Genotoxicity of p-nitrocinnamaldehyde and related alpha, beta-unsaturated carbonyl compounds in two bacterial assays.
Seventeen cinnamaldehydes, cinnamic acids, 2-furylacroleins and related compounds were tested in the Salmonella preincubation reversion assay and in the SOS chromotest. Of eight compounds containing nitrogroups, seven were clearly mutagenic in the presence of S9 mix and six in its absence; whereas none of the parent compounds not containing a nitrogroup and none of the congeners containing chlorine, methoxy or amino groups were mutagenic. Metabolic epoxidation was excluded in additional experiments using SKF525, an inhibitor of mono-oxygenases, and trichloropropene oxide, an inhibitor of epoxide hydrolases. Less or no mutagenicity was found in the nitroreductase deficient strains Salmonella typhimurium TA100NR or TA98NR and in the O-acetyltransferase deficient strains TA100/1,8-DNP6 or TA98/1,8-DNP6 except with 5-nitro-2-furylacrolein which exhibited decreased mutagenicity in TA100NR when compared with TA100 but the highest mutagenicity in TA100/1,8-DNP6. Less or no genotoxic activity was found in the SOS chromotest when using the nitroreductase deficient Escherichia coli strain PQ253 whereas all seven compounds tested were positive in strain PQ37. The results demonstrate the importance of the nitro group and that the compounds are activated either by bacterial nitroreductase or by the nitroreductase in the S9 mix. A chemical activation of the acrolein moiety by the negative inductive effect of the nitro group is unlikely. The genotoxicity of the cinnamyl compounds is dependent on the position of the nitro group in the phenyl ring. The genotoxicities of the p-nitro compounds were about two orders of magnitude higher than those of the ortho and meta congeners. The comparison between the Ames test and the SOS chromotest showed good agreement.
Eder
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E
Institute of Toxicology, University of Würzburg, FRG.
Deininger
C
C
Muth
D
D
D000171:Acrolein / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D001711:Biotransformation; D004926:Escherichia coli / Q000235:genetics; D016368:Frameshift Mutation; D016296:Mutagenesis; D009152:Mutagenicity Tests; D009154:Mutation; D009601:Nitroreductases / Q000378:metabolism; D013014:SOS Response, Genetics; D012486:Salmonella typhimurium / Q000235:genetics; D013329:Structure-Activity Relationship
C071678:4-nitrocinnamaldehyde; D000171:Acrolein; D009601:Nitroreductases; C012843:cinnamaldehyde