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.
D004269:DNA, Bacterial / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D066298:In Vitro Techniques; D009153:Mutagens / Q000633:toxicity*; D009154:Mutation; D009607:Nitrosourea Compounds / Q000633:toxicity*
D004269:DNA, Bacterial; D009153:Mutagens; D009607:Nitrosourea Compounds; C014541:1,1-ethylenebis(1-nitrosourea)