<p> Gulonolactone oxidase enzyme is important in the final stage of ascorbic acid biosynthesis. Gulonolactone oxidase is encoded by the Gulo gene. Most animals, such as mice, have the Gulo gene, through which they produce ascorbic acid from glucose, while humans, guinea pigs and primate animals carry a non functional Gulo gene. Ascorbic acid plays an important role in many biological processes. However, it is primarily essential as an antioxidant. Ascorbic acid protects genomic DNA from free radicals resulting from oxidative stress that might otherwise cause a variety of diseases such as cancer or heart disease. This thesis focuses on investigating the role of ascorbic acid in the elimination of oxidative stress-induced mutagenesis.</p> <p> To investigate how vitamin C decreases level of the DNA mutation frequency and protects DNA from free radicals, knockout Gulo and Big Blue mice were used as models to determine the ability of vitamin C to minimize oxidative stress. The Big Blue mice carry the cll gene which is a reporter gene through which DNA mutation rate can be detected in any part of body. Therefore, we generated double transgenic mice which are Gulo deficient or a Big Blue background. Homozygote Gulo cll positive (Gulo-/- cll+) were
obtained by crossing heterozygote Gulo cll Positive and homozygote Gulo mice. Five
Gulo-/-cll mice were placed under vitamin C deficient diet and another five were supplemented with vitamin C. DNA mutation frequency was analyzed in the two groups. There were no significant differences in mutation frequencies between homozygote Gulo-/- cll mice on vitamin C deficient diet and homozygote Gulo-/- cll+ mice fed vitamin C rich diet. One treatment mouse showed increased frequency in mutations but a second did not. Further tests can be done on other treated knockout mice to identify the mutation types generated by oxidative stress in the absence of vitamin C.</p> / Thesis / Master of Science (MSc)
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/21671 |
| Date | January 2007 |
| Creators | Shaban, Thuraya |
| Contributors | Schellhorn, H. E., Igdoura, S., Biology |
| Source Sets | McMaster University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis |
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