The objective of this proposal is to justify the need and obtain funds for the high resolution GC-MS-DS system to meet the requests of the scientists at Roswell Park Memorial Institute. This facility will also fulfill the need of the Buffalo Medical Foundation and of some of the scientists at the State University of New York at Buffalo. The requested instrument has a reverse geometry and is equipped with a capillary GC and fast atom bombardment ionization capability. The instrument will have the capability of accurate mass measurements to provide the elemental composition of unknown substances. This instrument will fulfill the need of several major on-going programs requiring structure elucidation of biological and chemical substances which affect the processes of growth and differentiation at the molecular level. The projects include the structure elucidation studies of the unknown compounds isolated from the urines of the cancer patients, structural characterization of the metabolites of cyclophosphamide and its complexes with macromolecules, and characterization of metabolites of new antitumor agents. The studies also include the role of carcinogens in cell proliferation, along with the studies in mutagenesis and radiation effects on nucleic acids and proteins. Among other studies included are, the synthesis of metalloporphyrins as magnetic resonance imaging contrast agents, effects of light and halogens on model nucleic acids, and the isolation and characterization of substances from cigarette smoke. Additional work that will utilize the GC-MS facility is, the studies of thiol-disulfide interchanges in peptides, characterization of tumor growth inhibitory factor isolated from the human fibroblasts, clinical pharmacology of new anticancer agents, structure elucidation of metabolites isolated from cell cultures and animal tissues. Structural studies will also conduct on the products encountered in the laser protolysis of oligonucleotides and synthetic products such as oligonucleotide probes. In the area of medicinal chemistry, studies include the synthesis of inhibitors of nucleic acid biosynthesis, development of antitumor agents and their metabolism in man. Twenty senior scientific investigators, four postdoctoral fellows and four graduate students will utilize these mass spectrometry facilities for their research.
