title: Chromosome-wide aneuploidy study (CWAS) in workers exposed to an established leukemogen, benzene.
abstract: Evidence suggests that de novo, therapy-related and benzene-induced acute myeloid leukemias (AML) occur via similar cytogenetic and genetic pathways, several of which involve aneuploidy, the loss or gain of chromosomes. Aneuploidy of specific chromosomes has been detected in benzene-related leukemia patients as well as in healthy benzene-exposed workers, suggesting that aneuploidy precedes and may be a potential mechanism underlying benzene-induced leukemia. Here, we analyzed the peripheral blood lymphocytes of 47 exposed workers and 27 unexposed controls using a novel OctoChrome fluorescence in situ hybridization (FISH) technique that simultaneously detects aneuploidy in all 24 chromosomes. Through this chromosome-wide aneuploidy study (CWAS) approach, we found heterogeneity in the monosomy and trisomy rates of the 22 autosomes when plotted against continuous benzene exposure. In addition, statistically significant, chromosome-specific increases in the rates of monosomy [5, 6, 7, 10, 16 and 19] and trisomy [5, 6, 7, 8, 10, 14, 16, 21 and 22] were found to be dose dependently associated with benzene exposure. Furthermore, significantly higher rates of monosomy and trisomy were observed in a priori defined 'susceptible' chromosome sets compared with all other chromosomes. Together, these findings confirm that benzene exposure is associated with specific chromosomal aneuploidies in hematopoietic cells, which suggests that such aneuploidies may play roles in benzene-induced leukemogenesis.
authors.affiliation: Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, CA 94720, USA. luoping@berkeley.edu
authors.forename: Luoping
authors.initials: L
authors.lastname: Zhang
authors.forename: Qing
authors.initials: Q
authors.lastname: Lan
authors.forename: Weihong
authors.initials: W
authors.lastname: Guo
authors.forename: Alan E
authors.initials: AE
authors.lastname: Hubbard
authors.forename: Guilan
authors.initials: G
authors.lastname: Li
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Rappaport
authors.forename: Cliona M
authors.initials: CM
authors.lastname: McHale
authors.forename: Min
authors.initials: M
authors.lastname: Shen
authors.forename: Zhiying
authors.initials: Z
authors.lastname: Ji
authors.forename: Roel
authors.initials: R
authors.lastname: Vermeulen
authors.forename: Songnian
authors.initials: S
authors.lastname: Yin
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Rothman
authors.forename: Martyn T
authors.initials: MT
authors.lastname: Smith
mesh_terms: D000328:Adult; D000782:Aneuploidy; D001554:Benzene / Q000633:toxicity*; D041321:Chromosomes, Human, X; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007938:Leukemia / Q000139:chemically induced*; D008297:Male; D016273:Occupational Exposure / Q000009:adverse effects*
chemical_list: D001554:Benzene