Cost-Effective Assay Developed to Study Chemical-Induced Epigenetic Changes

Chemicals used in food, cosmetics, pesticides, and industrial products are increasingly linked to health risks, including cancer, hormonal disruption, neurological disorders, and occupational poisoning. Many chemicals trigger carcinogenesis by causing genotoxic effects—damaging DNA replication and repair processes, leading to mutations. In addition to genotoxicity, epigenetic changes, such as DNA methylation and histone acetylation, play a significant role in chemically induced carcinogenesis. These reversible modifications regulate gene expression and have been associated with diseases caused by environmental chemicals like bisphenol A, arsenic, cadmium, and pesticides. Understanding these mechanisms is crucial for assessing chemical safety.

Traditional cell-based assays for detecting epigenetic changes are limited in scope, capturing only unidirectional effects on gene expression. To address this limitation, Akira Sassa from Chiba University and collaborators developed a bidirectional epi-genotoxicity assay to evaluate epigenetic changes caused by carcinogens. Their work was published in Scientific Reports last month.

Building on the thymidine kinase (TK) gene mutation assay—a conventional genotoxicity test—the researchers created an epi-TK reporter assay by methylating the TK promoter region. This assay reflects global epigenetic changes by measuring “TK reversion,” or the expansion of cells with silenced TK promoters after exposure to DNA methyl transferase inhibitors or other chemicals. For example, treatment with TPA, a non-genotoxic carcinogen, reduced TK revertant frequency and histone acetylation levels.

The epi-TK assay offers a simpler and cost-effective alternative to advanced sequencing techniques for evaluating chemical-induced epigenetic changes. Dr. Sassa emphasized its potential to improve chemical safety assessments globally, “Our research can enhance the understanding of the impact of chemicals on public health and disease prevention, thereby promoting safer management and use of chemicals. Understanding the relationship between environmental chemicals and diseases, and improving chemical safety evaluations, can aid the implementation of measures to reduce the exposure to harmful chemicals in both work and living environments.”