Gebel T, Koenig A
Medical Institute of General Hygiene and Environmental Health, University of Goettingen, Windausweg 2, D-37073, Goettingen, Germany.
Mutat Res. 1999 Aug 18;444(2):405-11. doi: 10.1016/s1383-5718(99)00111-4.
The bacterial SOS chromotest with Escherichia coli PQ37 was used for the assessment of genotoxicity of combined xenobiotic treatments. The modulation of test compound genotoxicity by dimethyl sulfoxide (DMSO), a common solvent for test compounds, was assessed as well. It was shown that DMSO modulated SOS chromotest genotoxicity of several xenobiotics: in comparison to test compound dissolution in water, the commonly used addition of 3.2% (v/v) DMSO as solvent lead to a significant increase in the genotoxicity of K(2)RhCl(5) and beta-propiolactone (BPL). However, the effects of cisplatin decreased significantly when DMSO was added. Thus, albeit DMSO is not genotoxic in this test itself, it can interfere with SOS chromotest responses. Further experiments were performed in the absence of DMSO. BPL and cisplatin in combination showed an over-additive synergism in SOS genotoxicity as well as K(2)RhCl(5) and cisplatin did. Addition of Pd(NH(3))(4)Cl(2) and NaAsO(2), which are non-genotoxic in the SOS chromotest, did not enhance the K(2)RhCl(5)- or BPL-mediated SOS sfiA induction. Nevertheless, at the highest subcytotoxic dose of NaAsO(2) tested (200 microM), a slight yet significant suppression of BPL-mediated SOS genotoxicity was observed. These results confirm that the SOS chromotest is a useful tool for the rapid evaluation of the combined genotoxicity of compound mixtures. However, the use of DMSO as test solvent has to be taken with caution.
采用大肠杆菌PQ37进行细菌SOS显色试验，以评估联合异源生物处理的遗传毒性。同时评估了二甲基亚砜（DMSO）（一种常用的受试化合物溶剂）对受试化合物遗传毒性的调节作用。结果表明，DMSO可调节几种异源生物在SOS显色试验中的遗传毒性：与受试化合物溶于水相比，常用的添加3.2%（v/v）DMSO作为溶剂会导致K(2)RhCl(5)和β-丙内酯（BPL）的遗传毒性显著增加。然而，添加DMSO后顺铂的效果显著降低。因此尽管DMSO本身在该试验中无遗传毒性，但它可能会干扰SOS显色试验的反应。在不使用DMSO的情况下进行了进一步实验。BPL和顺铂联合使用在SOS遗传毒性方面表现出超加性协同作用，K(2)RhCl(5)和顺铂联合使用也是如此。添加在SOS显色试验中无遗传毒性的Pd(NH(3))(4)Cl(2)和NaAsO(2)，不会增强K(2)RhCl(5)或BPL介导的SOS sfiA诱导。然而，在测试的NaAsO(2)最高亚细胞毒性剂量（200 microM）下，观察到对BPL介导的SOS遗传毒性有轻微但显著的抑制作用。这些结果证实，SOS显色试验是快速评估化合物混合物联合遗传毒性的有用工具。然而，使用DMSO作为受试溶剂时必须谨慎。
