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

Publication ,  Journal Article
Volz, DC; Leet, JK; Chen, A; Stapleton, HM; Katiyar, N; Kaundal, R; Yu, Y; Wang, Y
Published in: Environmental science & technology
September 2016

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.

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Published In

Environmental science & technology

DOI

EISSN

1520-5851

ISSN

0013-936X

Publication Date

September 2016

Volume

50

Issue

18

Start / End Page

10255 / 10263

Related Subject Headings

  • Zebrafish
  • Phosphates
  • Organophosphorus Compounds
  • Organophosphates
  • Humans
  • Flame Retardants
  • Environmental Sciences
  • DNA Methylation
  • Animals
 

Citation

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Volz, D. C., Leet, J. K., Chen, A., Stapleton, H. M., Katiyar, N., Kaundal, R., … Wang, Y. (2016). Tris(1,3-dichloro-2-propyl)phosphate Induces Genome-Wide Hypomethylation within Early Zebrafish Embryos. Environmental Science & Technology, 50(18), 10255–10263. https://doi.org/10.1021/acs.est.6b03656
Volz, David C., Jessica K. Leet, Albert Chen, Heather M. Stapleton, Neerja Katiyar, Rakesh Kaundal, Yang Yu, and Yinsheng Wang. “Tris(1,3-dichloro-2-propyl)phosphate Induces Genome-Wide Hypomethylation within Early Zebrafish Embryos.Environmental Science & Technology 50, no. 18 (September 2016): 10255–63. https://doi.org/10.1021/acs.est.6b03656.
Volz DC, Leet JK, Chen A, Stapleton HM, Katiyar N, Kaundal R, et al. Tris(1,3-dichloro-2-propyl)phosphate Induces Genome-Wide Hypomethylation within Early Zebrafish Embryos. Environmental science & technology. 2016 Sep;50(18):10255–63.
Volz, David C., et al. “Tris(1,3-dichloro-2-propyl)phosphate Induces Genome-Wide Hypomethylation within Early Zebrafish Embryos.Environmental Science & Technology, vol. 50, no. 18, Sept. 2016, pp. 10255–63. Epmc, doi:10.1021/acs.est.6b03656.
Volz DC, Leet JK, Chen A, Stapleton HM, Katiyar N, Kaundal R, Yu Y, Wang Y. Tris(1,3-dichloro-2-propyl)phosphate Induces Genome-Wide Hypomethylation within Early Zebrafish Embryos. Environmental science & technology. 2016 Sep;50(18):10255–10263.
Journal cover image

Published In

Environmental science & technology

DOI

EISSN

1520-5851

ISSN

0013-936X

Publication Date

September 2016

Volume

50

Issue

18

Start / End Page

10255 / 10263

Related Subject Headings

  • Zebrafish
  • Phosphates
  • Organophosphorus Compounds
  • Organophosphates
  • Humans
  • Flame Retardants
  • Environmental Sciences
  • DNA Methylation
  • Animals