Development of an enzymatic digestion method to probe the sequence specificity of carcinogen adduction in oligonucleotides
A carcinogen is defined as any substance, radiation, or radionucleotide that produces cancer through alteration of the metabolic processes in the cell or by directly damaging the cell's DNA. In cases where DNA is damaged, the carcinogen comes into contact with the DNA; the DNA performs a nucleo...
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| Main Author: | |
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| Format: | Dissertation |
| Language: | English |
| Published: |
Ann Arbor
ProQuest Dissertations & Theses
2014
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| Subjects: | |
| Online Access: | Get full text |
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| Summary: | A carcinogen is defined as any substance, radiation, or radionucleotide that produces cancer through alteration of the metabolic processes in the cell or by directly damaging the cell's DNA. In cases where DNA is damaged, the carcinogen comes into contact with the DNA; the DNA performs a nucleophilic attack on the electrophilic carcinogen, which permanently binds the two. This reaction between carcinogens and DNA generally exhibits sequence selectivity, the recognition of which may be important in understanding their mutagenic activities. A method could be developed to measure the effectiveness of several different DNA repair pathways. Exposing bacterial plasmids to carcinogens and monitoring the number of adductions present at both the outset and after a set time frame allows us to examine DNA repair pathways in an E. coli model system. In addition, by eliminating specific repair mechanisms in the bacteria, individual repair pathways could be further investigated. A method will be developed to excise a small 18-mer sequence, representative of a mutational hot spot found on the p53 gene linked to lung cancer, from increasingly larger strands of DNA, ranging from a 35-mer sequence 100-mer. The Vouros lab has demonstrated the potential to analyze this 18-mer sequence through liquid chromatography coupled with mass spectrometry (LC/MS). The excised DNA will be analyzed through LC/MS to quantitate the number of adducts on the DNA site as well as determine the location of said adducts |
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| Bibliography: | Source: Masters Abstracts International, Volume: 52-04. Adviser: Paul Vouros. Chemistry & Chemical Biology. |
| ISBN: | 1303654687 9781303654688 |