Enantioselective Cytotoxicity Profile of o,p’-DDT in PC 12 Cells 英文参考文献.docVIP

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Enantioselective Cytotoxicity Profile of o,p’-DDT in PC 12 Cells 英文参考文献.doc

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Enantioselective Cytotoxicity Profile of o,p’-DDT in PC 12 Cells 英文参考文献

EnantioselectiveCytotoxicityProfileofo,p’-DDTinPC12 Cells MeirongZhao1.,CuiWang1.,ChunlongZhang2,YuezhongWen3,WeipingLiu3* 1ResearchCenterofEnvironmentalScience,ZhejiangUniversityofTechnology,Hangzhou,China,2UniversityofHouston-ClearLake,Houston,Texas,UnitedStatesof America,3InstituteofEnvironmentalSciences,CollegeofEnvironmentalandResourceSciences,ZhejiangUniversity,Hangzhou,China Abstract Background: The continued uses of dichlordiphenyltrichloroethane (DDT) for indoor vector control in some developing countries have recently fueled intensive debates toward the global ban of this persistent legacy contaminant. Current approachesforecologicalandhealthriskassessmenthasignoredthechiralnatureofDDT.Inthisstudybyemployingan arrayofcytotoxicityrelatedendpoints,weinvestigatedtheenantioselectivecytotoxicityofo,p’-DDT. PrincipalFindings:wedemonstratedforthefirsttimethatR-(2)-o,p’-DDTcausedmoreneuroncelldeathbyinducingmore severe oxidative stress, which selectively imbalanced the transcription of stress-related genes (SOD1, SOD2, HSP70) and enzyme (superoxide dismutase and lactate dehydrogenase) activities, and greater cellular apoptosis compared to its enantiomer S-(+)-o,p’-DDT at the level comparable to malaria area exposure (parts per million). We further elucidated enantioselective modes of action using microarray combined with enzyme-linked immunosorbent assay. The enantioselectiveapoptosismightinvolvethreesignalingpathwaysviacaspase3,tumorprotein53(p53)andNFkB. Conclusions:BasedonDDTstereochemistryandresultsreportedforotherchiralpesticides,ourresultspointedtothesame directional enantioselectivity of chiral DDT toward mammalian cells. We proposed that risk assessment on DDT should considertheenantiomerratioandenantioselectivities. Citation:ZhaoM,WangC,ZhangC,WenY,LiuW(2012)EnantioselectiveCytotoxicityProfileofo,p’-DDTinPC12Cells.PLoSONE7(8):e43823.doi:10.1371/ journal.pone.0043823 Editor:AdityaBhushanPant,IndianInstituteofToxicologyResearch,India ReceivedJune7,201