Mutagenicity of a series of N-alkyl-, N-hydroxyalkyl-, N-haloalkyl- and N-carboxyalkyl-N-nitrosoureas in Escherichia coli tester strains: dependence on the uvrA DNA-repair system.
A series of N-alkyl-, N-hydroxyalkyl-, N-haloalkyl- and N-carboxyalkyl-N-nitrosoureas and some related derivatives were tested for mutagenicity in E. coli B (Arg-) H/r30R (wild-type) and its isogenic Hs30R (uvrA) tester strains. Mutagenic potency in Hs30R, in general, appears to depend on the substituent (-OH, -OCH3, -halogen, -COO- or -COOCH3) on the alkyl group, rather than the chain length or branching of the alkyl group. On the other hand, mutagenic potency in the wild-type H/r30R strain depends on buliness of the substituent and alkyl moiety. The term "uvrA-dependence" of mutation frequency is then defined as the ratio of the mutation frequency in Hs30R versus that in H/r30R at 1 mM dose of mutagens. Its dependence on structure is also discussed. A good correlation was found with the van der Waals volume of the substituted alkyl group, except for compounds having a carboxyalkyl or a branched alkyl group. The carboxyalkyl derivatives are the most weakly mutagenic and most seriously "uvrA-dependent", probably due to the negative charge of the molecule. The possibility of forming epoxides and lactones from N-hydroxyalkyl- and N-carboxyalkyl-N-nitrosoureas, respectively, and their participation in mutagenic potency are discussed. An attempt to correlate the partition property and activation rate of the N-nitrosoureas with mutagenic characteristics proved unsuccessful.
D001426:Bacterial Proteins / Q000235:genetics*; D004260:DNA Repair; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics* / Q000528:radiation effects; D007202:Indicators and Reagents; D009152:Mutagenicity Tests; D009153:Mutagens; D009154:Mutation; D009607:Nitrosourea Compounds / Q000138:chemical synthesis / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D001426:Bacterial Proteins; D007202:Indicators and Reagents; D009153:Mutagens; D009607:Nitrosourea Compounds