Evaluation of a Recombinant Yeast Cell Estrogen Screening Assay

Nick G. Coldham,¹ Mehul Dave,¹ Susila Sivapathasundaram,¹ Donald P. McDonnell,² Caroline Connor,² Maurice J. Sauer¹

¹BPP (Biochemistry Department), Veterinary Laboratories Agency, New Haw, Addlestone, Surrey, United Kingdom
²Department of Pharmacology, Duke University Medical Center, Durham, North Carolina 27710 USA

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Abstract
A wide range of chemicals with diverse structures derived from plant and environmental origins are reported to have hormonal activity. The potential for appreciable exposure of humans to such substances prompts the need to develop sensitive screening methods to quantitate and evaluate the risk to the public. Yeast cells transformed with plasmids encoding the human estrogen receptor and an estrogen responsive promoter linked to a reporter gene were evaluated for screening compounds for estrogenic activity. Relative sensitivity to estrogens was evaluated by reference to 17ß-estradiol (E₂) calibration curves derived using the recombinant yeast cells, MCF-7 human breast cancer cells, and a prepubertal mouse uterotrophic bioassay. The recombinant yeast cell bioassay (RCBA) was approximately two and five orders of magnitude more sensitive to E₂ than MCF-7 cells and the uterotrophic assay, respectively. The estrogenic potency of 53 chemicals, including steroid hormones, synthetic estrogens, environmental pollutants, and phytoestrogens, was measured using the RCBA. Potency values produced with the RCBA relative to E₂ (100) included estrone (9.6), diethylstilbestrol (74.3), tamoxifen (0.0047), -zearalanol (1.3), equol (0.085), 4-nonylphenol (0.005), and butylbenzyl phthalate (0.0004), which were similar to literature values but generally higher than those produced by the uterotrophic assay. Exquisite sensitivity, absence of test compound biotransformation, ease of use, and the possibility of measuring antiestrogenic activity are important attributes that argue for the suitability of the RCBA in screening for potential xenoestrogens to evaluate risk to humans, wildlife, and the environment. Key words: antiestrogens, environmental contaminants, estrogen, metabolism, phytoestrogens, potency, receptor, recombinant yeast cell bioassay, uterotrophic. Environ Health Perspect 105: 734-742(1997)

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Address correspondence to M.J. Sauer, BPP (Biochemistry Department), Veterinary Laboratories Agency, New Haw, Addlestone, Surrey KT15 3NB United Kingdom.

Work at the Veterinary Laboratories Agency was supported by the Ministry of Agriculture, Fisheries and Food, U.K and at Duke University Medical Center by NIH grant DK 48807.

Received 3 March 1997; accepted 6 March 1997.

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Last Update: July 23, 1997