Abstract
The functional relationship between chronic inflammation and cancer is well established, however the molecular mechanisms involved remain unclear. Immune cells release oxidants in response to infectious agents or irritants, which can be detrimental to neighbouring tissues when present in high and sustained quantities, such as in a state of chronic inflammation. The genomic landscape of a cancer cell is heterogenous, and the field of epigenetics is deepening our understanding of the molecular features that contribute to malignant phenotypes. DNA methylation is central in the regulation of gene expression, including tumour suppressor genes and proto-oncogenes. Profiling aberrant DNA methylation patterns in cancer may be useful for the development of targeted therapies and precision medicines, leading to improved clinical outcomes.
Previous research in our laboratory has shown that the neutrophil-produced oxidants, hydrogen peroxide and glycine chloramine, can interfere with the maintenance of DNA methylation patterns during cell replication. Therefore, we were interested in seeing whether a sub-lethal dose of the oxidant hypothiocyanous acid (HOSCN) in the Jurkat T-Lymphoma cell line could produce a similar effect. We designed two experimental assays that separately investigated whether the timing of cell replication was an important factor during HOSCN exposure, and whether a repeated exposure was necessary for DNA methylation change. In both experiments, there were no significant differentially methylated regions after adjusting for genome wide significance. However, HOSCN did induce significant changes in the variability of DNA methylation patterns in Jurkat cells. Top influenced gene pathways were associated with Alzheimer’s Disease, which has a known relationship with DNA methylation, inflammation and oxidative stress in the literature. Although results indicated HOSCN may be more well-tolerated than previously studied oxidants, these findings can provide direction for future studies on the molecular link between chronic inflammation and diseases such as cancer.