Reaction of epichlorohydrin and epibromohydrin with synthetic DNA oligomers
Document Type Dissertation/Thesis
Epichlorohydrin (ECH) has a variety of industrial uses, including the manufacture of epoxy resins, agricultural pesticides, adhesives, and plastics. The structure of ECH suggests that it should act as a bifunctional alkylator of DNA, which could account for its mutagenic properties in humans. We are using denaturing polyacrylamide gel electrophoresis (dPAGE) to investigate the reactivity of ECH and the related compound epibromohydrin (EBH) with synthetic DNA oligomers. Both compounds produce a low mobility band on denaturing gels consistent with an interstrand cross-link. This product is piperidine-cleavable, suggesting alkylation at N7 of guanine. Its rate of formation varies dramatically for ECH and EBH, with the ECH reaction showing a marked pH dependence. Our research may ultimately shed light on the way in which ECH and similar epoxides disrupt cellular systems.