Detection and characterization of DNA adducts at the femtomole level by desorption ionization mass spectrometry.
Current methodologies for the detection and isolation of carcinogen-DNA adducts have advanced beyond the capabilities of the methods used to elucidate their structures. This difficulty seriously limits the potential use of DNA-carcinogen adducts in human dosimetry. We have investigated two general strategies for the analysis of model arylamine-nucleoside adducts using desorption ionization mass spectrometry (MS). Using fast atom bombardment MS-MS with constant neutral loss scans, we can identify the protonated molecule of derivatized adducts in samples as small as 1 pmole, and then apply daughter ion MS-MS scans to obtain structure-specific fragmentation. Using this strategy we have differentiated adducts having the same carcinogen and different bases [e.g., N-(deoxyadenosin-8-yl)-4-aminobiphenyl and N-(deoxyguanosin-8-yl)-4- aminobiphenyl] or the same base and different carcinogens [e.g., N-(deoxyguanosin-8-yl)-4- aminobiphenyl and N-(deoxyguanosin-8-yl)-2-aminofluorene]. In the second approach we used laser desorption time-of-flight MS to obtain spectra from adduct samples as small as 20 fmole. These data indicate that MS can be used for the analysis of very low (picomole-femtomole) levels of nucleoside adducts, including isomers, and that desorption ionization MS and MS-MS have significant potential for applications in human dosimetry.
Lay
J O
JO
National Center for Toxicological Research, Jefferson, AR 72079.
Chiarelli
M P
MP
Bryant
M S
MS
Nelson
R W
RW
D002273:Carcinogens / Q000032:analysis / Q000633:toxicity*; D004247:DNA / Q000032:analysis* / Q000187:drug effects*; D004249:DNA Damage; D005069:Evaluation Studies as Topic; D006801:Humans; D008832:Microchemistry / Q000379:methods; D016339:Spectrometry, Mass, Fast Atom Bombardment / Q000379:methods*
D002273:Carcinogens; D004247:DNA