US EPA

1250852 

Technical Report 

Genomic and Proteomic Biomarkers of Biological Responses to Exposure 

Lamartiniere, C 

2010 

CRISP/2010/ES016003-04 

English 

DESCRIPTION (provided by applicant): 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. 

animal puberty; laboratory rat; biomarker; human puberty; middle childhood (6-11); cooperative study; human subject; immunologic assay /test; questionnaire; chemical related neoplasm /cancer; breast neoplasm; chemical carcinogenesis; phenol; phthalate; diethylhexylphthalate; mammary gland; method development; genistein; clinical research; matrix assisted laser desorption ionization; microarray technology; liquid chromatography mass spectrometry; environmental exposure; proteomics; two dimensional gel electrophoresis