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Key characteristics of 86 agents known to cause cancer in humans.
Journal of Toxicology and Environmental Health, Part B: Critical Reviews ( IF 7.2 ) Pub Date : 2019-10-22 , DOI: 10.1080/10937404.2019.1643536
Daniel Krewski 1, 2, 3 , Michael Bird 1 , Mustafa Al-Zoughool 1, 4 , Nicholas Birkett 3 , Mélissa Billard 1 , Brittany Milton 2 , Jerry M Rice 5 , Yann Grosse 6 , Vincent J Cogliano 7 , Mark A Hill 8 , Robert A Baan 9 , Julian Little 3 , Jan M Zielinski 1, 3
Affiliation  

Since the inception of the International Agency for Research on Cancer (IARC) in the early 1970s, the IARC Monographs Programme has evaluated more than 1000 agents with respect to carcinogenic hazard; of these, up to and including Volume 119 of the IARC Monographs, 120 agents met the criteria for classification as carcinogenic to humans (Group 1). Volume 100 of the IARC Monographs provided a review and update of Group 1 carcinogens. These agents were divided into six broad categories: (I) pharmaceuticals; (II) biological agents; (III) arsenic, metals, fibers, and dusts; (IV) radiation; (V) personal habits and indoor combustions; and (VI) chemical agents and related occupations. Data on biological mechanisms of action (MOA) were extracted from the Monographs to assemble a database on the basis of ten key characteristics attributed to human carcinogens. After some grouping of similar agents, the characteristic profiles were examined for 86 Group 1 agents for which mechanistic information was available in the IARC Monographs up to and including Volume 106, based upon data derived from human in vivo, human in vitro, animal in vivo, and animal in vitro studies. The most prevalent key characteristic was "is genotoxic", followed by "alters cell proliferation, cell death, or nutrient supply" and "induces oxidative stress". Most agents exhibited several of the ten key characteristics, with an average of four characteristics per agent, a finding consistent with the notion that cancer development in humans involves multiple pathways. Information on the key characteristics was often available from multiple sources, with many agents demonstrating concordance between human and animal sources, particularly with respect to genotoxicity. Although a detailed comparison of the characteristics of different types of agents was not attempted here, the overall characteristic profiles for pharmaceutical agents and for chemical agents and related occupations appeared similar. Further in-depth analyses of this rich database of characteristics of human carcinogens are expected to provide additional insights into the MOA of human cancer development.

中文翻译:

已知会导致人类癌症的86种药物的关键特征。

自1970年代初期国际癌症研究机构(IARC)成立以来,IARC专论计划已评估了1000多种致癌危险因子。其中,直到IARC专着第119卷并包括在内,共有120种药物符合对人类致癌的分类标准(第1组)。IARC专论的第100卷对第1组致癌物进行了回顾和更新。这些药物分为六大类:(I)药品;(二)生物制剂;(III)砷,金属,纤维和粉尘;(IV)辐射;(五)个人习惯和室内燃烧;(六)化学制剂及相关职业。从专着中提取有关生物学作用机制(MOA)的数据,以归因于人类致癌物的十项关键特征,建立一个数据库。在对相似的药剂进行分组之后,根据源自人体内,人体外,动物体内的数据,检查了在IARC专论中可获取机械信息的第1组药剂的特征资料,直至及包括第106卷。以及动物体外研究。最普遍的关键特征是“具有遗传毒性”,其次是“改变细胞增殖,细胞死亡或营养供应”和“诱导氧化应激”。大多数代理显示了十个关键特征中的几个,每个代理平均有四个特征,这一发现与人类癌症发展涉及多种途径的观点相吻合。有关关键特性的信息通常可从多个来源获得,许多代理商证明了人与动物来源之间的一致性,特别是在遗传毒性方面。尽管此处未尝试对不同类型的药剂的特性进行详细比较,但药剂,化学药剂和相关职业的总体特性概况似乎相似。预期对该丰富的人类致癌物特征数据库进行进一步的深入分析,将为人类癌症发展的MOA提供更多见解。许多药物证明了人与动物来源之间的一致性,特别是在遗传毒性方面。尽管此处未尝试对不同类型的药剂的特性进行详细比较,但药剂,化学药剂和相关职业的总体特性概况似乎相似。预期对该丰富的人类致癌物特征数据库进行进一步的深入分析,将为人类癌症发展的MOA提供更多见解。许多药物证明了人与动物来源之间的一致性,特别是在遗传毒性方面。尽管此处未尝试对不同类型的药剂的特性进行详细比较,但药剂,化学药剂和相关职业的总体特性概况似乎相似。预期对该丰富的人类致癌物特征数据库进行进一步的深入分析,将为人类癌症发展的MOA提供更多见解。
更新日期:2019-10-25
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