Metabolism of diethylstilbestrol in the C3H mouse: chromatographic systems for the quantitative analysis of DES metabolic products.

Abstract:

:Initial excretion studies with orally administered [monoethyl-1-3H] DES demonstrated the feces to be the principal mode of elimination of DES in the C3H mouse. Metabolic studies with tritiated DES and/or [UL-14C] DES were performed with orally dosed C3H high (MTV+) and low (MTV-) titer MMTV female mice. Extraction and partitioning of the fecal radioactivity demonstrated 77 to 86% (n = 4) to be benzene soluble and the remainder H2O soluble. The principal product in the organic phase following Sephadex LH-20 and HPLC purification was DES. The aqueous phase was resolved by LH-20 into two conjugate fractions that were partially hydrolyzed by beta-glucuronidase. The principal aglycone was chromatographically identical with authentic DES. The urinary conjugates were resolved into six fractions. The four major fractions were 80% hydrolyzable with beta-glucuronidase. Two of these fractions had trans-DES as the principal aglycone, whereas the other two had a major peak similar to but not chromatographically coincident with cis-DES. In certain experiments mice were sequentially dosed with tritium (24 hr) followed by a 14C dose (24 hr). Two mice (MTV+) were also previously fed 1000 ppb DES prior to these experiments. The tritated and 14C products were combined and analyzed simultaneously. This experiment did not reveal significant differences in the metabolism due to the modes of radioactive labeling, MMTV titer, or the prior feeding of DES. The developed methodology was judged to purify quantitatively 90% or more of the DES radioactive products.

journal_name

Steroids

journal_title

Steroids

authors

Helton ED,Gough BJ,King JW Jr,Thenot JP,Horning EC

doi

10.1016/0039-128x(78)90029-6

subject

Has Abstract

pub_date

1978-04-01 00:00:00

pages

471-84

issue

4

eissn

0039-128X

issn

1878-5867

pii

0039-128X(78)90029-6

journal_volume

31

pub_type

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