Gene expression profile and toxic effects in human bronchial epithelial cells exposed to zearalenone

PLoS One. 2014 May 2;9(5):e96404. doi: 10.1371/journal.pone.0096404. eCollection 2014.

Abstract

Zearalenone (ZEA), a mycoestrogen produced by Fusarium fungal species, is mainly found in cereal crops such as maize, wheat and barley. Although ZEA has been reported to be present in air, little is known about the health risk or the molecular basis of action when lung cells are exposed to ZEA. As ZEA has a similar structure to estrogen, its potential risk as an endocrine disrupting chemical (EDC) has thus aroused both environmental and public health concerns. The purpose of this study is to identify the responses and underlying molecular changes that occur when human bronchial epithelial BEAS-2B cells are exposed to ZEA. Differential gene expression profiles were identified in cells that were treated with 40 µM ZEA for 6 h and 24 h by high-throughput microarray analysis using Affymetrix Human Gene 2.0 GeneChip. The array results showed that after ZEA treatment, 262 genes at 6 h and 1073 genes at 24 h were involved in the differential regulation. Pathway analysis revealed that diverse cellular processes were affected when lung cells were exposed to ZEA resulting in impaired response to DNA damage, cell cycle arrest, down-regulation of inflammatory responses and alterations of epigenetic marks. Results of further experiments indicated that 40 µM ZEA decreased cell viability, induced apoptosis and promoted reactive oxygen species (ROS) generation in a time-dependent manner. Immuno-suppressive effects of ZEA were further revealed through the suppression of lipopolysaccharide (LPS)-induced expression of pro-inflammatory cytokines (IL-6, IL-8 and IL-1β). Interestingly, the level of global DNA methylation was markedly decreased after 24 h exposure to ZEA. Collectively, these observations suggested that a broad range of toxic effects are elicited by ZEA. Particularly, ROS may play a pivotal role in ZEA-induced cell death. These adverse effects observed in lung cells suggest that exposure to ZEA may increase susceptibility of lung cells to diseases and required further investigations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Bronchi / cytology*
  • Cell Cycle / drug effects
  • Cell Cycle / genetics
  • Cell Line
  • Cell Survival / drug effects
  • Cell Survival / genetics
  • Epithelial Cells / drug effects*
  • Epithelial Cells / metabolism
  • Estrogens, Non-Steroidal / pharmacology
  • Humans
  • Oligonucleotide Array Sequence Analysis
  • Reactive Oxygen Species / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Time Factors
  • Transcriptome / drug effects*
  • Transcriptome / genetics
  • Zearalenone / pharmacology*

Substances

  • Estrogens, Non-Steroidal
  • Reactive Oxygen Species
  • Zearalenone

Grants and funding

The work was supported by the Seed Funding Programme for Basic Research and CRCG grants for postgraduate students of the University of Hong Kong as well as funding from HKU School of Professional and Continuing Education (SPACE). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.