Acylfulvene (AF) is a bioreductive alkylating agent and semi-synthetic analogue of illudin S, a highly toxic mycotoxin, which exhibits selective toxicity for cancer cells over normal cells. Differential uptake and reactivity with important redox-regulating enzymes are thought to contribute to differences in toxicity between these structurally similar compounds. AF-DNA adducts have been previously identified, but damage to cellular DNA caused by these compounds has not been investigated, nor have differences between the DNA reactivity of AF and illudin S been addressed as a potential contributor to altered cytotoxicity.  In this study we have identified and quantified both AF-DNA adducts and novel illudin-DNA adducts in colon cancer cells by LC-MS. These data are compared with relative cytotoxicity data for both compounds, and are expected to improve our understanding of how chemical structure relates to DNA damage and how that contributes to cytotoxicity.

Role of DNA adduct formation in differential cytotoxicity between acylfulvene and illudin S

244th National Meeting (2012)

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