Biosciences, College of Life & Environmental Sciences, Geoffrey Pope Building, University of Exeter , Exeter EX4 4QD, United Kingdom.
Environ Sci Technol. 2015 Mar 3;49(5):3110-8. doi: 10.1021/es505498u. Epub 2015 Feb 12.
The herbicide linuron is used worldwide, and has been detected in surface waters as well as in food and drinking water. Toxicological studies have reported that linuron acts as an antiandrogen in vitro and in vivo and disrupts mammalian male reproductive function. However, global mechanisms of linuron toxicity are poorly documented. We used RNA-seq to characterize the hepatic transcriptional response of mature male brown trout exposed for 4 days to 1.7, 15.3, and 225.9 μg/L linuron. We identified a striking decrease in the expression of transcripts encoding the majority of enzymes forming the cholesterol biosynthesis pathway. We also measured a very significant decrease in total hepatic cholesterol in fish exposed to 225.9 μg/L linuron and a negative correlation between total cholesterol and linuron treatment concentration. We hypothesize that inhibition of cholesterol biosynthesis may result from the disruption of androgen signaling by linuron. Additionally, there was increased expression of a number of transcripts involved in cellular stress responses, including cyp1a (up to 560-fold), molecular chaperones, and antioxidant enzymes. We found some evidence of similar patterns of transcriptional change in fish exposed to an environmentally relevant concentration of linuron, and further research should investigate the potential for adverse effects to occur following chronic environmental exposure.
除草剂利谷隆在全世界范围内使用，已在地表水以及食物和饮用水中检出。毒理学研究报告称，利谷隆在体外和体内均具有抗雄激素作用，并破坏哺乳动物雄性生殖功能。然而，利谷隆毒性的全球机制尚未得到充分记录。我们使用 RNA-seq 技术来描述暴露于 1.7、15.3 和 225.9μg/L 利谷隆 4 天的成熟雄性褐鳟肝脏转录组的反应。我们发现编码胆固醇生物合成途径中大多数酶的转录本表达显著下降。我们还测量了暴露于 225.9μg/L 利谷隆的鱼的总肝胆固醇显著降低，并且总胆固醇与利谷隆处理浓度之间存在负相关。我们假设胆固醇生物合成的抑制可能是由于利谷隆破坏了雄激素信号。此外，还发现了许多与细胞应激反应相关的转录本的表达增加，包括 cyp1a（高达 560 倍）、分子伴侣和抗氧化酶。我们在暴露于环境相关浓度利谷隆的鱼类中发现了类似的转录变化模式的一些证据，进一步的研究应该调查在慢性环境暴露后发生不良影响的可能性。
