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HERO ID
2308978
Reference Type
Technical Report
Title
Estrogenic Properties Of DDT And Its Analogs
Author(s)
Kupfer, D; Bulger, WH
Year
1980
Report Number
NIOSH/00132494
Volume
McLachlan
Page Numbers
239-263
Abstract
The estrogenic effects of DDT (50293) and its analogs were studied in-vitro. In assays involving the estrogen receptor, sucrose gradient sedimentation analysis was made of labeled estradiol-17-beta (50282) binding to the cytosolic estrogen receptor from rat uteri or testes or from human tumors. Changes in distribution of uterine cytosolic receptor and nuclear receptor were determined after administration of estradiol-17-beta or o,p'-DDT form of DDT. Metabolic effects were studied by simultaneous incubation of a compound with rat liver microsomes in the presence of uteri from immature rats. Assays were made of the effect of DDT compounds on uterine ornithine decarboxylation in immature or ovariectomized rats. The formation of phenolic metabolites of DDT or methoxychlor (72435) was studied in liver microsomes. Base soluble products were isolated by chromatography. o,p'-DDT reduced cytosolic estrogen receptors and increased nuclear estrogen receptors, indicating that this compound acts like an estrogen. There was a lack of inhibition of estradiol-17-beta binding by methoxychlor or DDT, indicating that only estrogen DDT analogs bind to the testicular estrogen receptor. It appeared that o,p'-DDT acted as a typical estrogen on different biological parameters. However, this form also behaved like an anti estrogen with respect to causing inhibition of the induction of uterine ornithine decarboxylase in response to subsequent treatments with this form of DDT or estradiol-17-beta. It appeared that both o,p'-DDT and its metabolites were estrogenic. Methoxychlor appeared not to act as an estrogen, but the compound was metabolized by hepatic monooxygenase into active phenolic metabolites. In most cases, methoxychlor contained base soluble contaminants, apparently responsible for the estrogenic activity of the crude preparations. The authors note that methods used in these studies are effective in determining whether a compound is active or is a proestrogen.
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