Estimation of Estrogenic and Anti-estrogenic Activities of Some Phthalate Diesters and Monoesters by MCF-7 Cell Proliferation Assay in Vitro

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Abstract
Phthalates are man-made chemicals abundantly found in the environment. Estrogenic activities of phthalate di and monoesters were studied by in vitro assay of human breast cancer MCF-7 cell proliferation. Since phthalate monoesters are formed from diesters by degradation and are found in the environment, we selected some phthalate monoesters in addition to diesters. Among 19 compounds tested, dicyclohexyl phthalate (DCHP), di(2-ethylhexyl) phthalate (DEHP) and butyl benzyl phthalate (BBP) were found to have estrogenic activities, all of which were completely suppressed by the addition of pure anti-estrogen ICI 182,780. DCHP stimulated cell proliferation with maximal cell yield at 5×10−5 M. Its estrogenic potency was approximately 1700000 times less than that of 17β-estradiol. DEHP and BBP stimulated cell proliferation only slightly at >10−3 M. No other phthalate diesters or monoesters tested were estrogenic. Anti-estrogenic activities were also examined by estimating the suppression of cell proliferation in the presence of 10−11 M 17β-estradiol. Mono-n-pentyl phthalate (MPP), monocyclohexyl phthalate (MCHP), monobenzyl phthalate (MBZP), monoisopropyl phthalate (MIPrP) and BBP were suggested to have anti-estrogenic activities at higher than 10−4 M. Among commonly used phthalate esters and those with related structures, some were found to be estrogenic and others were anti-estrogenic in vitro.

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