Dichloroacetic Acid Metabolism In Vitro: I. Investigation of the Factors Influencing Dichloroacetic Acid Metabolism.
Interim rept. Apr 94-Apr 95,
MANTECH ENVIRONMENTAL TECHNOLOGY INC DAYTON OH
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Dichioroacetic acid DCA is a major metabolite of trichioroethylene TRI, a common groundwater contaminant. Dichioroacetic acid has been reported to cause hepatocarcinomas in rodents. We have shown that DCA metabolism is dependent on a cytosolic protein and, therefore, not P-450 dependent. However, the products of DCA metabolism have not been clearly identified. Initial experiments performed with nuclease and protease ruled out binding of DCA as an explanation for the disappearance of DCA from cytosolic incubations. Experiments were then conducted to determine if a specific cofactor dependence for DCA metabolism existed. Mouse liver cytosol was incubated with either nicotinamide or flavin cofactors at a concentration of 0.9 mM or 0.24-5 mM glutathione GSH and with 20.50 ugmI DCA for 3 to 20 minutes at 370C. The incubations were derivatized and analyzed to assess DCA removed from solution. Dichloroacetic acid metabolism increased with increasing concentration of GSH. Mouse liver cytosol was then incubated with 0.1-5 mM diethyl maleate DEM, TCA or monochloroacetic acid MCA and 20-30 ugml DCA for 5-30 minutes at 37 deg C. The same analysis was done to calculate pg DCA removed. While TCA appeared to have no effect of DCA metabolism, MCA and DEM had varying effects on DCA metabolism. Results from this research can be used to support further investigation of the products of DCA metabolism.
- Anatomy and Physiology
- Inorganic Chemistry
- Hydrology, Limnology and Potamology
- Water Pollution and Control