This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Since 1987, we have examined over 100 DNA bases and nucleosides that are modified with carcinogenic polycyclic aromatic hydrocarbons (PAH). More recently, we have expanded the research to include potentially carcinogenic steroid hormones (e.g., estrogens). These materials share a chemical property with that of PAH; that is both materials cause modification and depurination of DNA. One aspect of the method development work is a means of highly specific biomarker detection. We are currently working on the applicability of accurate mass measurement and/or full product ion spectra for this purpose. We have recently expanded the project to develop capillary LC coupled with ESI MS to provide a highly sensitive means of detection steroid biomarkers that may be implicated in breast cancer. The hypothesis is that estrogen oxidation affords quinones that undergo Michael addion to DNA bases, causing damage and leading to mutations. We are considering whether to look for the DNA modificaton or to use proteomic methods to look at the proteins involved in the estrogen metabolism. Analyzing tissue for modified DNA bases and relating that to estradiol seems to be an appropriate direction.
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