Tris(1,3-dichloro-2-propyl)phosphate Induces Genome-Wide Hypomethylation within Early Zebrafish Embryos.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Volz, DC; Leet, JK; Chen, A; Stapleton, HM; Katiyar, N; Kaundal, R; Yu, Y; Wang, Y

Published Date

  • September 9, 2016

Published In

Volume / Issue

  • 50 / 18

Start / End Page

  • 10255 - 10263

PubMed ID

  • 27574916

Pubmed Central ID

  • 27574916

Electronic International Standard Serial Number (EISSN)

  • 1520-5851

International Standard Serial Number (ISSN)

  • 0013-936X

Digital Object Identifier (DOI)

  • 10.1021/acs.est.6b03656


  • eng