Host: The Japanese Society of Toxicology
Name : The 51st Annual Meeting of the Japanese Society of Toxicology
Date : July 03, 2024 - July 05, 2024
The epigenome defines cellular identity. When environmental exposures induce epigenomic alterations, these alterations can be linked to the development of various diseases, including cancer, neurological disorder, and type 2 diabetes, as they are precisely inherited after cell division. In the context of cancer, epigenomic alterations occur in epithelial cells in normal-appearing tissues, which can produce the “field for cancerization.” We previously demonstrated that the severity of DNA methylation alterations was correlated with cancer risk [Gut, 64:388, 2015; Gut, 66:1751, 2017], and identified chronic inflammation as a trigger of DNA methylation alterations in epithelial cells [J Clin Invest, 130:5370, 2020]. Recently, we explored that intrinsic factor, such as chronic inflammation, aging, and hypoxia, changed DNA methylation and H3K27 acetylation in fibroblasts and endothelial cells, key components of the tissue microenvironment. Furthermore, in normal gastric fibroblasts, upregulation of H3K27 acetylation was involved in the formation of “field for cancerization” and influenced gastric cancer cell identity. These findings indicate that biological responses to the intrinsic factors induce epigenomic alterations within the normal tissue ecosystem. We are now investigating the role of extrinsic factors, chronic phycological stress, in epigenomic alterations and their impact on gastric cancer development. This presentation will introduce how epigenomic alterations driven by both intrinsic and extrinsic factors contributes to carcinogenesis.
