Changes in DNA methylation patterns in subjects exposed to low-dose benzene

Area of Science:

• Environmental Epigenetics
• Toxicology
• Molecular Epidemiology

Background:

• Aberrant DNA methylation is a hallmark of acute myelogenous leukemia (AML) and other cancers.
• Benzene is a widespread environmental pollutant linked to AML risk.
• Epigenetic alterations induced by low-level environmental carcinogen exposure in healthy individuals remain largely uncharacterized.

Purpose of the Study:

• To investigate if low-level benzene exposure induces DNA methylation changes in healthy subjects.
• To assess genome-wide and gene-specific DNA methylation alterations, including loss of imprinting (LOI), in relation to airborne benzene levels.

Main Methods:

• Blood DNA samples and personal airborne benzene exposure data were collected from gas station attendants, traffic police officers, and unexposed referents.
• Bisulfite-PCR pyrosequencing was used to quantify DNA methylation in LINE-1 and AluI repetitive elements (genome-wide surrogates) and MAGE-1 and p15 genes (gene-specific).
• Allele-specific pyrosequencing of the H19 gene was employed to detect LOI.

Main Results:

• Airborne benzene exposure was significantly associated with global hypomethylation of LINE-1 and AluI repetitive elements.
• Gene-specific methylation changes, including p15 hypermethylation and MAGE-1 hypomethylation, correlated with increasing benzene levels.
• Loss of imprinting (LOI) was detected exclusively in benzene-exposed subjects, though not significantly associated with exposure levels.

Conclusions:

• This is the first human study to demonstrate that low-level benzene exposure can induce aberrant DNA methylation patterns in healthy individuals.
• The observed epigenetic changes, including global hypomethylation and gene-specific alterations, resemble those found in malignant cells.
• These findings link environmental carcinogen exposure to epigenetic modifications relevant to cancer development.