The effect of pre-pubertal exposure of
Benzyl Butyl Phthalate (BBP) on the rat mammary gland.
Emily Lopes*; Julia S. Pereira; Ricardo Lopez; Fathima Sheriff;
Kara Snider and Jose Russo.
Breast Cancer Research Laboratory, Fox Chase
Cancer Center, Philadelphia, PA, 19111, USA.
Benzyl Butyl Phthalate (BBP) is an identified
carcinogen that has been linked to breast cancer through
studies conducted on Sprague Dawley rats. BBP is a commonly
used plasticizer found in toys, PVC, cosmetics, and carpeting.
This phthalate is absorbed into the body through inhalation,
dermal and oral exposure and accumulates in the fatty tissues
of the body. BBP can also be passed from mother to offspring
through the placenta and during lactation. BBP is capable
of binding to estrogen hormone receptors. The purpose of
this study was to examine the effects of BBP on the mammary
glands of Sprague Dawley rats. The animals were exposed
to BBP through mother’s lactation at a concentration
of 500µg/kg of body weight or equivalent volume of
sesame oil (control group). At 50 days of age the animals
were sacrificed and the mammary gland submitted to morphological
study through whole mount preparation. The number of terminal
end buds (TEBs) was counted in the abdominal mammary glands
for both groups (exposed to BBP and control). The effects
of the BBP were further analyzed by using cDNA-microarrays
to compare the gene expression profile between the experimental
and the control rats. There were not morphological differences
between the control and experimental group. However, there
were 80 genes significantly different in the mammary gland
of BBP exposed animals compared with the matching control.
The genes differentially expressed are involved in controlling
the circadian rhythm such as Dopa decarboxylase (Ddc), organ
development, androgen and estrogen receptors and apoptosis.
These genes potentially play a role in the development of
cancer cells. In conclusion, pre-pubertal exposure to BBP
did not alter the mammary gland structure, but it modifies
their genomic profile (*Emily Lopes was supported by the
Huntington Breast Cancer Action Coalition through the Students
and Scientist Environmental Research Scholarship Program.
This work was supported by NCI and NIEHS Grant UO1 ES012771)
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