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DDT Appears to Activate Human Estrogen Receptors

DDT Appears to Activate Human Estrogen Receptors

SAN DIEGO--Reports from the American Association for Cancer Research annual meeting have moved researchers closer to answering the question of whether DDT and its metabolites act as a risk factor for breast cancer by mimicking endogenous estrogen.

Even though DDT was outlawed in the 1970s, the pesticide, which has a half life of 150 years, is still present in the environment and the food chain, and tends to concentrate in the adipose tissue in the breasts and other organs.

A study from the University of Rochester School of Medicine and Dentistry found that DDT compounds could possibly be a more potent risk factor for breast cancer than scientists had previously thought.

Using a recombinant human estrogen receptor in radiolabeled ligand-binding assays, the Rochester scientists found that many DDT metabolites have a significantly higher affinity to human estrogen receptors than to rat estrogen receptors.

"This suggests that humans may be more susceptible to DDT metabolites than other species," said investigator Clarice W. Chen, MS. Both DDT isomers bind to the human estrogen receptor, she pointed out, while only one binds with measurable affinity to the rat estrogen receptor.

At concentrations found in human tissues, DDT compounds and some of their metabolites appear to activate the human estrogen receptor, Ms. Chen said. This potentially could lead to increased expression of estrogen-responsive genes that may be involved in cell proliferation and malignancy.

"Our data suggest the metabolites that activate the human estrogen receptor do so with approximately the same potency as the parent compounds, and this activation is additive to that of another DDT compound or estradiol," Ms. Chen said. She urged researchers to focus more attention on the mechanism of action of putative environmental estrogens.

Role in Breast Cancer Progression

To date, there is no conclusive proof that endogenous estrogens such as estradiol cause breast cancer, said Malathy Shekhar, PhD, of the Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit.

The only evidence comes from epidemiologic studies showing an association between an individual's total cumulative exposure to estrogen and breast cancer and from the observation of increased estrogen receptor expression in breast tumors.

In an attempt to provide stronger evidence for this association, Dr. Shekhar and her colleagues examined the effects of estradiol and five closely related organochlorine pesticides, including two DDT isomers, on cell growth in two estrogen-receptor-positive human breast epithelial cell lines.

The cells studied were the preneoplas-tic MCF10AneoT cells and the MCF-7 breast cancer cells.

They found that, administered individually, pesticides caused the human breast epithelial cells to proliferate, but only when given at levels 100- to 1,000-fold higher than estradiol. However, when the two DDT isomers were given in combination, they triggered cell proliferation similar to that detected with physiological concentrations of estradiol.

This led Dr. Shekhar to suggest that some pesticides, especially in combination, may be involved in breast cancer progression.

"We found that in both precancerous and cancerous human breast cell lines, both estradiol and the pesticides activated estrogen-mediated responses via estrogen receptors," she said. "This is an important finding because environmental estrogens such as DDT may still pose a threat to humans even though their use has been banned for many years."

 
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