Summary
Metronidazole (MNZ), a widely used therapeutic drug, was administered to male and female Swiss mice intragastrically at a dose of 2 mg MNZ/mouse per day, 5 days a week, every alternate week, throughout their life span to test its carcinogenicity. The treatment induced a significant increase in the overall incidence of tumors in female mice but not in male mice. At the same dose, no teratogenic effect was observed. Perinatal carcinogenicity was studied by following up animals till the end of the F2 generation. Though different groups of animals were considered, a significant increase in tumor incidence was observed only in F1 mice which received MNZ treatment during gestation as compared to the corresponding control mice which received distilled water. The F1 mice which received MNZ during gestation, lactation, and subsequently in adulthood, and the F2 progeny had a tumor incidence comparable to that observed in control mice.
Similar content being viewed by others
References
Antani JA, Sriniwas HV, Krishnamurthy KR, Borgaonkar AN (1972) Metronidazole in dracunculiasis. Am J Trop Med Hyg 21:178–181
Bhide SV, Bhalerao EB, Sarode AV, Maru GB (1984) Mutagenicity and carcinogenicity of monoacetyl hydrazine. Cancer Lett 23:235–240
Bost RG (1977) Metronidazole: toxicology, and teratology Proceedings of international metronidazole conference, Montreal. Excerpta Medica, ICS 438, 112–118
Cavaliere A, Bacci M, Amorosi A, Del Gaudio M, Vitali R (1983) Induction of lung tumors and lymphomas in Balb/c mice by metronidazole. Tumori 69:379–382
Chacko M (1984) Mutagenicity, teratonicity and carcinogenicity of metronidazole'. Ph D Thesis, University of Bombay
Cosar C, Julou L (1959) Activity of 1-(2-hydroxyethyl-2-methyl-5-nitroimidazole) (R.P. 8823) in experimental Trichomonas vaginalis infections. Ann Inst Pasteur 96:238–241
Dalc MJ (1975) Metronidazole: teratogenicity study the rat by the intravenous route. May & Baker Internal Report RES/2193
Davies AA, McFadzean JA, Squires S (1975) Treatment of Vincent's stomatitis with metronidazole. Antimicrob Agents Chemother 7:672–675
Dawson AB (1926) A note on the staining of the skeleton of cleared specimens with Alizarin red S. Stain Technol 1:123–124
Foster JL, Willson RL (1976) Metronidazole (Flagyl) in cancer radiotherapy. In: Chemotherapy Vol 7. Plenum Publ Corp, New York, p 215–222
Garcia LA, De Bonilla L (1975) Clinical trials with metronidazole in human balantidiasis. Am J Trop Med Hyg 24:781–783
Goodman LS, Gilman A (1975) The pharmacological basis of therapeutics. McMillan, New York, pp 1072–1073, 1086–1088
Hedstrom SA (1980) Treatment of anginose infectious mononucleosis with metronidazole. A controlled clinical and chemical laboratory study. Scand J Infect Dis 12:265–269
Ivanov I (1969) The effect of Trichomonacid on pregnancy in experimental animals. Akusherstro Ginekologiya Sofia 8:241–244
Khambatta RB (1971) Metronidazole in giardiasis. Am J Trop Med Parasitol 65:489
May & Baker, Internal Report (1975) Teratogenicity study in the rabit by the intravenous route. Report RES/2729
Powell SJ, McLead I, Wilmot AJ, Elsdon DR (1966) Metronidazole in amoebic dysentry and amoebic liver abscess. Lancet II:1239–1331
Ralph ED, Kirby WMM (1975) Unique bacterial action of metronidazole Bacteroides fraquilis and Colstridium perfrigens. Antimicrob Agents Chemother 8:409–414
Roe FJC (1979) Personal communication to May & Baker Ltd., cited in Flagyl published by May & Baker Ltd., on behalf of the Rhaepoulenc Group, p 107
Rust JH (1977) An assessment in the tumorigenicity studies in the mouse and rat. In: MNZ Proceedings of the international MNZ conference, Montreal. Excerpts Media ICS 438, pp 138–144
Rustia M, Shubik P (1972) Induction of lung tumors and lymphomas in mice by metronidazole. J Natl Cancer Inst 48:721–723
Rustia M, Shubik P (1979) Experimental induction of hepatomas mammary tumors and other tumors with metronidazole in noninbred Sas: MRC (WI) BR rats. J Natl Cancer Inst 63:863–867
Shah SS, Sarode AV, Bhide SV (1985) Experimental studies on mutagenic and carcinogenic effect of tobacco chewing. J Cancer Res Clin Oncol
Tally FP, Sutter VL, Finegold SM (1975) Treatment of amoebic infections with metronidazole. Antimicrob Agents Chemother 7:672–675
Ursing B, Kamme C (1975) Metronidazole for Crohn's disease. Lancet I:775–777
Wilson JG (1965) Methods for administering agents and detecting malformations in experimental animals. In: Wilson JG, Warkary (eds) Teratology: principles and techniques. p 262–277
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Chacko, M., Bhide, S.V. Carcinogenicity, perinatal carcinogenicity and teratogenicity of low dose metronidazole (MNZ) in Swiss mice. J Cancer Res Clin Oncol 112, 135–140 (1986). https://doi.org/10.1007/BF00404396
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00404396