The Effect Of Sodium Arsenite On The Expression Of P53, Mdm2, Kras Gene And Protein In INS-1Cellsn

Objective: Arsenic is a metalloid element that is ubiquitous in lithosphere as bothorganic and inorganic forms. The main way of human exposure to arsenic isenvironmental exposure. Especially be exposed to the high concentration of arsenic inwater. Recently, arsenic was confirmed to induce diabetes mellitus. It was proved thatarsenic have toxic effects on islet cells. Studies have shown that arsenic can causeapoptosis and DNA damage in islet cells. However, it is unclear whether arsenicexposure to islet cells can lead to the expression of oncogenes. The aims of this studywere to explore the mechanism of arsenic-induced p53, mdm2, Kras genes and proteinexpression in INS-1cells.Methods: INS-1cells were used as the test system. We used MTT experiment tostudy the toxicity of sodium arsenite in INS-1. We used real-time PCR to elucidate theeffect of wild type p53(Tp53), mdm2and Kras genes expression in INS-1whichexposed to sodium arsenite. We used Western blot to elucidate the mechanism ofmutant p53and mdm2protein expression in INS-1which exposed to sodium arsenite.Results: INS-1cells were exposed by sodium arsenite (0,2.5,5,10,20,40,80,160μM) for48hours and72hours in37℃. The OD value decreased with the increasingdose of the sodium arsenite. It explored that the cytoactive of the INS-1cells decreasedwith the increasing dose of the sodium arsenite. And the IC50of sodium arseniteexposed to INS-1cells is2.78μM; Expression of Tp53gene in cells exposed to sodiumarsenite for48h and72h decreased with the increasing dose of sodium arsenite. Theexpression of mdm2and Kras genes increased; Expression of mutant p53and mdm2protein in cells exposed to sodium arsenite for48h and72h increased with theincreasing dose of the sodium arsenite.Conclusion: Expression of Tp53gene in INS-1cells exposed to sodium arsenitedecreased. Expression of mdm2and Kras genes increased. Arsenic caused the transformation of Tp53to mutant p53.