Mode of Mutagenic Action of Methylnitrosocyanamide, a Potent Carcinogen¹

A potent carcinogen, methylnitrosocyanamide was used to induce revertants in a strain of Escherichia coli carrying an amber mutation in a gene for tryptophan (trp) biosynthesis and an ochre mutation in a gene for alkaline phosphatase biosynthesis. Trp⁺ revertants were purified and classified into seven categories based on their ability to support the growth of particular nonsense mutants of phage λ and on their content of alkaline phosphatase. About 90% of the Trp⁺ revertants induced by methylnitrosocyanamide were due to mutations in suppressor genes, and 85% of the suppressor mutations occurred in gene supE. Intragenic reversion cannot occur by a GC → AT base substitution mutation, whereas this is the obligate mode of mutation in gene supE. We conclude that methylnitrosocyanamide preferentially induces GC → AT transition mutations but that other base substitution mutations are also induced at about 10% of this frequency. N-Methyl-N-nitrosourea and, particularly, N-methyl-N′-nitro-N-nitro-soguanidine also preferentially induce GC → AT transition mutations.