THE BENZENE METABOLITE, HYDROQUINONE, INDUCES DOSE-DEPENDENT HYPOPLOIDY IN A HUMAN CELL-LINE

Chronic exposure to high concentrations of benzene can result in the d evelopment of myelodysplastic syndrome (MDS) and acute myelogenous leu kemia (AML). Studies of patients occupationally exposed to benzene sho w a pattern of cytogenetic aberrations involving high frequency of los s of all or part of chromosomes 5 and/or 7 as well as trisomy 8. The p attern of reoccurring chromosome abnormalities associated with the dev elopment of leukemia can be used as a guide in understanding the etiol ogy and pathogenesis of these diseases. Therefore, a research project was designed to determine whether a metabolite of benzene, hydroquinon e (HQ), could directly induce loss of chromosome 5 and/or 7 and gain o f chromosome 8. Using fluorescence in situ hybridization with chromoso me specific 5, 7 and a probes we demonstrate that 42, 49 and 26 mu M H Q induces manosomy 5, 7 and 8, respectively, in the human lymphoblast cell line GM09948. These results demonstrate for the first time that H Q induces a specific chromosome loss found in secondary MDS/AML. The p attern of chromosome 5 and/or 7 loss in benzene-induced MDS/AML is pro bably due to selective cell survival after HQ exposure rather than spe cific targeting of HQ for chromosomes 5 or 7.