Quantification of particle-induced inflammatory stress response a novel approach for toxicity testing of earth materials 英文参考文献.docVIP

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Quantification of particle-induced inflammatory stress response a novel approach for toxicity testing of earth materials 英文参考文献.doc

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Quantification of particle-induced inflammatory stress response a novel approach for toxicity testing of earth materials 英文参考文献

Harringtonetal.GeochemicalTransactions2012,13:4 /content/13/1/4 METHODOLOGY OpenAccess Quantificationofparticle-inducedinflammatory stressresponse:anovelapproachfortoxicity testingofearthmaterials AndreaDHarrington1,StellaETsirka2andMartinAASchoonen1* Abstract Background:Reactiveoxygenspecies(ROS)arevitalregulatorsofmanycellularfunctionsinthebody.The intracellularROSconcentrationishighlyregulatedbyabalancebetweenpro-oxidantsandanti-oxidants.Achronic excessofpro-oxidantsleadstoelevatedROSconcentrationsandinflammation,possiblyinitiatingorenhancing diseaseonset.Mineral-inducedgenerationofROS,theroleofmineralsinupregulatingcellularROS,andtheirrole inthedevelopmentofseveraloccupationaldiseasesarenowwidelyrecognized.However,thereisnostandard protocoltodeterminechangesinROSproductionincellsafterexposuretomineraldustorearthmaterialsin general.Inthisstudy,anewmethodfordeterminingthedegreeofcellulartoxicity(i.e.,cytotoxicity)ofparticlesis describedthatwillhelpbridgethegapinknowledge. Results:BymeasuringtheproductionofROSandtheviabilityofcells,aninflammatorystressresponse(ISR) indicatorisdefined.ThisapproachnormalizestheROSupregulationwithrespecttothenumberofviablecellsat thetimeofmeasurement.Weconductedexperimentsonaseriesofmineralsandsoilsthatrepresentmaterials thatareinert(i.e.,glassbeads,anatase,andasoilwithlowtraceelementcontent),moderatelyreactive(i.e.,soil withhightraceelementcontent),andhighlyreactive(i.e.,pyrite).InertmaterialsgeneratedthelowestISR, averaging350%comparedtothecontrol.AcidwashedpyriteproducedthehighestISR(1,100foldhigherthanthe control).Themeasurementsconductedasafunctionoftimeshowedacomplexresponse.Mostmaterialsshowed anincreaseinISRwithparticleloading. Conclusions:TheamountofcellularlygeneratedROSandcellviabilitycombinedprovideabetterunderstanding ofparticle-inducedoxidativestress.TheresultsindicatethatsomeearthmaterialsmaysolicitaninitialburstofROS, followedbyasecondphaseinwhichcellviabilitydecreasesandROSproductionincreases,leadingtoahighISR value