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(41-16) Enantiomer-specific toxicity of o,p'-DDT to rainbow trout hepatocytes. Hoekstra, Paul*,1, Dayeh, Vivian2, Sherry, Jim3, Solomon, Keith1, Bols, Niels2, Muir, Derek1,3, 1 University of Guelph, Guelph, Ontario2 University of Waterloo, Waterloo, Ontario3 Environment Canada, Burlington, Ontario ABSTRACT- The pesticide DDT (dichlorodiphenyltrichloroethane) is a persistent environmental contaminant found in soils and sediment in former use areas and is currently used in some regions for control of malaria vectors and other pest control applications. The o,p'-substituted isomer, o,p'-DDT, is chiral and may have enantiomer-specific toxicological properties. Previous experiments have demonstrated that (-)-o,p'-DDT enantiomer is a more active estrogen-mimic than the (+)-enantiomer in rats and humans. However, these results have not been extrapolated to fish. This study assessed the estrogenic activity and toxicity of o,p'-DDT enantiomers by quantifying the enantiomer-specific induction of vitellogenin by primary hepatocyte cultures and cellular toxicity to an immortalized culture of rainbow trout hepatocytes (RTL-W1). An enzyme-linked immunosorbent assay (ELISA) was employed to detect vitellogenin from rainbow trout (Oncorhynchus mykiss) primary hepatocytes induced from exposure to test compounds. The (-)-enantiomer of o,p'-DDT was a weak active estrogen mimic in primary hepatocyte cultures relative to estradiol. The estrogenic activity of (+)-o,p'-DDT was negligible. Enantiomer-selective degradation of (+)-o,p'-DDT by primary hepatocytes exposed to racemic o,p'-DDT was observed at relatively high concentrations. Enantiomer-specific in vitro cytotoxicity of o,p'-DDT was observed in the RTL-W1 rainbow trout cell line. This data demonstrates the need to consider stereochemistry of environmental contaminants and its potential influence on biological responses. Key words: chiral, DDT, biotransformation, vitellogenin |
