EPIGENETIC MARKERS IN ENVIRONMENTAL AND OCCUPATIONAL STUDIES

In the last few years, several investigations have examined the relation between exposure to environmental/occupational and epigenetics and identified several toxicants that modify epigenetic marks. Environmental and occupational exposure to inhalable particulate matter (PM) has been associated with increased risk of lung cancer. Epidemiologic and in-vivo studies suggest that the metal components of PM may be responsible for PM health effects, including lung cancer. Recent in-vitro studies have shown that carcinogenic metals cause DNA methylation and posttranslational epigenetic modifications of histone proteins, thus derailing the normal programming of gene expression . However, whether metals in inhalable air particles induce alterations of histone modifications and DNA methylation in human subjects has never been evaluated. However, whether metals in inhalable air particles induce alterations of histone modifications and DNA methylation in human subjects has never been evaluated. In the present work, we investigated both short- and long-term effects of particle exposure on histone modifications and DNA methylation in workers with well-characterized exposure to a wide range of PM level in a foundry steel plant. We measured Histone 3 Lysine 4 (H3K4) dimethylation and Histone 3 Lysine 9 (H3K9) acetylation and DNA methylation in Alu and long interspersed nuclear element-1 (LINE-1) repetitive elements – as a surrogate of genome-wide methylation content – in peripheral blood leukocytes from foundry workers with well-characterized exposure. Our results indicate that exposure to some metal components of PM, including nickel and arsenic , increased H3K4 dimethylation and H3K9 acetylation in blood leukocytes from a population of healthy steel workers. These changes in the genomic levels of histone modifications may produce aberrant activation of gene expression which may help explain the carcinogenic properties of inhalable nickel and arsenic. We showed also, for the first time, that PM exposure is associated with altered blood DNA methylation patterns that reproduce epigenetic changes found in cardiovascular disease, including decreased methylation in Alu and LINE-1 repetitive elements. Further studies are required to directly link these changes with exposure-related increases in the risk of cancer, as well as to identify specific genes and pathways that are affected by the exposure-related changes in histone modifications and DNA methylation.