This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Although it is generally accepted that estrogens potentiate the development of cancer by a receptor-mediated process, many recent studies suggest that estrogens are complete (but extremely weak) carcinogens capable of tumor initiation. It is believed that estrogens, including the natural hormones estrone (E1) and estradiol (E2), are associated with increased risk of breast and other types of human cancer. That is, catechol estrogen quinones (CEQ) derived from 4-hydroxyestrone (4-OHE1) and 4-hydroxyestradiol (4-OHE2) react with DNA and form depurinating -N7Gua and -N3Ade adducts that may be responsible for tumor initiation [Cavalieri, E.L., et al. (2000) JNCI Monograph, 27,75]. To determine whether this type of DNA damage occurs in humans, urine samples from prostate and breast cancer patients and healthy individuals will be analyzed in a blind study. A primary objective is determining whether any of the cancer patients had formed 4-OHE1(E2)-1-N3Ade, suspected to be one of the major adducts formed by CEQ. This is of great interest as it could provide a new biomarker(s) for cancer detection and prognosis. The methods for testing the hypothesis that metabolically activated endogenous estrogens are involved in the initiation of breast and prostate cancers include capillary electrophoresis (CE) with field amplified sample stacking (FASS) interfaced with low temperature (T) laser-induced phosphorescence (LIP) detection and a new biosensor methodology suitable for room-temperature detection of various CEQ-derived biomarkers in nipple aspirate, urine, and tissue samples from breast cancer cases and control women, as well as in prostate fluid from prostate cancer cases and control men. Detection in biochips will be based on a novel first-come-first-served approach and fluorescence based imaging. The technical merit and the potential of this approach for high throughput screening and future cancer risk assessment will be evaluated.
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