Metabolic fates of diethylstilboestrol sulphates in the rat

Abstract

The metabolic fates and modes of excretion of diethylstilboestrol mono [35S] Diethylstilboestrol has been used as a synthetic oestrogen in humans and in food-producing animals. It has been shown to have carcinogenic properties in a number of animal species (Umberger, 1975) and its use has been associated with the occurrence of tumours in humans (Herbst et al., 1972).The metabolic fate of diethylstilboestrol has been studied in several animal species (Abou-EI-Makarem et al., 1967) and it has been shown that biliary excretion as a glucuronic acid conjugate represents a major pathway for elimination (Klaasen, 1973). The disulphate ester of diethylstilboestrol, which is approximately half as active as diethylstilboestrol itself with respect to oestrogenic activity (Bishop et al., 1951), has been used as a water-soluble form of the synthetic oestrogen. Nevertheless, the metabolism of sulphated forms of diethylstilboestrol has not been reported.

Biliary excretion of some anionic derivatives of diethylstilboestrol and phenolphthalein in the guinea pig

“…Phenolphthalein di[35S]sulphate was excreted unchanged in bile. These findings are discussed in relation to studies carried out in the rat [Barford, Olavesen, Curtis & Powell (1977) Biochem. J.…”

“…Potassium diethylstilboestrol mono[5S]sulphate (8.9 mCi/mmol) and potassium diethylstilboestrol di[35S]sulphate (1l.OmCi/mmol) were prepared by the methods of Barford et al (1977). Potassium phenolphthalein di[35S]sulphate (8.9mCi/mmol) was prepared as described by Powell et al (1975).…”

“…This material was dissolved in 50% (v/v) ethanol at a concentration of 7mg/mi. Diethylstilboestrol mono- [35S]sulphate monoglucuronide was obtained from rat bile (Barford et al, 1977).…”

“…In the rat, the metabolic fates and modes of excretion of the synthetic oestrogens diethylstilboestrol monosulphate and diethylstilboestrol disulphate have been explained (Barford et al, 1977) on the basis of the enzyme complement of rat liver. The esters are desulphated to some extent in vivo, a finding consistent with the fact that both are substrates for microsomal arylsulphatase C. In contrast, phenolphthalein disulphate, which is not a substrate for arylsulphatase C, is eliminated unchanged in rat bile (Hirom et al, 1972).…”

Delayed Adverse Effects of Neonatal Exposure to Diethylstilbestrol and Their Dose Dependency in Female Rats

“…TOXICOLOGIC PATHOLOGY distributed in the whole body within twenty-four hours (Barford et al 1977) could be support that the concern could be excluded.…”