PMID- 31806443 OWN - NLM STAT- MEDLINE DCOM- 20201230 LR - 20201230 IS - 1873-3336 (Electronic) IS - 0304-3894 (Linking) VI - 388 DP - 2020 Apr 15 TI - Identification of adverse outcome pathway related to high-density polyethylene microplastics exposure: Caenorhabditis elegans transcription factor RNAi screening and zebrafish study. PG - 121725 LID - S0304-3894(19)31679-6 [pii] LID - 10.1016/j.jhazmat.2019.121725 [doi] AB - 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. CI - Copyright (c) 2019 Elsevier B.V. All rights reserved. FAU - Kim, Youngho AU - Kim Y AD - School of Environmental Engineering, University of Seoul, 163 Seoulsiripdae-ro, Dongdaemun-gu, Seoul, 02504, Republic of Korea. FAU - Jeong, Jaeseong AU - Jeong J AD - School of Environmental Engineering, University of Seoul, 163 Seoulsiripdae-ro, Dongdaemun-gu, Seoul, 02504, Republic of Korea. FAU - Lee, Seungki AU - Lee S AD - Department of Life Science, University of Seoul, 163 Seoulsiripdae-ro, Dongdaemun-gu, Seoul, 02504, Republic of Korea. FAU - Choi, Inhee AU - Choi I AD - Department of Life Science, University of Seoul, 163 Seoulsiripdae-ro, Dongdaemun-gu, Seoul, 02504, Republic of Korea. FAU - Choi, Jinhee AU - Choi J AD - School of Environmental Engineering, University of Seoul, 163 Seoulsiripdae-ro, Dongdaemun-gu, Seoul, 02504, Republic of Korea. Electronic address: jinhchoi@uos.ac.kr. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20191120 PL - Netherlands TA - J Hazard Mater JT - Journal of hazardous materials JID - 9422688 RN - 0 (Caenorhabditis elegans Proteins) RN - 0 (Environmental Pollutants) RN - 0 (Microplastics) RN - 0 (Transcription Factors) RN - 0 (Zebrafish Proteins) SB - IM MH - Adverse Outcome Pathways MH - Animals MH - Caenorhabditis elegans/*drug effects/genetics MH - Caenorhabditis elegans Proteins/genetics MH - Embryo, Nonmammalian/drug effects MH - Environmental Pollutants/*toxicity MH - Gene Expression Profiling MH - Humans MH - Microplastics/*toxicity MH - RNA Interference/*drug effects MH - Transcription Factors/*genetics MH - Transcriptome MH - Zebrafish/*genetics MH - Zebrafish Proteins/genetics OTO - NOTNLM OT - Adverse outcome pathway (AOP) OT - Caenorhabditis elegans OT - High-density polyethylene OT - Nucleotide excision repair (NER) OT - Transforming growth factor-beta (TGF-beta) COIS- Declaration of Competing Interest None. EDAT- 2019/12/07 06:00 MHDA- 2020/12/31 06:00 CRDT- 2019/12/07 06:00 PHST- 2019/08/31 00:00 [received] PHST- 2019/11/19 00:00 [revised] PHST- 2019/11/19 00:00 [accepted] PHST- 2019/12/07 06:00 [pubmed] PHST- 2020/12/31 06:00 [medline] PHST- 2019/12/07 06:00 [entrez] AID - S0304-3894(19)31679-6 [pii] AID - 10.1016/j.jhazmat.2019.121725 [doi] PST - ppublish SO - J Hazard Mater. 2020 Apr 15;388:121725. doi: 10.1016/j.jhazmat.2019.121725. Epub 2019 Nov 20.