Turner P C, Nikiema P, Wild C P
Molecular Epidemiology Unit, Algernon Firth Building, School of Medicine, University of Leeds, Leeds LS2 9JT, UK.
Mutat Res. 1999 Jul 15;443(1-2):81-93. doi: 10.1016/s1383-5742(99)00012-5.
Fumonisins, fungal toxins produced by Fusarium moniliforme, contaminate maize based foods and feeds throughout the world. They cause liver and kidney toxicity in animals in addition to leukoencephalomalacia in horses and pulmonary edema in pigs. Fumonisin B(1) is carcinogenic in rats and mice. Ecological studies have linked consumption of fumonisin contaminated maize with oesophageal cancer in human populations in South Africa and China. This review discusses the potential health risks for people exposed to the fumonisins, and describes how mechanistic studies of toxicity in animal models have allowed the development of putative biomarkers of fumonisin exposure at the individual level. The requirements for an applicable biomarker include sample availability as well as a high specificity and sensitivity for the exposure of interest. Most environmental toxic insults involve complex exposures both to other toxins and to infections; these confounding factors need to be considered in assessing both the validity of the biomarker and the exposure-disease associations. Fumonisins can be detected in the urine of animals in feeding studies but the sensitivity of the current methodology means only highly exposed people could be monitored. Mechanistic studies indicate that ceramide synthase, an enzyme involved in sphingolipid synthesis, is one cellular target for fumonisin toxicity and carcinogenicity, and this disruption to sphingolipid metabolism increases the ratio of two sphingoid precursors, sphinganine and sphingosine. The altered ratio has been observed in tissues, serum and urine for a number of animal models suggesting it as a good candidate marker of fumonisin exposure. Despite development of analytical methods to measure this biomarker there have been no studies to date correlating it to fumonisin intake in people. Given the toxic effects of fumonisins in animals and the widespread human exposure, which has been calculated to reach 440 micrograms kg(-1) body weight day(-1) in a population consuming high quantities (460 g day(-1)) of contaminated maize, then the development of biomarkers and their application in epidemiological studies should be a priority for research on these toxins.
伏马菌素是由串珠镰刀菌产生的真菌毒素，污染了全球以玉米为原料的食品和饲料。它们除了会导致马患白质软化症和猪患肺水肿外，还会对动物的肝脏和肾脏产生毒性。伏马菌素B1对大鼠和小鼠具有致癌性。生态学研究表明，食用受伏马菌素污染的玉米与南非和中国人群的食管癌有关。这篇综述讨论了接触伏马菌素的人群面临的潜在健康风险，并描述了动物模型中的毒性机制研究如何促成了个体水平上伏马菌素暴露推定生物标志物的开发。适用生物标志物的要求包括样本可获取性以及对目标暴露具有高特异性和高敏感性。大多数环境毒性侵害涉及对其他毒素和感染的复杂暴露；在评估生物标志物的有效性以及暴露与疾病的关联时，需要考虑这些混杂因素。在喂养研究中可以在动物尿液中检测到伏马菌素，但目前方法的灵敏度意味着只能监测高暴露人群。机制研究表明，参与鞘脂合成的神经酰胺合酶是伏马菌素毒性和致癌性的一个细胞靶点，这种对鞘脂代谢的破坏增加了两种鞘氨醇前体——神经鞘氨醇和神经鞘脂醇的比例。在许多动物模型的组织、血清和尿液中都观察到了这种变化的比例，这表明它是伏马菌素暴露的一个良好候选标志物。尽管已经开发出测量这种生物标志物的分析方法，但迄今为止尚无研究将其与人类的伏马菌素摄入量相关联。鉴于伏马菌素对动物的毒性作用以及人类的广泛暴露（据计算，在大量食用（每天460克）受污染玉米的人群中，伏马菌素暴露量可达440微克/千克体重/天），那么生物标志物的开发及其在流行病学研究中的应用应该是这些毒素研究的优先事项。
