Validation of Fumonisin and Microcystin Biomarkers

伏马菌素和微囊藻毒素生物标志物的验证

• 批准号: 6653099
• 负责人: JIA-SHENG WANG
• 金额: $ 18.25万
• 依托单位: TEXAS TECH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-30 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6653099
• 关键词: China; Chinese; bacterial toxins; biomarker; body fluids; cancer risk; clinical research; esophagus neoplasm; high performance liquid chromatography; human subject; liver neoplasms; mycotoxins; neoplasm /cancer epidemiology; parasite /microorganism carcinogen

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.

描述（由申请人提供）： 该研究项目的长期目标是研究之间的关系 接触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。伏马毒素和微囊藻毒素是新 鉴定出由产毒真菌产生的环境生物毒素， 分别是蓝细菌。伏马菌素是致癌物，并且两种伏马菌素 在动物模型中，微囊藻毒素是强肿瘤促进剂。人类 世界某些地区的人口暴露于较高水平的这些物质 日常生活中的毒素主要来自受污染的饮食成分 和/或饮用水。这两种毒素在病因学上都与 人类原发性肝癌和食管癌的高发地区 南非和中国地区。尽管分析方法检测 环境样本中的这些毒素已被报道，并且可能 生物标志物，例如伏马菌素和鞘脂代谢的破坏 微囊藻毒素对蛋白磷酸酶有抑制作用，已在动物身上发现 模型，在人类中验证这些生物标志物，特别是在高风险人群中 人群，尚未进行或报告。迄今为止，仍缺乏方法 用于同时检测环境样品中的这些毒素和 人体体液对于评估人类癌症风险至关重要， 因为高危人群同时接触这些生物毒素已 广泛报道。在这个探索性研究项目中，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 环境样本和人体体液。我们将使用分子 验证体液生物标志物方法的流行病学工具 原发性肝癌和食道癌病例和对照。工作中 本研究提案的假设是长期暴露于 伏马毒素和微囊藻毒素可能产生协同致癌作用 高风险个体和经过验证的生物标志物的应用可以改善 定量估计暴露于这些生物毒素的人类癌症风险。 具体目标是：1）开发快速、灵敏的分析阵列 测量伏马菌素和微囊藻毒素生物标志物的方法 先前开发的黄曲霉毒素和/或的免疫亲和-HPLC 方法 微囊藻毒素的 HPLC 酶联免疫吸附测定； 2）验证 测量食品中微囊藻毒素和伏马菌素生物标志物的方法， 水和体液，例如从两个人身上采集的血液和尿液样本 对高危人群进行为期一周的纵向生物监测研究 原发性肝癌和食管癌领域，以及 3) 进行 两个原发性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 探索暴露于伏马菌素和微囊藻毒素的癌症风险。