In vitro bioactivation of the environmental pollutant 3-methylsulphonyl-2,2-bis(4-chlorophenyl)-1,1-dichloroethene in the human adrenal gland

Add time:07/30/2019    Source:sciencedirect.com

The metabolic activation and covalent binding of 3-methylsulphonyl-2,2-bis(4-chlorophenyl)-1,1-dichloroethene (MeSO2-(14C)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 Km and Vmax values of 1.4 μM and 275 pmol/mg protein/h. As a comparison the activation of 2-(2-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 metabolites was inhibited by metyrapone, indicating the involvement of cytochrome P-450. Addition of reduced glutathione (GSH) to the incubation medium decreased the irreversible binding of MeSO2-DDE significantly whereas the binding of o,p′-DDD was only slightly affected. The above findings suggest that MeSO2-DDE may be toxic to the human adrenal gland, although further study is necessary to assess this potential.

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