Li Xiaomeng, Ni Mengmei, Yang Zhirui, Chen Xuxi, Zhang Lishi, Chen Jinyao
West China School of Public Health/West China Fourth Hospital and Healthy Food Evaluation Research Center, Sichuan University, Chengdu, China.
West China School of Public Health/West China Fourth Hospital and Healthy Food Evaluation Research Center, Sichuan University, Chengdu, China.
Environ Pollut. 2021 Jan 8;273:116469. doi: 10.1016/j.envpol.2021.116469.
Bisphenol A (BPA) is a classical chemical contaminant in food, and the mode of action (MOA) of BPA remains unclear, constraining the progress of risk assessment. This study aims to assess the potential MOAs of BPA regarding reproductive/developmental toxicity, neurological toxicity, and proliferative effects on the mammary gland and the prostate potentially related to carcinogenesis by using the Comparative Toxicogenomics Database (CTD)-based bioinformatics analysis and the quantitative weight of evidence (QWOE) approach on the basis of the principles of Toxicity Testing in the 21st Century. The CTD-based bioinformatics analysis results showed that estrogen receptor 1, estrogen receptor 2, mitogen-activated protein kinase (MAPK) 1, MAPK3, BCL2 apoptosis regulator, caspase 3, BAX, androgen receptor, and AKT serine/threonine kinase 1 could be the common target genes, and the apoptotic process, cell proliferation, testosterone biosynthetic process, and estrogen biosynthetic process might be the shared phenotypes for different target organs. In addition, the KEGG pathways of the BPA-induced action might involve the estrogen signaling pathway and pathways in cancer. After the QWOE evaluation, two potential estrogen receptor-related MOAs of BPA-induced testis dysfunction and learning-memory deficit were proposed. However, the confidence and the human relevance of the two MOAs were moderate, prompting studies to improve the MOA-based risk assessment of BPA.
双酚A（BPA）是食品中的一种典型化学污染物，其作用模式（MOA）尚不清楚，这制约了风险评估的进展。本研究旨在通过基于比较毒理基因组学数据库（CTD）的生物信息学分析以及基于21世纪毒性测试原则的定量证据权重（QWOE）方法，评估BPA在生殖/发育毒性、神经毒性以及对乳腺和前列腺的增殖作用（可能与致癌作用相关）方面的潜在作用模式。基于CTD的生物信息学分析结果表明，雌激素受体1、雌激素受体2、丝裂原活化蛋白激酶（MAPK）1、MAPK3、BCL2凋亡调节因子、半胱天冬酶3、BAX、雄激素受体和AKT丝氨酸/苏氨酸激酶1可能是共同的靶基因，凋亡过程、细胞增殖、睾酮生物合成过程和雌激素生物合成过程可能是不同靶器官的共同表型。此外，BPA诱导作用的KEGG途径可能涉及雌激素信号通路和癌症相关途径。经过QWOE评估，提出了BPA诱导睾丸功能障碍和学习记忆缺陷的两种潜在的与雌激素受体相关的作用模式。然而，这两种作用模式的可信度和与人类的相关性为中等，这促使开展研究以改进基于作用模式的BPA风险评估。
