title: Tris(1,3-dichloro-2-propyl)phosphate Induces Genome-Wide Hypomethylation within Early Zebrafish Embryos.
abstract: Tris(1,3-dichloro-2-propyl)phosphate (TDCIPP) is a high-production volume organophosphate-based plasticizer and flame retardant widely used within the United States. Using zebrafish as a model, the objectives of this study were to determine whether (1) TDCIPP inhibits DNA methyltransferase (DNMT) within embryonic nuclear extracts; (2) uptake of TDCIPP from 0.75 h postfertilization (hpf, 2-cell) to 2 hpf (64-cell) or 6 hpf (shield stage) leads to impacts on the early embryonic DNA methylome; and (3) TDCIPP-induced impacts on cytosine methylation are localized to CpG islands within intergenic regions. Within this study, 5-azacytidine (5-azaC, a DNMT inhibitor) was used as a positive control. Although 5-azaC significantly inhibited zebrafish DNMT, TDCIPP did not affect DNMT activity in vitro at concentrations as high as 500 μM. However, rapid embryonic uptake of 5-azaC and TDCIPP from 0.75 to 2 hpf resulted in chemical- and chromosome-specific alterations in cytosine methylation at 2 hpf. Moreover, TDCIPP exposure predominantly resulted in hypomethylation of positions outside of CpG islands and within intragenic (exon) regions of the zebrafish genome. Overall, these findings provide the foundation for monitoring DNA methylation dynamics within zebrafish as well as identifying potential associations among TDCIPP exposure, adverse health outcomes, and DNA methylation status within human populations.
authors: Department of Environmental Sciences, University of California, Riverside , Riverside, California 92521, United States.
authors: David C
authors: DC
authors: Volz
authors: Department of Environmental Health Sciences, University of South Carolina , Columbia, South Carolina 29208, United States.
authors: Jessica K
authors: JK
authors: Leet
authors: Division of Environmental Sciences and Policy, Duke University , Durham, North Carolina 27708, United States.
authors: Albert
authors: A
authors: Chen
authors: Division of Environmental Sciences and Policy, Duke University , Durham, North Carolina 27708, United States.
authors: Heather M
authors: HM
authors: Stapleton
authors: Bioinformatics Facility, Institute for Integrative Genome Biology, University of California, Riverside , Riverside, California 92521, United States.
authors: Neerja
authors: N
authors: Katiyar
authors: Bioinformatics Facility, Institute for Integrative Genome Biology, University of California, Riverside , Riverside, California 92521, United States.
authors: Rakesh
authors: R
authors: Kaundal
authors: Department of Chemistry, University of California, Riverside , Riverside, California 92521, United States.
authors: Yang
authors: Y
authors: Yu
authors: Department of Chemistry, University of California, Riverside , Riverside, California 92521, United States.
authors: Yinsheng
authors: Y
authors: Wang
mesh_terms: D000818:Animals; D019175:DNA Methylation / Q000187:drug effects*; D005411:Flame Retardants; D006801:Humans; D010755:Organophosphates; D009943:Organophosphorus Compounds / Q000633:toxicity*; D010710:Phosphates; D015027:Zebrafish / Q000196:embryology / Q000235:genetics / Q000378:metabolism
chemical_list: D005411:Flame Retardants; D010755:Organophosphates; D009943:Organophosphorus Compounds; D010710:Phosphates; C016805:tris(1,3-dichloro-2-propyl)phosphate