Chirality-dependent DNA reactivity as the possible cause of the differential mutagenicity of the two components in an enantiomeric pair of epoxides.
Chemical compounds containing an epoxy group are very reactive substances and, in many cases, they therefore exhibit strong mutagenic properties. Very often such epoxides contain an asymmetric C atom and thus exist as racemic mixtures of optical isomers, the so-called R- and S-enantiomers. It is well known that in many cases a biological activity resides completely in one of the two enantiomeric forms of a molecule. Also, the R- and S-enantiomeric forms of epoxystyrene exhibit different mutagenic activities in Salmonella typhimurium TA100, although their chemical reactivity does not differ to a recognizable extent. Neither could the higher mutagenic activity of the R-epoxystyrene be attributed to a slower enzymatic hydrolysis reaction. Thus, the intrinsic potential for eliciting mutagenic responses may not be the same for the two enantiomers, as there is evidence of qualitative differences in the binding to DNA, pointing strongly to an intrinsic difference in mutagenic activity of the two enantiomers.
Seiler
J P
JP
Intercantonal Office for the Control of Medicines, Bern, Switzerland.
D004269:DNA, Bacterial / Q000378:metabolism; D004852:Epoxy Compounds / Q000633:toxicity*; D009152:Mutagenicity Tests; D012486:Salmonella typhimurium / Q000235:genetics; D013237:Stereoisomerism
D004269:DNA, Bacterial; D004852:Epoxy Compounds; C013690:styrene oxide