Assessment of chronic toxicity and carcinogenicity in an accelerated cancer bioassay in rats of Nifurtimox, an antitrypanosomiasis drug

Experimental and Toxicologic Pathology

Volumn 57, Issue 5-6, 2006, Pages 397-404

  Iatropoulos, M J ^a   Wang, C X ^a   von Keutz, E ^b   Williams, G M ^a  

^a NEW YORK MEDICAL COLLEGE   (United States)

^b BAYER PHARMA AG   (Germany)

Author keywords

Accelerated bioassay; Antitrypanosomiasis drug; Carcinogenicity; Chronic toxicity; Nifurtimox

Indexed keywords

7,12 DIMETHYLBENZ[A]ANTHRACENE; ANTITRYPANOSOMAL AGENT; DIETHYLNITROSAMINE; DIETHYLSTILBESTROL; N BUTYL N (4 HYDROXYBUTYL)NITROSAMINE; NIFURTIMOX; NITRILOTRIACETIC ACID; PHENOBARBITAL;

ADENOCARCINOMA; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BIOASSAY; BLADDER; BODY WEIGHT; BONE MARROW; CANCER; CARCINOGENICITY; CHAGAS DISEASE; CHRONIC TOXICITY; COLON; CONTROLLED STUDY; FEMALE; HISTOPATHOLOGY; KIDNEY; KIDNEY CARCINOMA; LIVER; LIVER ADENOMA; LUNG; MALE; MAMMARY GLAND; MORTALITY; NONHUMAN; RAT; RAT STRAIN; SPLEEN; STOMACH; TOXICITY TESTING; WEIGHT GAIN;

ANIMALIA; RATTUS NORVEGICUS; RODENTIA;

EID: 33745135438     PISSN: 09402993     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.etp.2006.01.005     Document Type: Article

References (36)

1. Aguilar E.G., Koldobsky C., Torunzo E.G.D., and Castro J.A. Species and sex differences in the liver microsomal nitroreductase biotransformation of Nifurtimox and Benzniazole. Arch Int Pharmacodyn Ther 287 (1987) 187
2. Alejandre-Duran E., Claramunt R.M., Sanz D., Vilaplana M.J., Molina P., and Pueyo C. Study on the mutagenicity of nifurtimox and eight derivatives with the l-arabinose resistance test of Salmonella typhimurium. Mutat Res 206 (1988) 193-200
3. Bomhard E., and Rinke M. Frequency of spontaneous tumours in Wistar rats in 2-year studies. Exp Toxicol Pathol 46 (1994) 17-29
4. Castro J.A. Contributions of toxicology to the problem of Chagas' disease (American Trypanosomiasis)-a year 2000 update. Biomed Environ Sci 13 (2000) 271-279
5. Castro J.A., and de Toranzo E.G. Toxic effects of nifurtimox and benznidazole, two drugs used against American trypanosomiasis (Chagas' disease). Biomed Environ Sci 1 (1988) 19-33
6. Cerisola J.A. Serologic findings in patients with acute Chagas' disease treated with Bay 2502. Bol Chil Parasitol 24 (1969) 54-59
7. Cutts H.H., and Noble R.L. Estrone-induced mammary tumors in the rat. Induction and behavior of tumor. Cancer Res 24 (1964) 1116-1123
8. de Toranzo E.G.D., de Herrera D.M., and Castro J.A. Rat liver nuclear nifurtimox nitroreductase activity. Res Commun Mol Pathol 98 (1997) 249-254
9. Dunnett C.W. A multiple comparison procedure for comparing several treatments with a control. J Am Stat Assoc 50 (1955) 1096-1121
10. Ertürk E., Price J.M., Morris J.E., Cohen S., Leith R.S., von Esch A.M., and Crovetti A.J. The production of carcinoma of the urinary bladder in rats by feeding N-[4-(5-Nitro-2-furyl)-2-thiazolyl]formamide. Cancer Res 27 (1967) 1998-2002
11. Ferreira R.C., and Ferreira L.C. Mutagenicity of nifurtimox and benznidazole in the Salmonella/microsome assay. Braz J Med Biol Res 19 (1986) 19-25
12. Ferreira R.C., Schwarz U., and Ferreira L.C. Activation of anti-Trypanosoma cruzi drugs to genotoxic metabolites promoted by mammalian microsomal enzymes. Mutat Res 204 (1988) 577-583
13. Gorla N.B. Sister-chromatid exchange in spleenic lymphocytes of mice after exposure to nifurtimox or benznidazole. Mutat Res 188 (1987) 129-133
14. Gorla N.B., Ledesma O.S., Barbieri G.P., and Larripa I.B. Thirteenfold increase of chromosomal aberrations non-randomly distributed in chagasic children treated with nifurtimox. Mutat Res 224 (1989) 263-267
15. Gorla N.B., Ledesma O.S., Barbieri G.P., and Larripa I.B. Lack of sensitivity of sister-chromatid exchange for lymphocyte chromosomal damage detection caused by antichagasic treatment. Toxicol Lett 58 (1991) 225-230
16. Hiasa Y., Kitahori Y., Konishi N., Shimoyama T., and Miyashiro A. Trisodium nitriloacetate monohydrate: promoting effect in urinary bladder carcinogenesis in rats treated with N-butyl-N-(4-hydroxybutyl)nitrosamine. J Natl Cancer Inst 74 (1985) 235-239
17. Hirose M., Masuda A., Inoue T., Fukushima S., and Ito N. Modification by antioxidants and p,p-diamino-diphenylmethane of 7,12-dimethylbenz-(a)-anthracene-induced carcinogenesis of the mammary gland and ear duct in CD rats. Carcinogenesis 7 (1986) 1155-1159
18. Hoffmann K. Toxicological investigations on the tolerability of nifurtimox. Arzneim Forsch 22 (1972) 1590-1603
19. Iatropoulos M.J. Accelerated rodent bioassay predictive of chemical carcinogenesis. Exp Toxicol Pathol 44 (1992) 481-487
20. Iatropoulos M.J., Williams G.M., Wang C.X., Brunnemann K.D., and Leber A.P. Assessment of chronic toxicity and carcinogenicity in rats of Wingstay 100, a rubber antioxidant/antiozonant. Exp Toxicol Pathol 49 (1997) 153-165
21. Iatropoulos M.J., Jeffrey A.M., Enzmann H.G., von Keutz E., Schlueter G., and Williams G.M. Assessment of chronic toxicity and carcinogenicity in an accelerated cancer bioassay in rats of moxifloxacin, a quinolone antibiotic. Exp Toxicol Pathol 53 (2001) 345-357
22. Melo M.E., and Ferreira L.C. Screening the mutagenic activities of commonly used antiparasite drugs by the Simultest, a simplified Salmonella/microsome plate incorporation assay. Rev Inst Med Trop Sao Paulo 32 (1990) 269-274
23. Merletti F., Heseltine E., Saracci R., Simonato L., Vainio H., and Wilbourn J. Target organs for carcinogenicity of chemicals and industrial exposures in humans: a review of results in the IARC monographs on the evaluation of the carcinogenic risk of chemicals to humans. Cancer Res 44 (1984) 2244-2250
24. Moraga A.A., and Graf U. Genotoxicity testing of antiparasitic nitrofurans in the Drosophila wing somatic mutation and recombination test. Mutagenesis 4 (1989) 105-110
25. Morris J.E., Price J.M., Lalich .J., and Stein R.J. The carcinogenic activity of some 5-nitrofuran derivatives in the rat. Cancer Res 29 (1969) 2145-2156
26. Nagel R. Genotoxicity studies with two antichagasic drugs. Mutat Res 191 (1987) 17-20
27. Ohnishi T., Ohashi Y., Nozu K., and Inoki S. Mutagenicity of nifurtimox in Escherichia coli. Mutat Res 77 (1980) 241-244
28. Steinhoff D., and Grundmann E. Test for carcinogenicity of nifurtimox on oral and subcutaneous administration to rats. Arzneim Forsch (Drug Res) 22 (1972) 1607-1612
29. Williams G.M. The significance of chemically induced hepatocellular altered foci in rat liver and application to carcinogen detection. Toxicol Pathol 17 (1989) 663-674
30. Williams GM, Iatropoulos MJ. Principles of testing for carcinogenic activity. In: Hayes W. editor. Principles & methods of toxicology. Philadelphia, PA: Taylor & Francis; 2001. p. 959-1000.
31. Williams G.M. DNA reactive and epigenetic carcinogens. Exp Toxicol Pathol 44 (1992) 457-464
32. Williams G.M., Iatropoulos M.J., Wang C.X., Ali N., Rivenson A., Peterson L.A., Schultz C., and Gebhardt R. Diethylnitrosamine exposure-response for DNA damage, centrolobular cytotoxicity, cell proliferation and carcinogenesis in rat liver exhibts some non-linearities. Carcinogenesis 17 (1996) 2253-2258
33. Williams G.M., Iatropoulos M.J., and Weisburger J.H. Chemical carcinogen mechanisms of action and implications for testing methodology. Exp Toxicol Pathol 48 (1996) 101-111
34. Williams G.M., Iatropoulos M.J., Jeffrey A.M., Luo F.Q., Wang C.X., Thompson S., and Pittman B. Diethylnitrosamine exposure-responses for DNA ethylation, hepatocellular proliferation and initiation of carcinogenesis in the rat liver display non-linearities and thresholds. Arch Toxicol 73 (1999) 394-402
35. World Health Organization (WHO). Workshop on Guidelines for Standardized Protocols for the Chemotherapy of Chagas' Disease. (TDR/CHEMCHA/DCWKSHP/8/3), 1981. p. 1-12.
36. Zar J.H. Biostatistical analysis (1984), Prentice-Hall, Englewood Cliffs, NJ