A variety of physiological and pathophysiological processes as well as the metabolism of a number of drugs proceed through complex oxidative mechanisms in which transient, highly reactive intermediates such as superoxide anion, hydroxyl radical and singlet molecular oxygen play a major role. The ability to develop novel therapeutic approaches to modify these medically important processes requires a detailed knowledge of the identity of the intermediates involved, their concentrations and how these concentrations vary with experimental conditions. Of the intermediates most commonly postulated to be important, information about singlet molecular oxygen is particularly deficient. Instrumentation developed in this laboratory (using the characteristic infrared emission band of singlet oxygen at 1268 nm) provides a means to detect singlet oxygen in complex biological systems for the first time (J Biol Chem 258:5991-5993, 1983). Studies of singlet oxygen production by a number of anti- neoplastic drugs and related compounds will becarried out. Compounds to be studied include bleomycin, doxorubicin, daunorubicin, carminic acid, mithramycin, chromomycin A3, olivomycin, mitomycin C, VP-16 streptonigrin, procarbazine, paraquat, cis-platinum and gossypol. Preliminary studies in this laboratory have demonstrated signlet oxygen production by the bleomycin-ferric-ion-13- hydroperoxylinoleic acid system. Singlet oxygen production in this system will be correlated with the quantity and type of DNA degradation in model systems and with the ability to cause destructive lipid peroxidation in red blood cell ghosts. The mechanism of singlet oxygen in liver microsomes supplemented with 13-hydro-peroxylinoleic acid will be determined. Studies with purified cytochrome P-450 will also be done. Measurements of singlet oxygen production by prostaglandin synthestase will be made. prior studies have shown that lipoxygenases produce singlet oxygen. A search for singlet oxygen emission in the asbestos-fiber- catalyzed decomposition of hydrogen peroxide will be made.
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