TOXI 3 |
| Exposure of DNA to free radicals and other electrophiles results in strand breaks, as well as modified nucleotides (lesions) within intact strands of the biopolymer. DNA lesions can be genotoxic and have been implicated in aging and diseases such as cancer. Elegant methods exist for detecting specific sequences in DNA, which are useful for sensing mutations and single nucleotide polymorphisms. Sensitive detection of DNA lesions is mostly limited to mass spectrometric analysis of individual lesions (or their nucleobases) following complete chemical or enzyme degradation of the nucleic acids. Appropriately tagged alkoxy amines (e.g. aldehyde reactive probe, ARP), which selectively react with abasic sites (AP), are one of the few reagents available for directly detecting DNA lesions. We have developed reagents that take advantage of DNA lesion reactivity to selectively detect oxidized abasic sites (e.g. L) and modified purines (e.g. OxodG). When conjugated to a fluorophore or biotin, the probes are useful for quantifying the amount of the tagged lesion at femtomole levels.
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DNA-based Biomarkers
9:00 AM-11:50 AM, Sunday, August 19, 2007 BCEC -- 258C, Oral
Division of Chemical Toxicology |
