Extra-hepatic GSH-dependent metabolism of 1,2-dibromoethane (DBE) and 1,2-dibromo-3-chloropropane (DBCP) in the rat and mouse.
Although DBE is metabolized by both microsomal and cytosolic pathways, it is the latter, GSH-dependent route, that may lead to hepatic and extra-hepatic genotoxicity and mutagenicity. As both DBE and DBCP exhibit predominantly extra-hepatic toxicity, their in vitro GSH-dependent debromination was measured in cytosolic fractions prepared from liver, kidney, testes and stomachs of Sprague-Dawley rats and Swiss-Webster mice. There was a marked species difference between the rat and mouse, with the rat metabolizing DBCP more rapidly than DBE, and the mouse metabolizing DBE more rapidly than DBCP. Hepatic rates exceeded those seen in extra-hepatic tissues in every case. Extra-hepatic rates of debromination represented as much as 84% of the hepatic rates, and generally followed the order: kidney greater than testes greater than stomach. Rates of metabolism for DBE and DBCP represented only a small fraction of the total cytosolic GSH S-transferase activity. These findings suggest significant levels of GSH-dependent metabolism may occur within those tissues associated with the in vivo toxicity of DBE and DBCP.
D000818:Animals; D001711:Biotransformation; D003600:Cytosol / Q000378:metabolism; D015946:Ethylene Dibromide / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism*; D005982:Glutathione Transferase / Q000378:metabolism; D006842:Hydrocarbons, Brominated / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D011407:Propane / Q000031:analogs & derivatives* / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity; D013347:Subcellular Fractions / Q000378:metabolism; D013737:Testis / Q000378:metabolism
D006842:Hydrocarbons, Brominated; D015946:Ethylene Dibromide; C007318:1,2-dibromo-3-chloropropane; D005982:Glutathione Transferase; D005978:Glutathione; D011407:Propane