Ana M. Soto, Mariana F. Fernandez, Maria F. Luizzi, Anita S. Oles Karasko, and Carlos Sonnenschein
Tufts University School of Medicine, Department of Anatomy
and Cellular Biology, Boston, Massachusetts
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." -- Environ Health Perspect 105(Suppl 3):647-654 (1997)
Key words: xenoestrogens, estradiol equivalents, environmental exposure, p,p'-DDE, DDD, BBP, BPA, PCBs
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 6 June 1996; manuscript accepted 8 August 1996.
This work was partially supported by grants from the W. Alton Jones Foundation, U.S. Environmental Protection Agency (CR 820301), National Institutes of Health (CA-13410), National Science Foundation (DCB-9105594), the Silent Spring Institute, and the Massachusetts Department of Public Health (DPH 79005-214 H11). The assistance of The Center for Reproductive Research at Tufts University (P30 HD 28897) is gratefully acknowledged. We are also grateful to C. Michaelson for her skillful technical assistance.
Address correspondence to Dr. A.M. Soto, Tufts University School of Medicine, Department of Anatomy and Cellular Biology, Center for Reproductive Research, 136 Harrison Avenue, Boston, MA. Telephone: (617) 636-6954. Fax: (617) 636-6536. E-mail:asoto@opal.tufts.edu
Abbreviations used: BBP, benzylbutylphthalate; BPA, bisphenol-A; CD, charcoal-dextran; CDHuS, CD human serum in phenol red-free DMEM; DDD, dichlorodiphenyldichloroethane; DDE, dichlorodiphenyltrichloroethylene; DDT, dichlorodiphenyltrichloroethane; DES, diethylstilbestrol; DMEM, Dulbecco's modified Eagle's medium; DMSO, dimethyl sulfoxide; E2, 17ß-estradiol; EEqs, estradiol equivalents; HCB, hexachlorobiphenyl; HPLC, high-performance liquid chromatography; Pa, pascals; PCBs, polychlorinated biphenyls; PgR, progesterone receptor; RPE, relative proliferative effect; SHBG, sex hormone-binding globulin; tD, doubling time.
Last Update: April 10, 1997