ß-glucuronic acid

FIGURE 25.3 Reduction of chemically induced ACF in CF1 by orally administered natural and synthetic sphingolipids.63-67 Synthetic Sphingolipids

Changes in the sphingolipid structure can alter their physicochemical properties, thereby the metabolism in the cells, and their release into the body. It also can affect their signaling capacity. There are many reports on sphingolipid analogs, tested mostly in cell culture. Because these are intended for treatment of cancer, these reports are not included here.

The use of natural compounds gives rise to the risk that co-isolated contaminants alter the response to the treatment. However, synthetic sphingomyelin administered in the same fashion as the natural compounds (Figure 25.2A) lowered the number of ACF to the same degree as sphingomyelin extracted from buttermilk (Figure 25.3) demonstrating that the chemopreventive effect of the natural preparation was indeed due to the sphingomyelin in the diet and not altered by a co-purified contaminant.76 Synthetic sphingomyelin containing a sphinganine rather than a sphingosine base (lacks the 4,5-trans double bond) showed a comparable reduction. As ceramides that contain sphinganine (termed dihydroceramides) are inactive in most biological systems,77 this study suggests that the most important bioactive metabolites in ACF suppression may be the free

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