| The Estrogenicity of Bisphenol A-related Diphenylalkanes with Various Substituents at the Central Carbon and the Hydroxy Groups Pilar Perez,
1
Rosa Pulgar,
2
Fátima Olea-Serrano,
2
Mercedes Villalobos,
1
Ana Rivas,
1
Manfred Metzler,
3
Vicente Pedraza,
1
and Nicolás Olea
1
1
Laboratory of Medical Investigation, Department of Radiology, School of Medicine, HUSC-University of Granada, Granada, Spain
2
Department of Nutrition and Bromatology, School of Pharmacy, University of Granada, Granada, Spain
3
Department of Food Chemistry, University of Karlsruhe, Karlsruhe, Germany Abstract
The chemical structure of hydroxylated diphenylalkanes or bisphenols consists of two phenolic rings joined together through a bridging carbon. This class of endocrine disruptors that mimic estrogens is widely used in industry, particularly in plastics. Bisphenol F, bisphenol A, fluorine-containing bisphenol A (bisphenol AF) , and other diphenylalkanes were found to be estrogenic in a bioassay with MCF7 human breast cancer cells in culture (E-SCREEN assay) . Bisphenols promoted cell proliferation and increased the synthesis and secretion of cell type-specific proteins. When ranked by proliferative potency, the longer the alkyl substituent at the bridging carbon, the lower the concentration needed for maximal cell yield ; the most active compound contained two propyl chains at the bridging carbon. Bisphenols with two hydroxyl groups in the para position and an angular configuration are suitable for appropriate hydrogen bonding to the acceptor site of the estrogen receptor. Our data suggest that estrogenicity is influenced not only by the length of the substituents at the bridging carbon but also by their nature. Because diphenylalkane derivatives are widespread and their production and use are increasing, potential exposure of humans to estrogenic bisphenols is becoming a significant issue. The hazardous effects of inadvertent exposure to bisphenol-releasing chemicals in professional workers and the general populations therefore deserve investigation. Key words : bisphenol A, bisphenol F, endocrine-disrupting chemicals, hydroxylated diphenylalkanes, MCF7 breast cancer cells, xenoestrogens. Environ Health Perspect 106:167-174 (1998) . [Online 5 February 1998] http://ehpnet1.niehs.nih.gov/docs/1998/106p167-174perez/ abstract.html Address correspondence to N. Olea, Department of Radiology, University of Granada, 18071-Granada, Spain. The authors are grateful to Ana M. Soto and Carlos Sonnenschein of Tufts University for fruitful discussion and their critical review of the manuscript. The assistance of José Molina of the Organic Chemistry Department, University of Granada, is acknowledged. We thank Karen Shashok for editorial assistance. This research was supported by grants from the Spanish Ministry of Health (FIS, 95/1959) and the Andalusian Regional Government Department of Health (Consejería de Salud, 96/159) . This work was reported in part at the meeting Estrogens in the Environment IV: Linking Fundamental Knowledge, Risk Assessment, and Public Policy held in Washington, DC, 19-21 July 1997. Received 31 July 1997 ; accepted 3 November 1997.
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