title: Direct observation of the alkylation products of deoxyguanosine and DNA by fast atom bombardment mass spectrometry.
abstract: By the methods of fast atom bombardment (FAB) mass spectrometry, thin-layer chromatography and ultraviolet absorption spectroscopy adducts have been studied which are formed by an antitumour alkylating drug thiotepa both in a model system, containing only deoxyguanosine (dGuo), and in DNA. Analysis of the model reaction mixture (dGuo + thiotepa) by FAB mass spectrometry permitted observation of adducts dGuo thiotepa, 2dGuo thiotepa, and also the products of their further modification in solution, which occurs by hydrolysis of the glycosidic bond and also by opening of the imidazole ring. In the case of DNA FAB mass spectrometry made it possible to characterize adducts of thiotepa with guanosine (Gua) and adenosine (Ade) without their preliminary purification. The site of alkylation of Gua in both dGuo and DNA is N7, and that of Ade in DNA is N3. The application of the results to the study of the molecular mechanism of the antitumour action of thiotepa is discussed.
authors.affiliation: Kharkov Research Institute for Therapy, UkrSSR Ministry of Health, Kharkov.
authors.forename: G V
authors.initials: GV
authors.lastname: Andrievsky
authors.forename: L F
authors.initials: LF
authors.lastname: Sukhodub
authors.forename: T L
authors.initials: TL
authors.lastname: Pyatigorskaya
authors.forename: O A
authors.initials: OA
authors.lastname: Boryak
authors.lastname: Limanskaya OYu
authors.forename: V S
authors.initials: VS
authors.lastname: Shelkovsky
mesh_terms: D000477:Alkylating Agents / Q000737:chemistry*; D002855:Chromatography, Thin Layer; D004247:DNA / Q000737:chemistry*; D003849:Deoxyguanosine / Q000737:chemistry*; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013852:Thiotepa / Q000737:chemistry*
chemical_list: D000477:Alkylating Agents; D004247:DNA; D013852:Thiotepa; D003849:Deoxyguanosine