Gelderblom W C, Abel S, Smuts C M, Marnewick J, Marasas W F, Lemmer E R, Ramljak D
Programme on Mycotoxins and Experimental Carcinogenesis, Medical Research Council, Tygerberg, South Africa.
Environ Health Perspect. 2001 May;109 Suppl 2(Suppl 2):291-300. doi: 10.1289/ehp.01109s2291.
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.
我们综述了轮枝镰孢菌（=串珠镰孢菌）菌株MRC 826的真菌培养物对雄性BD IX大鼠的肝癌致癌作用。随后对所用培养材料中的伏马菌素B（FB）霉菌毒素含量进行化学分析，以及用纯化的FB1进行长期致癌研究，提供了关于剂量反应效应、FB1诱导致癌过程中肝毒性的相关性以及无效应阈值存在与否的信息。在大约2年的时间里，雄性BD IX大鼠每天摄入0.08至0.16毫克FB/100克体重会引发肝癌。暴露水平低于0.08毫克FB/100克体重/天虽不会诱发癌症，但会诱发轻度毒性和癌前病变。长期实验中所用饮食的营养状况在促脂物质和维生素方面略有不足，可能在伏马菌素诱导的肝癌发生过程中起到了重要的调节作用。在大鼠肝脏的癌症启动/促进模型中进行的短期研究，为这种明显无基因毒性的霉菌毒素在癌症发展初始阶段可能涉及的机制提供了重要信息。这些研究支持了长期调查的结果，表明癌症诱导需要细胞毒性/增殖反应，并且癌症诱导存在无效应阈值。文中强调了提出的癌症诱导机制，包括启动过程中氧化损伤的可能作用，以及脂质代谢紊乱、细胞膜完整性破坏和生长调节反应改变作为促进过程中的重要事件。
