title: Nonrandom aneuploidy of chromosomes 1, 5, 6, 7, 8, 9, 11, 12, and 21 induced by the benzene metabolites hydroquinone and benzenetriol.
abstract: The loss and gain of whole chromosomes (aneuploidy) is common in the development of leukemia and other cancers. In acute myeloid leukemia, the loss (monosomy) of chromosomes 5 and 7 and the gain (trisomy) of chromosome 8 are common clonal chromosomal abnormalities. Here, we have tested the hypothesis that metabolites of the human leukemogen benzene cause a higher rate of gain and loss among the chromosomes involved in leukemogenesis and, as such, are nonrandom and selective in their effects. Human peripheral blood was exposed to two metabolites of benzene, namely, hydroquinone (HQ) and benzenetriol (BT), and the ploidy status of nine different chromosomes (1, 5, 6, 7, 8, 9, 11, 12, and 21) was examined using fluorescence in situ hybridization of metaphase spreads. Poisson regression was used to provide interpretable incidence rate ratios and corresponding P values for all nine chromosomes. Statistically significant differences were found between the sensitivity of the nine chromosomes to gain or loss. Chromosomes 5 and 7 were highly sensitive to loss following HQ and BT exposure, whereas chromosomes 7, 8, and 21 were highly sensitive to gain in comparison to other chromosomes. Significant support for the a priori hypothesis that chromosomes 5 and 7 are more sensitive to loss induced by HQ and BT than the other seven chromosomes was also obtained. These data support the notion that benzene metabolites affect the ploidy status of specific chromosomes more than others and may initiate or promote leukemia induction through these specific effects.
authors.affiliation: Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, California 94720, USA.
authors.forename: Luoping
authors.initials: L
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Yang
authors.forename: Alan E
authors.initials: AE
authors.lastname: Hubbard
authors.forename: Martyn T
authors.initials: MT
authors.lastname: Smith
mesh_terms: D000208:Acute Disease; D001554:Benzene / Q000378:metabolism / Q000633:toxicity; D002478:Cells, Cultured; D002872:Chromosome Deletion; D002877:Chromosomes, Human / Q000235:genetics* / Q000648:ultrastructure; D005260:Female; D006801:Humans; D006873:Hydroquinones / Q000633:toxicity*; D017404:In Situ Hybridization, Fluorescence; D007951:Leukemia, Myeloid / Q000139:chemically induced; D008214:Lymphocytes / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D009006:Monosomy / Q000235:genetics*; D009153:Mutagens / Q000633:toxicity*; D016012:Poisson Distribution; D014314:Trisomy / Q000235:genetics*
chemical_list: D006873:Hydroquinones; D009153:Mutagens; C013038:hydroxyhydroquinone; D001554:Benzene; C031927:hydroquinone