Propiconazole-induced cytochrome P450 gene expression and enzymatic activities in rat and mouse liver

被引:78
作者
Sun, GB [1 ]
Thai, SF [1 ]
Tully, DB [1 ]
Lambert, GR [1 ]
Goetz, AK [1 ]
Wolf, DC [1 ]
Dix, DJ [1 ]
Nesnow, S [1 ]
机构
[1] US EPA, Off Res & Dev, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA
关键词
propiconazole; PCR; P450; alkoxyresorufin O-dealkylation; gene expression quantitative real-time RT-PCR;
D O I
10.1016/j.toxlet.2004.10.006
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
Propiconazole is a N-substituted triazole used as a fungicide on fruits, grains, seeds, hardwoods, and conifers. In the present study, propiconazole was examined for its effects on the expression of hepatic cytochrome P450 genes and on the activities of P450 enzymes in male Sprague-Dawley rats and male CD-1 mice. Rats and mice were administered propiconazole by gavage daily for 14 days at doses of 10, 75, and 150 mg/kg body weight/day. Quantitative real time RT-PCR assays of rat hepatic RNA samples from animals treated at the 150 mg/kg body weight/day dose revealed significant mRNA overexpression of the following genes compared to control: CYP1A2 (1.62-fold), CYP2B1 (10.8-fold), CYP3A1/CYP3A23 (2.78-fold), and CYP3A2 (1.84-fold). In mouse liver, propiconazole produced mRNA overexpression of Cyp2b10 (2.39-fold) and Cyp3a11 (5.19-fold), mRNA expression of CYP1A1 was not detected in liver tissues from treated or controls animals from either species. Propiconazole significantly induced both pentoxyresorufin O-dealkylation (PROD) and methoxyresorufin O-dealkylation (MROD) activities in both rat and mouse liver at the 150 mg/kg body weight/day and 75 mg/kg body weight/day doses. In summary, these results indicated that propiconazole induced CYP1A2 in rat liver and CYP2B and CYP3A families of isoforms in rat and mouse liver. (C) Published by Elsevier Ireland Ltd.
引用
收藏
页码:277 / 287
页数:11
相关论文
共 32 条
[1]   CYTOCHROME-P450 SPECIFICITIES OF ALKOXYRESORUFIN O-DEALKYLATION IN HUMAN AND RAT-LIVER [J].
BURKE, MD ;
THOMPSON, S ;
WEAVER, RJ ;
WOLF, CR ;
MAYER, RT .
BIOCHEMICAL PHARMACOLOGY, 1994, 48 (05) :923-936
[2]  
*CAL EPA, 2003, SUMM TOX DAT CAL ENV
[3]  
CHOMCZYNSKI P, 1987, ANAL BIOCHEM, V162, P156, DOI 10.1016/0003-2697(87)90021-2
[4]   LIVER MEDIUM-TERM BIOASSAY IN RATS FOR SCREENING OF CARCINOGENS AND MODIFYING FACTORS IN HEPATOCARCINOGENESIS [J].
HASEGAWA, R ;
ITO, N .
FOOD AND CHEMICAL TOXICOLOGY, 1992, 30 (11) :979-+
[5]   Drug-activated nuclear receptors CAR and PXR [J].
Honkakoski, P ;
Sueyoshi, T ;
Negishi, M .
ANNALS OF MEDICINE, 2003, 35 (03) :172-182
[6]   CODING NUCLEOTIDE-SEQUENCE OF 3-METHYLCHOLANTHRENE-INDUCIBLE CYTOCHROME-P-450D CDNA FROM RAT-LIVER [J].
KAWAJIRI, K ;
GOTOH, O ;
SOGAWA, K ;
TAGASHIRA, Y ;
MURAMATSU, M ;
FUJIIKURIYAMA, Y .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1984, 81 (06) :1649-1653
[7]   CYP1A2 is not the primary enzyme responsible for 4-aminobiphenyl-induced hepatocarcinogenesis in mice [J].
Kimura, S ;
Kawabe, M ;
Ward, JM ;
Morishima, H ;
Kadlubar, FF ;
Hammons, GJ ;
Fernandez-Salguero, P ;
Gonzalez, FJ .
CARCINOGENESIS, 1999, 20 (09) :1825-1830
[8]   Substrate specificity for rat cytochrome P450 (CYP) isoforms: screening with cDNA-expressed systems of the rat [J].
Kobayashi, K ;
Urashima, K ;
Shimada, N ;
Chiba, K .
BIOCHEMICAL PHARMACOLOGY, 2002, 63 (05) :889-896
[9]  
Kobayashi Y, 2001, J Toxicol Sci, V26, P141, DOI 10.2131/jts.26.141
[10]   Comparison of the effects of some CYP3A and other enzyme inducers on replicative DNA synthesis and cytochrome P450 isoforms in rat liver [J].
Lake, BG ;
Renwick, AB ;
Cunninghame, ME ;
Price, RJ ;
Surry, D ;
Evans, DC .
TOXICOLOGY, 1998, 131 (01) :9-20