Bioinformatics analysis and quantitative weight of evidence assessment to map the potential mode of actions of bisphenol A

Xiaomeng Li; Mengmei Ni; Zhirui Yang; Xuxi Chen; Lishi Zhang; Jinyao Chen

doi:10.1016/j.envpol.2021.116469

Bioinformatics analysis and quantitative weight of evidence assessment to map the potential mode of actions of bisphenol A

Environ Pollut. 2021 Jan 8:273:116469. doi: 10.1016/j.envpol.2021.116469. Online ahead of print.

Authors

Xiaomeng Li¹, Mengmei Ni¹, Zhirui Yang¹, Xuxi Chen¹, Lishi Zhang¹, Jinyao Chen²

Affiliations

¹ West China School of Public Health/West China Fourth Hospital and Healthy Food Evaluation Research Center, Sichuan University, Chengdu, China.
² West China School of Public Health/West China Fourth Hospital and Healthy Food Evaluation Research Center, Sichuan University, Chengdu, China. Electronic address: umbrellayy@163.com.

PMID: 33460868
DOI: 10.1016/j.envpol.2021.116469

Abstract

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.

Keywords: Bioinformatics analysis; Bisphenol A; Mode of action; Quantitative weight of evidence.