Oxidative metabolites of diethylstilbestrol in the fetal, neonatal and adult mouse

Abstract

Urinary metabolites of 14C-labeled diethylstilbestrol (DES) in adult female mice were identified by radio gas chromatography and gas chromatography-mass spectrometry as β-dienestrol and ω-hydroxy-derivatives of DES, ψ-DES and dienestrol. The metabolic β-dienestrol does not appear to be formed through a DES epoxide. Most of the metabolites found in adult mice were also detected by mass fragmentography in the whole-body homogenates obtained from mice of age 1.4 and 8 days, indicating that oxidative metabolism of DES is operative in neonatal mice. Furthermore, extensive conjugation of DES and its metabolites to glucuronic acid was found in adult and neonatal mice. Part of the administered radioactivity was unextractable from tissue macromolecules in neonatal mice. The biotransformation of DES and binding of its metabolites, implies a metabolic activation of this synthetic estrogen that might be associated with its teratogenic and carcinogenic potential for neonatal and fetal mice.