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Physical Sciences and Mathematics Commons

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Chemistry

Honors Theses

Carcinogens Cancer

Publication Year

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Full-Text Articles in Physical Sciences and Mathematics

Mapping Of Diepoxybutane Damage In The Cytochrome B Domain Of Mitochondrial Dna And The Β-Globin Domain Of Nuclear Chicken Dna Using Quantitative Pcr, Justin Juskewitch Jan 2004

Mapping Of Diepoxybutane Damage In The Cytochrome B Domain Of Mitochondrial Dna And The Β-Globin Domain Of Nuclear Chicken Dna Using Quantitative Pcr, Justin Juskewitch

Honors Theses

Diepoxybutane (DEB), a known industrial carcinogen, reacts with DNA primarily at the N7 position of deoxyguanosine residues and creates interstrand cross-links at the sequence 5'-GNC. Since N7-N7 cross-links cause DNA to fragment upon heating, quantative polymerase chain reaction (QPCR) is being used in this experiment to measure the amount of DEB damage (lesion frequency) with three different targets-mitochondrial (unpackaged), open chromatin region, and closed chromatin region. Initial measurements of DEB damage within these three targets were not consistent because the template DNA was not the limiting reagent in the PCR. Follow-up PCR trials using a limiting amount of DNA are …


Flanking Sequences Modulate Diepoxide Cross-Linking Efficiencies At The 5'-Gnc Sste, Gregory A. Sawyer Jan 2003

Flanking Sequences Modulate Diepoxide Cross-Linking Efficiencies At The 5'-Gnc Sste, Gregory A. Sawyer

Honors Theses

Diepoxybutane, diepoxyoctane, and mechlorethamine are cytotoxic DNA crosslinking agents that vary in their carcinogenic versus chemotherapeutic potentials. Interstrand cross-linking occurs between the N7 positions of deoxyguanosine residues on opposite strands of the DNA duplex. Each synthetic DNA oligomer used in this study contained four 5'-N\GN2CN3 sites (within a 32 base sequence) and we have systematically varied the bases in the N1 and N2 positions to determine the resulting cross-linking efficiencies of each cytotoxic agent. Each duplex was 5' -end labeled and incubated with cross-linking agent. Interstrand cross-links were purified through denaturing polyacrylamide gel electrophoresis and then subjected to piperidine cleavage. …


Quantitative Analysis Of Diepoxybutane Damage Within The Chicken Β-Globin Domain, André M. Pilon Jan 2003

Quantitative Analysis Of Diepoxybutane Damage Within The Chicken Β-Globin Domain, André M. Pilon

Honors Theses

In industrial polymer and synthetic rubber production facilities, workers are exposed to 1,3-butadiene. This compound is converted in vivo to 1,2,3,4-diepoxybutane (DEB) and has been linked to increased incidences of cancer in these individuals. Carcinogenesis has been attributed to formation of DEB induced DNA interstrand cross-links. Previous studies have demonstrated that DEB cross-links deoxyguanosine residues within 5'-GNC sequences in synthetic DNA, in restriction fragments, and in defined sequence nucleosomes. The current study utilized the polymerase chain reaction (PCR) to examine DEB damage frequencies within nuclear genes, found within "open" regions of chromatin, as compared to regions of unexpressed sequence that …