The benzene metabolite, hydroquinone, induces dose-dependent hypoploidy in a human cell line.
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.
Stillman
W S
WS
Molecular Toxicology and Environmental Health Sciences, School of Pharmacy, University of Colorado Health Sciences Center, Denver 80262, USA.
Varella-Garcia
M
M
Gruntmeir
J J
JJ
Irons
R D
RD
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
D015342:DNA Probes; D006873:Hydroquinones; C031927:hydroquinone