The safety of chemicals used in food preservation, cosmetics, pesticides, and other industrial materials is a growing concern as they have been linked to various diseases, including cancer. Researchers believe that a more efficient and accessible method to assess the potential carcinogenicity of these chemicals is crucial. To address this need, the researchers, from Japan, have developed a cell-based reporter assay capable of quantifying epigenetic changes induced by chemicals, offering a simpler, cost-effective alternative to advanced sequencing techniques.

The rise of chemical-induced health risks

The researchers say that chemicals commonly found in food preservatives, dyes, and industrial materials are increasingly recognized as health hazards. The widespread use of these chemicals has contributed to a rise in diseases like cancer, neurological disorders, hormonal disruption, and skin conditions. Many chemicals are known to cause carcinogenesis—cancer development—through genotoxic effects that interfere with DNA replication and repair, leading to mutations and chromosomal aberrations. While genotoxicity assays can help detect DNA damage, epigenetic alterations—changes in gene expression without altering the DNA sequence—are more challenging to assess but are crucial for understanding chemically induced carcinogenesis.

Epigenetics and carcinogenesis

Epigenetic changes, such as DNA methylation and histone modifications, play a significant role in regulating gene expression. These changes are reversible and can be induced by environmental factors, including exposure to carcinogens. Chemicals like bisphenol A, arsenic, and cadmium have been shown to alter epigenetic mechanisms, triggering diseases such as cancer. Understanding how chemicals induce these changes can significantly enhance the safety assessment of environmental chemicals and help mitigate the risks associated with their use.

The researchers added that while previous cell-based assays have focused on detecting unidirectional epigenetic changes (either gene silencing or activation), a bidirectional assay capable of detecting diverse epigenetic effects is needed. To fill this gap, researchers led by associate professor Akira Sassa of Chiba University and collaborators from Japan’s National Institute of Health Sciences have developed the epi-TK reporter assay, a new tool for evaluating carcinogen-induced epigenetic changes.

A simplified and cost-effective approach

The epi-TK assay builds on the thymidine kinase (TK) gene mutation assay, a conventional in vitro genotoxicity test. The researchers enhanced this assay by introducing methylation to the TK promoter region, making it more sensitive to epigenetic changes. The epi-TK assay can detect both DNA methylation—a process that silences gene expression—and histone acetylation—which activates gene expression—providing a comprehensive view of chemical-induced epigenetic alterations.

In their study, the researchers treated cells with DNA methyltransferase (DNMT) inhibitors, chemicals known to alter DNA methylation. They observed that the epi-TK assay accurately reflected the changes in the TK promoter region, showing a reversion of methylation and an increase in cell expansion. The assay also detected epigenetic alterations caused by 12-O-tetradecanoylphorbol-13-acetate (TPA), a widely studied carcinogen, further validating its ability to monitor both gene silencing and activation.

A game-changer for chemical safety evaluation

Unlike traditional sequencing methods, which are costly and require specialized equipment and expertise, the epi-TK reporter assay offers a more straightforward and affordable solution. The company believes this assay could revolutionize the way chemical-induced epigenetic toxicity is evaluated, making it more accessible to researchers and regulatory agencies.

Associate professor Sassa said: “Our research aims to promote safer chemical use worldwide. By providing a simple, cost-effective method for evaluating chemical-induced epigenetic changes, we can improve chemical safety assessments and prevent diseases caused by environmental exposure.”

This innovative approach could enhance our understanding of the impact of environmental chemicals on public health, enabling more effective disease prevention and safer chemical management practices. Through such advancements, the company believes that it is possible to reduce harmful chemical exposure and mitigate its associated risks in both workplace and everyday environments.