It is well known that ionizing radiation is genotoxic, and can trigger heritable mutations in the germ cells of an animal. Recently, researchers have used hypervariable expanded simple tandem repeat (ESTR) regions of DNA to explore this phenomenon. ESTRs facilitate the examination of induced genetic mutations using relatively low radiation doses and fewer mice than more traditional approaches. Numerous studies have examined the responses of ESTRs to radiation in the germ line; however the mechanism behind germ line mutations at ESTR loci is poorly understood. Current hypotheses propose that error-prone DNA repair, which allows for misalignment of DNA strands through replication slippage produces in changes in ESTR size. P53 is involved in DNA replication as well as repair of DNA damage, apoptosis and other cancer-related processes. We use p53-deficient heterozygous male mice to examine the role of p53 in germ line mutations at ESTR loci. Males were irradiated with a variety of dose combinations both prior to and post-meiosis, and were mated to unirradiated wildtype females. DNA from the adults and offspring was analyzed for mutations at ESTR loci using DNA fingerprinting. Surprisingly, the study found no significant differences in germ line mutation rate between any treatment groups, including the 0Gy and 1Gy treatments. I discuss the possibility that these results are due to the p53 deficiency of the males, and that p53 homozygosity is necessary for radiation-induced germ line mutations at ESTR loci to occur. I conclude that further studies need to be done, including a control study using wildtype males of the same background strain as that of the p53 deficient line in order to verify our results. / Thesis / Master of Science (MS)
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/23138 |
| Date | 09 1900 |
| Creators | Langlois, Nicole |
| Contributors | Quinn, James, Biology |
| Source Sets | McMaster University |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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