Skip to main content
PMC home page
Nucleic Acids Research logoLink to Nucleic Acids Research
. 1983 Aug 11;11(15):5223–5233. doi: 10.1093/nar/11.15.5223

N4-aminocytidine, a nucleoside analog that has an exceptionally high mutagenic activity.

K Negishi, C Harada, Y Ohara, K Oohara, N Nitta, H Hayatsu
PMCID: PMC326252  PMID: 6224136

Abstract

The reaction of cytidine with hydrazine to give N4-aminocytidine was greatly promoted by addition of a less-than-stoichiometric amount of bisulfite, and the product was isolated in a good yield. N4-Aminocytidine was strongly mutagenic to bacteria (Salmonella typhimurium TA100 and TA1535, and E. coli WP2 uvrA) and to phage (phi X174 am3). The activity did not require the presence of mammalian microsomal fraction in the system. The mutagenic potency of N4-aminocytidine in these systems was two orders of magnitude greater than that of N4-amino-2'-deoxycytidine, and more than two orders of magnitude greater than that of N4-hydroxycytidine. The greater activity of the riboside than the deoxyriboside was ascribed to the lack of deoxycytidine kinase in these cells. This compound may be useful as a powerful mutagen to induce a transition mutation in microorganisms.

Full text

PDF
5223

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ames B. N., Mccann J., Yamasaki E. Methods for detecting carcinogens and mutagens with the Salmonella/mammalian-microsome mutagenicity test. Mutat Res. 1975 Dec;31(6):347–364. doi: 10.1016/0165-1161(75)90046-1. [DOI] [PubMed] [Google Scholar]
  2. Budowsky E. I., Sverdlov E. D., Monastyrskaya G. S. New method of selective and rapid modification of the cytidine residues. FEBS Lett. 1972 Sep 1;25(1):201–204. doi: 10.1016/0014-5793(72)80485-x. [DOI] [PubMed] [Google Scholar]
  3. Budowsky E. I., Sverdlov E. D., Spasokukotskaya T. N. Mechanism of the mutagenic action of hydroxylamine. VII. Functional activity and specificity of cytidine triphosphate modified with hydroxylamine and O-methylhydroxylamine. Biochim Biophys Acta. 1972 Dec 6;287(2):195–210. doi: 10.1016/0005-2787(72)90370-x. [DOI] [PubMed] [Google Scholar]
  4. Chu B. C., Brown D. M., Burdon M. G. N(4)-amino-and N(4)-hydroxycytosines as base analogue mutagens. Mutat Res. 1974 May;23(2):267–273. doi: 10.1016/0027-5107(74)90147-x. [DOI] [PubMed] [Google Scholar]
  5. Hayatsu H. Bisulfite modification of nucleic acids and their constituents. Prog Nucleic Acid Res Mol Biol. 1976;16:75–124. doi: 10.1016/s0079-6603(08)60756-4. [DOI] [PubMed] [Google Scholar]
  6. Hayatsu H. Co-operative mutagenic actions of bisulfite and nitrogen nucleophiles. J Mol Biol. 1977 Sep;115(1):19–31. doi: 10.1016/0022-2836(77)90243-1. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. Janion C. On the ability of Salmonella typhimurium cells to form deoxycytidine nucleotides. Mol Gen Genet. 1977 Jun 8;153(2):179–183. doi: 10.1007/BF00264733. [DOI] [PubMed] [Google Scholar]
  9. Janion C. The efficiency and extent of mutagenic activity of some new mutagens of base-analogue type. Mutat Res. 1978 Jan;56(3):225–234. doi: 10.1016/0027-5107(78)90189-6. [DOI] [PubMed] [Google Scholar]
  10. McCann J., Choi E., Yamasaki E., Ames B. N. Detection of carcinogens as mutagens in the Salmonella/microsome test: assay of 300 chemicals. Proc Natl Acad Sci U S A. 1975 Dec;72(12):5135–5139. doi: 10.1073/pnas.72.12.5135. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Müller W., Weber H., Meyer F., Weissmann C. Site-directed mutagenesis in DNA: generation of point mutations in cloned beta globin complementary dna at the positions corresponding to amino acids 121 to 123. J Mol Biol. 1978 Sep 15;124(2):343–358. doi: 10.1016/0022-2836(78)90303-0. [DOI] [PubMed] [Google Scholar]
  12. Popowska E., Janion C. N4-hydroxycytidine-a new mutagen of a base analogue type. Biochem Biophys Res Commun. 1974 Jan 23;56(2):459–466. doi: 10.1016/0006-291x(74)90864-x. [DOI] [PubMed] [Google Scholar]
  13. Popowska E., Janion C. The metabolism of N4-hydroxycytidine-a mutagen for Salmonella typhimurium. Nucleic Acids Res. 1975 Jul;2(7):1143–1151. doi: 10.1093/nar/2.7.1143. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Salganik R. I., Vasjunina E. A., Poslovina A. S., Andreeva I. S. Mutagenic action of N4-hydroxycytidine on Escherichia coli B cyt-. Mutat Res. 1973 Oct;20(1):1–5. doi: 10.1016/0027-5107(73)90091-2. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. 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]
  17. Topal M. D., Hutchison C. A., 3rd, Baker M. S. DNA precursors in chemical mutagenesis: a novel application of DNA sequencing. Nature. 1982 Aug 26;298(5877):863–865. doi: 10.1038/298863a0. [DOI] [PubMed] [Google Scholar]
  18. 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]

Articles from Nucleic Acids Research are provided here courtesy of Oxford University Press

RESOURCES