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Impact of Endocrine Disruptors on the Mammary
Gland Development
Common, Estrogen-Mimicking Chemicals Found in Plastics Affect
Genomic Composition of Rat Mammary Gland Tissue
Compounds such as bisphenol A (BPA) and butyl benzyl phthalate
(BBP) that have xenoestrogenic effect are found in the plastic
packaging used for most foods, in dental sealants, in products
like compact discs, and in many cosmetics.
As part of studies funded by the NIEHS, Jose Russo, M.D., F.A.C.P.,
of the Fox Chase Cancer Center and Coral Lamartiniere, Ph.D, of
the University of Alabama at Birmingham, investigated these two
compounds to determine their influence on mammary gland development
in an experimental system. Dr. Russo presented the results of
research into the two compounds at the 2005 conference on “Emerging
Topics in Breast Cancer and the Environment Research.”
Russo and Lamartiniere tested the effects of BPA and BBP on mammary
gland development in laboratory rats by exposing pre-pubertal animals
through their mothers’ milk. The results were striking.
By the time the rats had attained puberty at the age of 21 days,
the genetic signatures—the patterns of active and inactive
genes—in their mammary glands had changed, Dr. Russo said.
The genetic signature is a snapshot of those genes that are upregulated,
or turned on, and those that are downregulated, or switched off
and inactive. Researchers seek genetic signatures for a variety
of disease entities, including cancer, to better understand the
mechanisms of disease progression and genetic susceptibility. “Among
the BPA-treated rats, the mammary glands at 21 days showed upregulated
genes related to proliferation and differentiation, whereas at 50
days, the upregulated genes were involved in metabolism, signal
transduction and immune surveillance,” he said. In other words,
from the ages of 21–100 days, the activity of these genes
changed, especially in areas that may promote or regulate growth
and differentiation.
The 21-day picture of BBP-treated rats also showed an upregulation
of genes involved in proliferation, differentiation and cell adhesion
(the ability of cells to stick together), but also in tumor suppression,
he said.
Besides these differences in upregulated genes, the research group
also identified one gene that was downregulated in both the BPA-
and BBP-treated rats, regardless of their age. It was a gene called
GAD1 that ultimately produces an enzyme known as glutamate decarboxylase
1. This enzyme is important for another compound, known as a neurotransmitter,
which helps nerves communicate with one another. Research has shown
that the GAD1 gene is often overexpressed, or much more active,
in primary breast cancer, and that it could play a part in tumor
development.
The research clearly shows that BPA and BBP are having an impact
on the genomic composition of the mammary gland, Dr. Russo said.
He added that the critical question surrounds the significance of
these changes in relation to the susceptibility or refractoriness
of this organ to carcinogenesis. Studies are in progress in Dr.
Lamartiniere’s laboratory to test this issue.
Dr. Russo is a senior member of the Fox Chase Cancer Center,
where he serves as director of the Breast Cancer Research Laboratory,
and the Breast Cancer and the Environment Research Center. Details
of his research appear in The Proceeding of the American Association
for Cancer Research 2005.
© 2006 BCERC. All Rights Reserved BCERC Coordinating Center,
UCSF
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