期刊
JOURNAL OF HAZARDOUS MATERIALS
卷 388, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.jhazmat.2019.121725
关键词
High-density polyethylene; Nucleotide excision repair (NER); Transforming growth factor-beta (TGF-beta); Adverse outcome pathway (AOP); Caenorhabditis elegans
资金
- Mid-Career Researcher Program through the National Research Foundation of Korea (NRF) - Ministry of Science and ICT [NRF-2017R1A2B3002242]
- Korean Ministry of Environment [2017001370001]
To gain insight into the human health implications of microplastics, in this study, we investigated the possible mechanisms affecting the toxicity of high-density polyethylene (HDPE) in the nematode Caenorhabditis elegans using RNAi screening and a bioinformatics-based unbiased approach. The candidate pathways identified from C. elegans study were also confirmed using vertebrate model, zebrafish, Danio rerio and human relevance was then inferred using Comparative Toxicogenomics Database (CTD) analysis. Prior to evaluating the toxicity, label-free Raman mapping was conducted to investigate whether or not the organisms could uptake HDPE. C. elegans transcription factor RNAi screening results showed that the nucleotide excision repair (NER) and transforming growth factor-beta (TGF-beta) signaling pathways were significantly associated with HDPE exposure, which was also confirmed in zebrafish model. Gene-disease interaction analysis using the CTD revealed the possible human health implications of microplastics. Finally, based on this finding, related AOPs were identified from AOP Wiki (http://aopwiki.org), which are Peroxisome proliferator-activated receptors gamma inactivation leading to lung fibrosis and AFB1: Mutagenic Mode-of-Action leading to Hepatocellular Carcinoma. Further studies are needed for the validation of these AOPs with various microplastics.
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