CHARACTERIZATION OF ENDOGENOUS DNA-ADDUCTS BY LIQUID-CHROMATOGRAPHY ELECTROSPRAY-IONIZATION TANDEM MASS-SPECTROMETRY

Endogenous carcinogens arising from normal metabolism are known to cau se modifications to DNA by reacting with bases to form adducts. Malond ialdehyde is a web characterized endogenous carcinogen that forms an a dduct with 2'-deoxyguanosine. This adduct has been detected in rat and human liver DNA by gas chromatography/electron capture negative-ion c hemical ionization mass spectrometry. A method has been developed base d on liquid chromatography/electrospray ionization tandem mass spectro metry for the characterization of endogenous DNA adducts. Using this m ethod, it was unequivocally established that the malondialdehyde adduc t of 2'-deoxyguanosine was a constituent of human liver DNA. The metho dology that has been developed should be applicable to the characteriz ation of other endogenous DNA adducts, There are few structural or bio logical data available to assess the importance of endogenous DNA addu cts as premutagenic lesions responsible for the develop ment of cancer . The availability of methodology based on liquid chromatography/elect rospray ionization tandem mass spectrometry for the characterization o f DNA adducts should greatly facilitate future studies in this area.