DNA interstrand cross-linking by a diepoxide mycotoxin

Jacob Conklin

Document Type Dissertation/Thesis


Diepoxides are widespread in nature and can act as cellular cross-linkers, leading to chromosomal aberrations and the induction of cancer. Repandiol, a diyne diol diepoxide, was isolated from the edible mushroom Hydnum repandum by Takahashi, Endo, and Nozoe in 1992 and reported to display potent cytotoxic activity, attributed to its bifunctional alkylaring capacity. We have purified repandiol from Hydnum repandum and used it for DNA interstrand cross-linking studies of defined sequence DNA oligomers. Preliminary results suggest that repandiol, like the diepoxyalkanes previously studied in our laboratory, shows a preference for alkylation at guanine residues. In addition, repandiol appears to cross-link a more biologically relevant 154mer sample of DN A, but with even less efficiency than it does the 19mer.