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

The administration of xenobiotics may significantly alter the expression of cytochromes P450 (CYPs), thereby leading to potentially toxic cellular, physiologic, and pharmacologic responses. Indeed, an important task in the development of new therapeutic entities is to evaluate efficiently and quantitatively their potential effects on the expression level of different CYPs. In this report, reverse transcriptase polymerase chain reaction (RT-PCR) was used to measure basal and induced mRNA of a wide range of rat CYP isoforms. Rats (n=3 per treatment) were treated with five prototype inducers of CYP isoforms or with vehicle only. RT and PCR efficiencies were determined using appropriate RNA and DNA standards. Messenger RNA was quantified by PicoGreen standard curves and normalized to cyclophilin. Quantitative RT-PCR was used successfully to demonstrate that CYP isoforms were induced at the mRNA level following drug administration. Notably, phenobarbital resulted in significant induction of CYP2B1, CYP2B2, CYP2C6, CYP2C13, CYP2E1, CYP3A1, and CYP3A2. 3-Methylcholanthrene induced CYP1A1, CYP1A2, and CYP1B1. CYP2C11 expression was highly variable and suppressed by pyridine, whereas the expression of CYP2E1 was suppressed by dexamethasone. We demonstrated that quantitative RT-PCR can be used to evaluate efficiently the effect of compounds on the expression of a wide range of CYP isoforms. The technique is advantageous over others in that it is very sensitive, efficient and applicable to highly homologous CYP isoforms.

Caron E ，Rioux N ，Nicolas O ，Lebel-Talbot H ，Hamelin BA ... -  《JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY》

An in vivo and in vitro comparison of CYP induction in rat liver and intestine using slices and quantitative RT-PCR.

Martignoni M ，de Kanter R ，Grossi P ，Mahnke A ，Saturno G ，Monshouwer M ... -  《CHEMICO-BIOLOGICAL INTERACTIONS》

Use of a novel real-time quantitative reverse transcription-polymerase chain reaction method to study the effects of cytokines on cytochrome P450 mRNA expression in mouse liver.

Pan J ，Xiang Q ，Ball S 《DRUG METABOLISM AND DISPOSITION》

Fluconazole-induced hepatic cytochrome P450 gene expression and enzymatic activities in rats and mice.

Sun G ，Thai SF ，Lambert GR ，Wolf DC ，Tully DB ，Goetz AK ，George MH ，Grindstaff RD ，Dix DJ ，Nesnow S ... -  《TOXICOLOGY LETTERS》

[Modulation of the activities and mRNA expression of cytochrome P450 isoenzymes in rat liver by Panax gingseng and coadministration with Veratrum nigrum].

Wang YG ，Gao Y ，Chai BX ，Chen P ，Tan HL ，Zhao YH ，Xiao CR ，Sun YY ，Zhu LJ ... -  《-》