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Epidemiology and Virology

Leukemia-related chromosomal loss detected in hematopoietic progenitor cells of benzene-exposed workers

Leukemia volume 26, pages 2494–2498 (2012)Cite this article

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Abstract

Benzene exposure causes acute myeloid leukemia and hematotoxicity, shown as suppression of mature blood and myeloid progenitor cell numbers. As the leukemia-related aneuploidies monosomy 7 and trisomy 8 previously had been detected in the mature peripheral blood cells of exposed workers, we hypothesized that benzene could cause leukemia through the induction of these aneuploidies in hematopoietic stem and progenitor cells. We measured loss and gain of chromosomes 7 and 8 by fluorescence in situ hybridization in interphase colony-forming unit–granulocyte-macrophage (CFU-GM) cells cultured from otherwise healthy benzene-exposed (n=28) and unexposed (n=14) workers. CFU-GM monosomy 7 and 8 levels (but not trisomy) were significantly increased in subjects exposed to benzene overall, compared with levels in the control subjects (P=0.0055 and P=0.0034, respectively). Levels of monosomy 7 and 8 were significantly increased in subjects exposed to <10 p.p.m. (20%, P=0.0419 and 28%, P=0.0056, respectively) and ⩾10 p.p.m. (48%, P=0.0045 and 32%, 0.0354) benzene, compared with controls, and significant exposure–response trends were detected (Ptrend=0.0033 and 0.0057). These data show that monosomies 7 and 8 are produced in a dose-dependent manner in the blood progenitor cells of workers exposed to benzene, and may be mechanistically relevant biomarkers of early effect for benzene and other leukemogens.

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Acknowledgements

We thank the participants for taking part in this study. This study was supported by NIH grants RO1ES06721, P42ES04705 and P30ES01896 (MTS), P42ES05948 and P30ES10126 (SMR), and NIH contract N01-CO-12400 with SAIC-Frederick, Inc.

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Author notes

  1. L Zhang and Q Lan: These authors contributed equally to this work.

Authors and Affiliations

  1. Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, CA, USA

    L Zhang, Z Ji, W Guo, A E Hubbard, C M McHale, S M Rappaport & M T Smith

  2. Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA

    Q Lan, M Shen, M S Linet & N Rothman

  3. Institute of Occupational Medicine, Chinese Center for Disease Control and Prevention, Beijing, China

    G Li & S Yin

  4. Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands

    R Vermeulen

  5. Division of Epidemiology, Department of Environmental Medicine, New York University School of Medicine, New York, NY, USA

    R B Hayes

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  1. L Zhang
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  2. Q Lan
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  3. Z Ji
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Corresponding authors

Correspondence to M T Smith or N Rothman.

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Competing interests

MTS and SMR have received consulting and expert testimony fees from law firms representing both plaintiffs and defendants in cases involving exposure to benzene. GL has received funds from the American Petroleum Institute for consulting on benzene-related health research. The remaining authors declare no conflict of interest.

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Zhang, L., Lan, Q., Ji, Z. et al. Leukemia-related chromosomal loss detected in hematopoietic progenitor cells of benzene-exposed workers. Leukemia 26, 2494–2498 (2012). https://doi.org/10.1038/leu.2012.143

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