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Wentzel C.A. Gelderblom,¹ Stefan Abel,¹ Cornelius M. Smuts,² Jeanine Marnewick,¹ Walter F.O. Marasas,¹ Eric R. Lemmer,³ and Danica Ramljak⁴

¹Programme on Mycotoxins and Experimental Carcinogenesis and ²National Research Programme for Nutrional Intervention, Medical Research Council, Tygerberg, South Africa; ³MRC/UCT Liver Research Centre, University of Cape Town, Cape Town, South Africa; ⁴Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, Frederick, Maryland, USA

Abstract

We review the hepatocarcinogenic effects of fungal cultures of Fusarium verticillioides (= Fusarium moniliforme) strain MRC 826 in male BD IX rats. Subsequent chemical analyses of the fumonisin B (FB) mycotoxin content in the culture material used and long-term carcinogenesis studies with purified FB₁ provide information about dose-response effects, relevance of hepatotoxicity during FB₁-induced carcinogenesis, and the existence of a no-effect threshold. 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. Exposure levels < 0.08 mg FB/100 g bw/day fail to induce cancer, although mild toxic and preneoplastic lesions are induced. The nutritional status of the diets used in the long-term experiments was marginally deficient in lipotropes and vitamins and could have played an important modulating role in fumonisin-induced hepatocarcinogenesis. Short-term studies in a cancer initiation/promotion model in rat liver provided important information about the possible mechanisms involved during the initial stages of cancer development by this apparently nongenotoxic mycotoxin. These studies supported the findings of long-term investigations indicating that a cytotoxic/proliferative response is required for cancer induction and that a no-effect threshold exists for cancer induction. The mechanisms proposed for cancer induction are highlighted and include the possible role of oxidative damage during initiation and the disruption of lipid metabolism, integrity of cellular membranes, and altered growth-regulatory responses as important events during promotion. Key words: fatty acids, fumonisins, Fusarium verticillioides, hepatocarcinogenesis, hypothesis, mechanisms, phospholipids. -- Environ Health Perspect 109(suppl 2) :291-300 (2001) .

http://ehpnet1.niehs.nih.gov/docs/2001/suppl-2/291-300gelderblom/abstract.html