Reaction products from N-methyl-N-nitrosourea and deoxyribonucleic acid containing thymidine residues. Synthesis and identification of a new methylation product, O4-methyl-thymidine |
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Authors: | P D Lawley D J Orr S A Shah P B Farmer and M Jarman |
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Institution: | Chester Beatty Research Institute, Institute of Cancer Research: Royal Cancer Hospital, London SW3 6JB, U.K. |
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Abstract: | 1. DNA was treated with N-methyl-N-nitrosourea at pH7-8, 37 degrees C, degraded to yield 3- and 7-methylpurines and deoxyribonucleosides and the reaction products were separated by chromatography on ion-exchange resins. The following methods for identification and determination of products were used: with unlabelled N-methyl-N-nitrosourea, u.v. absorption; use of methyl-(14)C-labelled N-methyl-N-nitrosourea and use of (14)C]thymine-labelled DNA. 2. The synthesis of O(4)-methylthymidine and its identification by u.v. and mass spectroscopy are reported. 3. 3-Methylthymidine and O(4)-methylthymidine were found as methylation products from N-methyl-N-nitrosourea with thymidine and with DNA, in relatively small yields. Unidentified products containing thymine were found in enzymic digests of N-methyl-N-nitrosourea-treated DNA, which may be phosphotriesters. 4. The possible role of formation of methylthymines in mutagenesis by N-methyl-N-nitrosourea is discussed. |
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