Aflatoxin M1 8,9-epoxide: preparation and mutagenic activity.
Treatment of aflatoxin M1 (AFM1) with dimethyldioxirane in an anhydrous mixture of CH2-Cl2 and acetone afforded the corresponding aflatoxin M1 8,9-epoxide (AFM1-E) in practically quantitative yield. This highly reactive intermediate was identified by 1H NMR and characterized by its neat conversion into the corresponding trans-methoxyhydrin derivative 1. The analysis of the 1H NMR spectrum of the above epoxide revealed that one stereoisomer, which should be that with the exo configuration, was present as major component. The mutagenicities of AFM1-E, the parent mycotoxin (AFM1), aflatoxin B1 (AFB1), and its epoxide (AFB1-E) were assessed by using a sensitive improved Ames test with the Salmonella typhimurium strain TA-100. AFM1 and AFB1 had specific mutagenic activities (SMA) of 13 and 121 revertants/ng, respectively, with S9 metabolic activation. AFM1-E was mutagenic with and without metabolic activation showing SMA of 13 and 12 revertants/ng, respectively. AFB1-E had a SMA of 42 and 29 revertants/ng, with and without S9 metabolic enzymes, respectively. These results suggest that the epoxidation of AFM1 can constitute a major route accounting for the cytotoxic effects elicited by this mycotoxin and that AFM1-E is not as active as AFB1-E in reacting with the constituents of the mutagenicity assay.
Bujons
J
J
Department of Biological Organic Chemistry, C.I.D. (C.S.I.C.), Barcelona, Spain.
Hsieh
D P
DP
Kado
N Y
NY
Messeguer
A
A
D016607:Aflatoxin M1 / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000633:toxicity*; D000818:Animals; D004852:Epoxy Compounds / Q000138:chemical synthesis / Q000633:toxicity*; D008099:Liver / Q000187:drug effects; D008297:Male; D009152:Mutagenicity Tests; D009153:Mutagens / Q000138:chemical synthesis / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
D004852:Epoxy Compounds; D009153:Mutagens; D016607:Aflatoxin M1