EVALUATION OF THE DISODIUM SALT OF 4,4'-DIAMINO-2,2'-STILBENE DISULFONIC ACID FOR ESTROGENIC ACTIVITY.

Autor: Hostetler, K. A., Leach, M. W ., Hyde, T. E., Wei, L. L.
Zdroj: Journal of Toxicology & Environmental Health; 6/7/1996, Vol. 48 Issue 2, p141-150, 10p
Abstrakt: 4,4'-Diam ino-2,2'-stilbene disulfonic acid (DAS) , a key intermediate in the synthesis of dyes and fluorescent whitening agents, has been purported to have weak estrogenic properties based on apparent structural similarity with diethylstilbestrol (DES) and unsubstantiated reports of male reproductive dysfunction in an industrial setting. In weanling rats, high doses of DAS (300 mg/kg ip; 1000-3000 m g/kg oral) have been associated with modest increases in the uterus/body weight ratio (Smith & Q uinn, 1992). In order to more directly and definitively determine if DAS possesses estrogenic activity, in vitro studies were conducted to establish its relative binding affinity to the human estrogen receptor (ER) in MCF-7 cells, a well-characterized breast cancer cell line. At concentrations approaching its solubility limit (10-4M), DAS failed to displace [3H]-17-betaestradiol (E2) from the ER. In contrast, DES and E demonstrated characteristic competitive binding curves (50% displacement of 3H-E2 at 3.33 x 10-9 and 1.33 x 10-8 M, respectively). Parallel in vivo comparisons of DAS (10 or 30 mg/animal) and DES (1 or 3 mug/animal) were also conducted to assess uterotropic effects. After three daily subcutaneous injections, DAS did not induce uterine weight gain. In contrast, DES consistently and m arkedly increased uterine weight and induced uterine water imbibition, with the latter effect being absent in DAS-treated rats. Under these experimental conditions, DAS was shown to possess negligible, if any, estrogenic activity, despite apparent structural sim ilarity with known estrogens. [ABSTRACT FROM AUTHOR]
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