Suppression of CYP3A2 mRNA expression in the warfarin-resistant roof rat, Rattus rattus: possible involvement of cytochrome P450 in the warfarin resistance mechanism.

Abstract	1. The continual use of warfarin as a rodenticide has caused the development of populations of warfarin-resistant roof rat. To study the biochemical mechanism of warfarin resistance, the mRNA expression levels of the major P450 forms in the warfarin-resistant and -susceptible roof rat liver following exposure to warfarin were quantified by competitive RT-PCR. 2. The constitutive levels of CYP2C11 and CYP3A2 mRNAs in the warfarin-resistant and -susceptible roof rat were extremely low compared with those in the STD rat. In response to warfarin administration, the CYP3A2 mRNA level in the warfarin-susceptible rat increased to about 3-fold of that before the treatment, whereas in the warfarin-resistant roof rat, CYP3A2 mRNA remained at a low level. 3. The present results suggest the possibility that reduced synthesis of CYP3A2 mRNA is involved in the warfarin-resistant mechanism in the roof rat.
Authors	S Sugano, T Kobayashi, T Tanikawa, Y Kawakami, H Kojima, K Nakamura, A Uchida, N Morishima, Y Tamai
Journal	Xenobiotica; the fate of foreign compounds in biological systems (Xenobiotica) Vol. 31 Issue 7 Pg. 399-407 (Jul 2001) ISSN: 0049-8254 [Print] England
PMID	11531004 (Publication Type: Comparative Study, Journal Article)
Chemical References	Membrane Proteins RNA, Messenger Rodenticides Warfarin Cytochrome P-450 Enzyme System Steroid Hydroxylases Aryl Hydrocarbon Hydroxylases CYP2C11 protein, rat Cyp3a2 protein, rat Cytochrome P-450 CYP3A Cytochrome P450 Family 2 Steroid 16-alpha-Hydroxylase steroid hormone 6-beta-hydroxylase
Topics	Animals Aryl Hydrocarbon Hydroxylases Cytochrome P-450 CYP3A Cytochrome P-450 Enzyme System (biosynthesis, physiology) Cytochrome P450 Family 2 Drug Resistance Liver (enzymology, metabolism) Male Membrane Proteins RNA, Messenger (metabolism) Rats Rats, Sprague-Dawley Reverse Transcriptase Polymerase Chain Reaction Rodenticides (pharmacology) Species Specificity Steroid 16-alpha-Hydroxylase Steroid Hydroxylases (biosynthesis) Warfarin (pharmacology)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.

Realize the full power of the drug-disease research graph!