The University of Illinois at Chicago has unique facilities and expertise for specialized liquid chromatography-tandem mass spectrometry (LC-MS-MS) measurements in support of cancer research including a unique LC-MS-MS assay for DNA oxidation products as surrogate end-point biomarkers for cancer prevention, and mass spectrometric-based screening of natural product mixtures and metabolite mixtures for the discovery of cancer chemoprevention agents. Existing mass spectrometry instrumentation for this resource includes two LC-MS quadrupole instruments, one magnetic sector mass spectrometer and a new electrospray triple quadrupole mass spectrometer. The instruments are managed by the P.I. who is both a tenured mass spectrometrist in the College of Pharmacy and an NCI-funded cancer researcher. Because no other mass spectrometry laboratory in the Chicago area is directed by a biomedical mass spectrometrist nor a cancer researcher, unique opportunities exist for providing analytical and educational support for cancer research. Developed in the laboratory of the P.I., the LC-MS-MS assay for DNA oxidation products simultaneously measures four oxidized nucleosides including 8-oxo-2'-deoxyguanosine (the only oxidation product measured by the standard HPLC with electrochemical detection method), 8-oxo-2'-deoxyadenosine, thymidine glycol and 5-hydroxymethyl-2'-uridine. Invented in the laboratory of the P.I., pulsed ultrafiltration mass spectrometry facilitates high throughput screening of natural product extracts as a means of drug discovery. Funds are requested to make these resources available to other cancer researchers on campus. In particular, the research of seven NCI-funded investigators is described with reference to how access to this unique mass spectrometry resource will increase their productivity. These research activities encompass both preclinical and clinical studies and include screening of natural products for potential new cancer chemoprevention agents, cancer prevention by selenium, mechanisms of carcinogenesis by estrogens, tamoxifen chemoprevention of breast cancer, and clinical investigations of cancer chemoprevention by the carotenoid lycopene.
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