Reaction products from N-methyl-N-nitrosourea and deoxyribonucleic acid containing thymidine residues. Synthesis and identification of a new methylation product, O4-methylthymidine.
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.
D000818:Animals; D002250:Carbon Radioisotopes; D002852:Chromatography, Ion Exchange; D004247:DNA; D006863:Hydrogen-Ion Concentration; D013058:Mass Spectrometry; D008697:Methane; D008738:Methyl Ethers; D009607:Nitrosourea Compounds; D012474:Salmon; D013936:Thymidine / Q000031:analogs & derivatives
D002250:Carbon Radioisotopes; D008738:Methyl Ethers; D009607:Nitrosourea Compounds; C008505:O-methylthymidine; D004247:DNA; D008697:Methane; D013936:Thymidine