Comparative study on the mutagenicity of three structurally related substituted aniline mustards in the Salmonella/microsome assay.

The ortho, meta and para isomers of N,N-bis(2-chloroethyl)aminocinnamic acid were tested for their ability to mutate Salmonella typhimurium strains in the Salmonella/microsome mutagenicity test. The aim of the work was to establish a structure-activity relationship between these three isomers. The drugs were found to induce base-pair substitutions, causing dose-dependent increases in his+ revertants, in strains TA100 and TA1535. The study showed that the position of the substituent groups influenced the mutagenic activity of the compounds. The ortho isomer exhibited a poorer mutagenic effect than meta and this was found to be a weaker mutagen than para. The presence of metabolic activation enzymes in the test system induced a further increase in his+ revertants, in strains TA100 and TA1535, which is consistent with the findings for melphalan, a cancer chemotherapeutic agent with a chemical structure similar to that of the isomers tested.