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

The 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.

Name thesis:degree_name

Master of Science (M.S.)

Level thesis:degree_level

Masters

Discipline thesis:degree_discipline

Environmental and Radiological Health Sciences

Grantor dc:publisher

Colorado State University. Libraries

Year dc:date.issued

2014

Authors dc:creator

• Engen, Anya, author
• Kato, Takamitsu, advisor
• Hanneman, William, advisor
• Legare, Marie, committee member
• Bouma, Gerrit, committee member

Statement dc:rights

• Copyright 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.

Language dc:language.iso

eng, English

Identifier URI

https://doi.org/10.25675/3.019004

OAI identifier oai:identifier

oai:mountainscholar.org:10217/82510