Gene expression profiling analysis of bisphenol A-induced perturbation in biological processes in ER-negative HEK293 cells

PLoS One. 2014 Jun 5;9(6):e98635. doi: 10.1371/journal.pone.0098635. eCollection 2014.

Abstract

Bisphenol A (BPA) is an environmental endocrine disruptor which has been detected in human bodies. Many studies have implied that BPA exposure is harmful to human health. Previous studies mainly focused on BPA effects on estrogen receptor (ER)-positive cells. Genome-wide impacts of BPA on gene expression in ER-negative cells is unclear. In this study, we performed RNA-seq to characterize BPA-induced cellular and molecular impacts on ER-negative HEK293 cells. The microscopic observation showed that low-dose BPA exposure did not affect cell viability and morphology. Gene expression profiling analysis identified a list of differentially expressed genes in response to BPA exposure in HEK293 cells. These genes were involved in variable important biological processes including ion transport, cysteine metabolic process, apoptosis, DNA damage repair, etc. Notably, BPA up-regulated the expression of ERCC5 encoding a DNA endonuclease for nucleotide-excision repair. Further electrochemical experiment showed that BPA induced significant DNA damage in ER-positive MCF-7 cells but not in ER-negative HEK293 cells. Collectively, our study revealed that ER-negative HEK293 cells employed mechanisms in response to BPA exposure different from ER-positive cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzhydryl Compounds / adverse effects
  • Benzhydryl Compounds / pharmacology*
  • Cell Proliferation / drug effects
  • DNA Damage / drug effects
  • Endocrine Disruptors / adverse effects
  • Endocrine Disruptors / pharmacology
  • Estrogens, Non-Steroidal / adverse effects
  • Estrogens, Non-Steroidal / pharmacology*
  • Gene Expression Profiling*
  • Gene Expression Regulation / drug effects*
  • Gene Regulatory Networks
  • HEK293 Cells
  • Humans
  • MCF-7 Cells
  • Phenols / adverse effects
  • Phenols / pharmacology*
  • Receptors, Estrogen / deficiency*
  • Transcriptome*

Substances

  • Benzhydryl Compounds
  • Endocrine Disruptors
  • Estrogens, Non-Steroidal
  • Phenols
  • Receptors, Estrogen
  • bisphenol A

Grants and funding

This study was supported in part by grants from the Ministry of Science and Technology of China (2010CB944901, 2011CB965104, 2012AA020405); and the National Natural Science Foundation of China (91019017, 31271373, 31200952); China Postdoctoral Science Foundation (2013M531207); the Shanghai Postdoctoral Sustentation Fund (13R21416700); Aurora Talent Project of Shanghai (10SG24); the program for Eastern Scholar of Shanghai; the Fundamental Research Funds for the Central Universities (20113048, 20113109); and IRT1168 from the Ministry of Education, China. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.