Overexpression of MDR1 is associated with acquired tolerance to arsenic in L-02 cells

ObjectiveTo study the relativity of multidrug resistance gene 1(MDR1)gene expression and acquired to lerance to arsenic in human hepatocyte cell line(L-02).MethodsThe levels of MDR1 mRNA were determined by real time quantitative PCR,and the expression of P-gly coprote in(P-gp)was examined by mimunohisto chemical SABC in both arsenite exposed cells and the control.Then the cells were incubated with fresh medium containing 0,2 5,5 0,10.0 mol/L NaAsO₂ in the pre sence or absence of 10 mol/L PSC833(an inhibitor for Pgp).Twenty four hours later,cellular total arsenic was determined using graphite furnace atomic absorption spectrometry,and 3-4,5-dimethy lthiazol-2-yl-2,5-diphenyl tetrzolium(MTT)was used to detect cell survival rate.ResultsThe expression of MDR 1 mRNA and P-gp in arsenite exposed cells(8.890±0.968,68.76±3.81%)was higher than in L-02 cells(1.014±0.189,24.44±4.03%), (P<0.001);the survival rate of arsenite exposed L-02 cells(109.630±0.511%,95.469±0.054%,78.890±0.024%) was apparently higher than that of L-02 cells(104.841±0.015%,91.534±0.026%,64.811±0.079%),(P<0.001); cellular arsenic content in arsenite exposed cells(0.68±3.65×10^-03,1.36±4.72×10^-03,3.27±9.62×10^-03 μg/L)was markedly decreased than in control(1.17±5.48×10^-04,3.66±1.95×10^-03,7.53±6.20×10^-03 μg/L).With 10 mol/L PSC 833,cellular arsenic content was markedly increased and survival rate of the cells was apparently decreased (P<0.001).ConclusionAcquired to lerance to arsenic is associated with increased expression of MDR1 with presentation of mRNA and prote in in human hepatocyte cell line.