Mode of mutagenic action of methylnitrosocyanamide, a potent carcinogen

Abstract

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 lambda 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 leads to AT base substitution mutation, whereas this is the obligate mode of mutation in gene supE. We conclude that methylnitrosocyanamide preferentially induces GC leads to 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-nitrosoguanidine also preferentially induce GC leads to AT transition mutations.