Cytotoxicityandgenome-widemicroarrayanalysisofintestinalsmoothmusclecellsinresponsetohexavalentchromiuminduction

Chronicingestionofhighconcentrationsofhexavalentchromium[Cr(VI)]indrinkingwaterinducesintestinaltumorsinmice;however,informationonitstoxicityonintestinalsmoothmusclecellsislimited.ThepresentstudyaimedtoassesstheinvitroandinvivotoxicologicaleffectsofCr(VI)onintestinalsmoothmusclecells.Humanintestinalsmoothmusclecells(HISMcells)wereculturedwithdifferentconcentrationsofCr(VI)toevaluateeffectsoncellproliferationability,oxidativestresslevels,andantioxidantsystem.Furthermore,tissuesectionsinCr(VI)exposedrabbitswereanalyzedtoevaluatetoxicityonintestinalmusclecellsinvivo.Genechipswereutilizedtoassessdifferentialgeneexpressionprofilesatthegenome-widelevelin1μmol/LCr(VI)treatedcells.IntestinaltissuebiopsyresultsshowedthatCr(VI)increasedtheincidencesofdiffuseepithelialhyperplasiainintestinaljejunumbutcausednoobviousdamagetothestructureofthemuscularis.Cellproliferationanalysisrevealedthathighconcentrations(≥64μmol/L)butnotlowconcentrationsofCr(VI)(≤16μmol/L)significantlyinhibitedthegrowthofHISMcells.Foroxidativestresslevels,theexpressionofreactiveoxygenspecies(ROS)andnitricoxide(NO)waselevatedathighconcentrations(≥64μmol/L)butnotatlowconcentrationsofCr(VI)(≤16μmol/L).Inaddition,dose-dependentincreasesintheactivityofoxidizedglutathione(GSSH)/total-glutathione(T-GSH)werealsoobserved.Genechipscreened491differentiallyexpressedgenesincludinggenesassociatedwithcellapoptosis,oxidations,andcytoskeletons.SomeofthesedifferentiallyexpressedgenesmaybeuniquetosmoothmusclecellsinresponsetoCr(VI)induction.