Differential Inducing Effect of Benzo[a]pyrene on Gene Expression and Enzyme Activity of Cytochromes P450 1A1 and 1A2 in Sprague-Dawley and Wistar Rats

被引：23

作者：

Floreani, Maura ^{[1
]}

Gabbia, Daniela ^{[1
]}

Barbierato, Massimo ^{[1
]}

De Martin, Sara ^{[1
]}

Palatini, Pietro ^{[1
]}

机构：

[1] Univ Padua, Dept Pharmaceut & Pharmacol Sci, I-35131 Padua, Italy

来源：

DRUG METABOLISM AND PHARMACOKINETICS | 2012年 / 27卷 / 06期

关键词：

CYP1A1; CYP1A2; benzo[a]pyrene induction; Sprague-Dawley rats; Wistar rats; ARYL-HYDROCARBON RECEPTOR; LIVER-MICROSOMES; SUBSTRATE-SPECIFICITY; STRAIN DIFFERENCES; INDUCTION; INDUCIBILITY; LANSOPRAZOLE; OMEPRAZOLE; INDUCERS; CYP1A1;

D O I：

10.2133/dmpk.DMPK-12-RG-035

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

The objective of this study was to compare RT-PCR, Western blot and determination of enzyme activity in the assessment of the induction of cytochromes P450 (CYPs) 1A1 and 1A2 by benzo[a]pyrene (BaP) in Sprague-Dawley and Wistar rats. Inhibition studies and kinetic analyses confirmed literature data indicating that methoxyresorufin is a specific CYP1A2 substrate in both uninduced and BaP-treated rats, whereas ethoxyresorufin is a specific CYP1A1 substrate only in BaP-treated rats. BaP treatment increased mRNA and protein expressions of both CYP1A enzymes to a greater extent in Wistar than Sprague-Dawley rats. It consistently caused a higher increase in mRNA and protein expression of the aryl hydrocarbon receptor in the former rats. By contrast, CYP1A2 enzyme activity was much more markedly increased in Sprague-Dawley than Wistar rats and CYP1A1 activity was induced to similar levels. A BaP-induced increase in the turnover number of CYP1A enzymes in Sprague-Dawley rats, relative to Wistar rats, may provide a plausible explanation for the differential effect of BaP on gene expression and enzyme activity. These results have methodological implications, since they show that RT-PCR and Western blot may not provide a quantitative measure of induction of CYP1A activity, which is the actual measure of the change in CYP1A-mediated metabolism.

引用

页码：640 / 652

页数：13

共 40 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] ETHOXYPHENOXAZONES, PENTOXYPHENOXAZONES, AND BENZYLOXYPHENOXAZONES AND HOMOLOGS - A SERIES OF SUBSTRATES TO DISTINGUISH BETWEEN DIFFERENT INDUCED CYTOCHROMES-P-450 [J].

BURKE, MD ;

THOMPSON, S ;

ELCOMBE, CR ;

HALPERT, J ;

HAAPARANTA, T ;

MAYER, RT .

BIOCHEMICAL PHARMACOLOGY, 1985, 34 (18) :3337-3345

[3] Quantification of the expression and inducibility of 12 rat cytochrome P450 isoforms by quantitative RT-PCR [J].

Caron, E ;

Rioux, N ;

Nicolas, O ;

Lebel-Talbot, H ;

Hamelin, BA .

JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, 2005, 19 (06) :368-378

[4]

CONNEY AH, 1982, CANCER RES, V42, P4875

[5]

Copeland RA, 2000, ENZYMES PRACTICAL IN

[6]

CURIPEDROSA R, 1994, J PHARMACOL EXP THER, V269, P384

[7] Exactly the Same but Different: Promiscuity and Diversity in the Molecular Mechanisms of Action of the Aryl Hydrocarbon (Dioxin) Receptor [J].

Denison, Michael S. ;

Soshilov, Anatoly A. ;

He, Guochun ;

DeGroot, Danica E. ;

Zhao, Bin .

TOXICOLOGICAL SCIENCES, 2011, 124 (01) :1-22

[8] Lack of drug interaction between omeprazole, lansoprazole, pantoprazole and theophylline [J].

Dilger, K ;

Zheng, ZC ;

Klotz, U .

BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 1999, 48 (03) :438-444

[9] Differential selectivity of cytochrome P450 inhibitors against probe substrates in human and rat liver microsomes [J].

Eagling, VA ;

Tjia, JF ;

Back, DJ .

BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 1998, 45 (02) :107-114

[10] Polycyclic aromatic hydrocarbon (PAH) metabolizing enzyme activities in human lung, and their inducibility by exposure to naphthalene, phenanthrene, pyrene, chrysene, and benzo(a)pyrene as shown in the rat lung and liver [J].

Elovaara, Eivor ;

Mikkola, Jouni ;

Stockmann-Juvala, Helene ;

Luukkanen, Leena ;

Keski-Hynnila, Helena ;

Kostiainen, Risto ;

Pasanen, Markku ;

Pelkonen, Olavi ;

Vainio, Harri .

ARCHIVES OF TOXICOLOGY, 2007, 81 (03) :169-182

← 1 2 3 4 →