super(3)H-labelled alkyl-nucleotides, -nucleosides and -bases for the immunoanalytical quantification of DNA damage and repair

• Published in: Journal of labelled compounds & radiopharmaceuticals Vol. 46; no. 9; pp. 815 - 835
• Main Authors: Drosdziok, W, Lutze, C, Krueger, K, Gluesenkamp, K-H, Rajewsky, M F
• Format: Journal Article
• Language: English
• Published: 01-08-2003
• ISSN: 0362-4803

Analysis of the formation and repair of structurally modified DNA is of particular interest in the study of carcinogenesis, cancer therapy and aging. The quantification of specific DNA lesions by sensitive immunoanalytical methods requires radiotracers with high specific activity. We describe the synthesis of super(3)H-labelled adenine-, cytosine-, guanine- and thymine-alkyl derivatives by nucleophilic N- and O-alkylation using alkyl halides and diazoalkanes: 3-alkyl-[8- super(3)H]adenine (Alkyl = Me, Et, n-Bu); O super(6)-alkyl-deoxy[1',2'- super(3)H]guanosine (Alkyl = Me, Et, i-Pro, n-Bu); O super(6)-ethyl-deoxyguanosine-5'-triphosphate ([2- super(3)H-Ethyl]; [8- super(3)H]); O super(6)-alkyl-9-hydroxyhexyl-[8- super(3)H] guanine (Alkyl=Me, Et); 7-ethyl-[8,5'- super(3)H]guanosine-3',5'-cyclic-phosphate; O super(2)- and O super(4)-alkyl-[methyl, 1',2'- super(3)H]thymidine (Alkyl = Me, Et); the conversion of super(3)H-labelled thymidine to the corresponding 5-methylcytidine; the synthesis of three different 8-oxoguanine tracers; and the generation of thymidine glycol (5,6-dihydroxy-5,6-dihydro-[methyl- super(3)H]thymidine) from thymidine. All radiotracers were successfully employed in competitive radioimmunoassays for the quantification of defined DNA alkylation products in DNA repair analyses.