Comparative studies on the mutagenicity of 1,1'-ethylene-bis-(1-nitrosourea) and related compounds in Escherichia coli in relation to the formation of DNA interstrand cross-links.

The alkyl-nitrosourea-mediated formation of interstrand cross-links in E. coli DNA was studied by means of hydroxyapatite column chromatography. DNA interstrand cross-links were detected after treatment with 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) but not after treatment with 1,1'-ethylene-bis(1-nitrosourea) (EBNU) or 1-methyl-1-nitrosourea (MNU). Thus, alkylation of DNA by EBNU seems to be monofunctional, as wtih MNU. The mutagenic and lethal activities of these three compounds were tested with a pair of Escherichia coli strains. EBNU gave slightly but significantly higher mutagenicity and lethality in a repairless (uvrA-) strain than in its parental strain and wild-type DNA repair, whereas CCNU and MNU showed equal mutagenicity and lethality in the two strains.