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Current understanding of the mechanism of benzene-induced leukemia in humans: implications for risk assessment.

Carcinogenesis (2011-12-15)
Cliona M McHale, Luoping Zhang, Martyn T Smith
ABSTRACT

Benzene causes acute myeloid leukemia and probably other hematological malignancies. As benzene also causes hematotoxicity even in workers exposed to levels below the US permissible occupational exposure limit of 1 part per million, further assessment of the health risks associated with its exposure, particularly at low levels, is needed. Here, we describe the probable mechanism by which benzene induces leukemia involving the targeting of critical genes and pathways through the induction of genetic, chromosomal or epigenetic abnormalities and genomic instability, in a hematopoietic stem cell (HSC); stromal cell dysregulation; apoptosis of HSCs and stromal cells and altered proliferation and differentiation of HSCs. These effects modulated by benzene-induced oxidative stress, aryl hydrocarbon receptor dysregulation and reduced immunosurveillance, lead to the generation of leukemic stem cells and subsequent clonal evolution to leukemia. A mode of action (MOA) approach to the risk assessment of benzene was recently proposed. This approach is limited, however, by the challenges of defining a simple stochastic MOA of benzene-induced leukemogenesis and of identifying relevant and quantifiable parameters associated with potential key events. An alternative risk assessment approach is the application of toxicogenomics and systems biology in human populations, animals and in vitro models of the HSC stem cell niche, exposed to a range of levels of benzene. These approaches will inform our understanding of the mechanisms of benzene toxicity and identify additional biomarkers of exposure, early effect and susceptibility useful for risk assessment.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Benzene, anhydrous, 99.8%
Sigma-Aldrich
Benzene, suitable for HPLC, ≥99.9%
Supelco
Benzene, analytical standard
Sigma-Aldrich
Benzene, ACS reagent, ≥99.0%
Supelco
Benzene, Pharmaceutical Secondary Standard; Certified Reference Material
Supelco
Benzene solution, certified reference material, TraceCERT®, 200 μg/mL in methanol
Sigma-Aldrich
Benzene, puriss. p.a., reag. Ph. Eur., ≥99.7%

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