Singlet oxygen (SO), an electronically excited oxygen molecule, is believed to be a major intermediate in a variety of physiologic, pathophysiologic and therapeutic processes including the neutrophil respiratory burst, the oxidative metabolism of microsomes, the actions of a number of antineoplastic drugs (daunorubicin, doxyrubicin, mitomycin C , procarbazine and bleomycin) and paraquat poisoning. Past chemiluminescent (CL) and wet chemical studies have been unable to determine the role of SO in these processes. A new CL spectrometer has been developed with the ability to automatically produce spectra from ultra-weak CL sources and with a sensitivity to the 1268 nm band of SO, 2,000 times that of previously described CL spectrometers. Preliminary results demonstrate that 1268 nm CL can detect SO at concentrations less than 1% of that detectable with the dimole CL (the conventional technique). The 1268 nm band appears free of interference from other CL sources. The measurement of both visible and 1268 nm Cl permits a clear distinction between SO CL and CL from other sources. CL studies of all the systems listed above are planned to clarify their underlying mechanisms. A number of chemical and enzymatic models of these processes will also be studied. Several clinical studies will be undertaken in patients with malignant neoplasms. This is a completely unexplored area. Patients with myeloproliferative diseases will be studied. Correlations between neutrophil CL, the type of disease (e.g., polycythemia vera), the current therapy and the course of the disease will be made.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM032974-02
Application #
3282245
Study Section
Biophysics and Biophysical Chemistry A Study Section (BBCA)
Project Start
1983-12-01
Project End
1986-11-30
Budget Start
1984-12-01
Budget End
1985-11-30
Support Year
2
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Edward Hines Jr VA Hospital
Department
Type
DUNS #
City
Hines
State
IL
Country
United States
Zip Code
60141
Kanofsky, J R; Sima, P (1991) Singlet oxygen production from the reactions of ozone with biological molecules. J Biol Chem 266:9039-42
Kanofsky, J R (1991) Singlet oxygen production from the reactions of superoxide ion in aprotic solvents: implications for hydrophobic biochemistry. Free Radic Res Commun 12-13 Pt 1:87-92
Baker, A; Kanofsky, J R (1991) Direct observation of singlet oxygen phosphorescence at 1270 nm from L1210 leukemia cells exposed to polyporphyrin and light. Arch Biochem Biophys 286:70-5
Kanofsky, J R (1991) Quenching of singlet oxygen by human red cell ghosts. Photochem Photobiol 53:93-9
Everett, R R; Kanofsky, J R; Butler, A (1990) Mechanistic investigations of the novel non-heme vanadium bromoperoxidases. Evidence for singlet oxygen production. J Biol Chem 265:4908-14
Kanofsky, J R (1990) Quenching of singlet oxygen by human plasma. Photochem Photobiol 51:299-303
Kanofsky, J R (1989) Singlet oxygen production by biological systems. Chem Biol Interact 70:1-28
Kanofsky, J R (1989) Singlet oxygen production from the peroxidase catalyzed formation of styrene glutathione adducts. Biochem Biophys Res Commun 159:1051-4
Kanofsky, J R (1989) Bromine derivatives of amino acids as intermediates in the peroxidase-catalyzed formation of singlet oxygen. Arch Biochem Biophys 274:229-34
Kanofsky, J R; Hoogland, H; Wever, R et al. (1988) Singlet oxygen production by human eosinophils. J Biol Chem 263:9692-6

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