Synthesis and genotoxicity of acetoxyoxirane, the epoxide of vinyl acetate.
Acetoxyoxirane, the epoxide of vinyl acetate and a potential reactive intermediate, was synthesized and characterized by 13C-nuclear magnetic resonance (13C-NMR) and mass spectroscopy. The compound induced lesions (endonuclease-sensitive and alkali-labile sites) in supercoiled PM2 DNA in vitro and was directly mutagenic toward Salmonella typhimurium TA100. The mutagenicity of the epoxide in phosphate buffer (pH 7.4, 37 degrees C) decreased, with an initial half-life of 2.8 minutes, and mutagenicity was completely abolished by addition of S-9 mix. Acetoxyoxirane did not induce unscheduled DNA synthesis on incubation with Syrian hamster embryo fibroblasts (SHE cells). These findings may possibly be explained by an effective inactivation of acetoxyoxirane by esterases when these are present in the biological system. This view is consistent with the lack of acetoxyoxirane detected in rat liver microsomal incubations of vinyl acetate.
Simon
P
P
Institut für Arbeitsphysiologie an der Universität Dortmund, FRG.
Epe
B
B
Mützel
P
P
Schiffmann
D
D
Wild
D
D
Ottenwälder
H
H
Fedtke
N
N
Bolt
H M
HM
Henschler
D
D
D000818:Animals; D002460:Cell Line / Q000187:drug effects; D006224:Cricetinae; D004247:DNA / Q000096:biosynthesis; D004249:DNA Damage; D004278:DNA, Superhelical; D004622:Embryo, Mammalian / Q000378:metabolism; D004852:Epoxy Compounds / Q000633:toxicity*; D004988:Ethers, Cyclic / Q000633:toxicity*; D008647:Mesocricetus; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D009152:Mutagenicity Tests; D051381:Rats; D011919:Rats, Inbred Strains; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics; D014753:Vinyl Compounds / Q000494:pharmacology
D004278:DNA, Superhelical; D004852:Epoxy Compounds; D004988:Ethers, Cyclic; D014753:Vinyl Compounds; C062918:acetoxyoxirane; D004247:DNA; C011566:vinyl acetate