CORE--ORGANIC SYNTHESIS FACILITY

点击翻译按钮获取中文摘要

The Organic Synthesis Facility has grown into an integrated, essential part of the AHFCC research program in chemical, environmental, and endogenous carcinogenesis. It is equally involved in the Cancer Center's research on the chemoprevention of cancer, the development of biomarkers of uptake and metabolic activation of carcinogens, and the identification of etiologically significant host factors. Research activities of the Facility encompass the development of syntheses of carcinogens, their detoxification products, reactive species of metabolic activation, and DNA adducts formed with such species. The activities include the identification and synthesis of biomarkers of uptake and activation of environmental carcinogens that required deuterated, tritiated, and 14C- labeled isotopes. Needed agents are furnished to the Cancer Center's investigators for research projects supported by the NCI, NIDCR, NIEH, the Health Department of the Commonwealth of Massachusetts, and agencies such as the American Cancer Society. Requests amounts range from picograms for reference compounds to multigrams for large-scale bioassays. The structural integrity and purity of all agents is ensured by state-of-the-science technology, including HPLC, GC-MS, GC-TEA, TLC, UV, IR, FTIR, MS, and NMR. Scientists in the Facility are highly experienced in developing efficient synthetic routes for non-radiolabel and radioisotope-labeled polycyclic aromatic hydrocarbons, tobacco- specific N-nitrosamines, and other environmental and nutritional carcinogens, their metabolites, and their DNA adducts. The Organic Synthesis Facility occupies 900 ft/2 in Unit 1 and, for the synthesis of isotope-labeled compounds 447 ft/2 of laboratory space at the lower level of NDI. The Facility's dedicated Carcinogen Synthesis Laboratory is equipped with several HPLCs, including one instrument with a beta-flow model IC radioactivity detector, and with a medium pressure liquid chromatograph. These instruments enable the analysis and purification of starting materials, intermediates, and end products. The laboratory hoods are equipped with glove boxes. There is also a walk-in hood, as required by regulatory statutes. The dedicated Selenium Laboratory, in which chemopreventive agents are prepared, has a special exhaust system in compliance with safety regulations for these chemicals. The dedicated Synthesis Laboratory for intermediates, nucleoside markers, and chemopreventive agents (other than selenium) is equipped with a photolysis set-up, HPLC with photo diode array detector, and two working hoods with a 24-h exhaust system. Radiolabeled syntheses are carried out in a dedicated laboratory that is accessed only upon approval by the Cancer Center's Safety Officer who also supervises adherence to safety regulations.