Skip to main content
Environmental Health Perspectives logoLink to Environmental Health Perspectives
. 1997 Apr;105(Suppl 3):647–654. doi: 10.1289/ehp.97105s3647

Developing a marker of exposure to xenoestrogen mixtures in human serum.

A M Soto 1, M F Fernandez 1, M F Luizzi 1, A S Oles Karasko 1, C Sonnenschein 1
PMCID: PMC1469891  PMID: 9168009

Abstract

It has been hypothesized that environmental estrogens may play a role in the increasing incidence of breast cancer, testicular cancer, and other problems of the reproductive system. While a single causal agent can be identified in cases in which humans have had occupational exposures, wildlife showing signs of reproductive damage have usually been exposed to a combination of endocrine disruptors that may act cumulatively. The development of appropriate biomarkers of cumulative exposure, and their measurement at developmental points where exposure is critical, are required to test the environmental estrogen hypothesis. Measuring levels of each of the xenoestrogens in blood is a better approximation of real exposure at the target organ level than inferring cumulative exposure by estimating from mass balance of dietary levels. However, the cumulative estrogenicity of mixtures cannot be directly concluded from individual xenoestrogen plasma levels. Two approaches may be used to assess total load: a) the development of methods to study mixtures of these xenoestrogens, to quantify their cumulative effects, and to begin to understand their interactions (i.e., additivity, synergy, antagonism, or independent action), so that plasma concentrations may be translated into units of activity such as "estradiol equivalents"; and b) the development of methods to separate xenoestrogens from ovarian estrogens in blood and to directly measure the estrogenic activity of the xenoestrogen extract using a bioassay. The cumulative activity may be used as a marker of exposure to xenoestrogens. This article reports the development of a method to extract and separate xenoestrogens from ovarian estrogens using human serum as a source, followed by using a bioassay for determination of the cumulative xenoestrogen load as "estradiol equivalents."

Full text

PDF
647

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Burse V. W., Head S. L., Korver M. P., McClure P. C., Donahue J. F., Needham L. L. Determination of selected organochlorine pesticides and polychlorinated biphenyls in human serum. J Anal Toxicol. 1990 May-Jun;14(3):137–142. doi: 10.1093/jat/14.3.137. [DOI] [PubMed] [Google Scholar]
  2. Davis D. L., Bradlow H. L., Wolff M., Woodruff T., Hoel D. G., Anton-Culver H. Medical hypothesis: xenoestrogens as preventable causes of breast cancer. Environ Health Perspect. 1993 Oct;101(5):372–377. doi: 10.1289/ehp.93101372. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Dewailly E., Dodin S., Verreault R., Ayotte P., Sauvé L., Morin J., Brisson J. High organochlorine body burden in women with estrogen receptor-positive breast cancer. J Natl Cancer Inst. 1994 Feb 2;86(3):232–234. doi: 10.1093/jnci/86.3.232. [DOI] [PubMed] [Google Scholar]
  4. Giwercman A., Carlsen E., Keiding N., Skakkebaek N. E. Evidence for increasing incidence of abnormalities of the human testis: a review. Environ Health Perspect. 1993 Jul;101 (Suppl 2):65–71. doi: 10.1289/ehp.93101s265. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Grossman J. What's hiding under the sink: dangers of household pesticides. Environ Health Perspect. 1995 Jun;103(6):550–554. doi: 10.1289/ehp.95103550. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Guillette L. J., Jr, Gross T. S., Masson G. R., Matter J. M., Percival H. F., Woodward A. R. Developmental abnormalities of the gonad and abnormal sex hormone concentrations in juvenile alligators from contaminated and control lakes in Florida. Environ Health Perspect. 1994 Aug;102(8):680–688. doi: 10.1289/ehp.94102680. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Katzenellenbogen B. S., Kendra K. L., Norman M. J., Berthois Y. Proliferation, hormonal responsiveness, and estrogen receptor content of MCF-7 human breast cancer cells grown in the short-term and long-term absence of estrogens. Cancer Res. 1987 Aug 15;47(16):4355–4360. [PubMed] [Google Scholar]
  8. Kelsey J. L., Berkowitz G. S. Breast cancer epidemiology. Cancer Res. 1988 Oct 15;48(20):5615–5623. [PubMed] [Google Scholar]
  9. Krieger N., Wolff M. S., Hiatt R. A., Rivera M., Vogelman J., Orentreich N. Breast cancer and serum organochlorines: a prospective study among white, black, and Asian women. J Natl Cancer Inst. 1994 Apr 20;86(8):589–599. doi: 10.1093/jnci/86.8.589. [DOI] [PubMed] [Google Scholar]
  10. Krishnan A. V., Stathis P., Permuth S. F., Tokes L., Feldman D. Bisphenol-A: an estrogenic substance is released from polycarbonate flasks during autoclaving. Endocrinology. 1993 Jun;132(6):2279–2286. doi: 10.1210/endo.132.6.8504731. [DOI] [PubMed] [Google Scholar]
  11. Medina M. B., Sherman J. T. High performance liquid chromatographic separation of anabolic oestrogens and ultraviolet detection of 17 beta-oestradiol, zeranol, diethylstilboestrol or zearalenone in avian muscle tissue extracts. Food Addit Contam. 1986 Jul-Sep;3(3):263–272. doi: 10.1080/02652038609373590. [DOI] [PubMed] [Google Scholar]
  12. Reiner G. C., Katzenellenbogen B. S. Characterization of estrogen and progesterone receptors and the dissociated regulation of growth and progesterone receptor stimulation by estrogen in MDA-MB-134 human breast cancer cells. Cancer Res. 1986 Mar;46(3):1124–1131. [PubMed] [Google Scholar]
  13. Safe S. H. Environmental and dietary estrogens and human health: is there a problem? Environ Health Perspect. 1995 Apr;103(4):346–351. doi: 10.1289/ehp.95103346. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Sharpe R. M., Skakkebaek N. E. Are oestrogens involved in falling sperm counts and disorders of the male reproductive tract? Lancet. 1993 May 29;341(8857):1392–1395. doi: 10.1016/0140-6736(93)90953-e. [DOI] [PubMed] [Google Scholar]
  15. Shutt D. A. The effects of plant oestrogens on animal reproduction. Endeavour. 1976 Sep;35(126):110–113. doi: 10.1016/0160-9327(76)90004-1. [DOI] [PubMed] [Google Scholar]
  16. Sonnenschein C., Soto A. M., Fernandez M. F., Olea N., Olea-Serrano M. F., Ruiz-Lopez M. D. Development of a marker of estrogenic exposure in human serum. Clin Chem. 1995 Dec;41(12 Pt 2):1888–1895. [PubMed] [Google Scholar]
  17. Soto A. M., Chung K. L., Sonnenschein C. The pesticides endosulfan, toxaphene, and dieldrin have estrogenic effects on human estrogen-sensitive cells. Environ Health Perspect. 1994 Apr;102(4):380–383. doi: 10.1289/ehp.94102380. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Soto A. M., Justicia H., Wray J. W., Sonnenschein C. p-Nonyl-phenol: an estrogenic xenobiotic released from "modified" polystyrene. Environ Health Perspect. 1991 May;92:167–173. doi: 10.1289/ehp.9192167. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Soto A. M., Silvia R. M., Sonnenschein C. A plasma-borne specific inhibitor of the proliferation of human estrogen-sensitive breast tumor cells (estrocolyone-I). J Steroid Biochem Mol Biol. 1992 Dec;43(7):703–712. doi: 10.1016/0960-0760(92)90296-u. [DOI] [PubMed] [Google Scholar]
  20. Soto A. M., Sonnenschein C. Cell proliferation of estrogen-sensitive cells: the case for negative control. Endocr Rev. 1987 Feb;8(1):44–52. doi: 10.1210/edrv-8-1-44. [DOI] [PubMed] [Google Scholar]
  21. Soto A. M., Sonnenschein C., Chung K. L., Fernandez M. F., Olea N., Serrano F. O. The E-SCREEN assay as a tool to identify estrogens: an update on estrogenic environmental pollutants. Environ Health Perspect. 1995 Oct;103 (Suppl 7):113–122. doi: 10.1289/ehp.95103s7113. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Soto A. M., Sonnenschein C. Mechanism of estrogen action on cellular proliferation: evidence for indirect and negative control on cloned breast tumor cells. Biochem Biophys Res Commun. 1984 Aug 16;122(3):1097–1103. doi: 10.1016/0006-291x(84)91204-x. [DOI] [PubMed] [Google Scholar]
  23. Soto A. M., Sonnenschein C. The role of estrogens on the proliferation of human breast tumor cells (MCF-7). J Steroid Biochem. 1985 Jul;23(1):87–94. doi: 10.1016/0022-4731(85)90265-1. [DOI] [PubMed] [Google Scholar]
  24. Toniolo P. G., Levitz M., Zeleniuch-Jacquotte A., Banerjee S., Koenig K. L., Shore R. E., Strax P., Pasternack B. S. A prospective study of endogenous estrogens and breast cancer in postmenopausal women. J Natl Cancer Inst. 1995 Feb 1;87(3):190–197. doi: 10.1093/jnci/87.3.190. [DOI] [PubMed] [Google Scholar]
  25. Wolff M. S., Toniolo P. G. Environmental organochlorine exposure as a potential etiologic factor in breast cancer. Environ Health Perspect. 1995 Oct;103 (Suppl 7):141–145. doi: 10.1289/ehp.95103s7141. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Wolff M. S., Toniolo P. G., Lee E. W., Rivera M., Dubin N. Blood levels of organochlorine residues and risk of breast cancer. J Natl Cancer Inst. 1993 Apr 21;85(8):648–652. doi: 10.1093/jnci/85.8.648. [DOI] [PubMed] [Google Scholar]
  27. Yu M. L., Hsu C. C., Guo Y. L., Lai T. J., Chen S. J., Luo J. M. Disordered behavior in the early-born Taiwan Yucheng children. Chemosphere. 1994 Nov-Dec;29(9-11):2413–2422. doi: 10.1016/0045-6535(94)90410-3. [DOI] [PubMed] [Google Scholar]
  28. Zysk J. R., Johnson B., Ozenberger B. A., Bingham B., Gorski J. Selective uptake of estrogenic compounds by Saccharomyces cerevisiae: a mechanism for antiestrogen resistance in yeast expressing the mammalian estrogen receptor. Endocrinology. 1995 Mar;136(3):1323–1326. doi: 10.1210/endo.136.3.7867588. [DOI] [PubMed] [Google Scholar]

Articles from Environmental Health Perspectives are provided here courtesy of National Institute of Environmental Health Sciences

RESOURCES