简介：RecognitionofDNAdamageisacriticalstepforDNAdamage-mediatedcellularresponse.XPCisanimportantDNAdamagerecognitionproteininvolvedinnucleotideexcisionrepair(NER).WehavestudiedtheXPCproteinincisplatinDNAdamagingtreatment-mediatedcellularresponse.ComparisonofthemicroarraydatafrombothnormalandXPCdefectivehumanfibroblastsidentified861XPC-responsivegenesinthecisplatintreatment(withminimumfoldchange≥1.5).Thecellcycleandcellproliferation-relatedgenesarethemostaffectedgenesbytheXPCdefectinthetreatment.Manyothercellularfunctiongenes,especiallytheDNArepairandsignaltransduction-relatedgenes,werealsoaffectedbytheXPCdefectinthetreatment.Tovalidatethemicroarraydata,thetranscriptionlevelsofsomemicroarray-identifiedgeneswerealsodeterminedbyanRT-PCRbasedrealtimePCRassay.TherealtimePCRresultsareconsistentwiththemicroarraydataformostofthetestedgenes,indicatingthereliabilityofthemicroarraydata.Tofurthervalidatethemicroarraydata,thecisplatintreatment-mediatedcaspase-3activationwasalsodetermined.TheWesternblothybridizationresultsindicatethattheXPCdefectgreatlyattenuatesthecisplatintreatment-mediatedCaspase-3activation.Weelucidatedtheroleofp53proteinintheXPCproteinDNAdamagerecognition-mediatedsignalingprocess.TheXPCdefectreducesthecisplatintreatment-mediatedp53response.TheseresultssuggestthattheXPCproteinplaysanimportantroleinthecisplatintreatment-mediatedcellularresponse.Itmayalsosuggestapossiblemechanismofcancercelldrugresistance.

简介：Telomeraseactivitywasinhibitedinadoseandtime-dependentmannerwiththetreatmentofcisplatinfor24,48,or72hinaconcentrationrangedfrom0.8to50μMinBEL-7404humanhepatomacells.Therewerenochangesinexpressionpatternofthreetelomerasesubunits,itscatalyticreversetranscriptasesubunit(hTERT),itsRNAcomponent(hTR)ortheassociatedproteinsubunit(TP1),aftercisplatintreatedfor72hwithindicatedconcentrations.Meantelomerelengthsweredecreasedbythecisplatintreatment.CellgrowthinhibitionandcellcycleaccumulationinG2/Mphasewerefoundtobecorrelatedwithtelomeraseinhibitioninthepresentstudy,butpercentagesofcellapoptosisdidnotchangemarkedlyduringtheprocess.