title: Genome-wide study of DNA methylation alterations in response to diazinon exposure in vitro.
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.
authors.affiliation: Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA. xiao-zhang@northwestern.edu
authors.forename: Xiao
authors.initials: X
authors.lastname: Zhang
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Wallace
authors.forename: Pan
authors.initials: P
authors.lastname: Du
authors.forename: Simon
authors.initials: S
authors.lastname: Lin
authors.forename: Andrea A
authors.initials: AA
authors.lastname: Baccarelli
authors.forename: Hongmei
authors.initials: H
authors.lastname: Jiang
authors.forename: Nadereh
authors.initials: N
authors.lastname: Jafari
authors.forename: Yinan
authors.initials: Y
authors.lastname: Zheng
authors.forename: Hehuang
authors.initials: H
authors.lastname: Xie
authors.forename: Marcelo Bento
authors.initials: MB
authors.lastname: Soares
authors.forename: Warren A
authors.initials: WA
authors.lastname: Kibbe
authors.forename: Lifang
authors.initials: L
authors.lastname: Hou
mesh_terms: D019175:DNA Methylation; D003976:Diazinon / Q000633:toxicity*; D055106:Genome-Wide Association Study; D006801:Humans; D007306:Insecticides / Q000633:toxicity*; D020014:K562 Cells
chemical_list: D007306:Insecticides; D003976:Diazinon