Mutagenicity of metronidazole: Activation by mammalian liver microsomes

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Abstract

The mutagenicity of metronidazole, a widely used chemotherapeutic agent, for Salmonella typhimurium was confirmed. Moreover using a mutant of of S. typhimurium unable to activate metronidazole to a genetically active metabolite, it is shown that this activation can be carried out by a microsomal preparation devived from rat liver. Heretofore it had been postulated that this metabolic event was catalyzed solely by enzymes present in protozoa and anaerobic bacteria. The present findings which indicate that mammalian enzymes can activate metronidazole to a genetically active intermediate may have a direct relevance to the carcinogenicity of this agent.

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