Abstract 227: How arsenic and particulate matter affect epigenetic gene regulation and cancer: bridging the gap between the environment and health: a review
Authors: Bianca Ehling
Journal: Cancer Research (2025)

Abstract There are numerous environmental factors that influence epigenetic gene regulation and can thus lead to the development of cancer. Two of these factors include metals and air pollutants. This review examines how arsenic and particulate matter affect epigenetic gene regulation and can lead to cancer. It is important to continue to learn about and understand these mechanisms in a preventative effort to reduce the risk of developing cancer, especially since wildfires are projected to increase in frequency, and they are a source of particulate matter (PM). Arsenic is widespread in the environment and it can be present in PM as well. The references for this review were collected by conducting database searches (PubMed and ScienceDirect) using keywords such as metals, air pollutants, epigenetics, and cancer. Arsenic has been found to be associated with DNA demethylation and the formation of malignancies in vitro in rats, which could possibly be due to the universal methyl group donor (SAM) methylating arsenic and thus having limited availability to methylate DNA and histones. Arsenic can also promote the creation of reactive oxygen species that can damage DNA and hinder its ability to be methylated. Arsenic can lead to the methylation-induced transcriptional silencing of tumor-suppressor genes, as well. In addition, the presence of arsenic is associated with the methylation of transposable elements, which is correlated with colon cancer. Arsenic can also lead to the activation of certain histone kinases, which can potentially demethylate certain histones and eventually lead to proto-oncogenes being induced. Arsenic has also been found to induce the “marking” of certain silent genes, to the point where they are not yet activated, but have the ability to be quickly activated. In addition, since alternative splicing of RNA (specifically, which parts of the RNA will become exons) is dependent on DNA methylation and histone modifications, exposure to arsenic could disrupt normal RNA alternative splicing patterns. Arsenic has also been found to potentially alter miRNA expression. PM can potentially contribute to DNA hypermethylation and thus the onset of lung cancer. The alteration of DNA methylation has also been associated with dysregulation of apoptosis. PM has been found to potentially decrease the expression of histone demethylase, which may lead to increased methylation of histone modifications. PM can also potentially suppress the expression of tumor suppressor miRNAs, enabling lung cancer to develop. Since environmental factors can often be confounding variables, especially when the exposome is taken into account, it is often difficult to discern which environmental factor is causing which epigenetic effect. To combat this, data science methods could be implemented in future research endeavors. Citation Format: Bianca Ehling. How arsenic and particulate matter affect epigenetic gene regulation and cancer: bridging the gap between the environment and health: a review [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 227.