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

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.

► We did a genome-wide examination of DNA methylation alterations in response to diazinon in vitro. ► 1069 CpG sites with significant methylation changes in 984 genes were observed. ► Some genes are implicated in cancer development or in cancer-related pathways. ► Diazinon may cause cancer via epigenetic mechanisms, such as DNA methylation alternation.