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

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.

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

“…It is speculated that genetic and lifestyle factors influence the toxic effects of benzene, but current evidence is inconclusive. 29,30 Scientists postulate that the resultants of benzene metabolites are responsible for benzene toxicity because these metabolites can alkylate proteins and DNA. 31 Previous studies have shown that individuals vary in their susceptibility to the adverse effects of benzene, probably due to differences in metabolic genes and corresponding enzymatic activity.…”

Regulation and practice of workers’ protection from chemical exposures during container handling

“…The main targets of toxic effect are the respiratory and the nervous system. Ethylene oxide, formaldehyde and benzene can damage DNA and induce cancer as recognised by the International Agency for Research on Cancer, while some fumigants, such as methyl bromide, are suspected carcinogens [2,[13][14][15].…”

Contaminação química, precarização, adoecimento e morte no trabalho: benzeno no Brasil

“…In addition to AML and MDS, studies point to a correlation of exposition to benzene with a broad spectrum of malignant diseases of the hematopoietic and lymphatic systems: Non-Hodgkin's Lymphoma, chronic or acute lymphoid leukemia, and multiple myeloma. It should be further emphasized that organic solvents -the chemical group of which benzene is a part and that is almost always present in the form of a mixture of products -are demonstrably associated with various other types of cancer such as breast and brain cancer [6][7][8] . Benzene and other chemical contaminants become increasingly important in light of the rapid and intense changes in recent decades, with a huge impact on the workplace, the environment, and on health.…”