Disease relevance of Fumonisin B

• An apparent no-effect threshold for kidney and liver damage is estimated to be between 0.11 and 0.18 mg FB/kg body weight (bw)/day, which corresponds to a feed contamination level of between 8.21 and 13.25 mg FB/kg bw diet [1].
• Fumonisin intake levels of between 0.08 and 0.16 mg FB/100 g body weight (bw)/day over approximately 2 years produce liver cancer in male BD IX rats [2].
• Where the mechanism has been studied most thoroughly, the accumulation of sphingoid bases is a primary cause of the toxicity of fumonisin B (FB) [3].
• These studies and others have indicated that the fumonisin B mycotoxins, although lacking mutagenicity in the Salmonella test or genotoxicity in the DNA repair assays in primary hepatocytes, appear to induce resistant hepatocytes similar to many known hepatocarcinogens [4].

High impact information on Fumonisin B

• The cancer-initiating potential of the fumonisin B (FB) mycotoxins produced by Fusarium moniliforme was screened in rat liver for their ability to induce rare hepatocytes with an acquired resistance to the mitoinhibitory effect of 2-acetyl-aminofluorene (2-AAF) [5].
• In addition, TNF-alpha down-regulated insulin-induced CCAAT/enhancer binding protein (C/EBP)-alpha gene expression and DNA binding activity, but fumonisin B precludes these effects [6].
• The fumonisin B mycotoxins (FB1 and FB2) have been purified and characterized from corn cultures of Fusarium moniliforme strain MRC 826 [4].

Biological context of Fumonisin B

• Moreover, inhibition of the ceramide biosynthesis with fumonisin B, which inhibits ceramide synthase, completely restored insulin-induced GLUT4 mRNA and protein accumulation as well as GLUT4-CAT transactivation in the presence of TNF-alpha [6].

Analytical, diagnostic and therapeutic context of Fumonisin B

• Short-term carcinogenesis studies in a rat liver bioassay indicated that over a period of 15 to 20 days, at dietary levels of 0.05-0.1%, FB2 and FB3 closely mimic the toxicological and cancer initiating activity of FB1 and thus could contribute to the toxicological effects of the fungus in animals [4].

References