title: Narcotic mechanisms of acute toxicity of chlorinated anilines in Folsomia candida (Collembola) revealed by gene expression analysis.
abstract: In order to clarify the mechanisms of reproductive toxicity in a QSAR approach, the transcriptional signatures upon the 2 day exposure to the 28 days EC₅₀ of a series of increasingly chlorinated aniline compounds and 1,2,3,4-tetrachlorobenzene were measured in Folsomia candida. In general, the transcriptional patterns associated with all compounds revealed toxicity at the cellular membranes and hence components of narcosis type I, but a principal component analysis revealed a deviating response by the pentachloroaniline and 2,3,5,6-tetrachloroaniline exposure. Moreover the expression of a subset of mainly biotransformation related genes showed a significant relationship with the logK(ow,) which stresses the presence of narcosis type I. This was confirmed by GO term enrichment at the level of cellular component. Genes involved in the three phases of xenobiotic biotransformation exhibited strict compound specific transcription patterns, which may reflect biotransformation processes in F. candida. Additional toxic mechanisms were especially observed for the 2,3,5,6-tetrachloroaniline, which possible works as an uncoupler or inhibitor of electron transport systems, which is revealed by the up-regulation of genes that encode different members of the electron transport chain. The aniline and 2,3,4-trichloroaniline exposure caused the induction of genes in the ROS defense system. Additional toxicity mechanisms were less clear, but they include the attack of microbial pathogens for the six other compounds and for 2,3,5,6-tetrachloroaniline an effect on mitochondrial protein folding.
authors.affiliation: Institute of Ecological Science, VU University Amsterdam, HV Amsterdam, The Netherlands.
authors.forename: T K S
authors.initials: TK
authors.lastname: Janssens
authors.forename: D
authors.initials: D
authors.lastname: Giesen
authors.forename: J
authors.initials: J
authors.lastname: Mariën
authors.forename: N M
authors.initials: NM
authors.lastname: van Straalen
authors.forename: C A M
authors.initials: CA
authors.lastname: van Gestel
authors.forename: D
authors.initials: D
authors.lastname: Roelofs
mesh_terms: D000814:Aniline Compounds / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D001181:Arthropods / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D001711:Biotransformation / Q000235:genetics; D002722:Chlorobenzenes / Q000378:metabolism / Q000633:toxicity; D004579:Electron Transport / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D025341:Principal Component Analysis; D021281:Quantitative Structure-Activity Relationship; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation; D015262:Xenobiotics / Q000378:metabolism / Q000633:toxicity
chemical_list: D000814:Aniline Compounds; D002722:Chlorobenzenes; D017382:Reactive Oxygen Species; D015262:Xenobiotics; C074538:2,3,5,6-tetrachloroaniline; C030386:1,2,3,4-tetrachlorobenzene; C027673:2,3,4,5,6-pentachloroaniline