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    The herbicide linuron inhibits cholesterol biosynthesis and induces cellular stress responses in brown trout.

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    URI
    http://hdl.handle.net/11287/618041
    Author
    Uren Webster, T. M.
    Perry, Mandy
    Santos, E. M.
    Date
    2015-03-03
    Journal
    Environmental science & technology
    Type
    Journal Article
    Research Support, Non-U.S. Gov't
    Publisher
    American Chemical Society
    DOI
    10.1021/es505498u
    Rights
    Archived with thanks to Environmental science & technology
    Metadata
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    Abstract
    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.
    Citation
    The herbicide linuron inhibits cholesterol biosynthesis and induces cellular stress responses in brown trout. 2015, 49 (5):3110-8 Environ. Sci. Technol.
    Publisher URL
    http://dx.doi.org/10.1021/es505498u
    Note
    This article is freely available via Open Access. Click on the 'Additional Link' above to access the full-text via the publisher's site.
    Collections
    • 2015 RD&E publications
    • Exeter Clinical Laboratory International (Blood Sciences, Genetics, Cellular Pathology & Microbiology)

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