title: Indirect evidence for the metabolic dehalogenation of tetrafluorodiethylstilbestrol by rat and hamster liver and kidney microsomes. Species- and organ-dependent differences.
abstract: In order to assess the significance of the catechol pathway for the carcinogenic activity of diethylstilbestrol (DES), the stability of 3',5',3",5"-tetrafluoro-DES (TF-DES) against metabolic catechol formation was examined in vitro. A radioenzymatic assay was used for determining the estrogen hydroxylase activity of liver and kidney microsomes from male and female Syrian golden hamsters and from male Wistar rats for the substrates TF-DES, DES, estradiol-17 beta and 2-fluoro-estradiol-17 beta. With all microsomes tested, catechols were formed from TF-DES to an extent similar to or, in some cases, even exceeding that observed with DES and the steroidal estrogens. The estrogen hydroxylase activity measured for the various microsomes depended on the species, organ and substrate. Analysis by high performance liquid chromatography showed that four products were formed in the radioenzymatic assay with DES and TF-DES. These data demonstrate that the fluorine substitution present in TF-DES does not prevent catechol formation and imply that the catechol pathway must be taken into account as a putative pathway for the metabolic activation of DES.
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D006224:Cricetinae; D004054:Diethylstilbestrol / Q000031:analogs & derivatives* / Q000378:metabolism*; D004958:Estradiol / Q000031:analogs & derivatives / Q000378:metabolism; D007668:Kidney / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008861:Microsomes / Q000378:metabolism; D008862:Microsomes, Liver / Q000378:metabolism*; D051381:Rats
chemical_list: C037475:2-fluoroestradiol; D004958:Estradiol; C019569:3,5,3',5'-tetrafluorodiethylstilbestrol; D004054:Diethylstilbestrol