"Structural Characterization of the Major Guanosine-Guanosine Cross-Lin" by Edward Chuang

Date of Award

2014

Document Type

Honors Thesis (Colby Access Only)

Department

Colby College. Chemistry Dept.

Advisor(s)

Julie T. Millard

Second Advisor

Thomas W. Shattuck

Abstract

Epichlorohydrin (ECH) is a potential human carcinogen that is used in the industrial production of epoxy resin, adhesives, plastics, insecticides, glycerin, and pharmaceuticals. ECH is a bifunctional alkylating agent with the ability to form monoadducts with DNA as well as to cross-link DNA covalently and has been linked to increased risks of cancer due to occupational exposure. In an in vitro study to characterize the mechanism of cross-linking, ECH was reacted with guanosine and liquid chromatography mass spectrometry was used to determine the intermediates and products of the reaction. It was found that the major product formed was a monoadduct with a chlorine atom, suggesting that the epoxide of ECH is the first electrophilic group to react. These data support a previous study that showed that the reaction is more efficient under acidic conditions. The final product with two guanosines cross-linked by ECH was also identified; however, the monoadduct with an epoxide was not found. Therefore, further data collection is required to fully characterize the mechanism of cross-linking by epichlorohydrin. These preliminary results have helped to understand how epichlorohydrin reacts with DNA.

Comments

Full-text download restricted to Colby College campus only.

Keywords

guanosine, epichlorohydrin, bifunctional alkylating agent, nucleic acid, cross-link, liquid chromatography mass spectrometry

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