Development and evaluation of an in vivo assay in Caenorhabditis elegans for screening of compounds for their effect on cytochrome P450 expression.

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dc.contributor.authorChakrapani, Baby P Sen_US
dc.contributor.authorKumar, Sandeepen_US
dc.contributor.authorSubramaniam, Jamuna Ren_US
dc.date.accessioned2008-06-07en_US
dc.date.accessioned2009-06-01T15:10:16Z
dc.date.available2008-06-07en_US
dc.date.available2009-06-01T15:10:16Z
dc.date.issued2008-06-07en_US
dc.description.abstractMost drugs and xenobiotics induce the expression of cytochrome P450 (CYP) enzymes, which reduce the bioavailability of the inducer and/or co-administered drugs. Therefore, evaluation of new drug candidates for their effect on CYP expression is an essential step in drug development. The available methods for this purpose are expensive and not amenable to high-throughput screening. We developed a fluorescence-based in vivo assay using transgenic Caenorhabditis elegans worms that express the green fluorescent protein (GFP) under the control of various CYP promoters. Using this assay, we found striking similarities between the worm CYPs and their human orthologs in their response to treatment with various drugs. For example,the antibiotic rifampicin, one of the strongest inducers of the human gene CYP3A4, was the strongest inducer of the worm ortholog CYP13A7. Since worms can be easily grown in liquid medium in microtitre plates, the assay described in this paper is suitable for the screening of a large number of potential lead compounds in the drug discovery process.en_US
dc.description.affiliationDepartment of Biological Sciences and Bioengineering, Indian Institute of Technology, Kanpur 208 016, India.en_US
dc.identifier.citationChakrapani BP, Kumar S, Subramaniam JR. Development and evaluation of an in vivo assay in Caenorhabditis elegans for screening of compounds for their effect on cytochrome P450 expression. Journal of Biosciences. 2008 Jun; 33(2): 269-77en_US
dc.identifier.urihttps://imsear.searo.who.int/handle/123456789/111352
dc.language.isoengen_US
dc.source.urihttps://www.ias.ac.in/jbiosci/index.htmlen_US
dc.subject.meshAmino Acid Sequenceen_US
dc.subject.meshAnimalsen_US
dc.subject.meshAnimals, Genetically Modified --geneticsen_US
dc.subject.meshBase Sequenceen_US
dc.subject.meshCaenorhabditis elegans --drug effectsen_US
dc.subject.meshCytochrome P-450 Enzyme System --chemistryen_US
dc.subject.meshDNA, Helminthen_US
dc.subject.meshDrug Evaluation, Preclinical --methodsen_US
dc.subject.meshGene Expression --drug effectsen_US
dc.subject.meshGenes, Reporter --drug effectsen_US
dc.subject.meshGreen Fluorescent Proteins --geneticsen_US
dc.subject.meshHumansen_US
dc.subject.meshMicroscopy, Fluorescenceen_US
dc.subject.meshMolecular Sequence Dataen_US
dc.subject.meshPromoter Regions, Genetic --drug effectsen_US
dc.subject.meshSequence Homology, Amino Aciden_US
dc.titleDevelopment and evaluation of an in vivo assay in Caenorhabditis elegans for screening of compounds for their effect on cytochrome P450 expression.en_US
dc.typeEvaluation Studiesen_US
dc.typeJournal Articleen_US
dc.typeResearch Support, Non-U.S. Gov'ten_US
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