David T. Zava,1,2 Marilyn Blen,1 and Gail Duwe1
1Aeron Biotechnology, San Leandro, California; 2Cancer Research Division, California Public Health Foundation, Berkeley, California
We investigated the estrogenic activity of various environmental pollutants (xenobiotics), in particular the xenoestrogen o,p-DDT, and compared their effects with those of endogenous estrogens, phytoestrogens, and mycoestrogens on estrogen receptor binding capacity, induction of estrogen end products, and activation of cell proliferation in estrogen-sensitive human breast cancer cells in monolayer culture. We also quantified the levels of phytoestrogens in extracts of some common foods, herbs, and spices and in human saliva following consumption of a high phytoestrogen food source (soy milk) to compare phytoestrogen abundance and bioavailability relative to the reported xenoestrogen burden in humans. Results show that natural endogenous estrogens, phytoestrogens, mycoestrogens, and xenoestrogens bind estrogen receptor (ER) in intact cells, but demonstrate marked differences in their ability to induce end products of estrogen action and to regulate cell proliferation. All of the different classes of estrogens stimulated cell proliferation at concentrations that half-saturated ER, but only some classes were able to induce estrogen-regulated end products. Genistein, a common phytoestrogen found in soy foods, differed from the xenoestrogen DDT in its effects on cell proliferation and ability to induce estrogen-regulated end products. Moreover, we found that many of the foods, herbs, and spices commonly consumed by humans contain significant amounts of phytoestrogens, and consumption of soy milk, a phytoestrogen-rich food, markedly increases the levels of phytoestrogens in saliva. In conclusion, our in vitro results predict that a diet high in phytoestrogens would significantly reduce the binding of weak xenoestrogens to ER in target tissues in vivo. -- Environ Health Perspect 105(Suppl 3):637-645 (1997)
Key words: xenoestrogens, phytoestrogens, endogenous estrogens, synthetic estrogens, breast cancer, reproduction
This paper was presented in part at the Workshop on Hormones, Hormone Metabolism, Environment, and Breast Cancer held 28-29 September 1995 in New Orleans, Louisiana. Manuscript received at EHP 18 June 1996; manuscript accepted 15 November 1996.
We thank A. Hackett and C. Dollbaum for critical review of the manuscript. The technical work of L. Mendelson is greatly appreciated. This work was supported by SBIR Phase II grant 2R44 HD27738-02.
Address correspondence to Dr. D.T. Zava, Aeron Biotechnology, Inc., 1933 Davis Street, Suite 310, San Leandro, CA 94577. Telephone: (510) 729-0375. Fax: (510) 729-0383. E-mail:aeron@aeron.com
Abbreviations used: ß-BHC, ß-hexachlorocyclohexane; BPBS, 0.1% bovine serum albumin in PBS; BSA, bovine serum albumin; CT-FRI, charcoal-treated fetal bovine serum (FBS) in RPMI media with insulin; dH2O, deionized water; ER, estrogen receptor; ERBA, estrogen receptor binding assay; HCB, hexachlorobenzene; HMEC, normal human mammary epithelial cells; OC, oxychlordane; PBS, phosphate-buffered saline; PCB-126, pentachlorobiphenyl; PCB-153, hexachlorobiphenyl; PR, progesterone receptor; TBPS, 0.1% Tween-20 in PBS; TCDD, 2,3,7,8-tetrachlorodibenzo-p-dioxin.
Last Update: April 10, 1997