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 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.
Gebel
T
T
Medical Institute of General Hygiene and Environmental Health, University of Goettingen, Windausweg 2, D-37073, Goettingen, Germany. tgebel@gwdg.de
Koenig
A
A
D002945:Cisplatin / Q000633:toxicity; D003124:Colorimetry; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics; D009152:Mutagenicity Tests; D013014:SOS Response, Genetics / Q000187:drug effects*
D002945:Cisplatin; D004121:Dimethyl Sulfoxide