Test of chiral recognition in the Salmonella typhimurium (TA100) mutagenicity of mucochloric acid-cysteine adducts.
A difference in biological response to enantiomers is not an uncommon observation and is, therefore, to be expected in various manifestations of genotoxicity. The bacterial mutagen mucochloric acid (2,3-dichloro-5-hydroxy-2(5H)-furanone) has one chiral center, at C-5, but this mutagen exists in racemic form because of the facile stereoisomerization occurring by the mechanism of ring-chain tautomerism. Two readily synthesized enantiomeric analogs of mucochloric acid, as well as the racemic form of the two, were prepared from mucochloric acid and (R)-(+)-, (S)-(-)-, and (R,S)-(+/-)-cysteine. Using Salmonella typhimurium (TA100), the enantiomeric compounds were assayed together in four dose/response assays along with mucochloric acid, the reference mutagen. In three of the same four assays, the racemic form was also assayed. Neither statistically significant differences in mutagenicity, as determined in slope responses, nor distinctions from the plotted curves were observed among the two enantiomers and their racemic form. Therefore, no enantiospecific interaction between enantiomers and chiral DNA or enzymes involved in repair or replication could be concluded.
LaLonde
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RT
Department of Chemistry, College of Environmental Science and Forestry, State University of New York, Syracuse.
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D000704:Analysis of Variance; D002942:Circular Dichroism; D003545:Cysteine / Q000378:metabolism / Q000633:toxicity*; D004249:DNA Damage; D004269:DNA, Bacterial / Q000378:metabolism; D005663:Furans / Q000737:chemistry / Q000633:toxicity*; D009152:Mutagenicity Tests; D009153:Mutagens / Q000737:chemistry / Q000633:toxicity*; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D004269:DNA, Bacterial; D005663:Furans; D009153:Mutagens; C014117:mucochloric acid; C067157:3,4-(dichloro)-5-hydroxy-2(5H)-furanone; D003545:Cysteine