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Oestrogenic activity of benzylparaben

Darbre, P. D., Byford, J. R., Shaw, L. E., Hall, S., Coldham, N. G., Pope, G. S. and Sauer, M. J. (2003) Oestrogenic activity of benzylparaben. Journal of Applied Toxicology, 23 (1). pp. 43-51. ISSN 0260-437X

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To link to this article DOI: 10.1002/jat.886

Abstract/Summary

Previous work has demonstrated that the alkyl esters of p-hydroxybenzoic acid (parabens) possess oestrogenic activity, which increases with length of alkyl chain from methylparaben to n-butylparaben and with branching in the alkyl chain from n-butylparaben to isobutylparaben. This study reports on the oestrogenic activity of benzylparaben in a variety of assays in vitro and in vivo. Benzylparaben was able to displace [H-3]oestradiol from cytosolic oestrogen receptor (ER) of MCF7 human breast cancer cells by 22% at 1000-fold molar excess, by 40% at 10000-fold molar excess, by 57% at 100000-fold molar excess and by 100% at 1000000-fold molar excess. It was able to increase expression of a stably transfected oestrogen responsive reporter gene (ERE-CAT) in MCF7 cells after 24 h at 10(-5)M/10(-4)M and after 7 days at 10(-6)M/10(-5)M/10(-4)M. Proliferation of MCF7 cells could be increased by 10(-6)M/10(-5)M benzylparaben and this could be inhibited by 10(-7)M pure anti-oestrogen ICI 182,780, indicating that growth effects were ER mediated. Further evidence for ER-mediation was provided from the ability of benzylparaben to increase the growth of a second oestrogen-dependent human breast cancer cell line ZR-75-1, but not the oestrogen-insensitive NIDA-MB-231 cell line. When tested in the presence of 10(-10)M 17beta-oestradiol, benzylparaben gave no antagonist response on the growth of either MCF7 or ZR-75-1 cells. Finally, benzylparaben could increase uterine weight in the immature mouse following topical application of three daily doses of 33 mg to dorsal skin. These results demonstrate that the oestrogenicity of methylparaben can be increased by the addition of an aryl group as well as by lengthening or branching the alkyl grouping. Copyright (C) 2003 John Wiley Sons, Ltd.

Item Type:Article
Refereed:Yes
Divisions:Faculty of Life Sciences > School of Biological Sciences
ID Code:10716
Uncontrolled Keywords:parabens, environmental oestrogen, xenoestrogen, breast cancer cells, MCF7 cells, ZR-75-1 cells, mouse uterus, SARs, aryl group, p-hydroxybenzoic acid, BREAST-CANCER-CELLS, IN-VITRO, PRESERVATIVES PARABENS, RECEPTOR, VIVO, CHEMICALS, ASSAY, IDENTIFICATION, BUTYLPARABEN, CULTURE

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