PMID- 23485034
OWN - NLM
STAT- MEDLINE
DCOM- 20140325
LR  - 20130416
IS  - 1520-5851 (Electronic)
IS  - 0013-936X (Linking)
VI  - 47
IP  - 8
DP  - 2013 Apr 16
TI  - Enantioselective induction of cytotoxicity by o,p'-DDD in PC12 cells: 
      implications of chirality in risk assessment of POPs metabolites.
PG  - 3909-17
LID - 10.1021/es3049306 [doi]
AB  - The increased release of chiral persistent organic pollutants (POPs) into the 
      environment has resulted in more attention to the role of enantioselectivity in 
      the fate and ecotoxicological effects of these compounds. Although the 
      enantioselectivity of chiral POPs has been considered in previous studies, little 
      effort has been expended to discern the enantiospecific effects of chiral POPs 
      metabolites, which may impede comprehensive risk assessments of these chemicals. 
      In the present study, o,p'-DDD, the chiral metabolite of o,p'-DDT, was used as a 
      model chiral metabolite. First, a preferential chiral separation at 100% ethanol 
      was employed to obtain a pure enantiomer. The enantioselective cytotoxicity of 
      o,p'-DDD in rat cells (PC12) was evaluated by detecting activation of the 
      cellular apoptosis and oxidative stress systems and microarray analysis. We have 
      documented for the first time that R-(+)-o,p'-DDD increases apoptosis by 
      selectively disturbing the oxidative system (enzymes and molecules) and 
      regulating the transcription of Aven, Bid, Cideb and Tp53. By comparing the data 
      from the present study to data derived from the parent compound, we concluded 
      that the R-enantiomer is the more detrimental stereostructure for both o,p'-DDT 
      and o,p'-DDD. This observed stereostructural effect is in line with the 
      structure-activity relationship formulated at other structural levels. Biological 
      activities of the chiral metabolites are likely to occur in the same absolute 
      configuration between chiral POPs and their metabolites provided that they have 
      the similar stereostructures.
FAU - Wang, Cui
AU  - Wang C
AD  - MOE Key Laboratory of Environmental Remediation and Ecosystem Health, College of 
      Environmental and Resource Sciences, Zhejiang University, Hangzhou 310058, China.
FAU - Li, Zhuoyu
AU  - Li Z
FAU - Zhang, Quan
AU  - Zhang Q
FAU - Zhao, Meirong
AU  - Zhao M
FAU - Liu, Weiping
AU  - Liu W
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130401
PL  - United States
TA  - Environ Sci Technol
JT  - Environmental science & technology
JID - 0213155
RN  - 0 (Air Pollutants)
RN  - 0 (Antioxidants)
RN  - 0 (Heat-Shock Proteins)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - V14159DF29 (Dichlorodiphenyldichloroethane)
SB  - IM
MH  - Air Pollutants/*chemistry/*toxicity
MH  - Animals
MH  - Antioxidants/metabolism
MH  - Apoptosis/drug effects/genetics
MH  - Chromatography, High Pressure Liquid
MH  - Dichlorodiphenyldichloroethane/*chemistry/isolation & purification/*toxicity
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Gene Expression Regulation/drug effects
MH  - Heat-Shock Proteins/genetics/metabolism
MH  - Oligonucleotide Array Sequence Analysis
MH  - Oxidative Stress/drug effects/genetics
MH  - PC12 Cells
MH  - Rats
MH  - Reproducibility of Results
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - *Risk Assessment
MH  - Stereoisomerism
MH  - Tumor Suppressor Protein p53/metabolism
EDAT- 2013/03/15 06:00
MHDA- 2014/03/26 06:00
CRDT- 2013/03/15 06:00
PHST- 2013/03/15 06:00 [entrez]
PHST- 2013/03/15 06:00 [pubmed]
PHST- 2014/03/26 06:00 [medline]
AID - 10.1021/es3049306 [doi]
PST - ppublish
SO  - Environ Sci Technol. 2013 Apr 16;47(8):3909-17. doi: 10.1021/es3049306. Epub 2013 
      Apr 1.