2024
CYP2E1 in 1,4-dioxane metabolism and liver toxicity: insights from CYP2E1 knockout mice study
Wang Y, Charkoftaki G, Orlicky D, Davidson E, Aalizadeh R, Sun N, Ginsberg G, Thompson D, Vasiliou V, Chen Y. CYP2E1 in 1,4-dioxane metabolism and liver toxicity: insights from CYP2E1 knockout mice study. Archives Of Toxicology 2024, 98: 3241-3257. PMID: 39192018, PMCID: PMC11500436, DOI: 10.1007/s00204-024-03811-5.Peer-Reviewed Original ResearchCYP2E1-null miceLiver toxicityDrinking waterOxidative DNA damageLiver carcinogenAbstract1,4-DioxaneDNA damage repair responseImpaired DNA damage repairWater contaminationOxidative stressElevated oxidative stressEnvironmental pollutionKnockout mouse studiesDamage repair responseCYP2E1-nullMale wildtypeWT miceDNA damageDX exposureRisk assessmentRedox dysregulationCYP2E1 inductionLiver oxidative stressHigh dosesMouse studies
2021
Oxidative stress and genotoxicity in 1,4-dioxane liver toxicity as evidenced in a mouse model of glutathione deficiency
Chen Y, Wang Y, Charkoftaki G, Orlicky DJ, Davidson E, Wan F, Ginsberg G, Thompson DC, Vasiliou V. Oxidative stress and genotoxicity in 1,4-dioxane liver toxicity as evidenced in a mouse model of glutathione deficiency. The Science Of The Total Environment 2021, 806: 150703. PMID: 34600989, PMCID: PMC8633123, DOI: 10.1016/j.scitotenv.2021.150703.Peer-Reviewed Original ResearchConceptsOxidative stressLiver cytotoxicityGlutamate-cysteine ligase modifier subunitWild-type micePrimary target organRecent mouse studiesCYP2E1 inductionLiver toxicitySubchronic exposureNrf2 inductionOxidative DNA damageCancer riskMouse modelAnti-oxidative responseDNA damageTarget organsAnimal studiesLiver carcinogenicityRedox dysregulationEarly changesHealth CanadaNull miceMouse studiesNuclear factorCarcinogenic mechanismsIdentification of Dose-Dependent DNA Damage and Repair Responses From Subchronic Exposure to 1,4-Dioxane in Mice Using a Systems Analysis Approach
Charkoftaki G, Golla JP, Santos-Neto A, Orlicky DJ, Garcia-Milian R, Chen Y, Rattray NJW, Cai Y, Wang Y, Shearn CT, Mironova V, Wang Y, Johnson CH, Thompson DC, Vasiliou V. Identification of Dose-Dependent DNA Damage and Repair Responses From Subchronic Exposure to 1,4-Dioxane in Mice Using a Systems Analysis Approach. Toxicological Sciences 2021, 183: 338-351. PMID: 33693819, PMCID: PMC8921626, DOI: 10.1093/toxsci/kfab030.Peer-Reviewed Original ResearchConceptsDX exposureBile acid quantificationRepair responseBDF-1 miceDNA damageDose-dependent DNA damageEffects of exposureHistopathological studySubchronic exposureImmunohistochemical analysisLiver carcinogenLiver carcinogenicityLiver transcriptomicsDrinking waterMetabolomic profilingMicePotential mechanismsLiverEnvironmental chemicalsState maximum contaminant levelToxic effectsCell deathExposureOxidative stress responsePresent study
2011
Aldehyde dehydrogenases are regulators of hematopoietic stem cell numbers and B-cell development
Gasparetto M, Sekulovic S, Brocker C, Tang P, Zakaryan A, Xiang P, Kuchenbauer F, Wen M, Kasaian K, Witty MF, Rosten P, Chen Y, Imren S, Duester G, Thompson DC, Humphries RK, Vasiliou V, Smith C. Aldehyde dehydrogenases are regulators of hematopoietic stem cell numbers and B-cell development. Experimental Hematology 2011, 40: 318-329.e2. PMID: 22198153, DOI: 10.1016/j.exphem.2011.12.006.Peer-Reviewed Original ResearchMeSH KeywordsAldehyde DehydrogenaseAldehyde Dehydrogenase 1 FamilyAldehydesAnimalsAnimals, CongenicB-LymphocytesBone Marrow TransplantationCell CountCell CycleCell LineageCells, CulturedColony-Forming Units AssayDNA DamageEnzyme InductionGene Expression RegulationHematopoiesisHematopoietic Stem CellsLymphopeniaMiceMice, Inbred C57BLMice, KnockoutP38 Mitogen-Activated Protein KinasesRadiation ChimeraReactive Oxygen SpeciesRetinal DehydrogenaseSignal TransductionConceptsB cell developmentHematopoietic stem cellsReactive oxygen speciesMitogen-activated protein kinase activityP38 mitogen-activated protein kinase activityProtein kinase activityExcess reactive oxygen speciesOxygen speciesReactive aldehydesStem cell numbersHematopoietic stem cell numbersReactive oxygen species levelsEarly B cellsNumber of HSCsHSC biologyCell cycle distributionKinase activityOxygen species levelsAldh1a1 deficiencyGene expressionSpecies levelIntracellular signalingAldehyde dehydrogenasesDNA damageCell cycling
2009
Early onset senescence occurs when fibroblasts lack the glutamate–cysteine ligase modifier subunit
Chen Y, Johansson E, Fan Y, Shertzer HG, Vasiliou V, Nebert DW, Dalton TP. Early onset senescence occurs when fibroblasts lack the glutamate–cysteine ligase modifier subunit. Free Radical Biology And Medicine 2009, 47: 410-418. PMID: 19427898, PMCID: PMC2773044, DOI: 10.1016/j.freeradbiomed.2009.05.003.Peer-Reviewed Original ResearchMeSH KeywordsAcetylcysteineAnimalsBeta-GalactosidaseCell Culture TechniquesCell CycleCell Growth ProcessesCellular SenescenceCyclin-Dependent Kinase Inhibitor p21DNA DamageFemaleFetusFibroblastsFree Radical ScavengersGlutamate-Cysteine LigaseGlutathioneMiceMice, Inbred C57BLMice, KnockoutPregnancyProtein SubunitsReactive Oxygen SpeciesTumor Suppressor Protein p53ConceptsGlutamate-cysteine ligasePremature senescenceCellular redox environmentCellular antioxidant glutathionePrimary murine fibroblastsSenescence-associated beta-galactosidase activityCell cycle arrestInduction of p53Beta-galactosidase activityPrevents premature senescenceCatalytic subunitCellular senescenceGrowth arrestGlutamate cysteine ligase modifierModifier subunitP21 proteinPhysiological roleSenescenceDNA damageRedox environmentCycle arrestMurine fibroblastsGSH synthesisN-acetylcysteine increasesPrimary cells
2006
TCDD decreases ATP levels and increases reactive oxygen production through changes in mitochondrial F0F1-ATP synthase and ubiquinone
Shertzer HG, Genter MB, Shen D, Nebert DW, Chen Y, Dalton TP. TCDD decreases ATP levels and increases reactive oxygen production through changes in mitochondrial F0F1-ATP synthase and ubiquinone. Toxicology And Applied Pharmacology 2006, 217: 363-374. PMID: 17109908, PMCID: PMC1783833, DOI: 10.1016/j.taap.2006.09.014.Peer-Reviewed Original ResearchConceptsReactive oxygen productionATP levelsMitochondria generate ATPMitochondrial glutathione redox stateMitochondrial oxidative DNA damageF0F1-ATP synthaseATP/O ratioGlutathione redox stateOxygen productionATP synthaseGenerate ATPSignal transductionMitochondrial targetsOxidative DNA damageGreater respiratory rateOxidoreductase activityATP synthesisCell deathDNA damageFutile cycleRedox stateCellular pathologyRespiratory control ratioTCDD treatmentATP
2005
Butylhydroquinone Protects Cells Genetically Deficient in Glutathione Biosynthesis from Arsenite-Induced Apoptosis Without Significantly Changing Their Prooxidant Status
Kann S, Estes C, Reichard JF, Huang MY, Sartor MA, Schwemberger S, Chen Y, Dalton TP, Shertzer HG, Xia Y, Puga A. Butylhydroquinone Protects Cells Genetically Deficient in Glutathione Biosynthesis from Arsenite-Induced Apoptosis Without Significantly Changing Their Prooxidant Status. Toxicological Sciences 2005, 87: 365-384. PMID: 16014739, DOI: 10.1093/toxsci/kfi253.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisArsenitesBlotting, WesternCell SurvivalCells, CulturedDNA, ComplementaryElectrophoretic Mobility Shift AssayFibroblastsGene Expression RegulationGlutamate-Cysteine LigaseGlutathioneHydroquinonesMiceMice, KnockoutNF-kappa BOligonucleotide Array Sequence AnalysisOxidantsOxidative StressRNATetrazolium SaltsThiazolesConceptsMouse embryo fibroblastsGlutathione biosynthesisGlobal gene expression profilesAntioxidant responseCell cycle regulationArsenite-induced apoptosisEffective antioxidant responseArsenic-induced apoptosisGene expression profilesExpression of genesGlutamate-cysteine ligaseOxidative stressProtein biosynthesisRole of glutathioneCycle regulationRate-limiting enzymeGene deregulationExpression profilesArsenic-induced oxidative stressEmbryo fibroblastsInduces oxidative stressModifier subunitApoptotic deathDNA damageToxicity of arsenic