Toxicology Letters 129 (2002) 55 – 63 Brominated phenols: characterization of estrogen-like activity in the human breast cancer cell-line MCF-7 Christel M. Olsen *, Elise T.M. Meussen-Elholm, Jørn A. Holme, Jan K. Hongslo Department of Enironmental Medicine, National Institute of Public Health, P.O. Box 4404 Nydalen, 0403 Oslo, Norway Received 11 July 2001; received in revised form 5 November 2001; accepted 7 November 2001 Abstract A large number of halogenated phenols are detected in the blood of humans, fish and wild-animals. We have characterized the estrogen-like activity of phenol, 4-bromophenol (4-BP), 2,4-dibromophenol (2,4-DBP), 2,4,6-tribro- mophenol (2,4,6-TBP) and 4-tert -butylphenol (tert -BP) using the estrogen-dependent human breast cancer cell line MCF-7. 4-BP, 2,4-DBP and 4-tert -BP all bind to the estrogen receptor (ER) with approximately 10 000-fold less affinity than 17-estradiol (17-E). 2,4,6-TBP was only able to displace 43% of radiolabelled estrogen when tested at concentrations up to 1 M, whereas phenol had no affinity for the ER. 4-tert -BP stimulated cell growth and induced estrogen-regulated proteins such as the progesterone receptor (PgR) and pS2. The brominated phenols, however, although binding to the ER, did not stimulate cell growth or increase the levels of the PgR or pS2, or reduce the level of 17-E induced pS2. On the contrary, 4-BP, 2,4-DBP and partly 4-tert -BP reduced 17-E-stimulated cell growth apparently by an ER independent mechanism. © 2002 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Brominated phenols; Xenoestrogen; Estrogen receptor; MCF-7-cells; Progesterone receptor; pS2 www.elsevier.com/locate/toxlet 1. Introduction During the last decade there has been an in- creasing concern about the hormone-like effects of many xenobiotics and naturally occurring sub- stances (Kavlock et al., 1996; Toppari et al., 1996). Several phenolic compounds have been shown to possess estrogen-like properties in ex- perimental systems (Chang and Liao, 1987; Krish- nan et al., 1993; White et al., 1994; Routledge and Sumpter, 1997; Soto et al., 1991, 1995), and to be able to disrupt reproduction in fish (Christiansen et al., 1998; Routledge and Sumpter, 1997; Soto et al., 1991; Sumpter and Jobling, 1995; Jobling et al., 1996). A large number of halogenated phenols are present in both human and salmon blood (Klasson et al., 1997; Asplund et al., 1999). We Abbreiations: 4-BP, 4-bromophenol; CD-FBS, charcoal- dextran treated foetal bovine serum; 2,4-DBP, 2,4-dibro- mophenol; 17-E, 17-estradiol; ER, estrogen receptor-; ERE, estrogen responsive element; PgR, progesterone recep- tor; PE, proliferative effect; RBA, relative binding affinity; RPE, relative proliferative effect; tert -BP, 4-tert -butylphenol; 2,4,6-TBP, 2,4,6-tribromophenol. * Corresponding author. Tel.: +47-22-04-2536; fax: +47- 22-35-3605. E-mail address: christel.olsen@folkehelsa.no (C.M. Olsen). 0378-4274/02/$ - see front matter © 2002 Elsevier Science Ireland Ltd. All rights reserved. PII:S0378-4274(01)00469-6