摘要
马兜铃酸(AAs)几乎满足致癌物的所有标准与条件并导致人体癌症,被确定为一级致癌剂。本文将围绕着化学致癌物评价标准与致癌作用机制过程进行探讨与比较,以马兜铃酸为代表性典型范例,针对有关理念与概念综述现有的研究进展解读以下关键问题:①确定致癌物必须清晰其作用机理吗?致癌机理对致癌物评判的影响是什么?②马兜铃酸为何被判定为一级致癌物?③碱基对替换突变特征是什么?④AAs经口暴露却为何更易致泌尿系统癌症?⑤肾脏与肝脏间代谢与转运差异及其对AAs致毒的影响是什么?综上,作者认为,通过马兜铃酸现代毒理学评价的主要关键点进行解读,可深入理解并遵循国际研究规范,力抓中药及其成分的分子毒理学评价与分类,对于比较易受忽视的基因毒评价领域,需以科学严谨的方式系统收集、整理相关有效评价与证据,这将为我国在相关类似事件研究与评价中提供借鉴与规范。
Aristolochic acid(AAs), a cancer-causing compound meeting almost all the definitions and criteria of carcinogenic materials, has been identified as a Group 1 carcinogen. This paper centered on the evaluation criteria for chemical carcinogen and molecular mechanisms involved in carcinogenesis. Taking aristolochic acid as a typical example, we summarized the latest research progress in this field in terms of concept development and addressed the following key questions:(1) Do we have to understand its mechanism of action when defining a carcinogen? What is the impact of carcinogenic mechanisms on carcinogen assessment?(2) Why is aristolochic acid classified as a Group 1 carcinogen?(3) What are the signatures of base substitution mutation?(4) Why does oral exposure to AAs more often cause urinary cancer?(5) What are the differences in metabolism and transport between kidney and liver, and what about their effects on AAs toxicity? We believe that the interpretation of key issues in modern toxicological evaluation of aristolochic acid will help us thoroughly understand and follow the international research guidelines, and provide molecular toxicological evaluation and classification on traditional Chinese medicine compositions. Regarding genotoxicity evaluation, a field that is often ignored, it would be necessary to systematically collect the relevant valuable evaluation and evidence in a scientific and rigorous way. This will provide references and guidelines for research evaluation of future cases similar to the AAs event.
作者
马红
黄超
王方园
王亦男
刘淑清
杨凌
Ma Hong;Huang Chao;Wang Fangyuan;Wang Yinan;Liu Shuqing;Yang Ling(Center for Systems Pharmacokinetics,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;Shanghai Institute of Acupuncture and Meridian,Shanghai 200030,China;College of Basic Medical Sciences,Dalian Medical University,Dalian 116044,China)
出处
《世界科学技术-中医药现代化》
CSCD
北大核心
2019年第7期1287-1294,共8页
Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology
关键词
马兜铃酸
致癌性
分子毒理学研究
生物激活
加合作用
突变标签
Aristolochic acid
Carcinogenesis
Molecular toxicology
Bioactivation
Adduction
Mutational signature
