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 myelogen ous Leukemia. Acute myelogenous leukemia developing in patients treated wit h alkylating agents for other cancers or occupationally exposed to benzene exhibit a pattern of cytogenetic aberrations predominantly involving loss o f 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 dos e-dependent Loss of chromosomes 5, 7, and 8 following treatment with the be nzene metabolite, hydroquinone, The purpose of this study was to determine the dose response and specificity of hydroquinone-induced aberrations on ch romosomes 5, 7, and 8 using human CD34(-)CD19(-) bone marrow cells. Materials and Methods. Fluorescence in situ hybridization analysis was perf ormed 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 bu t not chromosome 5 and no loss or gain of chromosome 8 in human CD34+CD19- cells. Conclusion. CD34(+) bone marrow cells are more susceptible and show a diffe rent pattern of cytogenetic aberrations as a result of hydroquinone exposur e compared to lymphocytes. CD34(+) bone marrow cells exhibit unique suscept ibility to the development of specific chromosome aberrations that have bee n identified as the earliest structural changes occurring in the developmen t of secondary myelodysplastic syndrome and acute myelogenous leukemia. (C) 2000 International Society for Experimental Hematology. Published by Elsev ier Science Inc.