Methods development toward the measurement of polyaromatic hydrocarbon-DNA adducts by mass spectrometry

The measurement of DNA adducts in human samples is at an early stage. The accuracy of some of the current measurements is not defined, the structures are unknown for a significant number of the adducts that have been detected, and there is little information about how many adducts remain to be discovered. This is due largely to the trace amounts of human DNA adducts in any sample. A consequence of this is that the true potential of DNA adducts as indicators of exposure and risk in human toxicology is far from realized. Mass spectrometry, a powerful technique for organic analysis, is the key to exploiting fully the usefulness of human DNA adducts as biomarkers of human exposure and risk. Mass spectrometry can make accurate measurements, discover unknown compounds, and determine the structures of these unknown compounds. However, the trace (very small) amounts of human DNA adducts have limited mass spectrometry's usefulness in analyzing such samples. This project focused on increasing the sensitivity of mass spectrometry for measuring human DNA adducts. Advances in sensitivity have been achieved for two modes of mass spectrometry applied to standards related to DNA adducts: gas chromatography with electron-capture negative ion mass spectrometry, and fast-atom-bombardment mass spectrometry. These advances involve both sample preparation and instrument conditions.