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Chromosome-wide aneuploidy study (CWAS) in workers exposed to an established leukemogen, benzene
- Publication Year :
- 2011
- Publisher :
- Oxford University Press, 2011.
-
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.
- Subjects :
- Adult
Male
Cancer Research
medicine.medical_specialty
Monosomy
Carcinogenesis
Aneuploidy
Biology
Occupational Exposure
medicine
Humans
Chromosomes, Human, X
Autosome
Leukemia
medicine.diagnostic_test
Dose-Response Relationship, Drug
Cytogenetics
Chromosome
Benzene
General Medicine
medicine.disease
Immunology
Cancer research
Female
Trisomy
Fluorescence in situ hybridization
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....7e2e235743dc2eeef33fa67e7dd48fb0