Impact of dimethyl sulfoxide and examples of combined genotoxicity in the SOS chromotest

The bacterial SOS chromotest with Escherichia coli PQ37 was used for the as sessment of genotoxicity of combined xenobiotic treatments. The modulation of test compound genotoxicity by dimethyl sulfoxide (DMSO), a common solven t for test compounds, was assessed as well. It was shown that DMSO modulate d SOS chromotest genotoxicity of several xenobiotics: in comparison to test compound dissolution in water, the commonly used addition of 3.2% (v/v) DM SO as solvent lead to a significant increase in the genotoxicity of K2RhCl5 and beta-propiolactone (BPL). However, the effects of cisplatin decreased significantly when DMSO was added. Thus, albeit DMSO is not genotoxic in th is test itself, it can interfere with SOS chromotest responses. Further exp eriments were performed in the absence of DMSO. BPL and cisplatin in combin ation showed an over-additive synergism in SOS genotoxicity as well as K2Rh Cl5 and cisplatin did. Addition of Pd(NH3)(4)Cl-2 and NaAsO2, which are non -genotoxic in the SOS chromotest, did not enhance the K2RhCl5- or BPL-media ted SOS sfiA induction. Nevertheless, at the highest subcytotoxic dose of N aAsO2 tested (200 mu M), a slight yet significant suppression of BPL-mediat ed SOS genotoxicity was observed. These results confirm that the SOS chromo test 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 t aken with caution. (C) 1999 Elsevier Science B.V. All rights reserved.