The mechanism of alkylation of DNA by 5-(3-methyl-1-triazeno)imidazole-4-carboxamide (MIC), a metabolite of DIC (NSC-45388). Non-involvement of diazomethane |
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Authors: | H T Nagasawa F N Shirota N S Mizuno |
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Institution: | Medical Research Laboratories, Veterans Administration Hospital, and the Departments of Medical Chemistry and Surgery, University of Minnesota, Minneapolis, Minn. 55417 U.S.A. |
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Abstract: | Comparison of the nuclear magnetic resonance spectra of chemically synthesized methyl-d1-methanol with the methanol produced in the solvolytic decompostion of 5-(3-methyl-1-triazeno)imidazole-4-carboxamide (MIC) in D2O under acidic, basic or neutral conditions indicated that no deuterium was exchanged for the hydrogens on the methyl group. Diazomethane can therefore be ruled out as an intermediate in this reaction.The methyl-d3-guanine isolated after incubation of methyl-d3-MIC with calfthymus DNA in vitro displayed, on chemical ionization mass spectrometry, a quasimolecular ion (MH+) at m/e 169, which was 3 mass units higher than the quasimolecular ion for an undeuterated 7-methylguanine standard. The major fragment ions for 7-methyl-d3-guanine on electron impact mass spectrometry likewise were situated at positions 3 mass units higher than the fragment ions for 7-methylguanine itself.These data indicate that the methylation of biological macromolecules by MIC must involve the transfer of an intact methyl group. |
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Keywords: | AIC 5-aminoimidazole-4-carboxamide CI chemical ionization DEN diethyl-nitrosamine DIC 5-(3 3-dimethyl-1-triazeno)imidazole-4-carboxamide DMN dimethylnitrosamine DSS 2 2-dimethyl-2-silapentane-5-sulfonate EI electron impact MIC 5-(3-methyl-1 -triazeno)imidazole-4-carboxamide MNNG MNU MS mass spectrometry NMR nuclear magnetic resonance |
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