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 manifestation s of genotoxicity. The bacterial mutagen mucochloric acid (2,3-dichlor o-5-hydroxy-2(5H)-furanone) has one chiral center, at C-5, but this mu tagen exists in racemic form because of the facile stereoisomerization occurring by the mechanism of ring-chain tautomerism. Two readily syn thesized enantiomeric analogs of mucochloric acid, as well as the race mic form of the two, were prepared from mucochloric acid and (R)-(+)-, (S)-(-)-, and (R,S)-(+/-)-cysteine. Using Salmonella typhimurium (TA1 00), the enantiomeric compounds were assayed together in four dose/res ponse assays along with mucochloric acid, the reference mutagen. In th ree of the same four assays, the racemic form was also assayed. Neithe r statistically significant differences in mutagenicity, as determined in slope responses, nor distinctions from the plotted curves were obs erved among the two enantiomers and their racemic form. Therefore, no enantiospecific interaction between enantiomers and chiral DNA or enzy mes involved in repair or replication could be concluded. (C) 1993 Wil ey-Liss, Inc.