Epoxides from aflatoxins

Figure 4. Some possible aflatoxin-thiol interactions A. addition to the double bond of AFBi to form an inactive thiol adduce B. interaction with AFBi epoxide which may prevent the epoxide from interacting with DNA C. displacement of an AFBi-DNA adduct blocking tumor formation.

Fig. 10.30. Structure of aflatoxin B1 exo-8,9-epoxide (10.132), the dihydrodiol resulting from hydrolysis (10.133), and the reactive a-hydroxy dialdehyde (10.134) that exists in equilibrium with the diol under alkaline conditions [204]...

Fortunately, nature provides an alternative nucleophile whose role is to mop up dangerous electrophiles such as aflatoxin Bi epoxide before they can do damage, and to remove them from the body. This compound is glutathione (see Box 6.6), a tripeptide composed of glutamic acid, cysteine, and glycine. 

Cytochrome P-450 hydroxylate many compounds. These include the hydroxylations of steroid hormone synthesis and the hydroxylation of thousands of xenobiotics (foreign compounds), including drugs such as phenobarbital and environmental carcinogens such as benzpyrene, a constituent of the smoke from tobacco and backyard grills. Hydroxylation of foreign substances usually increases their solubility and is a step in their detoxification, or metabolism and excretion. In some cases, however, some of these reactions activate potentially carcinogenic substances to more reactive species. Aflatoxin B, for example, is converted to a more reactive species either by hydroxylation or epoxidation. 

Conditions favouring aflatoxin production are very variable and studies suggest that temperature, substrate, water and a number of other factors may influence production. A recent study has suggested that the epoxides formed from unsaturated free fatty acids may increase aflatoxin production. 

---