Abstract
Oxidative stress is a common feature of inflammation-driven cancers, and promotes genomic instability and aggressive tumour phenotypes. It is known that oxidative stress transiently modulates gene expression through the oxidation of transcription factors and associated regulatory proteins. Neutrophils are our most abundant white blood cells and accumulate at sites of infection and inflammation. Activated neutrophils produce hypochlorous acid and chloramines, which can disrupt DNA methylation by oxidising methionine. In this study, we investigated whether chloramine exposure corresponds with changes in genomic DNA methylation that drive transcriptional output. Proliferating Jurkat T-lymphoma cells were exposed to sublethal doses of glycine-chloramine and DNA methylation patterns were compared using the IlluminaEPIC850Karray. We observed decreased genome-wide methylation four hours after exposure, which correlated with altered RNA expression for 24 and 48 hours, indicating sustained impacts on exposed cells. A large proportion of the differentially methylated CpG sites were situated towards chromosomal ends, suggesting that these regions are most susceptible to inhibition of maintenance DNA methylation. This may contribute to epigenetic instability of chromosomal ends in rapidly dividing cells, with potential implications for the regulation of telomere length and cellular longevity.
Poster presentation.