Direct-acting mutagenicity of N4-aminocytidine derivatives bearing alkyl groups at the hydrazino nitrogens

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Abstract
To investigate the mechanism of N 4 -aminocytidine-induced mutagenesis, N′-alkyl-N 4 -aminocytidines and N 4 -alkyl-N 4 -aminocytidines were prepared and their mutagenicity on bacteria were assayed. N′-Methyl-N 4 -aminocytidine, N′-(2-hydroxyethyl)-N 4 -aminocytidine and N′,N′-dimethyl-N 4 -aminocytidine showed direct-acting mutagenicity on S . typhimurium TA100 and E . coli WP2 uvr A, tester strains that are sensitive to base-pair substitutions. In contrast, N 4 -methyl-N 4 -aminocytidine, N 4 -(2-hydroxyethyl)-N 4 -aminocytidine and N 4 ,N′-dimethyl-N 4 -aminocytidine were not mutagenic on these bacteria. Since N′-methyl-N 4 -aminocytidine does not form hydrazones, the possibility that N 4 -aminocytidine causes mutation due to its reactivity with carbonyl compounds has been excluded. Furthermore, the fact that only those alkyl N 4 -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 N 4 -aminocytosine allowing an ambiguous base pairing is the cause of the mutagenesis.