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Published on: August 18, 2022
Genome-wide study of DNA methylation alterations in response to diazinon exposure in vitro
Xiao Zhang1, Andrew D Wallace, Pan Du
1Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA. xiao-zhang@northwestern.edu
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.
Insights
The common pesticide diazinon may alter DNA methylation patterns in human cells, potentially contributing to cancer development. This study provides evidence linking pesticide exposure to epigenetic changes relevant to cancer. Keywords: pesticide exposure, diazinon, DNA methylation, cancer.
Area of Science:
- Environmental Health
- Epigenetics
- Cancer Research
Background:
- Pesticide exposure is linked to various cancers, but underlying molecular mechanisms remain unclear.
- Organophosphate pesticides, like diazinon, are widely used and have been associated with increased cancer risk.
- Understanding how pesticides affect cellular processes is crucial for cancer prevention and treatment.
Purpose of the Study:
- To investigate whether diazinon exposure induces alterations in DNA methylation.
- To identify specific genes and pathways affected by diazinon-induced epigenetic changes.
- To explore the potential role of these epigenetic modifications in pesticide-associated carcinogenesis.
Main Methods:
- Genome-wide DNA methylation analysis was performed on human K562 cells exposed to diazinon or ethanol (control).
- The Illumina Infinium HumanMethylation27 BeadChip was utilized for high-throughput methylation profiling.
- Differential methylation was identified using Bayesian-adjusted t-tests, focusing on gene promoter CpG sites.
Main Results:
- Exposure to diazinon resulted in significant methylation changes at 1069 CpG sites across 984 genes.
- Key genes involved in tumor suppression (e.g., TP53INP1, PTEN) and cancer-related pathways (e.g., HDAC3) showed altered methylation.
- Gene ontology analysis revealed a mix of functionally known and unknown genes affected by diazinon.
Conclusions:
- Diazinon exposure can directly modify DNA methylation levels at gene promoters.
- These epigenetic alterations may contribute to the pathological mechanisms underlying cancer development.
- The findings highlight a potential molecular link between pesticide exposure and cancer etiology.
