Effects of the Environmental Oestrogens Bisphenol A, Tetrachlorobisphenol A, Tetrabromobisphenol A, 4‐Hydroxybiphenyl and 4,4′‐Dihydroxybiphenyl on Oestrogen Receptor Binding, Cell Proliferation and Regulation of Oestrogen Sensitive Proteins in the Human Breast Cancer Cell Line MCF‐7

Abstract

Bisphenol A is extensively used in the manufacturing of epoxy resins and polycarbonate plastics, whereas several brominated and chlorinated analogues are used as flame retardants and intermediates in the plastic industry. Due to the structural relationship between these chemicals and the high production volumes, we wanted to characterize and compare their potential oestrogen-like potency using several end-points in MCF-7 cells: induction of pS2 protein and progesterone receptor, reduction of oestrogen receptor level, and stimulation of cell growth. Bisphenol A, tetrachloro-and tetrabromobisphenol A, 4-hydroxybiphenyl and 4,4ø-dihydroxybiphenyl all showed oestrogen-like properties in MCF-7 cells. The chemicals tested had affinity to the oestrogen receptor isolated from MCF-7 cells, although their EC 50 s were 1,000 to 80,000 times higher than the EC 50 of 17b-oestradiol. Bisphenol A and 4-hydroxybiphenyl induced cell growth in MCF-7 cells, and the highest test concentrations induced responses, apparently exceeding the cell growth induced by 17b-oestradiol. The other chemicals tested induced less than 50% of the maximum 17b-oestradiol-stimulated cell growth. Bisphenol A, 4-hydroxybiphenyl, tetrabromobisphenol A and tetrachlorobisphenol A all increased the level of the oestrogen-regulated proteins, progesterone receptor and pS2, whereas 4,4ø-dihydroxybiphenyl showed no such effect. Bisphenol A was the only chemical tested that clearly mimicked 17b-oestradiol in its ability to reduce the level of cytosolic oestrogen receptors in MCF-7 cells. By measuring several oestrogen-dependent endpoints it seems that some xeno-oestrogens cause an imbalanced oestrogen-response. Their ability and potency in mimicking 17b-oestrogen in one parameter is not necessarily accompanied by a similar effect in another oestrogen-linked parameter.

Novel roles of prolactin and estrogens in breast cancer: resistance to chemotherapy

“…The low binding affinity of BPA to classical ERs explains its inability to exert a strong mitogenic activity in MCF7 cells. One study found increased cell proliferation in response to BPA only at 60 000 times higher concentrations than E 2 (Olsen et al 2003). Another group confirmed that BPA at a relatively high dose (1 mM) showed a modest stimulation of proliferation of MCF7 cells cultured in estrogen-depleted medium, while E 2 was effective at subnanomolar concentrations (Hess-Wilson et al 2006).…”

Toxicity of tetrabromobisphenol A (TBBPA) in zebrafish (Danio rerio) in a partial life-cycle test

“…Cultured MCF-7 breast cancer cells show a weak estrogenic response to TBBPA (Körner et al 1998;Olsen et al 2003), and TBBPA inhibits in vitro estradiol sulfonation (Hamers et al 2004), indicating potential for both direct and indirect estrogenic activity in vivo. Increased uterus weights in ovariectomized mice exposed to TBBPA for 3 days (20 mg/kg/day, intraperitoneal) confirm estrogenicity in vivo (Kitamura et al 2005a).…”

Xenoestrogens modulate vascular endothelial growth factor secretion in breast cancer cells through an estrogen receptor-dependent mechanism

“…In vitro investigations of the molecular mechanism of xenoestrogen effects have been focused on the proliferation test of ERa-expressing MCF-7 cells, binding assays with ERs (a and b), reporter gene assays using ERE (Soto et al 1995, Kuiper et al 1997, Andersen et al 1999, Legler et al 1999, Balaguer et al 2001, Diel et al 2002, Olsen et al 2003, or a few estrogen target gene promoters (Hall & Korach 2002). Recently, a DNA microarray was also developed to evaluate the estrogenic activity of industrial chemicals (Terasaka et al 2004).…”