Genome-wide study of DNA methylation alterations in response to diazinon exposure in vitro

Xiao Zhang*, Andrew D. Wallace, Pan Du, Simon Lin, Andrea A. Baccarelli, Hongmei Jiang, Nadereh Jafari, Yinan Zheng, Hehuang Xie, Marcelo Bento Soares, Warren A. Kibbe, Lifang Hou

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

Pesticide exposure has repeatedly been associated with cancers. However, molecular mechanisms are largely undetermined. In this study, we examined whether exposure to diazinon, a common organophosphate that has been associated with cancers, could induce DNA methylation alterations. We conducted genome-wide DNA methylation analyses on DNA samples obtained from human hematopoietic K562 cell exposed to diazinon and ethanol using the Illumina Infinium HumanMethylation27 BeadChip. Bayesian-adjusted t-tests were used to identify differentially methylated gene promoter CpG sites. We identified 1069 CpG sites in 984 genes with significant methylation changes in diazinon-treated cells. Gene ontology analysis demonstrated that some genes are tumor suppressor genes, such as TP53INP1 (3.0-fold, q-value. <0.001) and PTEN (2.6-fold, q-value. <0.001), some genes are in cancer-related pathways, such as HDAC3 (2.2-fold, q-value = 0.002), and some remain functionally unknown. Our results provided direct experimental evidence that diazinon may modify gene promoter DNA methylation levels, which may play a pathological role in cancer development.

Original languageEnglish (US)
Pages (from-to)959-968
Number of pages10
JournalEnvironmental Toxicology and Pharmacology
Volume34
Issue number3
DOIs
StatePublished - Nov 2012

Keywords

  • Carcinogenesis
  • DNA methylation alteration
  • Diazinon exposure

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology
  • Health, Toxicology and Mutagenesis

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