Triazole-induced gene expression changes in the zebrafish embryo.
The zebrafish embryo is considered to provide a promising alternative test model for developmental toxicity testing. Most systems use morphological assessment of the embryos, however, microarray analyses may increase sensitivity and predictability of the test by detecting more subtle and detailed responses. In this study, we investigated the possibility of relating gene expression profiles of structurally similar chemicals tested in a single concentration, to a complete transcriptomic concentration-response of flusilazole (FLU). We tested five other triazoles, hexaconazole (HEX), cyproconazole (CYP), triadimefon (TDF), myclobutanil (MYC), and triticonazole (TTC) at equipotent concentrations based on morphological evaluation. Results showed that every compound had a different degree of regulation within their anti-fungal and developmental toxicity pathways, steroid biosynthesis and retinol metabolism, respectively. Assuming that the ratio between these pathways is relevant for efficacy compared to developmental toxicity, we found TTC was more efficient and CYP was more toxic compared to the other triazoles. With the approach used in this study we demonstrated that gene expression data allow more comprehensive assessment of compound effects by discriminating relative potencies using these specific gene sets. The zebrafish embryo model can therefore be considered a useful vertebrate model providing information of relevant pathways related to anti-fungal mechanism of action and toxicological activity.
Laboratory for Health Protection Research, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. Sanne.Hermsen@rivm.nl
Sanne A B
SA
Hermsen
Tessa E
TE
Pronk
Evert-Jan
EJ
van den Brandhof
Leo T M
LT
van der Ven
Aldert H
AH
Piersma
D000818:Animals; D000935:Antifungal Agents / Q000633:toxicity*; D004625:Embryo, Nonmammalian / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D014230:Triazoles / Q000633:toxicity*; D015027:Zebrafish
D000935:Antifungal Agents; D014230:Triazoles