S12-03 Occupational Exposure to Benzene and Epigenetic Biomarkers of Effect: From Early Discoveries to Emerging Insights

Benzene is a well-established occupational and environmental carcinogen, classified by IARC as Group 1 with sufficient evidence for acute myeloid leukemia (AML) and limited evidence for other hematologic malignancies. While its leukemogenic potential at high doses is undisputed, increasing attention is now focused on the biological effects of long-term exposure to low concentrations, still frequent in various occupational and environmental settings.

Over the past two decades, epigenetic alterations have emerged as early and sensitive markers of toxicant exposure. In both experimental and epidemiological studies, benzene has been shown to induce DNA methylation changes affecting key biological pathways, including inflammation, oxidative stress, apoptosis, and immune and hematopoietic regulation. These epigenetic disruptions may serve as mechanistic intermediates between exposure and disease and are also implicated in the development of age-related conditions. As a result, growing emphasis is being placed on epigenetic biomarkers not only as indicators of early toxicity but also as tools to estimate biological age and capture the broader impacts of environmental exposures on health.

In our research group, we have been studying the impact of airborne benzene exposure on epigenetic biomarkers in peripheral blood mononuclear cells (PBMCs) from occupationally exposed individuals. Exposure levels were quantified using personal air monitoring across a wide concentration range, including levels well below current regulatory thresholds. Genome-wide DNA methylation profiling identified exposure-associated alterations at CpG sites involved in critical regulatory networks. Additionally, estimates of biological age and telomere length measured by qPCR showed consistent associations with benzene exposure, even at low concentrations (<0.1 ppm).

These findings underscore the role of epigenetic mechanisms in mediating early effects of benzene exposure and support their utility as biomarkers of effect in occupational and environmental health. Integrating quantitative exposure metrics with molecular endpoints may improve early detection of biological responses and inform future risk evaluation and prevention strategies.