Fumonisin-induced hepatocarcinogenesis: Mechanisms related to cancer initiation and promotion
Fumonisin-induced hepatocarcinogenesis: Mechanisms related to cancer initiation and promotion
复制标题
DOI：
10.2307/3435021
复制
发表时间：
2001-05-01
影响因子：
10.4
通讯作者：
Ramljak, D
中科院分区：
文献类型：
--
作者：
Gelderblom, WCA;Abel, S;Ramljak, D
我们回顾了真菌培养物轮枝镰刀菌（=串珠镰刀菌）菌株MRC 826在雄性艾德IX大鼠中的肝癌作用。随后对所用培养材料中伏马菌素B（FB）真菌毒素含量的化学分析和对纯化FB（1）的长期致癌性研究提供了有关剂量反应效应、FB（1）诱导致癌过程中肝毒性相关性以及无效应阈值存在的信息。在雄性艾德IX大鼠中，约2年内0.08至0.16 mg FB/100 g体重（bw）/天的伏马菌素摄入水平会导致肝癌。接触水平< 0.08 mg FB/100 g bw/天不会诱发癌症，但会诱发轻度毒性和肿瘤前病变。在长期实验中使用的饮食的营养状况是轻微缺乏脂肪和维生素，并可能在伏马菌素诱导的肝癌发生中发挥重要的调节作用。在大鼠肝脏中的癌症起始/促进模型中进行的短期研究提供了关于这种明显无遗传毒性的真菌毒素在癌症发展的初始阶段所涉及的可能机制的重要信息。这些研究支持长期研究的结果，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作用阈值。提出的机制远癌症诱导突出，包括在启动和破坏脂质代谢，细胞膜的完整性，并改变生长调节反应的重要事件在促进过程中的氧化损伤的可能作用。
We review the hepatocarcinogenic effects of fungal cultures of Fusarium verticillioides(= Fusarium moniliforme) strain MRC 826 in male ED IX rats. Subsequent chemical analyses of the fumonisin B (FB) mycotoxin content in the culture material used and long-term carcinogenesis studies with purified FB(1) provide information about dose-response effects, relevance of hepatotoxicity during FB(1)-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 ED 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 far 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.