The organospecific activity of metronidazole and azanidazole in the intrasanguineous host-mediated assay.
The genotoxicity of nitroimidazoles and, in particular, their potential carcinogenicity has been demonstrated. In order to investigate the specific target organ(s) for these drugs or their metabolites, a method for measuring mutations in microorganisms, with reference to the metabolism of mammals, was used in mice. Metronidazole and azanidazole were tested for their ability to induce genetic effects in a diploid strain (D7) of Saccharomyces cerevisiae in the Intrasanguineous Host-Mediated Assay. The test compounds showed dose-related increases of point mutation and mitotic gene conversion frequencies in liver, kidney and lung. Azanidazole seemed to favour the kidney and the liver, although increases in genotoxicity were observed also in the lung. Metronidazole was toxic and induced both point mutation and mitotic gene conversion when recovered from the liver. Yeast recovered from the kidney and the lung showed an increase especially in point mutation. This work provides more information about the mechanisms involved in the mutagenicity of nitroimidazoles at the site of action.
D000818:Animals; D000994:Antitrichomonal Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D008297:Male; D008795:Metronidazole / Q000494:pharmacology*; D051379:Mice; D009153:Mutagens; D009154:Mutation; D009593:Nitroimidazoles / Q000494:pharmacology*; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics*
D000994:Antitrichomonal Agents; D009153:Mutagens; D009593:Nitroimidazoles; D008795:Metronidazole; C023624:azanidazole