A comparison of the cytogenetic alterations and global DNA hypomethylation induced by the benzene metabolite, hydroquinone, with those induced by melphalan and etoposide
- 25 March 2010
- journal article
- research article
- Published by Springer Science and Business Media LLC in Leukemia
- Vol. 24 (5), 986-991
- https://doi.org/10.1038/leu.2010.43
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.Keywords
This publication has 46 references indexed in Scilit:
- The benzene metabolite, hydroquinone and etoposide both induce endoreduplication in human lymphoblastoid TK6 cellsMutagenesis, 2009
- Mechanisms of peroxisome proliferator-induced DNA hypomethylation in rat liverMutation Research, 2008
- Genetics of therapy-related myelodysplasia and acute myeloid leukemiaLeukemia, 2008
- Long term low-dose arsenic exposure induces loss of DNA methylationBiochemical and Biophysical Research Communications, 2006
- Alternative genetic pathways and cooperating genetic abnormalities in the pathogenesis of therapy-related myelodysplasia and acute myeloid leukemiaLeukemia, 2006
- Topoisomerase II inhibition by myeloperoxidase-activated hydroquinone: A potential mechanism underlying the genotoxic and carcinogenic effects of benzeneChemico-Biological Interactions, 2005
- The Nature of Chromosomal Aberrations Detected in Humans Exposed to BenzeneCritical Reviews in Toxicology, 2002
- DNA methylation, imprinting and cancerEuropean Journal of Human Genetics, 2002
- The process of leukemogenesis.Environmental Health Perspectives, 1996
- The Process of LeukemogenesisEnvironmental Health Perspectives, 1996