Abstract
To investigate the mechanism of N4-aminocytidine-induced mutagenesis, N'-alkyl-N4-aminocytidines and N4-alkyl-N4-aminocytidines were prepared and their mutagenicity on bacteria were assayed. N'-Methyl-N4-aminocytidine, N'-(2-hydroxyethyl)-N4-aminocytidine and N',N'-dimethyl-N4-aminocytidine showed direct-acting mutagenicity on S. typhimurium TA100 and E. coli WP2 uvrA, tester strains that are sensitive to base-pair substitutions. In contrast, N4-methyl-N4-aminocytidine, N4-(2-hydroxyethyl)-N4-aminocytidine and N4,N'-dimethyl-N4-aminocytidine were not mutagenic on these bacteria. Since N'-methyl-N4-aminocytidine does not form hydrazones, the possibility that N4-aminocytidine causes mutation due to its reactivity with carbonyl compounds has been excluded. Furthermore, the fact that only those alkyl N4-aminocytidines having a hydrogen on the nitrogen at position 4 are mutagenic is consistent with the previously proposed mechanism in which the tautomerization between the amino and the imino forms of N4-aminocytosine allowing an ambiguous base pairing is the cause of the mutagenesis.
Full text
PDF
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Brown D. M., Hewlins M. J., Schell P. The tautomeric state of N(4)-hydroxy- and of N(4)-amino-cytosine derivatives. J Chem Soc Perkin 1. 1968;15:1925–1929. doi: 10.1039/j39680001925. [DOI] [PubMed] [Google Scholar]
- Hayatsu H. Reaction of cytidine with semicarbazide in the presence of bisulfite. A rapid modification specific for single-stranded polynucleotide. Biochemistry. 1976 Jun 15;15(12):2677–2682. doi: 10.1021/bi00657a030. [DOI] [PubMed] [Google Scholar]
- Negishi K., Harada C., Ohara Y., Oohara K., Nitta N., Hayatsu H. N4-aminocytidine, a nucleoside analog that has an exceptionally high mutagenic activity. Nucleic Acids Res. 1983 Aug 11;11(15):5223–5233. doi: 10.1093/nar/11.15.5223. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nitta N., Kuge O., Yui S., Tsugawa A., Negishi K., Hayatsu H. A new reaction useful for chemical cross-linking between nucleic acids and proteins. FEBS Lett. 1984 Jan 23;166(1):194–198. doi: 10.1016/0014-5793(84)80071-x. [DOI] [PubMed] [Google Scholar]
- Shapiro R., Weisgras J. M. Bisulfite-catalyzed transamination of cytosine and cytidine. Biochem Biophys Res Commun. 1970 Aug 24;40(4):839–843. doi: 10.1016/0006-291x(70)90979-4. [DOI] [PubMed] [Google Scholar]
- Sverdlov E. D., Monastyrskaya G. S., Tarabakina N. S., Budowsky E. I. Reaction of the cytosine nucleus with hydrazine in the presence of bisulphite. FEBS Lett. 1976 Feb 15;62(2):212–214. doi: 10.1016/0014-5793(76)80055-5. [DOI] [PubMed] [Google Scholar]
- Yahagi T., Nagao M., Seino Y., Matsushima T., Sugimura T. Mutagenicities of N-nitrosamines on Salmonella. Mutat Res. 1977 Apr;48(2):121–129. doi: 10.1016/0027-5107(77)90151-8. [DOI] [PubMed] [Google Scholar]