Validation of Fumonisin and Microcystin Biomarkers

描述（由申请人提供）： 本研究项目的长期目标是研究 暴露于伏马菌素和微囊藻毒素与人类肝癌和食道癌 高危人群的风险。伏马菌素和微囊藻毒素是新发现的 确定了由产毒真菌产生的环境生物毒素， 蓝藻，分别。伏马菌素是致癌物质， 并且微囊藻毒素在动物模型中是强肿瘤促进剂。人类 世界某些地区的人口暴露于更高水平的这些 日常生活中的毒素主要是通过受污染的饮食成分 和/或饮用水。这两种毒素在病因学上都与 人原发性肝癌和食管癌高发区 在南非和中国。虽然检测的分析方法 据报道，环境样品中存在这些毒素， 生物标志物，如伏马菌素对鞘脂代谢的破坏， 已经在动物中发现微囊藻毒素抑制蛋白磷酸酶 模型，这些生物标志物在人类中的验证，特别是在高风险 人口，没有做或报告。到目前为止， 用于同时检测环境样品中的这些毒素， 人体体液对于评估人类癌症风险至关重要， 因为在高危人群中同时接触这些生物毒素， 广泛报道。在这个探索性的研究项目中，我们将开发和 验证分析阵列方法，以同时测量这些生物毒素， 包括环境样本和人体体液我们将使用分子 流行病学工具，以验证体液中生物标志物的方法， 原发性肝癌和食管癌病例及对照组。工作 这项研究建议的假设是，长期暴露于 伏马菌素和微囊藻毒素可诱导协同致癌作用， 高风险个体和经验证的生物标志物的应用可以改善 定量估计人类接触这些生物毒素的癌症风险。 具体目标是：1）研制快速、灵敏的分析阵列 用于测量伏马菌素和微囊藻毒素生物标志物的方法， 先前开发的用于黄曲霉毒素和/或 微囊藻毒素的HPLC-酶联免疫吸附测定法; 2）验证 用于测量食品中微囊藻毒素和伏马菌素的生物标志物的方法， 水和体液，如血液和尿液样本，从两个 在高风险人群中进行的为期一周的纵向生物监测研究 原发性肝癌和食管癌的区域，以及3）执行 两个原发性肝癌高危人群的分子流行病学研究 中国启东和淮安的肝癌和食道癌中国为 探索暴露于伏马菌素和微囊藻毒素的癌症风险。

DESCRIPTION (provided by applicant): The long-term goal of this research project is to study relationships between exposure to fumonisins and microcystins and human liver and esophageal cancer risks in high-risk populations. Fumonisins and microcystins are newly identified environmental biotoxins that are produced by toxicogenic fungi and cyanobacteria, respectively. Fumonisins are carcinogens and both fumonisins and microcystins are strong tumor promoters in animal models. Human populations in certain areas of world are exposed to higher levels of these toxins in their daily life mainly through contaminated dietary components and/or drinking water. Both of these toxins have been etiologically linked to high incidence of human primary liver cancer and esophageal cancer in several areas of South Africa and China. Although analytical methods for detecting these toxins in environmental samples have been reported and potential biomarkers, such as disruption of sphingolipids metabolism by fumonisins and inhibition of protein phosphatases by microcystins, have been found in animal models, validation of these biomarkers in humans, especially in high-risk populations, has not been done or reported. To date, methods are still lack for simultaneously detection of these toxins in environmental samples and human body fluids, which are critical for assessment of human cancer risks, because co-exposure to these biotoxins in high-risk populations has been widely reported. In this exploratory research project, we will develop and validate analytical array methods to simultaneously measure these biotoxins in both environmental samples and human body fluids. We will use molecular epidemiological tools to validate methods for biomarkers in body fluids of cases of primary liver cancer and esophageal cancer and controls. The working hypothesis underlying this research proposal is that long-term exposure to fumonisins and microcystins may induce synergistic carcinogenic effects in high-risk individuals and application of validated biomarkers can improve the quantitative estimation of human cancer risk from exposure to these biotoxins. The specific aims are: 1) to develop rapid and sensitive analytical array method(s) for measuring fumonisin and microcystin biomarkers based on previously developed immunoaffinity-HPLC method for aflatoxins and/or HPLC-enzyme-linked immunosorbent assay for microcystins; 2) to validate method(s) for measuring biomarkers of microcystins and fumonisins in food, water, and body fluids such as blood and urine samples collected from two one-week longitudinal biomonitoring studies in human subjects from high-risk areas of primary liver cancer and esophageal cancer, and 3) to perform molecular epidemiological studies in two high-risk populations of primary liver cancer and esophageal cancer in Qidong and Huaian, P.R. China, for exploring cancer risks from exposures to fumonisins and microcystins.