Nanoplastic-mediated non-B DNA mutagenicity

Plastic-derived materials have become persistent ecological contaminants since their industrial introduction in the mid-20th century ^1,2 . In that context, nanoplastics (NPs) have been discussed as an emerging, ubiquitous plastic-derived pollutant with unique physicochemical properties ^3–8 . Their increased surface-to-volume ratio enhances their adsorption, reactivity, and cellular penetration, driving distinct ecotoxicological behaviours when compared to larger plastic particles ^9,10 . In this study, we identify direct NP-induced DNA mutagenesis in Salmonella enterica . Using a combination of biochemical and biophysical studies, as well as mutagenicity assays, we show that functionalized and non-functionalized NPs induce mutations, depending on the energy state of the bacteria and the NP surface chemistry, by disrupting base-stacking and base-pairing – an intrinsic property of all DNA. Whole-genome analysis revealed that exposure to NPs alters the mutational spectrum and mutation frequency, while circular dichroism spectroscopy demonstrated NP-induced helical flipping from B- to non-B DNA conformations. These motifs preferentially adopt Z-like or A/B-hybrid structures associated with localised mutagenesis through DNA destabilisation. Our combined data reveal that NP-mediated mutagenesis is based on surface chemistry and DNA topology, linking surface chemistry on nanoplastics to genomic instability in vivo . The proposed mechanism redefines the current perspective on nanoplastic toxicity shifting it from an indirect stress to direct macromolecular interactions.

This mechanism provides a molecular framework for understanding how NPs could impose mutation bias, environmental selection pressure, and potential genomic risk across biological systems.