2019
Development and Application of a Life-Stage Physiologically Based Pharmacokinetic (PBPK) Model to the Assessment of Internal Dose of Pyrethroids in Humans
Mallick P, Moreau M, Song G, Efremenko A, Pendse S, Creek M, Osimitz T, Hines R, Hinderliter P, Clewell H, Lake B, Yoon M. Development and Application of a Life-Stage Physiologically Based Pharmacokinetic (PBPK) Model to the Assessment of Internal Dose of Pyrethroids in Humans. Toxicological Sciences 2019, 173: 86-99. PMID: 31593217, PMCID: PMC6944222, DOI: 10.1093/toxsci/kfz211.Peer-Reviewed Original ResearchMeSH KeywordsCarboxylesteraseCytochrome P-450 Enzyme SystemDose-Response Relationship, DrugHumansKineticsLiverMicrosomes, LiverModels, BiologicalNitrilesPermethrinPharmacokineticsPyrethrinsConceptsTarget tissue exposureTissue exposurePharmacokinetic modelLiver blood flowLow internal exposureAge-related sensitivityAge-dependent changesEfficient metabolic clearanceIndividual cytochrome P450Human hepatic metabolismAge-related differencesCis-permethrinHepatic metabolismBlood flowMetabolic clearanceCES enzymesHepatic CLintInternal doseIntrinsic clearanceTarget tissuesInternal exposureClearanceCarboxylesterase enzymesCytochrome P450Vivo extrapolationA Time-Embedding Network Models the Ontogeny of 23 Hepatic Drug Metabolizing Enzymes
Matlock M, Tambe A, Elliott-Higgins J, Hines R, Miller G, Swamidass S. A Time-Embedding Network Models the Ontogeny of 23 Hepatic Drug Metabolizing Enzymes. Chemical Research In Toxicology 2019, 32: 1707-1721. PMID: 31304741, PMCID: PMC6933754, DOI: 10.1021/acs.chemrestox.9b00223.Peer-Reviewed Original ResearchConceptsAge-dependent changesHepatic Drug Metabolizing EnzymesAdverse drug reactionsValproic acid toxicityDrug metabolizing enzymesDrug metabolism enzymesElimination of drugsPediatric patientsPediatric populationMetabolite exposureDrug reactionsClinical dataElevated riskOverall clearanceDrug toxicityFunction of ageDrug safetyFetal periodMetabolizing enzymesDrug metabolismDrug toxicity risksPotential mechanismsAcid toxicityEnzyme expressionDemographic factors
2007
Ontogeny of human hepatic cytochromes P450
Hines R. Ontogeny of human hepatic cytochromes P450. Journal Of Biochemical And Molecular Toxicology 2007, 21: 169-175. PMID: 17936930, DOI: 10.1002/jbt.20179.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAryl Hydrocarbon HydroxylasesChildChild, PreschoolCytochrome P-450 CYP2C19Cytochrome P-450 CYP2C9Cytochrome P-450 CYP2E1Cytochrome P-450 CYP3ACytochrome P-450 Enzyme SystemGene Expression Regulation, DevelopmentalGene Expression Regulation, EnzymologicHumansInfantLiverMixed Function OxygenasesConceptsHuman hepatic cytochrome P450Adverse drug reactionsConsiderable interindividual variabilityHepatic cytochrome P450Cytochrome P450Human liver samplesImportant endogenous functionsWeeks' gestationThird trimesterFirst trimesterDrug reactionsKey cytochrome P450Postnatal onsetPostnatal increaseTherapeutic efficacyInterindividual variabilityQuantitative Western blottingWestern blottingGestationLow levelsLiver samplesProbe substratesOnset of expressionTrimesterThird group
2006
Enzyme-Mediated Protein Haptenation of Dapsone and Sulfamethoxazole in Human Keratinocytes: I. Expression and Role of Cytochromes P450
Vyas P, Roychowdhury S, Khan F, Prisinzano T, Lamba J, Schuetz E, Blaisdell J, Goldstein J, Munson K, Hines R, Svensson C. Enzyme-Mediated Protein Haptenation of Dapsone and Sulfamethoxazole in Human Keratinocytes: I. Expression and Role of Cytochromes P450. Journal Of Pharmacology And Experimental Therapeutics 2006, 319: 488-496. PMID: 16857728, DOI: 10.1124/jpet.106.105858.Peer-Reviewed Original ResearchMeSH KeywordsAcetylationCells, CulturedCytochrome P-450 CYP3ACytochrome P-450 Enzyme SystemDapsoneHaptensHumansKeratinocytesSulfamethoxazoleConceptsCutaneous drug reactionsNormal human epidermal keratinocytesEnzyme-linked immunosorbent assayDrug reactionsProtein haptenationCommon adverse drug reactionsLife-threatening complicationsAdverse drug reactionsCytochrome P450Presence of CYP3A4Immunofluorescence confocal microscopyConfocal microscopyImmune responseHuman epidermal keratinocytesNumerous minorArylamine drugsImmunosorbent assayCellular proteinsCYP2C9 proteinEpidermal keratinocytesHaptenationHuman keratinocytesChemical inhibitorsProtein adductionCyclooxygenase
2005
SP1 AND SP3 REGULATE BASAL TRANSCRIPTION OF THE HUMAN CYP2F1 GENE
Wan J, Carr B, Cutler N, Lanza D, Hines R, Yost G. SP1 AND SP3 REGULATE BASAL TRANSCRIPTION OF THE HUMAN CYP2F1 GENE. Drug Metabolism And Disposition 2005, 33: 1244-1253. PMID: 15860659, DOI: 10.1124/dmd.105.004069.Peer-Reviewed Original ResearchMeSH KeywordsBase SequenceBinding SitesCell Line, TumorCytochrome P-450 Enzyme SystemCytochrome P450 Family 2DNAGene Expression RegulationGenes, ReporterHumansLuciferasesLungMolecular Sequence DataPromoter Regions, GeneticRepressor ProteinsSp1 Transcription FactorSp3 Transcription FactorTranscription, GeneticTranscriptional ActivationTransfectionConceptsSp3 expression vectorsExpression vectorCYP2F1 geneDrosophila Schneider line 2 cellsSchneider line 2 cellsSpecific protein-DNA complexesSp1 expression vectorSL-2 cellsProtein-DNA complexesProtein-DNA bindingTATA-less promoter regionA549 cellsCell nuclear extractsCompetitive electrophoretic mobilityBasal transcription elementProximal promoter elementsLuciferase reporter constructsSp1-like sitesSp3 factorsSp3 proteinsSelective transcriptionSupershift studiesGene transcriptionPromoter elementsTranscription elements
2003
Developmental Expression of the Major Human Hepatic CYP3A Enzymes
Stevens J, Hines R, Gu C, Koukouritaki S, Manro J, Tandler P, Zaya M. Developmental Expression of the Major Human Hepatic CYP3A Enzymes. Journal Of Pharmacology And Experimental Therapeutics 2003, 307: 573-582. PMID: 12975492, DOI: 10.1124/jpet.103.054841.Peer-Reviewed Original ResearchCharacterization of the Human Lung CYP2F1 Gene and Identification of a Novel Lung-specific Binding Motif*
Carr B, Wan J, Hines R, Yost G. Characterization of the Human Lung CYP2F1 Gene and Identification of a Novel Lung-specific Binding Motif*. Journal Of Biological Chemistry 2003, 278: 15473-15483. PMID: 12598524, DOI: 10.1074/jbc.m300319200.Peer-Reviewed Original ResearchConceptsCYP2F1 geneCompetitive electrophoretic mobility shift assaysBacterial artificial chromosome (BAC) clonesElectrophoretic mobility shift assaysDNA-protein complexesE-box motifArtificial chromosome clonesPrimer extension analysisTranscription start siteTissue-specific expressionDNA consensus siteMobility shift assaysTissue-specific regulationUntranslated exon 1Transient transfection studiesLuciferase reporter constructsBox motifChromosome clonesConsensus sitesE-boxNuclear proteinsStart siteExtension analysisCDNA endsUpstream sequencesGenotyping and site-directed mutagenesis of a cytochrome P450 meander Pro-X-Arg motif critical to CYP4B1 catalysis
Zheng Y, Henne K, Charmley P, Kim R, McCarver D, Cabacungan E, Hines R, Rettie A. Genotyping and site-directed mutagenesis of a cytochrome P450 meander Pro-X-Arg motif critical to CYP4B1 catalysis. Toxicology And Applied Pharmacology 2003, 186: 119-126. PMID: 12639503, DOI: 10.1016/s0041-008x(02)00028-5.Peer-Reviewed Original ResearchConceptsHeme bindingArg motifAmino acid sequence alignmentNonhuman primate speciesPrimate speciesRedox partner interactionsSite-directed mutagenesisCYP4B1 geneRestriction enzyme fragment length polymorphismArg triadFragment length polymorphismRabbit CYP4B1Sequence alignmentHuman allelesN-terminalCatalytic functionCommon laboratory animalsAmino acidsPro residuesLength polymorphismMeander regionHuman populationDistal ArgGenesGlu-Arg
2002
The Ontogeny of Human Drug-Metabolizing Enzymes: Phase I Oxidative Enzymes
Hines R, McCarver D. The Ontogeny of Human Drug-Metabolizing Enzymes: Phase I Oxidative Enzymes. Journal Of Pharmacology And Experimental Therapeutics 2002, 300: 355-360. PMID: 11805191, DOI: 10.1124/jpet.300.2.355.Peer-Reviewed Original ResearchMeSH KeywordsAgingAlcohol DehydrogenaseCytochrome P-450 Enzyme SystemHumansMixed Function OxygenasesMonoamine OxidasePharmaceutical PreparationsPharmacokinetics
1999
Flavin‐containing monooxygenase isoform 2: Developmental expression in fetal and neonatal rabbit lung
Larsen‐Su S, Krueger S, Yueh M, Lee M, Shehin S, Hines R, Williams D. Flavin‐containing monooxygenase isoform 2: Developmental expression in fetal and neonatal rabbit lung. Journal Of Biochemical And Molecular Toxicology 1999, 13: 187-193. PMID: 10098904, DOI: 10.1002/(sici)1099-0461(1999)13:3/4<187::aid-jbt9>3.0.co;2-6.Peer-Reviewed Original ResearchConceptsEarly developmental appearanceRabbit lungsNeonatal rabbit lungConstitutive cytochrome P450Developmental appearanceNeonatal lungToxic insultsLungMonooxygenase isoformsNumerous xenobioticsForeign chemicalsMonooxygenase functionCytochrome P450Major isoformsTissue-specific fashionDevelopmental expressionMammalian flavinIsoform 2Expression patternsIsoformsFMO2Individual isoformsNeonatesFetuses
1995
Partial Characterization of the Human CYP1A1 Negatively Acting Transcription Factor and Mutational Analysis of Its Cognate DNA Recognition Sequence
Boucher P, Piechocki M, Hines R. Partial Characterization of the Human CYP1A1 Negatively Acting Transcription Factor and Mutational Analysis of Its Cognate DNA Recognition Sequence. Molecular And Cellular Biology 1995, 15: 5144-5151. PMID: 7651431, PMCID: PMC230761, DOI: 10.1128/mcb.15.9.5144.Peer-Reviewed Original ResearchBase SequenceBinding SitesBinding, CompetitiveCells, CulturedCytochrome P-450 Enzyme SystemDNA Mutational AnalysisGene Expression Regulation, EnzymologicHumansMolecular Sequence DataNuclear ProteinsOxygenasesProtein BindingRegulatory Sequences, Nucleic AcidSequence Homology, Nucleic AcidTranscription FactorsIn vitro binding and functional studies comparing the human CYPIAI negative regulatory element with the orthologous sequences from rodent genes
Boucher P, Hines R. In vitro binding and functional studies comparing the human CYPIAI negative regulatory element with the orthologous sequences from rodent genes. Carcinogenesis 1995, 16: 383-392. PMID: 7859371, DOI: 10.1093/carcin/16.2.383.Peer-Reviewed Original ResearchConceptsNegative regulatory elementSpecific DNA-protein complexesDNA-protein complexesTransient expression assaysRegulatory elementsNuclear proteinsMouse fragmentsHeterologous promoterExpression assaysCell linesElectrophoretic mobility shift assaysMouse nuclear proteinMouse CYP1A1 geneSouthwestern blot analysisMobility shift assaysCYP1A1 geneNegative regulatory activitySimilar protection patternMouse hepatoma cell lineRodent cell linesCytosine-rich sequencesCytosine-rich regionsHuman CYP1A1 geneOrthologous sequencesRodent genes
1993
Expression of human cytochrome P450 1A1 in DNA repair deficient and proficient human fibroblasts stably transformed with an inducible expression vector
States J, Quan T, Hines R, Novak R, Runge-Morris M. Expression of human cytochrome P450 1A1 in DNA repair deficient and proficient human fibroblasts stably transformed with an inducible expression vector. Carcinogenesis 1993, 14: 1643-1649. PMID: 8353849, DOI: 10.1093/carcin/14.8.1643.Peer-Reviewed Original ResearchMeSH Keywords7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxideAnimalsBase SequenceBenzo(a)pyreneBenzoflavonesBiotransformationCadmiumCadmium CompoundsChimeraCytochrome P-450 Enzyme SystemDNA RepairEnzyme InductionFibroblastsGene Expression Regulation, EnzymologicGenetic VectorsHumansIsoenzymesMiceMolecular Sequence DataPlasmidsRNA, MessengerSulfatesTransfectionTransformation, GeneticXeroderma PigmentosumConceptsCytochrome P450 1A1P450 1A1Inducible CYP1A1Inducible mouse metallothionein-I promoterLow dosesHuman skin fibroblastsProficient cellsPotent mutagenic agentCYP1A1 expressionCYP1A1 activityHuman cytochrome P450 1A1DNA repairCYP1A1Mouse metallothionein-I promoterCytotoxic effectsMetallothionein-I promoterSkin fibroblastsDifferential cytotoxicityDNA repair-proficient cellsToxic effectsMore cytotoxicCytochrome P450Normal cellsRepairHuman CYP1A1Specific nuclear protein binding to a negative regulatory element on the human CYP1A1 gene
Boucher P, Ruch R, Hines R. Specific nuclear protein binding to a negative regulatory element on the human CYP1A1 gene. Journal Of Biological Chemistry 1993, 268: 17384-17391. PMID: 8349622, DOI: 10.1016/s0021-9258(19)85346-2.Peer-Reviewed Original ResearchConceptsNegative regulatory activityNuclear proteinsElectrophoretic mobility shift assaysCellular trans-acting factorsTrans-acting factorsRegulatory activityStrand-specific mannerCo-transfection studiesMethylation interference experimentsMobility shift assaysNegative regulatory elementSpecific nuclear proteinCytosine-rich sequencesHuman CYP1A1 genePromoter/enhancerRegulatory elementsShift assaysTransient expressionReporter geneDNase IChimeric plasmidsCYP1A1 promoterImportant sequencesCYP1A1 genePalindromes
1990
Expression of CYP1A1 Gene in Patients With Lung Cancer: Evidence for Cigarette Smoke-Induced Gene Expression in Normal Lung Tissue and for Altered Gene Regulation in Primary Pulmonary Carcinomas
McLemore T, Adelberg S, Liu M, McMahon N, Yu S, Hubbard W, Czerwinski M, Wood T, Storeng R, Lubet R, Eggleston J, Boyd M, Hines R. Expression of CYP1A1 Gene in Patients With Lung Cancer: Evidence for Cigarette Smoke-Induced Gene Expression in Normal Lung Tissue and for Altered Gene Regulation in Primary Pulmonary Carcinomas. Journal Of The National Cancer Institute 1990, 82: 1333-1339. PMID: 2380990, DOI: 10.1093/jnci/82.16.1333.Peer-Reviewed Original ResearchMeSH KeywordsCytochrome P-450 CYP1A1Cytochrome P-450 Enzyme SystemFemaleGene Expression Regulation, NeoplasticHumansIsoenzymesLungLung NeoplasmsMaleMiddle AgedOxidoreductasesRNA, MessengerRNA, NeoplasmSmokingConceptsNormal lung tissuesLung tissueLung cancerFormer smokersCigarette smokersCYP1A1 gene expressionCYP1A1 geneActive cigarette smokersPrimary pulmonary carcinomasHuman pulmonary tissueMessenger RNA expressionPulmonary carcinogenesisCigarette smokingPulmonary carcinomaTime-dependent decreasePulmonary tissueGene expressionSmokersCarcinoma tissuesPatientsCancerTumorsRNA expressionMRNA levelsCYP1A1 mRNAImmunochemical and molecular biological studies on human placental cigarette smoke-inducible cytochrome P-450-dependent monooxygenase activities
Pasanen M, Haaparanta T, Sundin M, Sivonen P, Vakakangas K, Raunio H, Hines R, Gustafsson J, Pelkonen O. Immunochemical and molecular biological studies on human placental cigarette smoke-inducible cytochrome P-450-dependent monooxygenase activities. Toxicology 1990, 62: 175-187. PMID: 1693794, DOI: 10.1016/0300-483x(90)90108-s.Peer-Reviewed Original ResearchMeSH Keywords7-Alkoxycoumarin O-DealkylaseAryl Hydrocarbon HydroxylasesBlotting, NorthernCytochrome P-450 CYP1A1Cytochrome P-450 Enzyme InhibitorsCytochrome P-450 Enzyme SystemEnzyme InductionFemaleGene Expression Regulation, EnzymologicHumansImmunoblottingImmunodiffusionMicrosomesNADPH-Ferrihemoprotein ReductaseOxidoreductasesOxygenasesPlacentaPregnancyRNASmokingConceptsMaternal cigarette smokingAryl hydrocarbon hydroxylaseHuman placental microsomesSmoking mothersCigarette smokingPlacental microsomesHuman placentaMonoclonal antibodiesO-deethylase activityMaternal smokingMonooxygenase activitySmoking statusSignificant inhibitory effectPlacental tissueMAb 2ERDE activitySmokingMAb 1Inhibitory effectLiver NADPH-cytochrome PO-deethylaseECDE activitiesPlacentaCYPIA1 geneAntibodies
1989
Altered Regulation of the Cytochrome P4501A1 Gene: Novel Inducer-Independent Gene Expression in Pulmonary Carcinoma Cell Lines
McLemore T, Adelberg S, Czerwinski M, Hubbard W, Yu S, Storeng R, Wood T, Hines R, Boyd M. Altered Regulation of the Cytochrome P4501A1 Gene: Novel Inducer-Independent Gene Expression in Pulmonary Carcinoma Cell Lines. Journal Of The National Cancer Institute 1989, 81: 1787-1794. PMID: 2555530, DOI: 10.1093/jnci/81.23.1787.Peer-Reviewed Original ResearchConceptsPulmonary carcinoma cell linesLung cancer cell linesCarcinoma cell linesCancer cell linesLung cancerCell linesCYP1A1 gene expressionNon-small cell linesSmall cell lung carcinomaHuman lung cancer cell linesHeavy cigarette smokersHuman pulmonary carcinoma cell linesNon-small cell lung carcinoma cell lineSmall cell lung cancer linesNon-small cellCell lung carcinomaNormal human lungCell lung cancer linesHuman lung cancerCYP1A1 mRNACell lung carcinoma cell lineLung cancer cellsAryl hydrocarbon hydroxylase activityCYP1A1 geneLung carcinoma cell lineGlucocorticoid regulation of the rat cytochrome P450c (P450IA1) gene: Receptor binding within intron I
Mathis J, Houser W, Bresnick E, Cidlowski J, Hines R, Prough R, Simpson E. Glucocorticoid regulation of the rat cytochrome P450c (P450IA1) gene: Receptor binding within intron I. Archives Of Biochemistry And Biophysics 1989, 269: 93-105. PMID: 2916850, DOI: 10.1016/0003-9861(89)90090-8.Peer-Reviewed Original ResearchConceptsGlucocorticoid receptorConcentrations of dexamethasoneUntreated cellsMRNA contentFetal rat hepatocytesHalf-maximal increaseAddition of dexamethasonePresence of dexamethasoneCultured fetal rat hepatocytesGlucocorticoid-responsive elementRat hepatocytesDexamethasoneCytochrome P450cGlucocorticoid regulationHepG2 hepatoma cellsGlucocorticoidsAcetyltransferase activityHepatic cytochromeChloramphenicol acetyltransferase activityReceptorsNorthern blot analysisBlot analysisHepatoma cellsReceptor fraction
1988
Identification of multiple regulatory elements on the human cytochrome P450IA1 gene
Hines R, Mathis J, Jacob C. Identification of multiple regulatory elements on the human cytochrome P450IA1 gene. Carcinogenesis 1988, 9: 1599-1605. PMID: 3409463, DOI: 10.1093/carcin/9.9.1599.Peer-Reviewed Original ResearchInduction of cytochrome P-450IA1 gene expression in human breast tumour cell lines
Pasanen M, Stacey S, Lykkesfeldt A, Briand P, Hines R, Autrup H. Induction of cytochrome P-450IA1 gene expression in human breast tumour cell lines. Chemico-Biological Interactions 1988, 66: 223-232. PMID: 2456161, DOI: 10.1016/0009-2797(88)90073-7.Peer-Reviewed Original ResearchConceptsBreast tumor cell linesHuman breast tumor cell linesTumor cell linesTCDD treatmentCell linesDifferent breast tumor cell linesConcentrations of TCDDZR-75BT-20Cytochrome P-450IA1NM TCDDCAMA-1Basal expression levelsControl cellsExpression levelsMCF-7Northern blot analysisBlot analysisTCDDTreatmentTotal RNAP-450IA1TCDD inductionDiol metabolitesInduction