Identification of adverse outcome pathway related to high-density polyethylene microplastics exposure: Caenorhabditis elegans transcription factor RNAi screening and zebrafish study

• Published in: Journal of hazardous materials Vol. 388; p. 121725
• Main Authors: Kim, Youngho, Jeong, Jaeseong, Lee, Seungki, Choi, Inhee, Choi, Jinhee
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.04.2020
• Subjects: Adverse outcome pathway (AOP); Adverse Outcome Pathways; Animals; Caenorhabditis elegans; Caenorhabditis elegans - drug effects; Caenorhabditis elegans - genetics; Caenorhabditis elegans Proteins - genetics; Embryo, Nonmammalian - drug effects; Environmental Pollutants - toxicity; Gene Expression Profiling; High-density polyethylene; Humans; Microplastics - toxicity; Nucleotide excision repair (NER); RNA Interference - drug effects; Transcription Factors - genetics; Transcriptome; Transforming growth factor-beta (TGF-β); Zebrafish - genetics; Zebrafish Proteins - genetics; Transforming growth factor-beta (TGF-β); Caenorhabditis elegans; High-density polyethylene; Adverse outcome pathway (AOP); Nucleotide excision repair (NER)
• ISSN: 0304-3894; 1873-3336
• DOI: 10.1016/j.jhazmat.2019.121725

[Display omitted] •Toxicity mechanism of HDPE MPs was identified using C. elegans RNAi and zebrafish.•NER and TGF-β signaling pathways were involved in the toxicity of HDPE.•Human health implications of HDPE toxicity were suggested using CTD analysis.•Related AOPs were identified from AOP Wiki. 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-β) 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 γ 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.