Aflatoxin M1 8,9-epoxide: preparation and mutagenic activity
J Bujons1, D P Hsieh, N Y Kado
1Department of Biological Organic Chemistry, C.I.D. (C.S.I.C.), Barcelona, Spain.
Chemical Research in Toxicology
|April 1, 1995
Summary
The epoxidation of aflatoxin M1 (AFM1) yields a reactive epoxide (AFM1-E). This AFM1 epoxide exhibits mutagenicity, suggesting epoxidation is a key pathway for AFM1
Area of Science:
- Mycotoxicology
- Organic Chemistry
- Mutagenesis Studies
Background:
- Aflatoxin M1 (AFM1) is a toxic metabolite found in food.
- Understanding AFM1's cytotoxic effects is crucial for public health.
- Epoxidation is a known activation pathway for related mycotoxins.
Purpose of the Study:
- To synthesize and characterize aflatoxin M1 8,9-epoxide (AFM1-E).
- To assess the mutagenicity of AFM1-E and compare it to parent AFM1 and aflatoxin B1 (AFB1) and its epoxide (AFB1-E).
- To investigate the role of AFM1 epoxidation in its cytotoxic effects.
Main Methods:
- Synthesis of AFM1-E using dimethyldioxirane in a CH2-Cl2/acetone mixture.
- Characterization of AFM1-E using 1H NMR spectroscopy.
- Mutagenicity testing using the Ames test with Salmonella typhimurium TA-100, with and without S9 metabolic activation.
Main Results:
- AFM1-E was synthesized in high yield and characterized.
- AFM1-E demonstrated mutagenicity with and without metabolic activation (SMA 13 and 12 revertants/ng, respectively).
- AFM1-E was less mutagenic than AFB1-E (SMA 42 and 29 revertants/ng, with/without S9).
Conclusions:
- Epoxidation of AFM1 is a significant pathway contributing to its cytotoxic effects.
- AFM1-E is a mutagenic intermediate, though less potent than AFB1-E.
- These findings enhance our understanding of mycotoxin activation and toxicity mechanisms.
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