Detection of CYP2E1, a Genetic Biomarker of Susceptibility to Benzene Metabolism Toxicity in Immortal Human Lymphocytes Derived from the Han Chinese Population.pdfVIP

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Detection of CYP2E1, a Genetic Biomarker of Susceptibility to Benzene Metabolism Toxicity in Immortal Human Lymphocytes Derived from the Han Chinese Population.pdf

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Detection of CYP2E1, a Genetic Biomarker of Susceptibility to Benzene Metabolism Toxicity in Immortal Human Lymphocytes Derived from the Han Chinese Population.pdf

300 BiomedEnvironSci，2010；24(3)：300—309 OriginalArticle DetectionofCYP2E1，aGeneticBiomarkerofSusceptibilitytoBenzeneMetabolism ToxiciytinImmortalHumanLymphocytesDerivedfr0mtheHanChinesePopulation ZHANGJuan，YIN LiHong，LIANG GeYu，LIU Ran，FAN KaiHong，andPU YuePu KeyLaboratoryofEnvironmentalMedicineEngineering,Ministry ofEducation,SchoolofPublicHealth SoutheastUniversity，Nanjing210009，Jiangsu，China Abstract Objective CytochromeP4502E1(CYP2E1)isanimportantmetabolizingenzymeinvolvedinoxidative stressresponsestobenzene，achemicalassociatedwithbonemarrow toxicityandleukemia．W eaimed to identify the CYP2E1 genetic biomarkers of susceptibility to benzene toxicity in support of environmentaland occupationalexposure prevention，and totestwhetheramodelusing immortal humanlymphocytesmightbeanefficienttoolfordetectinggeneticbiomarkers． Methods ImmortalizedhumanlymphocytecelllineswithindependentgenotypesonfourCYP2E1SNP siteswereinducedwithO．01％pheno1．ametaboliteofbenzene．CYP2E1genefunctionwasevaluatedby mRNAexpressionandenzymeactivity．DNA damagewasmeasuredbySingle—CellGelElectr0Dhoresis (SCGE)． Results AmongthefourSNPs，cellswithrs2070673TT and rs2030920CC showed higher levelsof CYP2E1transcriptionandenzymaticactivitythantheothergenotypesinthesameSNPsite．Cellswith highergene expression genotypes also showed highercomet rates compared with lowergene expressiongenotypes． Conclusion These resultssuggestthat CYP2E1 rs2070673 and rs2030920 might be the genetic biomarkersofsusceptibilitytobenzenetoxicityandthattheimmortalizedhumanlymphocytesmodel mightbeanefficienttoolforthedetectionofgeneticbiomarkersofsusceptibilitytochemicals． Key words：Cytochrome P450 2E1；Single—nucleotide polymorphism；Genetic biomarker；Human immortalizedBlymphoc