It is our goal to develop genomic and proteomic technologies for identification of biomarkers of exposure in girls and rats exposed to bisphenol A (BPA), butyl benzyl phthalate (BBP), di-2-ethylhexyl phthalate (DEHP) and genistein that are measurable in the population.
Our specific aims are: 1) to use microarray technology to measure genomic biomarkers of exposure from blood serum and buffy coat, and buccal swabs from (pre)pubertal girls and rats exposed to these chemicals;2) to develop sensitive and reproducible methods (2D-PAGE and mass spectrometry) to measure protein biomarkers of exposure in blood plasma of (pre)pubertal girls and rats that are expressing high and low levels of these chemicals. An important aspect of this application is not only in the development of new, and use of present state of the art technology for identification of biomarkers of biological responses, but in the experimental design of using a rat model of exposure and a human cohort in similar biological conditions (puberty), also exposed to the same compounds. This unique experimental design will compare the genomic and proteomic changes in a target organ, in this case the rat mammary gland with the presence of peripheral changes in the animals. Whereas in humans we can not detect the changes in the target tissue, the experimented data will give us unbiased information on the target tissue and the peripheral tissue/body fluids that will be important to bioinformatically correlate with the human data. These studies can have a double relevance by first customizing biomarkers identified in a custom array for genes and proteins and second by providing the basis for future assessing these changes for evaluating risk in a larger population. This body of work will be possible because we are utilizing already procured samples from (pre)pubescent girls identified to have high chemical exposures and will have circulating hormone concentrations as indicators of puberty and exposure. From girls (and rats) going through puberty whose urine identifies them as being exposed to high or low concentrations of specific environmental chemicals, we will measure differentially regulated genes and proteins from the blood as biological indicators of chemical exposure. In the rats, we will also measure genes and proteins in the mammary glands as a function of exposure and puberty to gain insight into how environmental chemical exposure early in life predisposes for breast cancer later in life.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01ES016003-04
Application #
7849080
Study Section
Special Emphasis Panel (ZES1-LKB-E (BR))
Program Officer
Shaughnessy, Daniel
Project Start
2007-08-15
Project End
2013-05-31
Budget Start
2010-06-01
Budget End
2013-05-31
Support Year
4
Fiscal Year
2010
Total Cost
$471,237
Indirect Cost
Name
University of Alabama Birmingham
Department
Pharmacology
Type
Schools of Medicine
DUNS #
063690705
City
Birmingham
State
AL
Country
United States
Zip Code
35294
Betancourt, Angela; Mobley, James A; Wang, Jun et al. (2014) Alterations in the rat serum proteome induced by prepubertal exposure to bisphenol a and genistein. J Proteome Res 13:1502-14
Betancourt, Angela M; Wang, Jun; Jenkins, Sarah et al. (2012) Altered carcinogenesis and proteome in mammary glands of rats after prepubertal exposures to the hormonally active chemicals bisphenol a and genistein. J Nutr 142:1382S-8S
Wang, Jun; Betancourt, Angela M; Mobley, James A et al. (2011) Proteomic discovery of genistein action in the rat mammary gland. J Proteome Res 10:1621-31
Hsu, Pei-Yin; Hsu, Hang-Kai; Singer, Gregory A C et al. (2010) Estrogen-mediated epigenetic repression of large chromosomal regions through DNA looping. Genome Res 20:733-44