Chagas' disease: carcinogenic activity of the antitrypanosomal nitroarenes in mice.
The carcinogenic activity of antitrypanosomal 2-nitroimidazole, 5-nitroimidazole and 5-nitrofuran derivatives was assessed in female Swiss mice of the same age group. A statistically significantly higher incidence of growths was seen in mice into which 2-nitro had been injected than in mice receiving 5-nitro derivatives intraperitoneally. A histologic type of lymphoblastic lymphoma that invades lymph nodes, spleen, liver, lungs and lymphatic tissue elsewhere was frequently found in nitroarene-treated mice. Further, it is shown that the potency of the drug, rather than the duration of its administration, was usually associated with the growth of lymphomas. The 2-nitro derivative which induced the highest incidence of lymphomas significantly decreased the survival of treated mice; this probably occurred because it undergoes enzymatic reduction of the nitro group more efficiently than the 5-nitro compounds used. The differences of incidence of lymphomas in mice receiving any of these nitroarenes and in control mice that received daily injections of 0.15 M saline were statistically significant (alpha = 0.05). The indiscriminate use of these nitroarenes to treat Trypanosoma cruzi infections in man could therefore induce a significant number of lymphomas.
Teixeira
A R
AR
Laboratory for Multidisciplinary Research in Chagas' Disease, Faculty of Health Sciences, University of Brasilia, Brazil.
Calixto
M A
MA
Teixeira
M L
ML
D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects; D014355:Chagas Disease / Q000188:drug therapy*; D005260:Female; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008198:Lymph Nodes / Q000187:drug effects / Q000473:pathology; D008223:Lymphoma / Q000139:chemically induced* / Q000473:pathology; D051379:Mice; D015394:Molecular Structure; D009547:Nifurtimox / Q000627:therapeutic use / Q000633:toxicity; D009593:Nitroimidazoles / Q000627:therapeutic use / Q000633:toxicity; D014344:Trypanocidal Agents / Q000627:therapeutic use / Q000633:toxicity*
D002273:Carcinogens; D009593:Nitroimidazoles; D014344:Trypanocidal Agents; C022191:MK 436; D009547:Nifurtimox; C009999:benzonidazole