PUBLICATION
Identification of adverse outcome pathway related to high-density polyethylene microplastics exposure: Caenorhabditis elegans transcription factor RNAi screening and zebrafish study
- Authors
- Kim, Y., Jeong, J., Lee, S., Choi, I., Choi, J.
- ID
- ZDB-PUB-191207-2
- Date
- 2019
- Source
- Journal of hazardous materials 388: 121725 (Journal)
- Registered Authors
- Keywords
- Adverse outcome pathway (AOP), Caenorhabditis elegans, High-density polyethylene, Nucleotide excision repair (NER), Transforming growth factor-beta (TGF-β)
- MeSH Terms
-
- Adverse Outcome Pathways
- Environmental Pollutants/toxicity*
- Embryo, Nonmammalian/drug effects
- Humans
- Caenorhabditis elegans/drug effects*
- Caenorhabditis elegans/genetics
- Transcription Factors/genetics*
- RNA Interference/drug effects*
- Zebrafish Proteins/genetics
- Zebrafish/genetics*
- Microplastics/toxicity*
- Animals
- Caenorhabditis elegans Proteins/genetics
- Gene Expression Profiling
- Transcriptome
- PubMed
- 31806443 Full text @ J. Hazard. Mater.
Citation
Kim, Y., Jeong, J., Lee, S., Choi, I., Choi, J. (2019) Identification of adverse outcome pathway related to high-density polyethylene microplastics exposure: Caenorhabditis elegans transcription factor RNAi screening and zebrafish study. Journal of hazardous materials. 388:121725.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping