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 ResearchConceptsTarget 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 extrapolation
2017
Determination of Human Hepatic CYP2C8 and CYP1A2 Age-Dependent Expression to Support Human Health Risk Assessment for Early Ages
Song G, Sun X, Hines R, McCarver D, Lake B, Osimitz T, Creek M, Clewell H, Yoon M. Determination of Human Hepatic CYP2C8 and CYP1A2 Age-Dependent Expression to Support Human Health Risk Assessment for Early Ages. Drug Metabolism And Disposition 2017, 45: dmd.116.074583. PMID: 28228413, DOI: 10.1124/dmd.116.074583.Peer-Reviewed Original ResearchConceptsCYP2C8 expressionOntogeny dataMonths postnatal ageProtein levelsLiver microsomal samplesAge-dependent expressionMultiple cytochrome P450Weeks' gestationPostnatal agePostnatal dayYoung infantsPostnatal samplesFetal samplesMicrosomal samplesCYP1A2 expressionQuantitative Western blottingPyrethroid metabolismCYP2C8Western blottingHealth risk assessmentHuman health risk assessmentRisk assessmentAgeCarboxylesterase enzymesCytochrome P450
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 groupRegulation of CYP3A4 Expression by PAR Transcription Factors
Mantei K, Le M, Klick D, Vyhlidal C, Hines R. Regulation of CYP3A4 Expression by PAR Transcription Factors. The FASEB Journal 2007, 21: a1183-a1183. DOI: 10.1096/fasebj.21.6.a1183-a.Peer-Reviewed Original ResearchD-element binding proteinCYP3A4 expressionHepatic leukemia factorCYP3A4 promoter activityAdult human liverAbundant cytochrome P450CYP3A4 promoterHuman liverPostnatal liverProtein 4DBP expressionPAR familyEmbryonic factorsHepG2 cellsTranscription factorsCytochrome P450LiverFunctional significanceCo-transfection experimentsBinding proteinPromoter activityExpressionReporter constructsFactorsFactor family
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 ResearchConceptsCutaneous 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 adductionCyclooxygenaseThe Role of Flavin-Containing Monooxygenase (FMO) in the Metabolism of Tamoxifen and Other Tertiary Amines
Krueger S, VanDyke J, Williams D, Hines R. The Role of Flavin-Containing Monooxygenase (FMO) in the Metabolism of Tamoxifen and Other Tertiary Amines. Drug Metabolism Reviews 2006, 38: 139-147. PMID: 16684653, DOI: 10.1080/03602530600569919.Peer-Reviewed Original ResearchConceptsMetabolism of tamoxifenBreast cancer therapyHuman liver microsomesFlavin-Containing MonooxygenaseMetabolic activation pathwayEndometrial cancerTamoxifen metabolismN-oxide productionLiver microsomesTamoxifenMetabolic activationDNA adductionCancer therapyActivation pathwayCytochrome P450Detoxication pathwayN-oxygenationRiskMetabolismLow levelsPathwayChemopreventionNeoplasiaTherapyCancer
2001
Molecular regulation of genes encoding xenobiotic-metabolizing enzymes: mechanisms involving endogenous factors.
Hines R, Luo Z, Cresteil T, Ding X, Prough R, Fitzpatrick J, Ripp S, Falkner K, Ge N, Levine A, Elferink C. Molecular regulation of genes encoding xenobiotic-metabolizing enzymes: mechanisms involving endogenous factors. Drug Metabolism And Disposition 2001, 29: 623-33. PMID: 11302926.Peer-Reviewed Original ResearchConceptsDevelopmental-specific expressionSignal transduction pathwaysMolecular regulationTransduction pathwaysCommon signal transduction pathwayReceptor-mediated signal transduction pathwaysRegulation of xenobioticGenome levelTranscription factorsMolecular mechanismsMolecular biologyEndogenous factorsGenesRegulatory systemXenobiotic-metabolizing enzymesEnzymeRegulationExpressionCytochrome P450Fundamental rolePathwayRapid proliferationTissueBiologyExperimental therapeutics
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
1994
The Mammalian Flavin-Containing Monooxygenases: Molecular Characterization and Regulation of Expression
Hines R, Cashman J, Philpot R, Williams D, Ziegler D. The Mammalian Flavin-Containing Monooxygenases: Molecular Characterization and Regulation of Expression. Toxicology And Applied Pharmacology 1994, 125: 1-6. PMID: 8128486, DOI: 10.1006/taap.1994.1042.Peer-Reviewed Original ResearchConceptsFlavin-containing monooxygenaseRegulation of expressionSpecies-specific differencesFlavin-Containing MonooxygenasesMixture of cisSubstrate specificityMammalian speciesToxicant susceptibilitySoft nucleophilesMolecular characterizationEnzyme's abilitySecondary alkylMultiple tissuesEarly stepsActive derivativesEnzyme systemUnique stereoselectivityFlavin enzymesHuman FMO3Toxic intermediatesFMO expressionThiocarbamideSpeciesChemical toxicityCytochrome P450
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 CYP1A1
1984
Induction of cytochrome P450 by xenobiotics.
Bresnick E, Foldes R, Hines R. Induction of cytochrome P450 by xenobiotics. Pharmacological Reviews 1984, 36: 43s-51s. PMID: 6433366.Peer-Reviewed Original Research