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
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
"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."