Transcriptional profiling reveals barcode-like toxicogenomic responses in the zebrafish embryo.
BACKGROUND
Early life stages are generally most sensitive to toxic effects. Our knowledge on the action of manmade chemicals on the developing vertebrate embryo is, however, rather limited. We addressed the toxicogenomic response of the zebrafish embryo in a systematic manner by asking whether distinct chemicals would induce specific transcriptional profiles.


RESULTS
We exposed zebrafish embryos to a range of environmental toxicants and measured the changes in gene-expression profiles by hybridizing cDNA to an oligonucleotide microarray. Several hundred genes responded significantly to at least one of the 11 toxicants tested. We obtained specific expression profiles for each of the chemicals and could predict the identity of the toxicant from the expression profiles with high probability. Changes in gene expression were observed at toxicant concentrations that did not cause morphological effects. The toxicogenomic profiles were highly stage specific and we detected tissue-specific gene responses, underscoring the sensitivity of the assay system.


CONCLUSIONS
Our results show that the genome of the zebrafish embryo responds to toxicant exposure in a highly sensitive and specific manner. Our work provides proof-of-principle for the use of the zebrafish embryo as a toxicogenomic model and highlights its potential for systematic, large-scale analysis of the effects of chemicals on the developing vertebrate embryo.
Yang
Lixin
L
Institute of Toxicology and Genetics, Forschungszentrum Karlsruhe, Postfach 3640, 76021 Karlsruhe, Germany. lixin.yang@itg.fzk.de
Kemadjou
Jules R
JR
Zinsmeister
Christian
C
Bauer
Matthias
M
Legradi
Jessica
J
Müller
Ferenc
F
Pankratz
Michael
M
Jäkel
Jens
J
Strähle
Uwe
U
D000818:Animals; D018076:DNA, Complementary / Q000235:genetics; D004625:Embryo, Nonmammalian / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D009676:Noxae / Q000633:toxicity*; D020411:Oligonucleotide Array Sequence Analysis; D043922:Toxicogenetics / Q000379:methods*; D015027:Zebrafish / Q000235:genetics / Q000378:metabolism*
D018076:DNA, Complementary; D009676:Noxae