The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Anthony M Brown - One of the best experts on this subject based on the ideXlab platform.
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measurement of cytochrome p450 gene induction in human hepatocytes using quantitative real time reverse transcriptase polymerase chain reaction
Drug Metabolism and Disposition, 2000Co-Authors: Wayne P Bowen, Jae E Carey, Asik Miah, Heather F Mcmurray, Peter W Munday, Rowena S James, Robert A Coleman, Anthony M BrownAbstract:Drug-induced changes in expression of cytochrome (CYP) P450 genes are a key cause of drug-drug interactions. Consequently, preclinical prediction of these changes by novel compounds is an integral component of drug development. To date, in vitro models of CYP induction have used mRNA measurement, Immunodetection, and substrate metabolism as reporters. Here, we describe the application of quantitative real-time reverse transcriptase polymerase chain reaction to study CYP1A1 and CYP3A4 gene induction in 5-day-old cultures of human hepatocytes by known CYP inducers. After 5 days in culture, CYP1A1 expression was significantly elevated (5.1- to 26-fold; P <.01) in all four livers studied. In direct contrast, CYP3A4 mRNA levels consistently decreased during culture (80- to 300-fold; P <.001). In three independent experiments, a 48-h exposure to 3-methylcholanthrene, omeprazole, and lansoprazole significantly induced CYP1A1 expression in comparison to untreated cultures (P <.05). Rifampicin and solvent were without effect on CYP1A1 expression. Under identical experimental conditions, rifampicin and lansoprazole significantly elevated CYP3A4 mRNA expression (P <.05), whereas 3-methylcholanthrene, omeprazole, and dimethyl sulfoxide were without significant effect. These data demonstrate the applicability of quantitative reverse transcriptase polymerase chain reaction to the determination of gene dynamics in human hepatocytes. This offers a highly specific alternative to quantification of drug effects on CYP expression using Immunodetection and substrate metabolism.
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measurement of cytochrome p450 gene induction in human hepatocytes using quantitative real time reverse transcriptase polymerase chain reaction
Drug Metabolism and Disposition, 2000Co-Authors: Wayne P Bowen, Jae E Carey, Asik Miah, Heather F Mcmurray, Peter W Munday, Rowena S James, Robert A Coleman, Anthony M BrownAbstract:Drug-induced changes in expression of cytochrome (CYP) P450 genes are a key cause of drug-drug interactions. Consequently, preclinical prediction of these changes by novel compounds is an integral component of drug development. To date, in vitro models of CYP induction have used mRNA measurement, Immunodetection, and substrate metabolism as reporters. Here, we describe the application of quantitative real-time reverse transcriptase polymerase chain reaction to studyCYP1A1 and CYP3A4 gene induction in 5-day-old cultures of human hepatocytes by known CYP inducers. After 5 days in culture, CYP1A1 expression was significantly elevated (5.1- to 26-fold; P
Wayne P Bowen - One of the best experts on this subject based on the ideXlab platform.
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measurement of cytochrome p450 gene induction in human hepatocytes using quantitative real time reverse transcriptase polymerase chain reaction
Drug Metabolism and Disposition, 2000Co-Authors: Wayne P Bowen, Jae E Carey, Asik Miah, Heather F Mcmurray, Peter W Munday, Rowena S James, Robert A Coleman, Anthony M BrownAbstract:Drug-induced changes in expression of cytochrome (CYP) P450 genes are a key cause of drug-drug interactions. Consequently, preclinical prediction of these changes by novel compounds is an integral component of drug development. To date, in vitro models of CYP induction have used mRNA measurement, Immunodetection, and substrate metabolism as reporters. Here, we describe the application of quantitative real-time reverse transcriptase polymerase chain reaction to study CYP1A1 and CYP3A4 gene induction in 5-day-old cultures of human hepatocytes by known CYP inducers. After 5 days in culture, CYP1A1 expression was significantly elevated (5.1- to 26-fold; P <.01) in all four livers studied. In direct contrast, CYP3A4 mRNA levels consistently decreased during culture (80- to 300-fold; P <.001). In three independent experiments, a 48-h exposure to 3-methylcholanthrene, omeprazole, and lansoprazole significantly induced CYP1A1 expression in comparison to untreated cultures (P <.05). Rifampicin and solvent were without effect on CYP1A1 expression. Under identical experimental conditions, rifampicin and lansoprazole significantly elevated CYP3A4 mRNA expression (P <.05), whereas 3-methylcholanthrene, omeprazole, and dimethyl sulfoxide were without significant effect. These data demonstrate the applicability of quantitative reverse transcriptase polymerase chain reaction to the determination of gene dynamics in human hepatocytes. This offers a highly specific alternative to quantification of drug effects on CYP expression using Immunodetection and substrate metabolism.
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measurement of cytochrome p450 gene induction in human hepatocytes using quantitative real time reverse transcriptase polymerase chain reaction
Drug Metabolism and Disposition, 2000Co-Authors: Wayne P Bowen, Jae E Carey, Asik Miah, Heather F Mcmurray, Peter W Munday, Rowena S James, Robert A Coleman, Anthony M BrownAbstract:Drug-induced changes in expression of cytochrome (CYP) P450 genes are a key cause of drug-drug interactions. Consequently, preclinical prediction of these changes by novel compounds is an integral component of drug development. To date, in vitro models of CYP induction have used mRNA measurement, Immunodetection, and substrate metabolism as reporters. Here, we describe the application of quantitative real-time reverse transcriptase polymerase chain reaction to studyCYP1A1 and CYP3A4 gene induction in 5-day-old cultures of human hepatocytes by known CYP inducers. After 5 days in culture, CYP1A1 expression was significantly elevated (5.1- to 26-fold; P
Robert A Coleman - One of the best experts on this subject based on the ideXlab platform.
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measurement of cytochrome p450 gene induction in human hepatocytes using quantitative real time reverse transcriptase polymerase chain reaction
Drug Metabolism and Disposition, 2000Co-Authors: Wayne P Bowen, Jae E Carey, Asik Miah, Heather F Mcmurray, Peter W Munday, Rowena S James, Robert A Coleman, Anthony M BrownAbstract:Drug-induced changes in expression of cytochrome (CYP) P450 genes are a key cause of drug-drug interactions. Consequently, preclinical prediction of these changes by novel compounds is an integral component of drug development. To date, in vitro models of CYP induction have used mRNA measurement, Immunodetection, and substrate metabolism as reporters. Here, we describe the application of quantitative real-time reverse transcriptase polymerase chain reaction to study CYP1A1 and CYP3A4 gene induction in 5-day-old cultures of human hepatocytes by known CYP inducers. After 5 days in culture, CYP1A1 expression was significantly elevated (5.1- to 26-fold; P <.01) in all four livers studied. In direct contrast, CYP3A4 mRNA levels consistently decreased during culture (80- to 300-fold; P <.001). In three independent experiments, a 48-h exposure to 3-methylcholanthrene, omeprazole, and lansoprazole significantly induced CYP1A1 expression in comparison to untreated cultures (P <.05). Rifampicin and solvent were without effect on CYP1A1 expression. Under identical experimental conditions, rifampicin and lansoprazole significantly elevated CYP3A4 mRNA expression (P <.05), whereas 3-methylcholanthrene, omeprazole, and dimethyl sulfoxide were without significant effect. These data demonstrate the applicability of quantitative reverse transcriptase polymerase chain reaction to the determination of gene dynamics in human hepatocytes. This offers a highly specific alternative to quantification of drug effects on CYP expression using Immunodetection and substrate metabolism.
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measurement of cytochrome p450 gene induction in human hepatocytes using quantitative real time reverse transcriptase polymerase chain reaction
Drug Metabolism and Disposition, 2000Co-Authors: Wayne P Bowen, Jae E Carey, Asik Miah, Heather F Mcmurray, Peter W Munday, Rowena S James, Robert A Coleman, Anthony M BrownAbstract:Drug-induced changes in expression of cytochrome (CYP) P450 genes are a key cause of drug-drug interactions. Consequently, preclinical prediction of these changes by novel compounds is an integral component of drug development. To date, in vitro models of CYP induction have used mRNA measurement, Immunodetection, and substrate metabolism as reporters. Here, we describe the application of quantitative real-time reverse transcriptase polymerase chain reaction to studyCYP1A1 and CYP3A4 gene induction in 5-day-old cultures of human hepatocytes by known CYP inducers. After 5 days in culture, CYP1A1 expression was significantly elevated (5.1- to 26-fold; P
Jae E Carey - One of the best experts on this subject based on the ideXlab platform.
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measurement of cytochrome p450 gene induction in human hepatocytes using quantitative real time reverse transcriptase polymerase chain reaction
Drug Metabolism and Disposition, 2000Co-Authors: Wayne P Bowen, Jae E Carey, Asik Miah, Heather F Mcmurray, Peter W Munday, Rowena S James, Robert A Coleman, Anthony M BrownAbstract:Drug-induced changes in expression of cytochrome (CYP) P450 genes are a key cause of drug-drug interactions. Consequently, preclinical prediction of these changes by novel compounds is an integral component of drug development. To date, in vitro models of CYP induction have used mRNA measurement, Immunodetection, and substrate metabolism as reporters. Here, we describe the application of quantitative real-time reverse transcriptase polymerase chain reaction to study CYP1A1 and CYP3A4 gene induction in 5-day-old cultures of human hepatocytes by known CYP inducers. After 5 days in culture, CYP1A1 expression was significantly elevated (5.1- to 26-fold; P <.01) in all four livers studied. In direct contrast, CYP3A4 mRNA levels consistently decreased during culture (80- to 300-fold; P <.001). In three independent experiments, a 48-h exposure to 3-methylcholanthrene, omeprazole, and lansoprazole significantly induced CYP1A1 expression in comparison to untreated cultures (P <.05). Rifampicin and solvent were without effect on CYP1A1 expression. Under identical experimental conditions, rifampicin and lansoprazole significantly elevated CYP3A4 mRNA expression (P <.05), whereas 3-methylcholanthrene, omeprazole, and dimethyl sulfoxide were without significant effect. These data demonstrate the applicability of quantitative reverse transcriptase polymerase chain reaction to the determination of gene dynamics in human hepatocytes. This offers a highly specific alternative to quantification of drug effects on CYP expression using Immunodetection and substrate metabolism.
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measurement of cytochrome p450 gene induction in human hepatocytes using quantitative real time reverse transcriptase polymerase chain reaction
Drug Metabolism and Disposition, 2000Co-Authors: Wayne P Bowen, Jae E Carey, Asik Miah, Heather F Mcmurray, Peter W Munday, Rowena S James, Robert A Coleman, Anthony M BrownAbstract:Drug-induced changes in expression of cytochrome (CYP) P450 genes are a key cause of drug-drug interactions. Consequently, preclinical prediction of these changes by novel compounds is an integral component of drug development. To date, in vitro models of CYP induction have used mRNA measurement, Immunodetection, and substrate metabolism as reporters. Here, we describe the application of quantitative real-time reverse transcriptase polymerase chain reaction to studyCYP1A1 and CYP3A4 gene induction in 5-day-old cultures of human hepatocytes by known CYP inducers. After 5 days in culture, CYP1A1 expression was significantly elevated (5.1- to 26-fold; P
Asik Miah - One of the best experts on this subject based on the ideXlab platform.
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measurement of cytochrome p450 gene induction in human hepatocytes using quantitative real time reverse transcriptase polymerase chain reaction
Drug Metabolism and Disposition, 2000Co-Authors: Wayne P Bowen, Jae E Carey, Asik Miah, Heather F Mcmurray, Peter W Munday, Rowena S James, Robert A Coleman, Anthony M BrownAbstract:Drug-induced changes in expression of cytochrome (CYP) P450 genes are a key cause of drug-drug interactions. Consequently, preclinical prediction of these changes by novel compounds is an integral component of drug development. To date, in vitro models of CYP induction have used mRNA measurement, Immunodetection, and substrate metabolism as reporters. Here, we describe the application of quantitative real-time reverse transcriptase polymerase chain reaction to study CYP1A1 and CYP3A4 gene induction in 5-day-old cultures of human hepatocytes by known CYP inducers. After 5 days in culture, CYP1A1 expression was significantly elevated (5.1- to 26-fold; P <.01) in all four livers studied. In direct contrast, CYP3A4 mRNA levels consistently decreased during culture (80- to 300-fold; P <.001). In three independent experiments, a 48-h exposure to 3-methylcholanthrene, omeprazole, and lansoprazole significantly induced CYP1A1 expression in comparison to untreated cultures (P <.05). Rifampicin and solvent were without effect on CYP1A1 expression. Under identical experimental conditions, rifampicin and lansoprazole significantly elevated CYP3A4 mRNA expression (P <.05), whereas 3-methylcholanthrene, omeprazole, and dimethyl sulfoxide were without significant effect. These data demonstrate the applicability of quantitative reverse transcriptase polymerase chain reaction to the determination of gene dynamics in human hepatocytes. This offers a highly specific alternative to quantification of drug effects on CYP expression using Immunodetection and substrate metabolism.
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measurement of cytochrome p450 gene induction in human hepatocytes using quantitative real time reverse transcriptase polymerase chain reaction
Drug Metabolism and Disposition, 2000Co-Authors: Wayne P Bowen, Jae E Carey, Asik Miah, Heather F Mcmurray, Peter W Munday, Rowena S James, Robert A Coleman, Anthony M BrownAbstract:Drug-induced changes in expression of cytochrome (CYP) P450 genes are a key cause of drug-drug interactions. Consequently, preclinical prediction of these changes by novel compounds is an integral component of drug development. To date, in vitro models of CYP induction have used mRNA measurement, Immunodetection, and substrate metabolism as reporters. Here, we describe the application of quantitative real-time reverse transcriptase polymerase chain reaction to studyCYP1A1 and CYP3A4 gene induction in 5-day-old cultures of human hepatocytes by known CYP inducers. After 5 days in culture, CYP1A1 expression was significantly elevated (5.1- to 26-fold; P
