damage and genomic instability across biological systems. This systematic review addresses two core questions: (1) How do MNPs induce genotoxic effects and/or genomic instability in invertebrates, vertebrates, and human cell lines? (2) Through which molecular mechanisms and cellular pathways do these particles exert genotoxic effects? To answer these questions, the review employs an analytical framework integrating mechanistic toxicology, comparative organismal evidence, and pathway-level synthesis. Using PRISMA-guided methods, data were compiled from studies assessing oxidative stress, DNA strand breaks, chromosomal alterations, and disruption of repair pathways. Across aquatic and terrestrial organisms, as well as human epithelial and fly model models, MNP exposure consistently activated oxidative stress pathways, impaired base-excision and nucleotide-excision repair, triggered inflammatory signaling (e.g., NF-κB), and induced apoptosis or cell-cycle arrest. The framework highlights converging mechanisms-including ROS overproduction, mitochondrial dysfunction, and direct nuclear interactions-that collectively compromise genome integrity. These` findings reveal a coherent pattern of genotoxicity across taxa and underscore the growing public-health and ecological risks associated with rising MNP pollution. The review identifies critical knowledge gaps, particularly in chronic low-dose exposures, polymer diversity, and environmentally aged particles, and calls for standardized mechanistic research to inform regulatory interventions.