Abstract
Oxidative stress is a hallmark of aging as well as of many tumors and is caused by an imbalance of production and clearance of reactive oxygen species (ROS). High levels of ROS directly damage proteins, lipids, and DNA. Oxidative lesions of DNA lead to increased chromosomal breakage numbers and genomic instability. Besides, ROS induce activation of signaling cascades and regulate transcription factors, which result in changes in proliferation, angiogenesis, and metastasis, all characteristics of malignant transformation. Additionally, it has also been shown that oxidative stress directly changes DNA methyltransferase (DNMT1) DNA-binding affinities or inhibits DNA and histone demethylases and α-ketoglutarate-dependent dioxygenases. Readouts of the oxidative stress burden are found as GC→TA transversions. These transversions, frequently observed in tissues with high ROS, are utilized as markers of oxidative stress. The contribution of ROS to epigenetic patterning in cancer as well as genomic alterations contributing to metabolic imbalances and thus indirectly influencing the cellular epigenome is in the focus of this chapter. Since cancer-related alterations are found as changes in the distribution of modified cytosines (5mC, 5hmC, 5fC, and 5caC), new high-throughput technologies, provided for the discrimination of these modifications, are summarized at the end of the chapter.
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Hussong, M., Schweiger, M.R. (2016). Oxidative Stress and Cancer Epigenomics. In: Doerfler, W., Böhm, P. (eds) Epigenetics - A Different Way of Looking at Genetics. Epigenetics and Human Health. Springer, Cham. https://doi.org/10.1007/978-3-319-27186-6_11
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