DDT Appears to Activate Human Estrogen Receptors

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Oncology NEWS InternationalOncology NEWS International Vol 6 No 6
Volume 6
Issue 6

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.

SAN DIEGO--Reports from the American Association for Cancer Researchannual meeting have moved researchers closer to answering the questionof whether DDT and its metabolites act as a risk factor for breast cancerby mimicking endogenous estrogen.

Even though DDT was outlawed in the 1970s, the pesticide, which hasa half life of 150 years, is still present in the environment and the foodchain, and tends to concentrate in the adipose tissue in the breasts andother organs.

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

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

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

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

"Our data suggest the metabolites that activate the human estrogenreceptor 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 mechanismof action of putative environmental estrogens.

Role in Breast Cancer Progression

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

The only evidence comes from epidemiologic studies showing an associationbetween an individual's total cumulative exposure to estrogen and breastcancer and from the observation of increased estrogen receptor expressionin breast tumors.

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

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

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

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

"We found that in both precancerous and cancerous human breastcell lines, both estradiol and the pesticides activated estrogen-mediatedresponses via estrogen receptors," she said. "This is an importantfinding because environmental estrogens such as DDT may still pose a threatto humans even though their use has been banned for many years."

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