IN-VITRO BIOACTIVATION OF THE ENVIRONMENTAL-POLLUTANT ULFONYL-2,2-BIS(4-CHLOROPHENYL)-1,1-DICHLOROETHENE IN THE HUMAN ADRENAL-GLAND

The metabolic activation and covalent binding of 3-methylsulphonyl-2,2 -bis(4-chlorophenyl)1, 1-dichloroethene (MeSO2-(C-14)DDD) were studied in vitro in the human adrenal gland. The mitochondrial bioactivation was twice as high as the microsomal, thus the study was focused on the mitochondria. The irreversible binding was time and protein dependent with apparent K(m) and V(max) values of 1.4 muM and 275 pmol/mg prote in/h. As a comparison the activation of chlorophenyl)-2(4-chlorophenyl )-1,1-dichloroethane (o,p'-DDD), a well-known adrenolytic compound in humans, was studied. The irreversible binding of both these DDT metabo lites was inhibited by metyrapone, indicating the involvement of cytoc hrome P-450. Addition of reduced glutathione (GSH) to the incubation m edium decreased the irreversible binding of MeSO2-DDE significantly wh ereas the binding of o,p'-DDD was only slightly affected. The above fi ndings suggest that MeSO2-DDE may be toxic to the human adrenal gland, although further study is necessary to assess this potential.