2. Academic Validation
  3. Polyvinyl chloride nanoplastics suppress homology-directed repair and promote oxidative stress to induce esophageal epithelial cellular senescence and cGAS-STING-mediated inflammation

Polyvinyl chloride nanoplastics suppress homology-directed repair and promote oxidative stress to induce esophageal epithelial cellular senescence and cGAS-STING-mediated inflammation

  • Free Radic Biol Med. 2025 Jan:226:288-301. doi: 10.1016/j.freeradbiomed.2024.11.012.
Yixing Huang 1,  Xiao Li 2,  Shengfeng Xu 3,  Dan Zu 4,  Haidong Liu 5,  Hanyi He 5,  Qimei Bao 6,  Yanhua He 5,  Chen Liang 6,  Yin Shi 7,  Xiangdong Cheng 8,  Yaoshu Teng 9,  Zu Ye 10
Affiliations

Affiliations

  • 1 Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, 310022, China; Zhejiang University School of Medicine, Hangzhou, 310058, China; Department of Otorhinolaryngology, Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China.
  • 2 Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, 310022, China; The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
  • 3 Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, 77030, USA.
  • 4 Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, 310022, China; School of Life Sciences, Tianjin University, Tianjin, 300100, China.
  • 5 Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, 310022, China; Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province, Hangzhou, 310022, China; Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, Zhejiang Cancer Hospital, Hangzhou, 310022, China.
  • 6 Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, 310022, China.
  • 7 Department of Biochemistry, and Department of Pulmonology, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China.
  • 8 Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, 310022, China; Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province, Hangzhou, 310022, China; Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, Zhejiang Cancer Hospital, Hangzhou, 310022, China. Electronic address: yezuqscx@gmail.com.
  • 9 Department of Otorhinolaryngology, Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China. Electronic address: tengyaoshu@163.com.
  • 10 Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, 310022, China; Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province, Hangzhou, 310022, China; Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, Zhejiang Cancer Hospital, Hangzhou, 310022, China; Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Nanning, 530021, China; Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education, Nanning, 530021, China. Electronic address: yezuqscx@zju.edu.cn.
PMID: 39515594 DOI: 10.1016/j.freeradbiomed.2024.11.012
Abstract

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.

Keywords

Cellular senescence; HDR; Inflammation; PVC nanoplastics; cGAS-STING.

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