Assuntos
Reparo do DNA/efeitos dos fármacos , Testes de Mutagenicidade/métodos , Mutagênicos , Resposta SOS em Genética/efeitos dos fármacos , 5-Amino-3-((5-nitro-2-furil)vinil)-1,2,4-oxadiazol/farmacologia , DDT/farmacologia , Dietilestilbestrol/farmacologia , Escherichia coli/efeitos dos fármacos , Hidroxibenzoatos/farmacologia , Metronidazol/farmacologia , Nitrofuranos/farmacologia , Perexilina/análogos & derivados , Perexilina/farmacologia , Fenacetina/farmacologia , Quercetina/farmacologia , Ticrinafeno/farmacologia , Uretana/farmacologiaRESUMO
Several pharmaceutical drugs show strong hepatotoxicity during therapeutic use. We have studied 6 of them: aminophenazone, clofibrate, nifuroxazide, oxamniquine, perhexiline maleate, tienilic acid. Their mutagenicity was assessed in the Ames test on 6 strains of Salmonella typhimurium, and in V79 Chinese hamster lung cells using a rat-hepatocyte-mediated metabolic activation system and the HGPRT and Na+/K+ ATPase assay. Nifuroxazide was positive in the Ames test in two Salmonella strains (TA100, and TA100 Fr1). In the hepatocyte-mediated mammalian V79 cell system, nifuroxazide, clofibrate and aminophenazone were negative; oxamniquine and tienilic acid were positive with and without metabolic activation in tests looking for ouabain and 6-thioguanine resistance. Perhexiline maleate was negative for the direct induction of 6-thioguanine resistance without metabolic activation, and positive after metabolisation mediated by primary rat's hepatocytes. These results suggest the need for some caution in the use of some pharmaceutical drugs because of hepatotoxicity and because 3 out of 6 drugs were shown to be slightly mutagenic in mammalian cells.
Assuntos
Aminopirina/farmacologia , Clofibrato/farmacologia , Glicolatos/farmacologia , Hipoxantina Fosforribosiltransferase/metabolismo , Fígado/patologia , Mutagênicos , Mutação , Nitrofuranos/farmacologia , Nitroquinolinas/farmacologia , Oxamniquine/farmacologia , Perexilina/farmacologia , ATPase Trocadora de Sódio-Potássio/metabolismo , Ticrinafeno/farmacologia , Animais , Biotransformação , Linhagem Celular , Cricetinae , Cricetulus , Resistência a Medicamentos , Fígado/efeitos dos fármacos , Pulmão , Microssomos Hepáticos/metabolismo , Testes de Mutagenicidade/métodos , Ouabaína/farmacologia , Ratos , Ratos Endogâmicos , Salmonella typhimurium/efeitos dos fármacos , Tioguanina/farmacologiaRESUMO
The nitroimidazole derivatives used in human therapy have shown a strong mutagenic activity in bacterial tests using Ames strains of Salmonella typhimurium. Our study compared the response of 4 products of this family on bacterial target cells as well as on mammalian target cells (Chinese hamster V79 cells). The strong positive response on TA100 was greatly reduced on the nitroreductase-deficient strain TA100 Frl. Furthermore, no mutagenic activity was found in V79 mammalian cells that we examined for ouabain and 6-thioguanine resistance.