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Cytogenetics and Molecular Genetics

A comparison of the cytogenetic alterations and global DNA hypomethylation induced by the benzene metabolite, hydroquinone, with those induced by melphalan and etoposide

Leukemia volume 24, pages 986–991 (2010)Cite this article

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Abstract

Specific cytogenetic alterations and changes in DNA methylation are involved in leukemogenesis. Benzene, an established human leukemogen, is known to induce cytogenetic changes through its active metabolites including hydroquinone (HQ), but the specific alterations have not been fully characterized. Global DNA hypomethylation was reported in a population exposed to benzene, but has not been confirmed in vitro. In this study, we examined cytogenetic changes in chromosomes 5, 7, 8, 11 and 21, and global DNA methylation in human TK6 lymphoblastoid cells treated with HQ for 48 h, and compared the HQ-induced alterations with those induced by two well-known leukemogens, melphalan, an alkylating agent, and etoposide, a DNA topoisomerase II inhibitor. We found that rather than inducing cytogenetic alterations distinct from those induced by melphalan and etoposide, HQ induced alterations characteristic of each agent. HQ induced global DNA hypomethylation at a level intermediate to melphalan (no effect) and etoposide (potent effect). These results suggest that HQ may act similar to an alkylating agent and also similar to a DNA topoisomerase II inhibitor in living cells, both of which may be potential mechanisms of benzene toxicity. In addition to cytogenetic changes, global DNA hypomethylation may be another mechanism underlying the leukemogenicity of benzene.

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Acknowledgements

We are grateful to Ms Anh Duong for editing the manuscript. This study was supported by National Institutes of Health Grants P42ES004705 and R01ES006721 to MTS.

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

    Z Ji, L Zhang, V Peng, X Ren, C M McHale & M T Smith

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Correspondence to M T Smith.

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Dr Smith has received consulting and expert testimony fees from lawyers representing both plaintiffs and defendants in cases involving claims related to exposure to benzene.

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Ji, Z., Zhang, L., Peng, V. et al. A comparison of the cytogenetic alterations and global DNA hypomethylation induced by the benzene metabolite, hydroquinone, with those induced by melphalan and etoposide. Leukemia 24, 986–991 (2010). https://doi.org/10.1038/leu.2010.43

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