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

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

Environmental toxicology and pharmacology (2012-09-12)
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
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.

MATERIALS
Product Number
Brand
Product Description

Supelco
Diazinon solution, 100 μg/mL in acetonitrile, PESTANAL®, analytical standard
Supelco
Diazinon, PESTANAL®, analytical standard
Supelco
Diazinon, certified reference material, TraceCERT®