Pest Management Science (2008) 64, 239-248

Mette D.K. Markussen, Ann-Charlotte Heiberg, Merete Fredholm and Michael Kristensen (2008)
Differential expression of cytochrome P450 genes between bromadiolone-resistant and anticoagulant-susceptible Norway rats: a possible role for pharmacokinetics in bromadiolone resistance
Pest Management Science 64 (3), 239-248
Abstract: BACKGROUND: Anticoagulant resistance in Norway rats, Rattus norvegicus (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-resistant rat strain (with an Y139C-VKORC1 mutation) were compared with profiles from an anticoagulant-susceptible strain.
RESULTS: 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.
CONCLUSION: Results suggest that bromadiolone resistance in a Danish strain of Norway rats involves enhanced anticoagulant metabolism catalysed by cytochrome P450-2e1, -3a2 and -3a3. This pharmacokinetically based bromadiolone resistance is to some extent sex differentiated, as female resistance furthermore seems to involve overexpression of cytochrome P450-2c13 and suppression of P450-2c12, whereas male resistance appears to involve P450-2a1 overexpression.
(The abstract is excluded from the Creative Commons licence and has been copied with permission by the publisher.)
Link to article at publishers website
Database assignments for author(s): Mette Drude Kjaer Markussen, Michael Kristensen, Ann-Charlotte Heiberg

Research topic(s) for pests/diseases/weeds:
pesticide resistance of pest

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Pest and/or beneficial records:

Beneficial	Pest/Disease/Weed	Crop/Product	Country	Quarant.
	Rattus norvegicus		Denmark