{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:03:34Z","timestamp":1791245014349,"version":"4.1.0"},"reference-count":58,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2007,12,13]],"date-time":"2007-12-13T00:00:00Z","timestamp":1197504000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["scijournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pest Management Science"],"published-print":{"date-parts":[[2008,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:bold>BACKGROUND:<\/jats:bold> Anticoagulant resistance in Norway rats, <jats:italic>Rattus norvegicus<\/jats:italic> (Berk.), has been suggested to be conferred by mutations in the VKORC1 gene, encoding the target protein of anticoagulant rodenticides. Other factors, e.g. pharmacokinetics, may also contribute to resistance, however. To examine the involvement of pharmacokinetics in bromadiolone resistance in male and female rats, liver expression profiles of seven cytochrome P450 genes from a Danish bromadiolone\u2010resistant rat strain (with an Y139C\u2010VKORC1 mutation) were compared with profiles from an anticoagulant\u2010susceptible strain.<\/jats:p><jats:p><jats:bold>RESULTS:<\/jats:bold> In the presence of bromadiolone, the Cyp2e1, Cyp2c13, Cyp3a2 and Cyp3a3 genes were significantly overexpressed, while Cyp2c12 expression was suppressed in resistant female rats compared with susceptible females. Relative to susceptible males, resistant males showed significant overexpression of the Cyp2a1, Cyp2e1, Cyp3a2 and Cyp3a3 genes. On exposure to bromadiolone, females had higher Cyp2e1 expression than males, which possibly explains why female rats are generally more tolerant to anticoagulants than male rats.<\/jats:p><jats:p><jats:bold>CONCLUSION:<\/jats:bold> Results suggest that bromadiolone resistance in a Danish strain of Norway rats involves enhanced anticoagulant metabolism catalysed by cytochrome P450\u20102e1, \u20103a2 and \u20103a3. This pharmacokinetically based bromadiolone resistance is to some extent sex differentiated, as female resistance furthermore seems to involve overexpression of cytochrome P450\u20102c13 and suppression of P450\u20102c12, whereas male resistance appears to involve P450\u20102a1 overexpression. Copyright \u00a9 2007 Society of Chemical Industry<\/jats:p>","DOI":"10.1002\/ps.1506","type":"journal-article","created":{"date-parts":[[2007,12,13]],"date-time":"2007-12-13T11:47:12Z","timestamp":1197546432000},"page":"239-248","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Differential expression of cytochrome P450 genes between bromadiolone\u2010resistant and anticoagulant\u2010susceptible Norway rats: a possible role for pharmacokinetics in bromadiolone resistance"],"prefix":"10.1002","volume":"64","author":[{"given":"Mette 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