Ferreira R C, Schwarz U, Ferreira L C
Departamento de Biofísica e Radiobiologia, Cidade Universitária, Recife.
Mutat Res. 1988 Apr;204(4):577-83. doi: 10.1016/0165-1218(88)90060-2.
Salmonella typhimurium TA100 and its nitroreductase-deficient derivative, TA100 NR, were used to reevaluate the mutagenic activities of benznidazole and nifurtimox. Mutagenicity and toxicity of nifurtimox were abolished in the TA100 NR tester strain under aerobic or anaerobic conditions and addition of rat liver extracts did not alter the results. However, benznidazole showed a significant mutagenicity and toxicity to the nitroreductase-deficient strain TA100 NR under hypoxic conditions. Addition of rat liver extracts enhanced the observed mutagenicity and toxicity of benznidazole even more. In the presence of O2 the genotoxic activities of benznidazole to the TA100 NR tester strain were eliminated. These results lead us to conclude that bacterial enzymes were responsible for the previously observed genotoxic effects of nifurtimox and benznidazole on S. typhimurium TA100. Moreover, under anaerobic conditions, only benznidazole could be metabolized by mammalian nitroreductases into a mutagenic derivative.
鼠伤寒沙门氏菌TA100及其硝基还原酶缺陷型衍生物TA100 NR被用于重新评估苯硝唑和硝呋替莫的致突变活性。在需氧或厌氧条件下，硝呋替莫在TA100 NR测试菌株中的致突变性和毒性均被消除，添加大鼠肝脏提取物也未改变结果。然而，在缺氧条件下，苯硝唑对硝基还原酶缺陷型菌株TA100 NR表现出显著的致突变性和毒性。添加大鼠肝脏提取物甚至进一步增强了所观察到的苯硝唑的致突变性和毒性。在有氧存在的情况下，苯硝唑对TA100 NR测试菌株的遗传毒性活性被消除。这些结果使我们得出结论，细菌酶是之前观察到的硝呋替莫和苯硝唑对鼠伤寒沙门氏菌TA100的遗传毒性作用的原因。此外，在厌氧条件下，只有苯硝唑可被哺乳动物硝基还原酶代谢为一种致突变衍生物。
