Global Gene Expression Profiling of a Population Exposed to a Range of Benzene Levels

Abstract

BackgroundBenzene, an established cause of acute myeloid leukemia (AML), may also cause one or more lymphoid malignancies in humans. Previously, we identified genes and pathways associated with exposure to high (> 10 ppm) levels of benzene through transcriptomic analyses of blood cells from a small number of occupationally exposed workers.ObjectivesThe goals of this study were to identify potential biomarkers of benzene exposure and/or early effects and to elucidate mechanisms relevant to risk of hematotoxicity, leukemia, and lymphoid malignancy in occupationally exposed individuals, many of whom were exposed to benzene levels < 1 ppm, the current U.S. occupational standard.MethodsWe analyzed global gene expression in the peripheral blood mononuclear cells of 125 workers exposed to benzene levels ranging from < 1 ppm to > 10 ppm. Study design and analysis with a mixed-effects model minimized potential confounding and experimental variability.ResultsWe observed highly significant widespread perturbation of gene expression at all exposure levels. The AML pathway was among the pathways most significantly associated with benzene exposure. Immune response pathways were associated with most exposure levels, potentially providing biological plausibility for an association between lymphoma and benzene exposure. We identified a 16-gene expression signature associated with all levels of benzene exposure.ConclusionsOur findings suggest that chronic benzene exposure, even at levels below the current U.S. occupational standard, perturbs many genes, biological processes, and pathways. These findings expand our understanding of the mechanisms by which benzene may induce hematotoxicity, leukemia, and lymphoma and reveal relevant potential biomarkers associated with a range of exposures.

Are polymorphisms in metabolism protective or a risk for reduced white blood cell counts in a Chinese population with low occupational benzene exposures?

“…24 This study found evidence of low-level benzene concentrations having an effect on peripheral blood WBCs. This finding is consistent with other studies conducted in China among shoemakers, [25][26][27] but contrary to a study in the Netherlands. 28 It is possible that the doserelationship between low benzene exposure in exposed workers and the life exposure in internal controls was modified by other factors in the Netherlands study, such as small numbers, worker protection, and life factors (e.g.…”

Health Effects of Benzene Exposure among Children Following a Flaring Incident at the British Petroleum Refinery in Texas City

“…D'Andrea and G. K. Reddy epidemiologic study by Rothman and coworkers showed that adult Chinese workers (mean age of 35 years), exposed to benzene had significantly reduced total WBC and platelet counts compared with those other workers who had not been exposed to benzene [28]. Similarly, McHale et al reported that adult subjects who were exposed to benzene had significantly reduced total WBC and platelet counts compared with those not exposed to benzene [29].…”

Distinct genotype-dependent differences in transcriptome responses in humans exposed to environmental carcinogens

“…Environmental exposures and harmful health effects have previously been linked to changes in gene expression (4)(5)(6)(7)(8). In a previous FLEHS study (9,10), the correlation between exposure levels to certain pollutants (metals and organochlorines) and global gene expression levels in peripheral lymphocytes has been investigated in 39 non-smoking adults.…”