title: The benzene metabolite, hydroquinone, induces dose-dependent hypoploidy in a human cell line.
abstract: Chronic exposure to high concentrations of benzene can result in the development of myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML). Studies of patients occupationally exposed to benzene show a pattern of cytogenetic aberrations involving high frequency of loss of all or part of chromosomes 5 and/or 7 as well as trisomy 8. The pattern of reoccurring chromosome abnormalities associated with the development of leukemia can be used as a guide in understanding the etiology and pathogenesis of these diseases. Therefore, a research project was designed to determine whether a metabolite of benzene, hydroquinone (HQ), could directly induce loss of chromosome 5 and/or 7 and gain of chromosome 8. Using fluorescence in situ hybridization with chromosome-specific 5, 7 and 8 probes we demonstrate that 42, 49 and 26 microM HQ induces monosomy 5, 7 and 8, respectively, in the human lymphoblast cell line GM09948. These results demonstrate for the first time that HQ induces a specific chromosome loss found in secondary MDS/AML. The pattern of chromosome 5 and/or 7 loss in benzene-induced MDS/AML is probably due to selective cell survival after HQ exposure rather than specific targeting of HQ for chromosomes 5 or 7.
authors.affiliation: Molecular Toxicology and Environmental Health Sciences, School of Pharmacy, University of Colorado Health Sciences Center, Denver 80262, USA.
authors.forename: W S
authors.initials: WS
authors.lastname: Stillman
authors.forename: M
authors.initials: M
authors.lastname: Varella-Garcia
authors.forename: J J
authors.initials: JJ
authors.lastname: Gruntmeir
authors.forename: R D
authors.initials: RD
authors.lastname: Irons
mesh_terms: D002478:Cells, Cultured; D002869:Chromosome Aberrations / Q000139:chemically induced*; D002872:Chromosome Deletion; D025063:Chromosome Disorders; D002895:Chromosomes, Human, Pair 5; D002897:Chromosomes, Human, Pair 7; D002898:Chromosomes, Human, Pair 8; D015342:DNA Probes; D006801:Humans; D006873:Hydroquinones / Q000494:pharmacology*; D017404:In Situ Hybridization, Fluorescence
chemical_list: D015342:DNA Probes; D006873:Hydroquinones; C031927:hydroquinone