Mutagenicity studies of a carcinogenic nitrofuran and some analogues.
Earlier studies showed a strong carcinogenicity of the nitrofuran compound 1,2-dihydro-2-(5'nitro-2'furyl)-3-hydroxy-quinazoline-4-one since carcinomas of the urinary bladder in rats and dogs appeared already after six months of treatment. In order to compare possible mutagenic properties of the compound and to get some information on the genotoxic moiety of the molecule, the genotoxicity of four nitrofuran derivatives and of two chemical analogues without the nitrofuran residue was tested in the Ames Test, E. coli WP2 uvrA, and in the rec-assay with Bacillus subtilis. 2-Nitrofuran was also included in this study. Only 2-nitrofuran and the nitrofuran containing derivatives were active in these bacterial test systems. Metabolic activation by liver homogenate was not needed to demonstrate the genotoxic effects. 1,2-dihydro-2-(5'nitro-2'furyl)-3-hydroxy-quinazoline-4-one was more active in the mutagenicity tests in the presence of exogenous metabolic activation. Further studies revealed that this compound was able to induce unscheduled DNA synthesis but was not mutagenic in the micronucleus test.
D000818:Animals; D002273:Carcinogens; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D009152:Mutagenicity Tests / Q000379:methods; D009153:Mutagens; D009581:Nitrofurans / Q000378:metabolism / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D002273:Carcinogens; D009153:Mutagens; D009581:Nitrofurans; D004247:DNA