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dc.contributor.advisorLiebler, Daniel C.en_US
dc.contributor.advisorFrench, Eden_US
dc.contributor.authorBaker, Daniel Lee, 1970-*
dc.creatorBaker, Daniel Lee, 1970-en_US
dc.date.accessioned2013-04-18T10:01:26Z
dc.date.available2013-04-18T10:01:26Z
dc.date.issued1998en_US
dc.identifier.urihttp://hdl.handle.net/10150/282742
dc.description.abstractRecent intervention trials reported that smokers given dietary β-carotene supplementation were at increased risk of lung cancer and overall mortality. These results were unexpected based on previous observational epidemiology, which suggested β-carotene would decrease the onset of lung cancer in these individuals. The mechanism by which β-carotene supplementation results in increased lung cancer among smokers has yet to be defined. However, one proposed explanation is that β-carotene acts as a prooxidant in lungs exposed to cigarette smoke and exacerbates oxidative damage. This project has examined the consequences resulting from interactions of cigarette smoke with β-carotene in model systems. A novel β-carotene oxidation product, 4-nitro-β-carotene has been identified from smoke oxidation of beta-carotene in solution. This product has been isolated by both reverse-phase and cyano-column HPLC, and characterized by UV-vis spectroscopy, APCI-LC-MS, and NMR spectrometry. This class of products includes cis and all-trans isomers of 4-nitro-β-carotene. A new method for measuring primary products of lipid peroxidation has been developed. This method is specific and sensitive for the determination of 9- and 13-hydroxy fatty acid methyl esters of octadecadienoic acid as pentafluorobenzoyl esters by GC-ECD. These compounds are derived from the first stable products of linoleic acid oxidation. Using the method discussed above, the interactions between β-carotene and cigarette smoke were examined in a liposomal model system. DLPC liposomes showed little differences in oxidative damage with or without β-carotene incorporation. This result was consistent with gas-phase or whole smoke exposures. The effect of β-carotene on the oxidation of other antioxidants was also examined. Both the lipid soluble antioxidant α-tocopherol and the water soluble antioxidant ascorbate showed lower oxidation rates due to smoke exposure in the presence of β-carotene than without. These data indicate that β-carotene does not have prooxidant effects in this system. β-carotene is oxidized by cigarette smoke in model systems. 4-Nitro-β-carotene is one of several classes of products resulting from cigarette smoke oxidation of β-carotene. β-Carotene incorporation did not increase oxidation of lipid or other antioxidants upon smoke exposure. It is unlikely a prooxidant effect of β-carotene is responsible for increased lung cancer observed in recent intervention trials.
dc.language.isoen_USen_US
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.subjectHealth Sciences, Toxicology.en_US
dc.subjectHealth Sciences, Pharmacology.en_US
dc.subjectChemistry, Analytical.en_US
dc.titleInteractions of beta-carotene with cigarette smoke in vitroen_US
dc.typetexten_US
dc.typeDissertation-Reproduction (electronic)en_US
thesis.degree.grantorUniversity of Arizonaen_US
thesis.degree.leveldoctoralen_US
dc.identifier.proquest9901773en_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.disciplinePharmacology and Toxicologyen_US
thesis.degree.namePh.D.en_US
dc.identifier.bibrecord.b38838278en_US
refterms.dateFOA2018-09-05T21:15:50Z
html.description.abstractRecent intervention trials reported that smokers given dietary β-carotene supplementation were at increased risk of lung cancer and overall mortality. These results were unexpected based on previous observational epidemiology, which suggested β-carotene would decrease the onset of lung cancer in these individuals. The mechanism by which β-carotene supplementation results in increased lung cancer among smokers has yet to be defined. However, one proposed explanation is that β-carotene acts as a prooxidant in lungs exposed to cigarette smoke and exacerbates oxidative damage. This project has examined the consequences resulting from interactions of cigarette smoke with β-carotene in model systems. A novel β-carotene oxidation product, 4-nitro-β-carotene has been identified from smoke oxidation of beta-carotene in solution. This product has been isolated by both reverse-phase and cyano-column HPLC, and characterized by UV-vis spectroscopy, APCI-LC-MS, and NMR spectrometry. This class of products includes cis and all-trans isomers of 4-nitro-β-carotene. A new method for measuring primary products of lipid peroxidation has been developed. This method is specific and sensitive for the determination of 9- and 13-hydroxy fatty acid methyl esters of octadecadienoic acid as pentafluorobenzoyl esters by GC-ECD. These compounds are derived from the first stable products of linoleic acid oxidation. Using the method discussed above, the interactions between β-carotene and cigarette smoke were examined in a liposomal model system. DLPC liposomes showed little differences in oxidative damage with or without β-carotene incorporation. This result was consistent with gas-phase or whole smoke exposures. The effect of β-carotene on the oxidation of other antioxidants was also examined. Both the lipid soluble antioxidant α-tocopherol and the water soluble antioxidant ascorbate showed lower oxidation rates due to smoke exposure in the presence of β-carotene than without. These data indicate that β-carotene does not have prooxidant effects in this system. β-carotene is oxidized by cigarette smoke in model systems. 4-Nitro-β-carotene is one of several classes of products resulting from cigarette smoke oxidation of β-carotene. β-Carotene incorporation did not increase oxidation of lipid or other antioxidants upon smoke exposure. It is unlikely a prooxidant effect of β-carotene is responsible for increased lung cancer observed in recent intervention trials.


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