The role of alcohols as solvents in the genotoxicity testing of alpha,beta-unsaturated ketones in the SOS chromotest.
alpha,beta-Unsaturated ketones are bifunctional compounds which form promutagenic 1,N(2)-propanodeoxyguanosine adducts like carcinogenic alpha,beta-unsaturated aldehydes and are mutagenic and genotoxic like these aldehydes. They are important industrial chemicals, are found in our environment and are widespread in our food. We investigated the SOS repair inducing activities of five ketones in the SOS chromotest and compared these results with that of the Ames test. Alkyl substitution at the beta-position of the alpha, beta-unsaturated carbonyl moiety leads to a decrease or loss in genotoxicity. Genotoxicity is higher if using ethanol as solvent instead of dimethylsulfoxide (DMSO). An increasing effect is also observed with methanol and n-propanol. Addition of the alcohol dehydrogenase inhibitor 4-methylpyrazole does not significantly influence the genotoxicity indicating that it is unlikely that the solvent effect depends on competitive inhibition of alcohol dehydrogenase by the alcohols used as solvents. Since other possible explanations e.g. ketal formation or solubility effects are also unlikely, the mechanism of this solvent effect observed with three different E. coli PQ-strains remains unresolved. No significant difference in genotoxicity of ethyl vinyl ketone was found between the strains PQ 37 and PQ 243 indicating that base excision repair does not play a role in the repair of 1,N(2)-propanodeoxyguanosine adducts, the main adducts of the alpha,beta-unsaturated ketones.
Eder
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Department of Toxicology, University of Würzburg, Versbacher Str. 9, 97078, Würzburg, Germany. eder@toxi.uni-wuerzburg.de
Deininger
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D000438:Alcohols; D000469:Alkaline Phosphatase / Q000378:metabolism; D002074:Butanones / Q000633:toxicity; D004926:Escherichia coli / Q000187:drug effects; D007659:Ketones / Q000737:chemistry / Q000633:toxicity*; D009152:Mutagenicity Tests / Q000379:methods*; D010422:Pentanones / Q000633:toxicity; D013014:SOS Response, Genetics; D012486:Salmonella typhimurium / Q000187:drug effects; D012997:Solvents
D000438:Alcohols; D002074:Butanones; D007659:Ketones; D010422:Pentanones; D012997:Solvents; C057920:3-buten-2-one; D000469:Alkaline Phosphatase; C057461:1-pentene-3-one