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, 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
2022
Oxidative stress, glutathione, and CYP2E1 in 1,4-dioxane liver cytotoxicity and genotoxicity: insights from animal models
Wang Y, Charkoftaki G, Davidson E, Orlicky D, Tanguay R, Thompson D, Vasiliou V, Chen Y. Oxidative stress, glutathione, and CYP2E1 in 1,4-dioxane liver cytotoxicity and genotoxicity: insights from animal models. Current Opinion In Environmental Science & Health 2022, 29: 100389. PMID: 37483863, PMCID: PMC10361651, DOI: 10.1016/j.coesh.2022.100389.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsOxidative stressUnique mouse modelRelevant low dosesDirect genotoxic effectsLiver cytotoxicityCYP2E1 activationMouse modelAnimal modelsHuman studiesCarcinogenic pathwaysLiver carcinogenicityLow dosesCausal roleGenotoxic effectsHuman exposureUndetermined mechanismPublic healthCarcinogenicityLiver genotoxicityDrinking water contaminantsMechanistic dataGenotoxicityFuture animalCytotoxicityCYP2E1Oxidative stress induces inflammation of lens cells and triggers immune surveillance of ocular tissues
Thompson B, Davidson EA, Chen Y, Orlicky DJ, Thompson DC, Vasiliou V. Oxidative stress induces inflammation of lens cells and triggers immune surveillance of ocular tissues. Chemico-Biological Interactions 2022, 355: 109804. PMID: 35123994, PMCID: PMC9136680, DOI: 10.1016/j.cbi.2022.109804.Peer-Reviewed Original ResearchMeSH KeywordsAcetylcysteineAnimalsButhionine SulfoximineCell LineChemokine CCL7CytokinesDown-RegulationEpithelial CellsEpithelial-Mesenchymal TransitionEyeGlutamate-Cysteine LigaseImmunity, InnateLens, CrystallineLeukocytesMiceMice, Inbred C57BLMice, KnockoutOxidative StressReactive Oxygen SpeciesUp-RegulationConceptsPosterior capsule opacificationCytokine expressionKO miceImmune surveillanceOxidative stressLens epithelial cellsOcular structuresLens cellsDevelopment of PCOEpithelial cellsInnate immune cellsExpression of cytokinesEx vivo inductionOcular surface tissuesExpression of markersImmune response genesCON miceControl miceCapsule opacificationImmune cellsPostnatal dayΑ-SMAMouse modelOcular tissuesVivo induction
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 mechanisms