Institute of Ecological Science, VU University Amsterdam, HV Amsterdam, The Netherlands.
Environ Int. 2011 Jul;37(5):929-39. doi: 10.1016/j.envint.2011.03.012. Epub 2011 Apr 9.
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.
为了在定量构效关系(QSAR)方法中阐明生殖毒性的机制,在 Folsomia candida 中测量了一系列氯代苯胺化合物和 1,2,3,4-四氯苯在 28 天 EC₅₀ 的 2 天暴露下的转录特征。一般来说,与所有化合物相关的转录模式表明细胞膜毒性,因此属于 I 型麻醉类型,但主成分分析显示五氯苯胺和 2,3,5,6-四氯苯胺暴露存在不同的反应。此外,一组主要与生物转化相关的基因的表达与 logK(ow)呈显著相关,这强调了 I 型麻醉的存在。这在细胞成分水平的 GO 术语富集中得到了证实。参与外源生物转化三个阶段的基因表现出严格的化合物特异性转录模式,这可能反映了 F. candida 中的生物转化过程。对于 2,3,5,6-四氯苯胺,还观察到了其他毒性机制,它可能作为解偶联剂或电子传递系统抑制剂,这是通过编码电子传递链不同成员的基因的上调来揭示的。苯胺和 2,3,4-三氯苯胺暴露导致 ROS 防御系统基因的诱导。其他毒性机制不太清楚,但它们包括六种其他化合物和 2,3,5,6-四氯苯胺对微生物病原体的攻击,以及对线粒体蛋白折叠的影响。