案例信息

标题：AFB1肝毒性分子标志的60年Odyssey—基于环境监测和现代毒理学的思考

【专业学位类别】公共卫生

【专业领域/方向】卫生毒理学，环境卫生学

【作者】林育纯

【单位】厦门大学公共卫生学院

【关键词】AFB1、毒理学评价、分子标志物、管理毒理学

【适用课程】卫生毒理学，环境卫生学，转化医学

【版权说明】真实性案例，仅用于教学目的

【案例摘要】

黄曲霉毒素是由曲霉菌产生的一类致病真菌毒素，会污染世界上大部分的食品供应。黄曲霉毒素B1(AFB1)是这些化合物中影响最深远的，它具有一系列生物活性，包括急性毒性、致畸性、致突变性和致癌性等，此外它还是一种强烈的嗜肝毒素，可引起人类和动物肝脏免疫损伤、肝炎、肝硬化甚至肝细胞癌(HCC)。本案例运用多种毒理学方法，从多角度，多方位，多层次研究AFB1暴露导致肝损伤的过程。运用机制毒理学和分子毒理学方法，研究AFB1在生物体内的药代动力学(ADME)和转化过程，阐明AFB1致肝损伤的毒作用通路与机制；运用系统毒理学的相关方法，利用高通量技术和多组学研究AFB1暴露与生物系统的交互作用，定量描述生物功能、表型和行为，发现新的生物标志；运用管理毒理学和计算毒理学的相关方法，利用QSAR、AOP、qAOP和机器学习等指导预测AFB1暴露相关的毒性通路，提出行之有效的安全性与毒理学评价技术和方法，构建规范标准的AFB1暴露致肝损伤安全性评价体系。

Tittle: 60 years of Odyssey on the molecular signature of AFB1 hepatotoxicity——Thinking based on environmental monitoring and modern toxicology

Professional Degree Category: Master of Public Health

Specialized fields: Health toxicology, Environmental health

Authors: Yu-Chun Lin

Affiliation: School of Public Health, Xiamen University, Translational medicine

Key words: AFB1, Toxicological Evaluation, Molecular Markers, Management Toxicology

Abstract

Aflatoxins are a group of pathogenic fungal toxins produced by Aspergillus that are known to contaminate much of the world's food supply. Aflatoxin B1 (AFB1) is the most potent of these compounds, with a range of biological activities including acute toxicity, teratogenicity, mutagenicity and carcinogenicity, in addition to being a potent hepatotoxin that can cause hepatitis, liver immune damage, cirrhosis and even hepatocellular carcinoma (HCC) in humans and animals. In this case, multiple toxicological approaches were used to study the process of liver injury caused by AFB1 exposure from multiple angles, directions and levels. Using mechanistic toxicology and molecular toxicology methods, the pharmacokinetic (ADME) and transformation processes of AFB1 in organisms are studied to elucidate the toxic pathways and mechanisms of liver injury caused by AFB1. We will apply the relevant methods of systemic toxicology and computational toxicology to study the interaction between AFB1 exposure and biological systems using high-throughput technology and multi-omics to quantitatively describe the biological functions, phenotypes and behaviors, and discover new biomarkers.

【案例正文】

【案例说明书】