Transcriptional modulation of a human monocytic cell line exposed to PM(10) from an urban area

Insight intothemechanismsbywhichambientairparticulatemattermediatesadversehealtheffectsis needed toprovidebiologicalplausibilitytoepidemiologicalstudiesdemonstratinganassociation betweenPM10 exposureandincreasedmorbidityandmortality. In vitro studies oftheeffectsofair pollutiononhumancellshelptoestablishconditionsfortheanalysisofcause-effectrelationships.One of themajorchallengesistotestnativeatmosphereinitscomplexity,ratherthanthevarious componentsindividually.Wehavedevelopedan in vitro system inwhichhumanmonocyte-macro- phage U937cellsaredirectlyexposedtofilterscontainingdifferentamountsofPM10 collected inthe city ofRome. Transcriptionalprofilingobtainedaftershortexposure(1h)ofcellstoafiltercontaining1666 mg PM10 (77.6 mg/cm2) usingamacroarraypanelof1176genesrevealsasignificantchangeinthemRNA level (42 fold)for87genesrelativetocellsexposedtoacontrolfilter.Overall,9outof87modulated geneswereannotatedas''lungcancer''.qRT-PCRconfirmedtheinductionofrelevantgenesinvolvedin DNA repairandapoptosis,specifically: ERCC1, TDG, DAD1 and MCL1. Incellsexposedfor10min,1hand 3 htodifferentamountsofPM10, transcriptionof TNFa and TRAP1, whichcodeforakeypro- inflammatorycytokineandamitochondrialproteininvolvedincellprotectionfromoxidativestress, respectively,wasshowntobemodulatedinatime-dependent,butnotadose-dependentmanner. Taken together,thesedataindicatethatitispossibletoanalyzetheeffectsofuntreatedparticulate matteronhumancellsbythedirect-exposureapproachwehavedeveloped,possiblyprovidingnew clues totraffic-relatedhealthhazard.