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Comparison of dose-dependent outcomes in induction of cytogenotoxic responses by novel glucosyl flavonoids

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dc.contributor.authorEngen, Anya, author
dc.contributor.authorKato, Takamitsu, advisor
dc.contributor.authorHanneman, William, advisor
dc.contributor.authorLegare, Marie, committee member
dc.contributor.authorBouma, Gerrit, committee member
dc.date.accessioned2007-01-03T06:39:06Z
dc.date.available2015-06-30T05:57:00Z
dc.date.issued2014
dc.description.abstractThe flavonoids quercetin, and its glucosides isoquercetin and rutin, are phytochemicals commonly consumed in plant-derived foods. They are associated with potential health-promoting effects such as anti-inflammation, anti-viral, anti-carcinogenesis, neuro- and cardio-protection, etc. Semi-synthetic water soluble quercetin glucosides, maltooligosyl isoquercetin (MI), monoglucosyl rutin (MO) and maltooligosyl rutin (MA) were developed to overcome solubility challenges for improved incorporation in food and medicinal applications. Quercetin and its glucosides are known to induce genetic instability and decrease cell proliferation, which are possible mechanisms of anti-carcinogenesis in in vitro and animal studies. Using an in vitro system of Chinese hamster ovary (CHO) cells, this thesis project examined the differences in cytogenotoxic responses induced by natural and novel flavonoids. Treatments with flavonoids at a concentration range of 0.1 and 1,000 ppm induced sister chromatid exchanges (SCE) and micronuclei (MN) in CHO cells. Compared to spontaneous occurrences, significant increases in SCE and MN were observed in both natural and synthetic flavonoid-treated cells in a dose-dependent manner. The natural flavonoids exhibited greater potency than the synthetic compounds, where quercetin was most potent. An analysis of the effects of flavonoids on DNA repair via the poly(ADP ribose) polymerase (PARP) pathway using ELISA showed that all three natural flavonoids along with MI and MO were capable of inhibiting PARP activity by 50%. Quercetin was observed to be the strongest natural inhibitor of PARP. In growth studies using the same treatment dosages as the SCE-MN experiments, colony formation data corroborate those of the growth inhibition studies, in which all flavonoids exerted varying inhibitory effects on cell proliferation. These cytogenetic studies demonstrated that quercetin, isoquercetin and rutin generally exerted more potency than the synthetic compounds, requiring lower doses to achieve efficacy. The ability of both the natural and the synthetic flavonoids to cause genomic instability and impair cell growth may have human health implications for chemoprevention.
dc.format.mediumborn digital
dc.format.mediummasters theses
dc.identifierEngen_colostate_0053N_12223.pdf
dc.identifier.urihttp://hdl.handle.net/10217/82510
dc.languageEnglish
dc.language.isoeng
dc.publisherColorado State University. Libraries
dc.relation.ispartof2000-2019
dc.rightsCopyright and other restrictions may apply. User is responsible for compliance with all applicable laws. For information about copyright law, please see https://libguides.colostate.edu/copyright.
dc.titleComparison of dose-dependent outcomes in induction of cytogenotoxic responses by novel glucosyl flavonoids
dc.typeText
dcterms.embargo.expires2015-06-30
dcterms.embargo.terms2015-06-30
dcterms.rights.dplaThis Item is protected by copyright and/or related rights (https://rightsstatements.org/vocab/InC/1.0/). You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s).
thesis.degree.disciplineEnvironmental and Radiological Health Sciences
thesis.degree.grantorColorado State University
thesis.degree.levelMasters
thesis.degree.nameMaster of Science (M.S.)

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