title: Enantioselective cytotoxicity profile of o,p'-DDT in PC 12 cells.
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 approaches for ecological and health risk assessment has ignored the chiral nature of DDT. In this study by employing an array of cytotoxicity related endpoints, we investigated the enantioselective cytotoxicity of o,p'-DDT.
  
  
  RESULTS
  we demonstrated for the first time that R-(-)-o,p'-DDT caused more neuron cell death by inducing more 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 enantioselective apoptosis might involve three signaling pathways via caspase 3, tumor protein 53 (p53) and NF(k)B.
  
  
  CONCLUSIONS
  Based on DDT stereochemistry and results reported for other chiral pesticides, our results pointed to the same directional enantioselectivity of chiral DDT toward mammalian cells. We proposed that risk assessment on DDT should consider the enantiomer ratio and enantioselectivities.
authors.affiliation: Research Center of Environmental Science, Zhejiang University of Technology, Hangzhou, China.
authors.forename: Meirong
authors.initials: M
authors.lastname: Zhao
authors.forename: Cui
authors.initials: C
authors.lastname: Wang
authors.forename: Chunlong
authors.initials: C
authors.lastname: Zhang
authors.forename: Yuezhong
authors.initials: Y
authors.lastname: Wen
authors.forename: Weiping
authors.initials: W
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D003603:Cytotoxins / Q000633:toxicity*; D003634:DDT / Q000633:toxicity*; D004968:Estrogens, Non-Steroidal / Q000633:toxicity*; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D016716:PC12 Cells; D051381:Rats; D013237:Stereoisomerism; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D000099156:Superoxide Dismutase 2
chemical_list: D003603:Cytotoxins; D003634:DDT; D004968:Estrogens, Non-Steroidal; D018840:HSP70 Heat-Shock Proteins; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D000099156:Superoxide Dismutase 2; C016340:o,p'-DDT; C000606292:Sod1 protein, rat