Zebrafish embryos as a screen for DNA methylation modifications after compound exposure.

Autor: Bouwmeester MC; Center for Health Protection, National Institute for Public Health and the Environment (RIVM), PO Box 1, 3720 BA Bilthoven, The Netherlands., Ruiter S; Center for Health Protection, National Institute for Public Health and the Environment (RIVM), PO Box 1, 3720 BA Bilthoven, The Netherlands., Lommelaars T; Center for Health Protection, National Institute for Public Health and the Environment (RIVM), PO Box 1, 3720 BA Bilthoven, The Netherlands., Sippel J; Center for Health Protection, National Institute for Public Health and the Environment (RIVM), PO Box 1, 3720 BA Bilthoven, The Netherlands., Hodemaekers HM; Center for Health Protection, National Institute for Public Health and the Environment (RIVM), PO Box 1, 3720 BA Bilthoven, The Netherlands., van den Brandhof EJ; Center for Environmental Quality, National Institute for Public Health and the Environment (RIVM), PO Box 1, 3720 BA Bilthoven, The Netherlands., Pennings JL; Center for Health Protection, National Institute for Public Health and the Environment (RIVM), PO Box 1, 3720 BA Bilthoven, The Netherlands., Kamstra JH; Institute for Environmental Studies (IVM), VU University, De Boelelaan 1085, 1081 HV Amsterdam, The Netherlands., Jelinek J; Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, PA, USA., Issa JP; Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, PA, USA; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Legler J; Institute for Environmental Studies (IVM), VU University, De Boelelaan 1085, 1081 HV Amsterdam, The Netherlands., van der Ven LT; Center for Health Protection, National Institute for Public Health and the Environment (RIVM), PO Box 1, 3720 BA Bilthoven, The Netherlands. Electronic address: leo.van.der.ven@rivm.nl.
Jazyk: angličtina
Zdroj: Toxicology and applied pharmacology [Toxicol Appl Pharmacol] 2016 Jan 15; Vol. 291, pp. 84-96. Date of Electronic Publication: 2015 Dec 19.
DOI: 10.1016/j.taap.2015.12.012
Abstrakt: Modified epigenetic programming early in life is proposed to underlie the development of an adverse adult phenotype, known as the Developmental Origins of Health and Disease (DOHaD) concept. Several environmental contaminants have been implicated as modifying factors of the developing epigenome. This underlines the need to investigate this newly recognized toxicological risk and systematically screen for the epigenome modifying potential of compounds. In this study, we examined the applicability of the zebrafish embryo as a screening model for DNA methylation modifications. Embryos were exposed from 0 to 72 h post fertilization (hpf) to bisphenol-A (BPA), diethylstilbestrol, 17α-ethynylestradiol, nickel, cadmium, tributyltin, arsenite, perfluoroctanoic acid, valproic acid, flusilazole, 5-azacytidine (5AC) in subtoxic concentrations. Both global and site-specific methylation was examined. Global methylation was only affected by 5AC. Genome wide locus-specific analysis was performed for BPA exposed embryos using Digital Restriction Enzyme Analysis of Methylation (DREAM), which showed minimal wide scale effects on the genome, whereas potential informative markers were not confirmed by pyrosequencing. Site-specific methylation was examined in the promoter regions of three selected genes vasa, vtg1 and cyp19a2, of which vasa (ddx4) was the most responsive. This analysis distinguished estrogenic compounds from metals by direction and sensitivity of the effect compared to embryotoxicity. In conclusion, the zebrafish embryo is a potential screening tool to examine DNA methylation modifications after xenobiotic exposure. The next step is to examine the adult phenotype of exposed embryos and to analyze molecular mechanisms that potentially link epigenetic effects and altered phenotypes, to support the DOHaD hypothesis.
(Copyright © 2015 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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