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

Publication ,  Journal Article
Zhang, X; Wallace, AD; Du, P; Lin, S; Baccarelli, AA; Jiang, H; Jafari, N; Zheng, Y; Xie, H; Soares, MB; Kibbe, WA; Hou, L
Published in: Environ Toxicol Pharmacol
November 2012

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.

Duke Scholars

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Published In

Environ Toxicol Pharmacol

DOI

EISSN

1872-7077

Publication Date

November 2012

Volume

34

Issue

3

Start / End Page

959 / 968

Location

Netherlands

Related Subject Headings

  • Toxicology
  • K562 Cells
  • Insecticides
  • Humans
  • Genome-Wide Association Study
  • Diazinon
  • DNA Methylation
  • 4105 Pollution and contamination
  • 4104 Environmental management
  • 3214 Pharmacology and pharmaceutical sciences
 

Citation

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Zhang, X., Wallace, A. D., Du, P., Lin, S., Baccarelli, A. A., Jiang, H., … Hou, L. (2012). Genome-wide study of DNA methylation alterations in response to diazinon exposure in vitro. Environ Toxicol Pharmacol, 34(3), 959–968. https://doi.org/10.1016/j.etap.2012.07.012
Zhang, Xiao, Andrew D. Wallace, Pan Du, Simon Lin, Andrea A. Baccarelli, Hongmei Jiang, Nadereh Jafari, et al. “Genome-wide study of DNA methylation alterations in response to diazinon exposure in vitro.Environ Toxicol Pharmacol 34, no. 3 (November 2012): 959–68. https://doi.org/10.1016/j.etap.2012.07.012.
Zhang X, Wallace AD, Du P, Lin S, Baccarelli AA, Jiang H, et al. Genome-wide study of DNA methylation alterations in response to diazinon exposure in vitro. Environ Toxicol Pharmacol. 2012 Nov;34(3):959–68.
Zhang, Xiao, et al. “Genome-wide study of DNA methylation alterations in response to diazinon exposure in vitro.Environ Toxicol Pharmacol, vol. 34, no. 3, Nov. 2012, pp. 959–68. Pubmed, doi:10.1016/j.etap.2012.07.012.
Zhang X, Wallace AD, Du P, Lin S, Baccarelli AA, Jiang H, Jafari N, Zheng Y, Xie H, Soares MB, Kibbe WA, Hou L. Genome-wide study of DNA methylation alterations in response to diazinon exposure in vitro. Environ Toxicol Pharmacol. 2012 Nov;34(3):959–968.
Journal cover image

Published In

Environ Toxicol Pharmacol

DOI

EISSN

1872-7077

Publication Date

November 2012

Volume

34

Issue

3

Start / End Page

959 / 968

Location

Netherlands

Related Subject Headings

  • Toxicology
  • K562 Cells
  • Insecticides
  • Humans
  • Genome-Wide Association Study
  • Diazinon
  • DNA Methylation
  • 4105 Pollution and contamination
  • 4104 Environmental management
  • 3214 Pharmacology and pharmaceutical sciences