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.

Current understandings and perspectives on non-cancer health effects of benzene: A global concern

“…Zhang et al (2011) has reported dose-dependent chromosomal aneuploidies (monosomy & trisomy) in the peripheral blood lymphocytes of 47 workers exposed to benzene . In another study published by Zhang et al (2012) an increased monosomy 7 and 8 level was found in 28 benzene-exposed workers in comparison to control subjects .…”

Utilização de biomarcadores de genotoxicidade e expressão gênica na avaliação de trabalhadores de postos de combustíveis expostos a vapores de gasolina

“…Alguns estudos relacionaram a trissomia do cromossomo 21 a um estágio de "pré-leucemia", tendo visto que pacientes com este câncer têm alta incidên-cia dessa alteração em nível celular [62][63][64] . Euploidia é o fenômeno onde uma célula apresenta um valor múltiplo do número de cromossomos haplóides (n).…”

Chromosomics: Detection of Numerical and Structural Alterations in All 24 Human Chromosomes Simultaneously Using a Novel OctoChrome FISH Assay

“…It is also very useful for examining most specific chromosomal rearrangements related to human leukemia and lymphoma in populations exposed to potential leukemogens and lymphomagens and for studying the aneuploidy-inducing effects of chemicals in a chromosome-wide manner. Our previous CWAS study using this technique demonstrated that certain chromosomes may be more affected than others by exposure to benzene 8,10 , a primary industrial chemical and a ubiquitous environmental pollutant that causes human leukemia 14 . This phenomenon of "selective aneuploidy" could be explored in other chemical exposures using CWAS.…”

“…We have applied this new Chromosomic approach in a CWAS study of benzene-exposed Chinese workers 8,10 .…”