The benzene metabolite, hydroquinone, selectively induces 5q31- and -7 in human CD34+CD19- bone marrow cells.
OBJECTIVE
Chronic exposure to high concentrations of benzene is associated with an increased incidence of myelodysplastic syndrome and acute myelogenous leukemia. Acute myelogenous leukemia developing in patients treated with alkylating agents for other cancers or occupationally exposed to benzene exhibit a pattern of cytogenetic aberrations predominantly involving loss of all or part of chromosomes 5 and/or 7. In contrast, trisomy 8 is observed equally in both de novo and secondary acute myelogenous leukemia. Studies using peripheral lymphocytes or lymphoblastoid cell lines have observed dose-dependent loss of chromosomes 5, 7, and 8 following treatment with the benzene metabolite, hydroquinone. The purpose of this study was to determine the dose response and specificity of hydroquinone-induced aberrations on chromosomes 5, 7, and 8 using human CD34+CD19 bone marrow cells.


METHODS
Fluorescence in situ hybridization analysis was performed on CD34+CD19- bone marrow cells using the locus-specific probes, 5q31, 5p15.2, and centromeric probes specific for human chromosomes 7 and 8 following hydroquinone exposure.


RESULTS
Hydroquinone exposure results in -7, selective deletion of 5q31 but not chromosome 5 and no loss or gain of chromosome 8 in human CD34+CD19- cells.


CONCLUSIONS
CD34+ bone marrow cells are more susceptible and show a different pattern of cytogenetic aberrations as a result of hydroquinone exposure compared to lymphocytes. CD34+ bone marrow cells exhibit unique susceptibility to the development of specific chromosome aberrations that have been identified as the earliest structural changes occurring in the development of secondary myelodysplastic syndrome and acute myelogenous leukemia.
Stillman
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WS
The Molecular Toxicology and Environmental Health Sciences Program, School of Pharmacy, University of Colorado Health Sciences Center, Denver 80262, USA.
Varella-Garcia
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Irons
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D001554:Benzene / Q000633:toxicity; D002895:Chromosomes, Human, Pair 5; D002897:Chromosomes, Human, Pair 7; D002898:Chromosomes, Human, Pair 8; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D006873:Hydroquinones / Q000633:toxicity*; D015470:Leukemia, Myeloid, Acute / Q000139:chemically induced / Q000235:genetics; D009153:Mutagens / Q000633:toxicity*; D009190:Myelodysplastic Syndromes / Q000139:chemically induced / Q000235:genetics; D017384:Sequence Deletion / Q000187:drug effects
D006873:Hydroquinones; D009153:Mutagens; D001554:Benzene; C031927:hydroquinone