Institute of Ecological and Environmental Science, Sichuan Agriculture University, Chengdu 611130, Sichuan province, China; Colleges of the Environment, Sichuan Agricultural University, Chengdu, 611130, Sichuan province, China.
Environmental Monitoring Center of Chengdu, Sichuan province, Chengdu, 610041, Sichuan, China.
Toxicol In Vitro. 2019 Aug;58:13-25. doi: 10.1016/j.tiv.2019.03.017. Epub 2019 Mar 14.
Cancer is a leading cause of human mortality around the globe. In this study, mechanism-based SAR (Structure-Activity Relationship) was employed to investigate the carcinogenicity of aromatic amines and nitroaromatics based on CPDB. Principal component analysis and cluster analysis were used to construct the SAR model. Principle component analysis generated three principal components from 12 mechanism-based descriptors. The extracted principal components were later used for cluster analysis, which divided the selected 55 chemicals into six clusters. The three principal components were proposed to describe the "transport", "reactivity" and "electrophilicity" properties of the chemicals. Cluster analysis indicated that the relevant "transport" properties positively correlated with the carcinogenic potential and were contributing factors in determining the carcinogenicity of the studied chemicals. The mechanism-based SAR analysis suggested the electron donating groups, electron withdrawing groups and planarity are significant factors in determining the carcinogenic potency for studied aromatic compounds. The present study may provide insights into the relationship between the three proposed properties and the carcinogenesis of aromatic amines and nitroaromatics.
癌症是全球范围内导致人类死亡的主要原因之一。在这项研究中，我们基于 CPDB 采用基于机制的 SAR（结构-活性关系）来研究芳香胺和硝基芳烃的致癌性。主成分分析和聚类分析用于构建 SAR 模型。主成分分析从 12 个基于机制的描述符中生成了三个主成分。提取的主成分随后用于聚类分析，将选择的 55 种化学物质分为六组。这三个主成分用于描述化学物质的“运输”、“反应性”和“亲电性”特性。聚类分析表明，相关的“运输”特性与致癌潜力呈正相关，是决定研究中化学物质致癌性的因素之一。基于机制的 SAR 分析表明，供电子基团、吸电子基团和平坦性是决定研究芳香族化合物致癌能力的重要因素。本研究可能为三个提出的性质与芳香胺和硝基芳烃致癌之间的关系提供了一些见解。
