Diazinon may increase the risk of acute lymphoblastic leukemia by inducing MGMT promoter methylation

Abstract Background and objective Acute lymphoblastic leukemia (ALL) is the most frequent childhood malignancy, which is impacted by genetic, epigenetic, and environmental variables. Aberrant methylation of genes, such as O6-methylguanine-DNA-methyltransferase (MGMT), is one of the key mechanisms in carcinogenesis. The aim of the present study was to examine the association of exposure to diazinon with MGMT gene methylation and expression levels in children with ALL. Methods This case-control research was performed on 136 children with ALL and 136 healthy children as the control group. Demographic data were gathered using a questionnaire and blood sampling. Serum concentrations of diazinon were determined using gas chromatography (GC). DNA was extracted from nucleated cells, followed by bisulfite treatment and examination of MGMT gene promoter methylation using methylation-specific polymerase chain reaction (MSP). Gene expression levels were also determined using real-time Polymerase chain reaction (PCR). Acetylcholinesterase (AChE) activity and malondialdehyde (MDA) concentrations were evaluated as indicators of pesticide toxicity and oxidative stress. Results Diazinon levels were significantly increased in ALL patients compared to controls (P < .001) and were positively associated with elevated methylation levels of MGMT gene promoter. The odds ratio of ALL development was significantly higher in children with both increased diazinon concentrations and elevated MGMT methylation levels. Moreover, patients exhibited reduced AChE activity and higher MDA concentrations, suggesting the induction of neurotoxicity and oxidative stress triggered by diazinon. Conclusion Exposure to diazinon might contribute to the development and progression of ALL by triggering aberrant methylation of the MGMT gene, decreasing DNA repair capacity, and promoting oxidative damage. This study highlights the importance of minimizing pesticide exposure and suggests the use of MGMT methylation as a biomarker for the diagnosis and prognosis of ALL.