IARC MONOGRAPHS ON THE EVALUATION OF CARCINOGENIC ...

FUMONISIN B 1
Figure 5. A model for the proposed interference by fumonisin B 1 (FB 1) with delta 6
(Δ6) desaturase activity and consequent effects on the fatty acid composition of
phosphatidylcholine (PC) and phosphatidylethanolamine (PE) and changes in the
cyclo-oxygenase metabolic pathway
For additional details, see Gelderblom et al. (2001a).
PGE 1 and PGE 2, prostaglandin E 1 and E 2
observed in the liver of rats and mice exposed to hepatotoxic levels of fumonisin B 1
(Figure 6). Increased expression of c-myc and TGF β 1 may also play a role in the
promotion of liver tumours by fumonisin B 1 (Lemmer et al., 1999a).
( f ) Altered cell cycle progression
Fumonisin B 1 disruption of sphingolipid metabolism and altered membrane phospholipids
in the liver of BD IX rats have been suggested to cause the changes seen in
several proteins (e.g., cyclin D1, retinoblastoma protein) that regulate cell cycle progression.
Accumulation of cyclin D1 was due to post-translational stabilization of the
protein (Ramljak et al., 2000).
Fumonisin B 1-induced alterations in cellular glycerophospholipid content and the
sphingomyelin cycle have been proposed to interact so as to modify a variety of cellular
processes, resulting in the increased apoptosis and altered hepatocyte proliferation that
are seen in liver of rats fed toxic doses of fumonisin B 1 (Figure 6). The balance between
lipid mediators generated via the cyclo-oxygenase-2 and ceramide cycle could regulate
processes related to cell proliferation and apoptosis. As summarized in Figure 6, fumonisin
B 1-induced changes in ceramide, prostaglandins and other lipid mediators could
alter the growth and survival of normal hepatocytes. Overexpression of TGF β 1 and
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