Acyclic nucleoside phosphonates: a study on cytochrome P450 gene expression
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ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Peter Juvan
PROVIDER: E-GEOD-47698 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Focused on the cytochromes P450 (CYPs), we studied gene expression changes in mice treated with acyclic nucleoside antivirals adefovir and tenofovir. Positive control group was treated by prototypic CYP inducers phenobarbital and beta-naphthoflavone. Expression profiling with Steroltalk cDNA arrays revealed major changes in CYP mRNA expression in the inducers-treated group but only minor changes in CYP expression in the adefovir and tenofovir groups.
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Project description:The soil nematode Caenorhabditis elegans is one of the simplest animals having the status of a laboratory model. Its genome contains 80 cytochrome P450 genes (CYP). In order to study CYP gene expression in C. elegans mixed stages and synchronized hermaphrodites were exposed to 18 known xenobiotic cytochrome P450 inducers. Messenger RNA expression was detected by DNA arrays and semiquantitative RT-PCR. Using subfamily-specific primers, a pooled set of exon-rich CYP fragments could be amplified. In this way it was possible to systematically check the influence of different inducers on CYP expression at the same time. The well-known CYP1A inducers beta-naphthoflavone, PCB52, and lansoprazol were the most active and in particular they strongly induced almost all CYP35 isoforms. A few number of further CYP forms were found to be inducible by other xenobiotics like phenobarbital, atrazine, and clofibrate. In addition, a transgenic C. elegans line expressing GFP under control of the CYP35A2 promoter showed a strong induction of the fusion by beta-naphthoflavone in the intestine. Copyright 2001 Academic Press. Set of arrays organized by shared biological context, such as organism, tumors types, processes, etc. Computed
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Project description:The soil nematode Caenorhabditis elegans is one of the simplest animals having the status of a laboratory model. Its genome contains 80 cytochrome P450 genes (CYP). In order to study CYP gene expression in C. elegans mixed stages and synchronized hermaphrodites were exposed to 18 known xenobiotic cytochrome P450 inducers. Messenger RNA expression was detected by DNA arrays and semiquantitative RT-PCR. Using subfamily-specific primers, a pooled set of exon-rich CYP fragments could be amplified. In this way it was possible to systematically check the influence of different inducers on CYP expression at the same time. The well-known CYP1A inducers beta-naphthoflavone, PCB52, and lansoprazol were the most active and in particular they strongly induced almost all CYP35 isoforms. A few number of further CYP forms were found to be inducible by other xenobiotics like phenobarbital, atrazine, and clofibrate. In addition, a transgenic C. elegans line expressing GFP under control of the CYP35A2 promoter showed a strong induction of the fusion by beta-naphthoflavone in the intestine. Copyright 2001 Academic Press. Set of arrays organized by shared biological context, such as organism, tumors types, processes, etc. Keywords: Logical Set
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Project description:High cholesterol diet and xenobiotic treatment induce changes in cholesterol homeostasis and drug metabolism. Mice were either 7 days on high cholesterol diet or were treated with phenobarbital. Liver samples were analyzed using Sterolgene v0 cDNA microarrays. Sterolgene microarray is a tool designed to enable focused studies of cholesterol homeostasis and drug metabolism. We show that one week of cholesterol diet down-regulates cholesterol biosynthesis and up-regulates xenobiotic metabolism (Cyp3 family). Phenobarbital treatment also up-regulates xenobiotic metabolism (Cyp2b and Cyp3a families). We can conclude that the Sterolgene series of cDNA microarrays represent novel original tool, enabling focused and cost-wise studies of cholesterol homeostasis and drug metabolism. Keywords: Treatment and diet effects One group of mice was treated i.p. with 50 mg/kg of phenobarbital in vehicle (5% DMSO in corn oil). Untreated group was injected vehicle. Third group was 7 days on 1 % (w/w) cholesterol diet prior vehicle treatment. After 10 h animals were sacrificed and livers were stored. Pools of total RNA from two animals were mixed. Three pools of untreated and phenobarbital treated groups, and two pools of cholesterol diet group were co-hybridized with liver reference on Sterolgene v0 cDNA microarray. No dye-swaps were performed.
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