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

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.

A new approach to the synthesis of a protected 2-aminopurine derivative and its incorporation into oligodeoxynucleotides containing the Eco RI and Bam HI recognition sites

“…Although the purine hydrazino derivative described here was prepared solely as an intermediate in the synthesis of the desired 2-aminopurine chromophore, such nucleosides may additionally exhibit significant mutagenic activity as has been reported for pyrimidine hydrazino compounds (47,48). Differences in base stacking interactions present in these two sequences should be minimal since the flanking purines are the same in both cases (some minor stacking effects reflecting the difference between thymine or cytosine in the complementary strand may be present).…”

Detection of Genotoxic Nucleosides, 8-Hydroxydeoxyguanosine, 8-Hydroxyguanosine and Free Base 8-Hydroxyguanine, in Fish Food Products

“…DNA base-and nucleoside-analogues, such as 2-amino-N 6 -hydroxyadenine and N 4 -aminocytidine, have extremely high mutagenic activities (8,9). However, these compounds are synthetic compounds and are not detected in either food or the environment.…”

Induction of mutation in mouse FM3A cells by N4-aminocytidine-mediated replicational errors.

“…N4-Aminocytidine was obtained from Funakoshi Chemicals, Tokyo, Japan. N4-Aminodeoxycytidine was prepared as described earlier (21). These compounds were dissolved in water and diluted with phosphate-buffered saline to obtain appropriate concentrations for treating the cells.…”

“…is strongly mutagenic to procaryotes, e.g., Escherichia coli, Salmonella typhimurium, and bacteriophages (21,22). This compound also shows mutagenicity in eucaryotes, such as Chinese hamster lung V79 cells in culture (23) and Drosophila sp.…”

“…Because of its high potency, N4-aminocytidine offers an excellent opportunity for studying the mechanism of base analog mutagenesis. Using E. coli DNA polymerase I large fragment in an in vitro DNA-synthesizing system, we have previously shown, that N4-aminodeoxycytidine 5'-triphosphate (dCarTP) can be incorporated ambiguously, giving rise to a base pair transition, AT to GC (21,28) (Fig. 2).…”