2020
Physiologically Based Pharmacokinetic Modeling in Risk Assessment: Case Study With Pyrethroids
Mallick P, Song G, Efremenko A, Pendse S, Creek M, Osimitz T, Hines R, Hinderliter P, Clewell H, Lake B, Yoon M, Moreau M. Physiologically Based Pharmacokinetic Modeling in Risk Assessment: Case Study With Pyrethroids. Toxicological Sciences 2020, 176: 460-469. PMID: 32421774, PMCID: PMC7416317, DOI: 10.1093/toxsci/kfaa070.Peer-Reviewed Original ResearchConceptsAge-related pharmacokinetic differencesPharmacokinetic differencesPBPK modelTarget tissue exposureAge-related sensitivityHuman PBPK modelAge-dependent changesAge-related differencesRat modelTissue exposureVivo rat dataPharmacokinetic modellingPharmacokinetic modelingInternal exposureRat dataRisk assessmentVivo extrapolationRisk assessment purposesExposureAdultsExternal exposureSensitive populationsChildrenMetabolic capacityAssessment
2016
FutureTox III: Bridges for Translation
Juberg D, Knudsen T, Sander M, Beck N, Faustman E, Mendrick D, Fowle J, Hartung T, Tice R, Lemazurier E, Becker R, Fitzpatrick S, Daston G, Harrill A, Hines R, Keller D, Lipscomb J, Watson D, Bahadori T, Crofton K. FutureTox III: Bridges for Translation. Toxicological Sciences 2016, 155: 22-31. PMID: 27780885, PMCID: PMC6080854, DOI: 10.1093/toxsci/kfw194.Peer-Reviewed Original Research
2015
Use of the RISK21 roadmap and matrix: human health risk assessment of the use of a pyrethroid in bed netting
Doe J, Lander D, Doerrer N, Heard N, Hines R, Lowit A, Pastoor T, Phillips R, Sargent D, Sherman J, Tanir J, Embry M. Use of the RISK21 roadmap and matrix: human health risk assessment of the use of a pyrethroid in bed netting. Critical Reviews In Toxicology 2015, 46: 54-73. PMID: 26517449, PMCID: PMC4732465, DOI: 10.3109/10408444.2015.1082974.Peer-Reviewed Original Research
2014
Tolerance to Acetaminophen Hepatotoxicity in the Mouse Model of Autoprotection Is Associated with Induction of Flavin-Containing Monooxygenase-3 (FMO3) in Hepatocytes
Rudraiah S, Rohrer P, Gurevich I, Goedken M, Rasmussen T, Hines R, Manautou J. Tolerance to Acetaminophen Hepatotoxicity in the Mouse Model of Autoprotection Is Associated with Induction of Flavin-Containing Monooxygenase-3 (FMO3) in Hepatocytes. Toxicological Sciences 2014, 141: 263-277. PMID: 24973094, PMCID: PMC4271123, DOI: 10.1093/toxsci/kfu124.Peer-Reviewed Original ResearchConceptsMale C57BL/6J miceAPAP hepatotoxicityFlavin-Containing Monooxygenase 3Protein expressionC57BL/6J miceFemale miceMouse modelMRNA levelsFirst time inductionNovel protective functionSingle doseAPAP treatmentMale miceAPAP cytotoxicityAcetaminophen pretreatmentHepatotoxic doseHigh doseAcetaminophen hepatotoxicityHepatotoxicityMice resultsCell line clonesMRNA expressionFMO3 expressionMiceAPAP
2011
Hepatic differentiation of amniotic epithelial cells
Marongiu F, Gramignoli R, Dorko K, Miki T, Ranade A, Serra M, Doratiotto S, Sini M, Sharma S, Mitamura K, Sellaro T, Tahan V, Skvorak K, Ellis E, Badylak S, Davila J, Hines R, Laconi E, Strom S. Hepatic differentiation of amniotic epithelial cells. Hepatology 2011, 53: 1719-1729. PMID: 21374689, PMCID: PMC3103747, DOI: 10.1002/hep.24255.Peer-Reviewed Original ResearchConceptsHuman amniotic epithelial cellsRat amniotic epithelial cellsHepatocyte-like cellsAmniotic epithelial cellsEpithelial cellsEmbryonic stem cellsExtracellular matrix proteinsStem cell-derived hepatocytesProgeny of cellsSCID/beige miceCell-derived hepatocytesGerm layersAdult liver tissueLiver genesMatrix proteinsGene characteristicsHepatic differentiationStem cellsFunctional hepatocytesNoncontroversial sourceProtein expressionEndodermal originLiver diseaseMature hepatocytesBeige mice
2008
The ontogeny of drug metabolism enzymes and implications for adverse drug events
Hines R. The ontogeny of drug metabolism enzymes and implications for adverse drug events. Pharmacology & Therapeutics 2008, 118: 250-267. PMID: 18406467, DOI: 10.1016/j.pharmthera.2008.02.005.Peer-Reviewed Original ResearchConceptsAdverse drug eventsDrug eventsDrug metabolism enzymesDME groupPediatric patientsThird trimesterCurrent knowledgeFirst trimesterDrug therapyDrug dispositionPharmacokinetic modelLow levelsEnzyme levelsTrimesterEnzyme expressionGestationSecond groupFetusesMetabolism enzymesBirthPhysiological factorsDevelopmental expression patternsMinimal changesReviewGroup
2006
Developmental and tissue-specific expression of human flavin-containing monooxygenases 1 and 3
Hines R. Developmental and tissue-specific expression of human flavin-containing monooxygenases 1 and 3. Expert Opinion On Drug Metabolism & Toxicology 2006, 2: 41-49. PMID: 16863467, DOI: 10.1517/17425255.2.1.41.Peer-Reviewed Original ResearchConceptsAnimal modelsMost animal modelsHuman fetal liverAdult human liverAdverse reactionsToxicant dispositionTherapeutic efficacyDrug metabolismHuman liverFetal liverToxicant metabolismDrugsEnzyme expressionCytochrome P450-dependent monooxygenasesLiverP450-dependent monooxygenasesFamily membersFMO enzymesRecent studiesMonooxygenases 1FMO3MetabolismExpression patternsExpressionA Tiered Approach to Life Stages Testing for Agricultural Chemical Safety Assessment
Cooper R, Lamb J, Barlow S, Bentley K, Brady A, Doerrer N, Eisenbrandt D, Fenner-Crisp P, Hines R, Irvine L, Kimmel C, Koeter H, Li A, Makris S, Sheets L, Speijers G, Whitby K. A Tiered Approach to Life Stages Testing for Agricultural Chemical Safety Assessment. Critical Reviews In Toxicology 2006, 36: 69-98. PMID: 16708695, DOI: 10.1080/10408440500541367.Peer-Reviewed Original ResearchConceptsAgricultural Chemical Safety Assessment (ACSA) Technical CommitteeRat reproductionInterpretation of studiesCompound potentialsGuideline studiesAdverse effectsSeverity of effectsHuman exposure potentialEnvironmental Sciences InstituteYoung animalsADME dataILSI HealthTiered approachEndpointExposure durationTask ForceExtent of testingTesting strategiesExposure potentialToxicity informationToxicological endpointsAnimalsChemical safety assessmentThe 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
2005
Discovery of Novel Flavin-Containing Monooxygenase 3 (FMO3) Single Nucleotide Polymorphisms and Functional Analysis of Upstream Haplotype Variants
Koukouritaki S, Poch M, Cabacungan E, McCarver D, Hines R. Discovery of Novel Flavin-Containing Monooxygenase 3 (FMO3) Single Nucleotide Polymorphisms and Functional Analysis of Upstream Haplotype Variants. Molecular Pharmacology 2005, 68: 383-392. PMID: 15858076, DOI: 10.1124/mol.105.012062.Peer-Reviewed Original ResearchConceptsFlavin-containing monooxygenasesFunctional analysisSingle nucleotide polymorphism (SNP) discoveryMembrane interaction domainHaplotype variantsSite-directed mutagenesisConsensus splice sitesFMO3 expressionUpstream SNPsGene functionPolymorphism discoveryNear complete lossRossmann foldFAD bindingInteraction domainSingle nucleotide polymorphismsRegion haplotypesHaplotype 8Exon SNPsFMO enzymesPromoter activityIntron SNPSequence analysisSNP frequenciesLuciferase construct
2004
NTP‐CERHR Expert Panel Report on the reproductive and developmental toxicity of fluoxetine
Hines R, Adams J, Buck G, Faber W, Holson J, Jacobson S, Keszler M, McMartin K, Segraves R, Singer L, Sipes I, Williams P. NTP‐CERHR Expert Panel Report on the reproductive and developmental toxicity of fluoxetine. Birth Defects Research Part B Developmental And Reproductive Toxicology 2004, 71: 193-280. PMID: 15334524, DOI: 10.1002/bdrb.20014.Peer-Reviewed Original Research
2003
Workshop Overview: Use of Genomic Data in Risk Assessment
Cunningham M, Bogdanffy M, Zacharewski T, Hines R. Workshop Overview: Use of Genomic Data in Risk Assessment. Toxicological Sciences 2003, 73: 209-215. PMID: 12700425, DOI: 10.1093/toxsci/kfg071.Peer-Reviewed Original ResearchConceptsGenomic technologiesGenomic researchHigh-throughput genomic technologiesHigh-throughput proteomicsHuman Genome ProjectPosttranslational eventsGenetic compositionThroughput proteomicsNew high-throughput genomic technologiesGenetic variabilityGenome ProjectGenomic dataDNA microarraysDifferent genesExpression levelsSpecific cellsGenesToxicological responsesToxicant exposureRecent advancesProteomicsMicroarrayBetter understandingIndividual adaptiveExpressionBiochemical and clinical aspects of the human flavin-containing monooxygenase form 3 (FMO3) related to trimethylaminuria.
Cashman J, Camp K, Fakharzadeh S, Fennessey P, Hines R, Mamer O, Mitchell S, Nguyen G, Schlenk D, Smith R, Tjoa S, Williams D, Yannicelli S. Biochemical and clinical aspects of the human flavin-containing monooxygenase form 3 (FMO3) related to trimethylaminuria. Current Drug Metabolism 2003, 4: 151-70. PMID: 12678693, DOI: 10.2174/1389200033489505.Peer-Reviewed Original ResearchConceptsMonooxygenase form 3Rare metabolic disorderFoul body odorPrimary genetic formsTreatment of individualsNutritional supportVitamin supplementationPlasma cholineTreatment strategiesClinical aspectsClinical basisDrug treatmentMetabolic disordersChildhood formUrinary trimethylamineBody secretionsAbnormal amountsGenetic formsDisease statesDietary sourcesTrimethylamine N-oxideTrimethylaminuriaVariant formDisordersBody odorTrichloroethylene Decreases Heat Shock Protein 90 Interactions with Endothelial Nitric Oxide Synthase: Implications for Endothelial Cell Proliferation
Ou J, Ou Z, McCarver D, Hines R, Oldham K, Ackerman A, Pritchard K. Trichloroethylene Decreases Heat Shock Protein 90 Interactions with Endothelial Nitric Oxide Synthase: Implications for Endothelial Cell Proliferation. Toxicological Sciences 2003, 73: 90-97. PMID: 12657742, DOI: 10.1093/toxsci/kfg062.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlotting, WesternCalcimycinCattleCell DivisionCells, CulturedEndothelial CellsEnzyme InhibitorsHSP90 Heat-Shock ProteinsIonophoresNG-Nitroarginine Methyl EsterNitric OxideNitric Oxide SynthaseNitric Oxide Synthase Type IIIPhosphorylationPrecipitin TestsSuperoxidesTrichloroethyleneVascular Endothelial Growth Factor AConceptsEndothelial cell proliferationCell proliferationNormal blood vessel growthHeat shock protein 90Shock protein 90Serine 1179Hsp90 interactionEndothelial cellsProtein 90Blood vessel growthENOS functionImportant roleProteinActivation stateInhibited VEGFVessel growthGrowth factorBalance of NONew insightsProliferationVascular endothelial growth factorNitric oxideEndothelial growth factorEndothelial nitric oxide synthaseEnvironmental pollutantsGenetics and Susceptibility to Toxic Chemicals: Do You (or Should You) Know Your Genetic Profile?
Lash L, Hines R, Gonzalez F, Zacharewski T, Rothstein M. Genetics and Susceptibility to Toxic Chemicals: Do You (or Should You) Know Your Genetic Profile? Journal Of Pharmacology And Experimental Therapeutics 2003, 305: 403-409. PMID: 12606672, DOI: 10.1124/jpet.102.039925.Peer-Reviewed Original ResearchConceptsSpecific enzyme systemsExperimental Biology meetingTransgenic technologyGenetic determinantsEnzyme systemGenetic profileToxic chemicalsGeneticsDivision of ToxicologyComplex interplayHuman healthIndividual susceptibilityPharmacogenomicsExperimental therapeuticsPhysiologySusceptibilityChemicalsDivisionTherapeuticsGenotyping 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
GENETIC POLYMORPHISMS OF FLAVIN-CONTAINING MONOOXYGENASE (FMO)
Krueger S, Williams D, Yueh M, Martin S, Hines R, Raucy J, Dolphin C, Shephard E, Phillips I. GENETIC POLYMORPHISMS OF FLAVIN-CONTAINING MONOOXYGENASE (FMO). Drug Metabolism Reviews 2002, 34: 523-532. PMID: 12214664, DOI: 10.1081/dmr-120005653.Peer-Reviewed Original ResearchConceptsFlavin-Containing MonooxygenaseAdult human liverPercent of individualsPlethora of drugsTrimethylamine N-oxygenationDrug metabolismHuman liverGenetic polymorphismsHispanic descentPremature stop codonPolymorphic expressionLungPreliminary evidenceFunctional FMO2African descentXenobiotic toxicityMammalian flavinN-oxygenationFMO2TrimethylaminuriaEthylene thioureaPolymorphismAllelesPatientsExpression
2001
Regulation of Flavin-Containing Monooxygenase 1 Expression by Ying Yang 1 and Hepatic Nuclear Factors 1 and 4
Luo Z, Hines R. Regulation of Flavin-Containing Monooxygenase 1 Expression by Ying Yang 1 and Hepatic Nuclear Factors 1 and 4. Molecular Pharmacology 2001, 60: 1421-1430. PMID: 11723251, DOI: 10.1124/mol.60.6.1421.Peer-Reviewed Original ResearchAnimalsBase SequenceDNA-Binding ProteinsEnhancer Elements, GeneticErythroid-Specific DNA-Binding FactorsGene Expression Regulation, EnzymologicHepatocyte Nuclear Factor 1Hepatocyte Nuclear Factor 1-alphaHepatocyte Nuclear Factor 1-betaHumansMolecular Sequence DataNuclear ProteinsOxygenasesPromoter Regions, GeneticRabbitsSequence Homology, Nucleic AcidTranscription FactorsTransfectionTumor Cells, CulturedYY1 Transcription Factor
2000
Regulation of DHP receptor expression by elements in the 5′-flanking sequence
Liu L, Fan Q, El-Zaru M, Vanderpool K, Hines R, Marsh J. Regulation of DHP receptor expression by elements in the 5′-flanking sequence. AJP Heart And Circulatory Physiology 2000, 278: h1153-h1162. PMID: 10749709, DOI: 10.1152/ajpheart.2000.278.4.h1153.Peer-Reviewed Original ResearchMeSH Keywords5' Untranslated Regions8-Bromo Cyclic Adenosine MonophosphateAdrenergic alpha-AgonistsAdrenergic beta-AgonistsAnimalsBase SequenceCalcium Channels, L-TypeCells, CulturedElectrophoresisGene ExpressionGenes, ReporterGenetic Complementation TestGonadal Steroid HormonesIn Vitro TechniquesIsoproterenolLuciferasesMolecular Sequence DataMuscle Fibers, SkeletalMuscle, Smooth, VascularMyocardiumPhenylephrinePromoter Regions, GeneticRatsRNA, MessengerTestosteroneTranscription, GeneticTransfectionConceptsNeonatal rat cardiac ventricular myocytesVascular smooth muscle cellsRat cardiac ventricular myocytesSmooth muscle cellsCardiac ventricular myocytesCardiac-specific transcription factor Nkx2.5Receptor expressionResponse elementTranscription factor Nkx2.5Hormone responsivenessVentricular myocytesMuscle cellsSubunit gene promoterModulating activityHormone response elementsCAMP response elementPromoter-luciferase reporter gene constructsGene promoterTransient transfection experimentsRatsFusion geneSubunit geneAP-1 siteDevelopmental regulation of the L-type calcium channel α1C subunit expression in heart
Leu L, O'Hara D, Cala S, Poornima I, Hines R, Marsh J. Developmental regulation of the L-type calcium channel α1C subunit expression in heart. Molecular And Cellular Biochemistry 2000, 205: 101-109. PMID: 10821427, DOI: 10.1023/a:1007013900827.Peer-Reviewed Original ResearchConceptsRNase protection assaysProtection assaysNorthern analysisΑ1C subunitSize of proteinsAlternative splicingAbundance of mRNADevelopmental regulationSmaller transcriptTranscript sizeNative proteinKD proteinMolecular massDevelopmental stagesProteinSubunitsAdult ventriclesTranscriptsPostnatal developmentAbundanceExpressionSubunit expressionCalcium channel propertiesChannel propertiesReceptor message
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