Fumonisin-induced hepatocarcinogenesis: mechanisms related to cancer initiation and promotion.

Publisher: National Institute of Environmental Health Sciences Country of Publication: United States NLM ID: 0330411 Publication Model: Print Cited Medium: Print ISSN: 0091-6765 (Print) Linking ISSN: 00916765 NLM ISO Abbreviation: Environ Health Perspect Subsets: MEDLINE

Original Publication: Research Triangle Park, N. C. National Institute of Environmental Health Sciences.

Fumonisins*; Carboxylic Acids/*toxicity ; Carcinogens, Environmental/*toxicity ; Liver Neoplasms, Experimental/*chemically induced ; Mycotoxins/*toxicity; Animal Nutritional Physiological Phenomena ; Animals ; Body Weight/drug effects ; Carboxylic Acids/isolation & purification ; Carcinogens, Environmental/isolation & purification ; Cells, Cultured ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Fatty Acids, Unsaturated/metabolism ; Fusarium/chemistry ; Fusarium/classification ; Lipids/biosynthesis ; Liver Neoplasms, Experimental/metabolism ; Male ; Mycotoxins/isolation & purification ; Phospholipids/metabolism ; Rats

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.

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0 (Carboxylic Acids)
0 (Carcinogens, Environmental)
0 (Fatty Acids, Unsaturated)
0 (Fumonisins)
0 (Lipids)
0 (Mycotoxins)
0 (Phospholipids)
3ZZM97XZ32 (fumonisin B1)

Date Created: 20010522 Date Completed: 20010802 Latest Revision: 20181113

20250114

PMC1240678

10.1289/ehp.01109s2291

11359698