Comparison of an array of in vitro assays for the assessment of the estrogenic potential of natural and synthetic estrogens, phytoestrogens and xenoestrogens

Many chemicals in surface waters and sediments have recently been discovere d to have estrogenic/antiestrogenic activity. Among these compounds, known as 'endocrine disrupters', are natural and synthetic hormones, phytoestroge nes and a variety of industrial chemicals, such as certain detergents and p esticides. These substances are supposed to affect the development and repr oduction in wildlife and humans and may also be involved in the induction o f cancer. In order to assess the estogenic/antiestrogenic potential of pure compounds and complex environmental samples we compared an array of in vit ro test systems, (i) two luciferase reporter gene assays using transgenic h uman MVLN cells (derived from MCF-7 cells) and HGELN cells (derived from He La cells); (ii) a competitive binding assay with recombinant human estrogen receptors (ER) alpha and beta and (iii) a proliferation assay with MCF7-ce lls (E-Screen). The sensitivity of the assays for 17-beta -estiadiol decrea sed in the order: NIVLN-cclis = E-Screen > HGELN-cells > binding to ER-alph a >binding to ER-beta. A good correlation was obtained between the estrogen ic potencies of 11 compounds (17-beta -estradiol (E-2), estrone (E-1), estr iol (E-3), ethinylestradiol (EE2), diethylstilbestrol (DES), coumestrol, be ta -sitosterol, genistein, 4-nonylphenol, 4-octylphenol, bisphenol A) in th e three tissue culture assays. The relative potencies of the compounds obta ined by the cell free binding assays were one to two orders of magnitude hi gher compared with the cell culture assays. The phytoestrogens showed a pre ference to bind to ER-beta, but only genistein showed a much lower activity in the E-Screen (growth induction in breast cancer cells) compared with th e luciferase induction in MVLN and HGELN-cells. (C) 2001 Published by Elsev ier Science Ireland Ltd.