Differential gene expression profiles of human leukemia cell lines exposed to benzene and its metabolites.
Environ Toxicol Pharmacol
; 32(2): 285-95, 2011 Sep.
Article
en En
| MEDLINE
| ID: mdl-21843810
Benzene is a well-known environmental pollutant that can induce hematotoxicity, aplastic anemia, acute myelogenous leukemia, and lymphoma. Benzene toxicity is likely mediated through metabolites induced by means of multiple pathways. Although benzene metabolites are known to induce oxidative stress and disrupt the cell cycle, the mechanism underlying leukemogenesis is not fully understood. The aim of this study was to analyze the genome-wide expression profiles of human promyelocytic leukemia HL-60 cells that had been exposed to benzene and its metabolites. This was carried out using whole human genome oligonucleotide microarrays to ascertain potential biomarkers. Genes that were differentially expressed (>1.5-fold and p-values <0.05) after exposure to benzene (BZ), hydroquinone (HQ), and 1,4-benzoquinone (BQ) were then classified with GO, KEGG and GSEA pathway annotation. All genes that were identified were then functionally categorized as being involved in the cell cycle, the p53 signaling pathway, apoptosis, the MAPK signaling pathway, or the T cell receptor signaling pathway. Functionally important genes were further validated by means of real-time RT-PCR. The results showed that EGR1, PMAIP1, AR, CCL2, CD69, HSPA8, SLC7A11, HERPUD1, ELK1, and MKI57 genes altered their expression profiles. Similar expression profiles were also found in human erythromyeloblastoid leukemia K562 cells and in human leukemic monocyte lymphoma U937 cells. In conclusion, gene expression profiles along with GO, KEGG and GSEA pathway annotation analysis have provided an insight into the leukemogenesis as well as highlighted potential gene-based biomarkers of human leukemia cell lines when they are exposed to benzene and its metabolites.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Benceno
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Expresión Génica
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Benzoquinonas
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Células HL-60
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Células K562
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Células U937
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Hidroquinonas
Límite:
Humans
Idioma:
En
Revista:
Environ Toxicol Pharmacol
Año:
2011
Tipo del documento:
Article
Pais de publicación:
Países Bajos