Blumer J L, Friedman A, Meyer L W, Fairchild E, Webster L T, Speck W T
Cancer Res. 1980 Dec;40(12):4599-605.
Niridazole is a nitrothiazole anthelmintic agent used to treat schistosomiasis. Its antibacterial activity was found to require the presence of the nitro group; a synthetic desnitro analog was completely inactive. Niridazole was mutagenic for Salmonella tester strains TA1538, TA98, and TA100, suggesting that it was both a frame-shift- and a base substitution-type mutagen. It was effective under both aerobic and anaerobic conditions, while similar testing of the desnitro niridazole produced consistently negative results. Addition of rat liver S-9 fraction under either aerobic or anaerobic conditions did not enhance mutagenicity. However, since bacterial killing limited the dose of niridazole to 0.33 microgram/plate in standard tester strains (1/20 Km for the mammalian liver enzymes), further studies were performed using niridazole-resistant, histidine-dependent mutants derived from strains TA98 and TA100. These mutants were found to be nitroreductase deficient and to resist the mutagenic effects of niridazole, in the presence or absence of S-9, up to concentrations of 10 microgram/plate. In addition, even at niridazole concentrations of up to 100 microgram/plate, rat liver S-9 was ineffective in enhancing the mutagenicity of niridazole. These results suggest that the mutagenicity of niridazole is dependent on its aromatic nitro group and a specific bacterial nitroreductase.
硝唑咪是一种用于治疗血吸虫病的硝基噻唑驱虫剂。已发现其抗菌活性需要硝基的存在；一种合成的去硝基类似物完全无活性。硝唑咪对沙门氏菌测试菌株TA1538、TA98和TA100具有致突变性，表明它既是一种移码型又是一种碱基取代型诱变剂。它在需氧和厌氧条件下均有效，而去硝基硝唑咪的类似测试结果始终为阴性。在需氧或厌氧条件下添加大鼠肝脏S-9组分均未增强致突变性。然而，由于细菌杀伤作用将硝唑咪在标准测试菌株中的剂量限制为0.33微克/平板（为哺乳动物肝脏酶的1/20 Km），因此使用从TA98和TA100菌株衍生的耐硝唑咪、组氨酸依赖型突变体进行了进一步研究。发现这些突变体缺乏硝基还原酶，并且在有或没有S-9的情况下，对高达10微克/平板浓度的硝唑咪的诱变作用具有抗性。此外，即使在硝唑咪浓度高达100微克/平板时，大鼠肝脏S-9也无法增强硝唑咪 的致突变性。这些结果表明，硝唑咪的致突变性取决于其芳香硝基和特定的细菌硝基还原酶。
