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We have characterized how Caenorhabditis elegans metabolizes and excretes TBZ. We have shown that TBZ directly binds to the nuclear hormone receptor (NHR)-176 and that this receptor is required for the induction by TBZ of the cytochrome P450 (CYP) encoded by cyp-35d1. Further, RNAi inhibition of cyp-35d1 in animals exposed to TBZ causes a reduction in the quantity of a hydroxylated TBZ metabolite and its glucose conjugate that is detected in C. elegans tissue by HPLC. This final metabolite is unique to nematodes and we also identify two P-glycoproteins (PGPs) necessary for its excretion. Finally, we have shown that inhibiting the metabolism we describe increases the susceptibility of C. elegans to TBZ in wild-type and in resistant genetic backgrounds.<\/jats:p>","DOI":"10.1042\/bj20141296","type":"journal-article","created":{"date-parts":[[2014,11,21]],"date-time":"2014-11-21T11:31:58Z","timestamp":1416569518000},"page":"37-44","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["NHR-176 regulates<i>cyp-35d1<\/i>to control hydroxylation-dependent metabolism of thiabendazole in<i>Caenorhabditis elegans<\/i>"],"prefix":"10.1042","volume":"466","author":[{"given":"Laura\u00a0M.","family":"Jones","sequence":"first","affiliation":[{"name":"School of Biology, University of Leeds, Leeds LS2 9JT, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony\u00a0J.","family":"Flemming","sequence":"additional","affiliation":[{"name":"Syngenta, Jealotts Hill International Research Centre, Bracknell RG42 6EY, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter\u00a0E.","family":"Urwin","sequence":"additional","affiliation":[{"name":"School of Biology, University of Leeds, Leeds LS2 9JT, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2015,2,6]]},"reference":[{"key":"2021112216135926600_B1","doi-asserted-by":"publisher","first-page":"436","DOI":"10.2174\/138920011795495259","article-title":"Advances in human cytochrome p450 and personalized medicine","volume":"12","author":"Chen","year":"2011","journal-title":"Curr. 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