Protection against Aflatoxin B1 in Rat—A New Look at the Link between Toxicity, Carcinogenicity, and Metabolism

The ability of aflatoxin B1 (AFB1) to cause liver cancer has a profound impact on the health of many people living in certain regions of the developing world. A clearer understanding of the metabolism of this toxin in model systems may ultimately lead to effective strategies for preventing its harmful effects. To this end, the work described by Roebuck et al. in this issue of Toxicological Sciences illustrates how transgenic animals have been used to determine not only which routes of metabolism prevail in vivo, but also whether these contribute to the prevention of toxicity and carcinogenicity. By overexpressing AKR7A1, an aldo–keto reductase known to be capable of metabolizing AFB1, they also show that in the rat, the link between metabolism, toxicity and carcinogenicity is not as clear-cut as previously thought. Although the AKR7A1 enzyme is shown to be involved in the metabolism of AFB1in vivo, its effect in reducing toxicity is surprisingly muted. This work makes a significant contribution to our understanding of AFB1 metabolism and toxicity and the relative roles of specific enzymes in mediating protection.