The following is a summary of “Targeting the ‘DNA methylation mark’: Analysis of early epigenetic-alterations in children chronically exposed to arsenic,” published in the December 2023 issue of Oncology by Sanyal et al.

Chronic arsenic exposure poses serious health risks, especially among children, triggering adverse effects. This exposure often induces aberrant epigenetic modifications, including disrupted DNA methylation patterns, which are significant precursors to cell transformation leading to malignancy. Their prior investigations in arsenic-exposed adults unveiled substantial alterations in DNA methylation, impacting vital biological pathways. However, a gap exists in understanding the influence of altered DNA methylation on telomere regulation, mitochondrial function, and DNA damage repair in arsenic-exposed children. Thus, their study aimed to identify distinctive epigenetic patterns associated with telomere elongation, mitochondrial function, and DNA damage repair in arsenic-exposed children, focusing mainly on DNA methylation.

To achieve this, the researchers collected biological samples (blood and urine) along with drinking water from 52 children residing in arsenic-exposed regions of Murshidabad district, contrasted with 50 children from unexposed areas in East Midnapur districts, West Bengal, India. Using methylation-specific PCR, the study group analyzed the methylation status in the targeted genes’ subtelomeric and promoter regions. The results uncovered significant deviations in DNA methylation profiles among the exposed children compared to the unexposed group. Notably, promoter hypermethylation in the MLH1 and MSH2 genes indicated potential inefficiencies in DNA damage repair mechanisms (p < 0.05 and p < 0.001, respectively). Additionally, hypomethylation in the mitochondrial D-loop (p < 0.05) and TFAM promoter region (p < 0.05), accompanied by an upsurge in mitochondrial DNA copy number, was observed among the exposed children. Furthermore, a substantial increase in telomere length and region-specific subtelomeric hypermethylation (XpYp, p < 0.05) was evident.

Additional analysis highlighted a noteworthy depletion of S-Adenosyl Methionine (SAM) (p < 0.001) and elevated levels of oxidative DNA damage (p < 0.001) in arsenic-exposed subjects. These findings underscored crucial methylation patterns in arsenic-exposed children, potentially serving as predictive early-stage biomarkers. Future comprehensive investigations involving larger sample sizes and transcriptomic analyses are imperative for a deeper mechanistic understanding of these observations.

Source: sciencedirect.com/science/article/abs/pii/S0048969723076799