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Polyvinyl chloride nanoplastics suppress homology-directed repair and promote oxidative stress to induce esophageal epithelial cellular senescence and cGAS-STING-mediated inflammation
Summary
Researchers found that PVC nanoplastics caused premature aging and inflammation in esophageal cells by triggering oxidative stress and blocking the cell's ability to repair DNA damage. The nanoplastics specifically shut down a key DNA repair pathway, leading to genomic instability that activated inflammatory immune signaling. This study identifies the esophagus as a vulnerable organ to nanoplastic damage, which is concerning since the esophagus is directly exposed to plastics swallowed in food and drink.
Nanoplastics (NPs), which are characterized by plastic particles smaller than 1 μm, have emerged as pervasive environmental pollutants, raising concerns about their potential toxicity to living organisms. Numerous investigations have highlighted the tendency of NPs to accumulate in organs, resulting in toxic effects. Despite polyvinyl chloride (PVC) being one of the most prevalent NPs, its impact on the esophagus and the associated underlying mechanisms remain largely unknown. In this study, we investigated the impact of PVC NPs on the esophagus and found that PVC NPs exposure induces oxidative stress and elicits DNA damage responses. Further analysis revealed that PVC NPs inhibit the homology-directed repair (HDR) pathway by suppressing the expression of breast cancer susceptibility gene 2 (BRCA2) and growth factor receptor-bound protein 2 (GRB2), resulting in genomic instability. Additionally, the release of free DNA activates cGAS-STING and the downstream NF-κB signaling, elevating inflammatory factors and chemokines, which further leads to cellular senescence. In vivo experiments corroborated these findings, showing that PVC NPs induced oxidative stress, inflammation, and cellular senescence, subsequently impacting mouse behavior. This study contributes novel insights into the health risks associated with PVC NPs exposure and identifies potential therapeutic targets.