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Wednesday, January 8, 1997, 12:00 a.m. EDT
NIEHS Finds Trio of Tests Can Quickly Screen for Estrogen-Like Activity in Environmental Chemicals
With scientists speculating that estrogen-like chemicals in the environment could cause breast cancer, impotence and infertility, there's been a need for better ways to screen chemicals and profile their estrogenic activity quickly, at a reasonable cost.
Scientists at the National Institute of Environmental Health Sciences today reported they've found that a set of three existing tests used in combination provides a rapid assessment of potential estrogenicity. Screening with all three tests, run at the same time, could be completed in six weeks or less.
One test determines, in a cell-free laboratory test, if a chemical can bind to an estrogen receptor site; another is conducted in a cell line to detect activation of estrogen responsive genes, and a third uses a standard strain of lab mouse, CD-1, to determine the effects on estrogen-responsive tissue in a whole animal.
The combination of assays was used to screen ten chemicals with known or suspected estrogenic activity: 17beta-estradiol, diethylstilbestrol (DES), tamoxifen, 4-hydroxytamoxifen, methoxychlor, the methoxychlor metabolite HPTE, endosulfan, nonylphenol, o,p-DDT, and kepone.
The results came out "right." That is, according to Michael D. Shelby, Ph.D., acting chief of the NIEHS Laboratory of Toxicology in the Environmental Toxicology Program, "The results were consistent with what is known about the estrogenic activities of the chemicals studied."
The trio of assays also provided this informative profile of estrogenic activity, Dr. Shelby said, "at a reasonable cost."
The research is described today in the NIEHS scientific journal Environmental Health Perspectives. NIEHS is one of the National Institutes of Health. It is located off NIH's Bethesda (Md.) campus in Research Triangle Park, NC, and the National Toxicology Program is headquartered at the Institute in RTP as well.
Shelby's coauthors on the article were Retha R. Newbold; Douglas B. Tully, Ph.D.; Kun Chae, Ph.D.; and Vicki L. Davis, Ph.D. Partial financial support for the study came from the Agency for Toxic Substances and Disease Registry, a federal agency in Atlanta, Ga.Many man-made and naturally occurring chemicals are suspected environmental hormones, but predicting which chemicals have this property has been difficult because of the diversity of their molecular structures.
Studies began appearing in the 1950s showing reproductive risks to birds from residues of DDT, but the human health effects of only a few chemicals, such as kepone, are well defined.
The trio of scientifically sound screening tests should help detect chemicals needing further study.
While there is concern about chemicals that might disrupt any of the major endocrine systems-which include the pituitary, parathyroids, thyroid, adrenals, pancreas-most of the focus has been on whether the ovaries and testes are affected by chemicals that mimic the female hormone estrogen, which prepares the female body for pregnancy, childbirth and motherhood, and produces secondary sexual characteristics such as menstruation and breast development.
After being used for two decades in attempts to prevent miscarriages, a potent synthetic estrogen, DES, was banned in 1971 after being linked to a rare vaginal cancer in the daughters of the women for whom it had been prescribed.
Experimental Support for Link to 'Gator Abnormalities: Two Pesticides in Spill Shown to Block Natural Hormones
A new study links residual DDT and another pesticide, dicofol, to the declining populations of alligators in Florida's Lake Apopka, near Orlando, and to the males' abnormal testes and small penises and the female alligators' reproductive tract abnormalities.
Both pesticides have been speculated as possible causes. They were among the chemicals in a major spill in the lake in 1980. The new research shows how the two pesticides could interfere with the action of natural hormones on animal cells.
The research, published today in Environmental Health Perspectives, the journal of the National Institute of the Environmental Health Sciences, was conducted by scientists Peter M. Vonier, D. Andrew Crain, John A. McLachlan, Louis J. Guillette Jr., and Steven F. Arnold at the Tulane-Xavier Center for Bioenvironmental Research in New Orleans.
They tested a series of synthetic chemicals in the laboratory to see to what degree they block the alligators' sex hormones, estrogen and progesterone.
Hormones in animals, including humans, act by attaching to specialized molecules in the cell called receptors. These then relay the hormone "messages" to the cell. If a synthetic or other natural chemical mimics the attachment of the hormones, it can block or modify these messages-and normal development and reproduction may be thwarted. In the study, DDT (which was banned from most U.S. uses in 1972) and similar chemicals produced from it by the body, as well as dicofol (used to kill mites) and other chemicals and combinations of chemicals showed binding to the hormone receptor sites.
The researchers believe the study provides further support for a role for these pesticides in the alligators' reproductive problems.
The research was supported by an Environmental Protection Agency cooperative agreement, a W. Alton Jones Foundation grant, the Department of Zoology at the University of Florida, and the Tulane-Xavier Center for Bioenvironmental Research.