Dichloroacetic Acid Metabolism In Vitro: I. Investigation of the Factors Influencing Dichloroacetic Acid Metabolism.
Abstract
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 ug/mI 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 ug/ml 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.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 1995
- Accession Number
- ADA324575
Entities
People
- D. A. Mahle
- G. W. Buttler
- J. C. Lipscomb