Macromolecular action of nitrosoguanidine in Escherichia coli

Abstract

1. The effects of the mutagen N-methyl- N′-nitro- N-nitrosoguanidine on macromolecules and their synthesis have been studied in several strains of Escherichia coli. 2. Nitrosoguanidine treatment at pH 5.0 results in some alteration of DNA that is recognized and repaired by the same mechanism involved in the dark repair of DNA damaged by ultraviolet light. This alteration, if unrepaired, is lethal to the cell. This is the principal cause of lethality in strain B s-1 which is deficient in the dark repair mechanism. 3. Nitrosoguanidine inactivates the enzyme β-galactosidase within the cells. This action on proteins, however, is not sufficient to account for lethality. 4. Nitrosoguanidine exhibits a pronounced inhibitory effect on protein synthesis and a much lesser effect on RNA synthesis. This effect involves the reduction in rate of synthesis of proteins and the production of small amounts of non-functional proteins. Several indications exist that this is the principal cause of lethality on strains that can repair DNA damage. 5. The presence of streptomycin enhances the survival of nitrosoguanidine-treated streptomycin-resistant cells, suggesting that nitrosoguanidine causes misreading of the genetic code that can be suppressed by streptomycin.