Ameliorative Effects of Dimetylthiourea and N-Acetylcysteine on Nanoparticles Induced Cyto-Genotoxicity in Human Lung Cancer Cells-A549 英文参考文献.docVIP

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Ameliorative Effects of Dimetylthiourea and N-Acetylcysteine on Nanoparticles Induced Cyto-Genotoxicity in Human Lung Cancer Cells-A549 英文参考文献.doc

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Ameliorative Effects of Dimetylthiourea and N-Acetylcysteine on Nanoparticles Induced Cyto-Genotoxicity in Human Lung Cancer Cells-A549 英文参考文献

AmeliorativeEffectsofDimetylthioureaandN- AcetylcysteineonNanoparticlesInducedCyto- GenotoxicityinHumanLungCancerCells-A549 RiteshKumarSrivastava1,2,QamarRahman3,MahendraPratapKashyap1,2,MohtashimLohani3 ,Aditya BhushanPant1,2 * 1Indian Institute of Toxicology Research, Lucknow, India, 2Council of Scientific and Industrial Research, New Delhi, India, 3Department of Biotechnology, Integral University,Lucknow,India Abstract We study the ameliorative potential of dimetylthiourea (DMTU), an OHN radical trapper and N-acetylcysteine (NAC), a glutathione precursor/H2O2 scavenger against titanium dioxide nanoparticles (TiO2-NPs) and multi-walled carbon nanotubes(MWCNTs)inducedcyto-genotoxicityinculturedhumanlungcancercells-A549.Cytogenotoxicitywasinduced by exposing the cells to selected concentrations (10 and 50mg/ml) of either of TiO2-NPs or MWCNTs for 24h. Anti- cytogenotoxicityeffectsofDMTUandNACwerestudiedintwogroups,i.e.,treatmentof30minutespriortotoxicinsult (shorttermexposure),whiletheothergroupreceivedDMTUandNACtreatmentduringnanoparticlesexposure,i.e.,24h (long term exposure). Investigations were carried out for cell viability, generation of reactive oxygen species (ROS), micronuclei(MN),andexpressionofmarkersofoxidativestress(HSP27,CYP2E1),genotoxicity(P53)andCYP2E1dependent n-nitrosodimethylamine-demethylase(NDMA-d)activity.Ingeneral,thetreatmentofbothDMTUandNACwasfoundtobe effectivesignificantlyagainstTiO2-NPsandMWCNTsinducedcytogenotoxicityinA549cells.Long-termtreatmentofDMTU and NAC during toxic insults has shown better prevention than short-term pretreatment. Although, cells responded significantlytobothDMTUandNAC,butresponseswerechemicalspecific.Inpart,TiO2-NPsinducedtoxicresponseswere N mediatedthroughOH radicalsgenerationandreductionintheantioxidantdefensesystem.WhileinthecaseofMWCNTs, adverseeffectswereprimarilyduetoaltering/hamperingtheenzymaticantioxidantsystem.Dataindicatetheapplicability of human lung cancer cells-A549 as a pre-screening tool to