Chemical research in toxicology aims to understand chemical-level details of toxicity mechanisms.  Many cancers are linked to dietary factors that promote the formation of reactive electrophiles resulting in chemical alterations in nucleic acid structure in cells of the gastrointestine.  Of particular mutagenic relevance appears to be alkylation of deoxyguanosine at the 6-position.  A complex network of biochemical pathways controls bioactivation and adduct formation, as well as subsequent DNA repair, DNA synthesis, and gene transcription.  Because these processes contribute in different ways to increasing or mitigating a key event in the initiation of carcinogenesis, our ability to quantify risk and promote prevention strategies is limited.  DNA adduct-targeting probes offer a new approach for examining on the level of hydrogen bonding and hydrophobic interactions how DNA-processing enzymes respond to guanine alkylation.  A practical outcome of addressing such interactions is the capacity to quantify DNA adduct formation as a chemical biomarker influencing the flow of genetic information.

DNA adduct-targeting probes: From mechanisms of mutation to damage detection

248th National Meeting (2014)

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