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Mutation Research, 38 (1976) 203--206 © Elsevier Scientific Publishing Company, Amsterdam -- Printed in The Netherlands
Short communication MUTAGENICITY OF METRONIDAZOLE: STRUCTURE-ACTIVITY RELATIONSHIPS
HERBERT S. ROSENKRANZ, JR., WILLIAM T. SPECK and JOHN E. STAMBAUGH
Departments of Microbiology and Pediatrics, College of Physicians and Surgeons, Columb& University, New York, N. Y. 10032 and Department of Pharmacology, Jefferson Medical College, Philadelphia, Pennsylvania (U.S.A.) (Received August 13th, 1975) (Revision received December 12th, 1975) (Accepted December 12th, 1975)
Recent reports [4,12] of the mutagenicity of metronidazole (1-(2-hydroxyethyl)-2-methyl-5-nitroimidazole) for bacterial species have caused concern regarding the safety of this widely used antiprotozoan and antibacterial agent [8]. Because it might be possible to synthesize derivatives of metronidazole devoid of genetic activity yet still retaining cbemotherapeutic effectiveness (see for example ref. [3], it was thought of interest to examine the mutagenic activity of several simple derivatives of metronidazole. For this study the mutagenicity assay developed by Ames and his associates [1] was used. A histidine-requiring strain of Salmonella typhimurium (TA100) together with the test agent were incorporated into the agar overlay [1,7]. The plates were incubated in the dark [11] for 2 days and revertants to histidine-independence were enumerated. Results are expressed as the averages of replicate plates from which the spontaneous background values (180--200 colonies per plate) were subtracted. The results of a typical set of experiments are summarized in Table I. Significant mutagenic activity was detected only with metronidazole, 1-methyl and 1,2
Mutation Research, 38 (1976) 203--206 © Elsevier Scientific Publishing Company, Amsterdam -- Printed in The Netherlands
Short communication MUTAGENICITY OF METRONIDAZOLE: STRUCTURE-ACTIVITY RELATIONSHIPS
HERBERT S. ROSENKRANZ, JR., WILLIAM T. SPECK and JOHN E. STAMBAUGH
Departments of Microbiology and Pediatrics, College of Physicians and Surgeons, Columb& University, New York, N. Y. 10032 and Department of Pharmacology, Jefferson Medical College, Philadelphia, Pennsylvania (U.S.A.) (Received August 13th, 1975) (Revision received December 12th, 1975) (Accepted December 12th, 1975)
Recent reports [4,12] of the mutagenicity of metronidazole (1-(2-hydroxyethyl)-2-methyl-5-nitroimidazole) for bacterial species have caused concern regarding the safety of this widely used antiprotozoan and antibacterial agent [8]. Because it might be possible to synthesize derivatives of metronidazole devoid of genetic activity yet still retaining cbemotherapeutic effectiveness (see for example ref. [3], it was thought of interest to examine the mutagenic activity of several simple derivatives of metronidazole. For this study the mutagenicity assay developed by Ames and his associates [1] was used. A histidine-requiring strain of Salmonella typhimurium (TA100) together with the test agent were incorporated into the agar overlay [1,7]. The plates were incubated in the dark [11] for 2 days and revertants to histidine-independence were enumerated. Results are expressed as the averages of replicate plates from which the spontaneous background values (180--200 colonies per plate) were subtracted. The results of a typical set of experiments are summarized in Table I. Significant mutagenic activity was detected only with metronidazole, 1-methyl and 1,2
