Human bronchial epithelial cells malignantly transformed by hexavalent chromium exhibit an aneuploid phenotype but no microsatellite instability

Rodrigues, Carlos; Urbano, Ana M.; Matoso, Eunice; Carreira, Isabel M.; Almeida, Anabela; Santos, P.; Botelho, Maria Filomena; Carvalho, Lina; Alves, Margarida; Monteiro, Carolino; Costa, André Nuno; Moreno, Virtudes; Alpoím, Maria C.

doi:10.1016/j.mrfmmm.2009.07.004

Cited by 45 publications

(28 citation statements)

References 56 publications

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“…We chose this particular model system also because it has been previously shown that environmental exposures can induce cell transformation of these cells (Lu et al 2015; Park et al 2015; Son et al 2012; Vales et al 2015; Zhang et al 2012). The BEAS-2B cells have been used for about 30 years in various biomedical research studies, including toxicological studies that tested chemicals, including organic, inorganic and particular agents (Fuentes-Mattei et al 2010; Garcia-Canton et al 2013; Lansley 2015; Rodrigues et al 2009; Steerenberg et al 1998; Sun et al 1995; Verstraelen et al 2014). …”

Section: Discussionmentioning

confidence: 99%

The impact of oil spill to lung health—Insights from an RNA-seq study of human airway epithelial cells

Liu

Roy-Engel

Baddoo

et al. 2016

Gene

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The Deepwater Horizon oil spill (BP oil spill) in the Gulf of Mexico was a unique disaster event, where a huge amount of oil spilled from the sea bed and a large volume of dispersants were applied to clean the spill. The operation lasted for almost three months and involved >50,000 workers. The potential health hazards to these workers may be significant as previous research suggested an association of persistent respiratory symptoms with exposure to oil and oil dispersants. To reveal the potential effects of oil and oil dispersants on the respiratory system at the molecular level, we evaluated the transcriptomic profile of human airway epithelial cells grown under treatment of crude oil, the dispersants Corexit 9500 and Corexit 9527 and oil-dispersant mixtures. We identified a very strong effect of Corexit 9500 treatment, with 84 genes (response genes) differentially expressed in treatment vs. control samples. We discovered an interactive effect of oil-dispersant mixtures; while no response gene was found for Corexit 9527 treatment alone, cells treated with Corexit 9527 + oil mixture showed an increased number of response genes (46 response genes), suggesting a synergic effect of 9527 with oil on airway epithelial cells. Through GO (gene ontology) functional term and pathway-based analysis, we identified upregulation of gene sets involved in angiogenesis and immune responses and downregulation of § Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. HHS Public Access Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript gene sets involved in cell junctions and steroid synthesis as the prevailing transcriptomic signatures in the cells treated with Corexit 9500, oil or Corexit 9500 + oil mixture. Interestingly, these key molecular signatures coincide with important pathological features observed in common lung diseases, such as asthma, cystic fibrosis and chronic obstructive pulmonary disease. Our study provides mechanistic insights into the detrimental effects of oil and oil dispersants to the respiratory system and suggests significant health impacts of the recent BP oil spill to those people involved in the cleaning operation.

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Section: Discussionmentioning

confidence: 99%

The impact of oil spill to lung health—Insights from an RNA-seq study of human airway epithelial cells

Liu

Roy-Engel

Baddoo

et al. 2016

Gene

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“…Cr(VI) has been shown by multiple studies and multiple groups to be aneugenic as measured by both chromosome assays and centromere positive micronuclei assays [15,16,31,33–38]. The aneugenic effect of Cr(VI) particles was significantly enhanced with continuing or prolonged treatments including an increase in polyploid or near polyploid cells [33–36]. The mechanisms for the aneuploidy are uncertain.…”

Section: Carcinogenic Metalsmentioning

confidence: 99%

Aneuploidy as an early mechanistic event in metal carcinogenesis

Wise

2010

Biochemical Society Transactions

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“…Mutations in tyrosine kinase (TK) domain of the EGFR gene in NSCLCs were discovered and presence of these mutations corrected with sensitivity to the EGFR inhibitor (9). It has been reported that EGFR mRNA level was increased in BEAS-2B cells exposed to 1 M of Cr(VI) up to 8 culture passages (14). Our previous study has demonstrated that chronic exposure of BEAS-2B cells to Cr(VI) was able to induce malignant cell transformation (17).…”

Section: Discussionmentioning

confidence: 87%

“…This protein is overexpressed in 40 -80% of non-small cell lung cancer (NSCLC), and a subgroup of patients with a specific mutation in its gene have a marked clinical response to EGFR tyrosine kinase inhibitors. Although it has been reported that chromium-treated cells exhibited an increased EGFR expression (14,15), the role of EGFR in Cr(VI)-induced tumorigenesis remains to be investigated. The present study has shown that chronic-exposure of Cr(VI) induced EGFR signaling and caused cell transformation.…”

Section: Cr(vi)-transformed Cells In Summary the Present Study Suggmentioning

confidence: 99%

Constitutive Activation of Epidermal Growth Factor Receptor Promotes Tumorigenesis of Cr(VI)-transformed Cells through Decreased Reactive Oxygen Species and Apoptosis Resistance Development

Kim

Dai

Fai

et al. 2015

Journal of Biological Chemistry

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Background: Chronic exposure to Cr(VI) causes cell transformation. Results: Cr(VI)-transformed cells exhibit activated EGFR, reduced ROS generation, and development of apoptosis resistance. Conclusion: Constitutive activation of EGFR promotes tumorigenesis of Cr(VI)-transformed cells.Significance: The findings provide a new understanding on carcinogenic mechanisms of not only Cr(VI) but also other metals, such as arsenic and nickel. It also can be used to formulate cancer prevention strategies.

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Human bronchial epithelial cells malignantly transformed by hexavalent chromium exhibit an aneuploid phenotype but no microsatellite instability

Cited by 45 publications

References 56 publications

The impact of oil spill to lung health—Insights from an RNA-seq study of human airway epithelial cells

The impact of oil spill to lung health—Insights from an RNA-seq study of human airway epithelial cells

Aneuploidy as an early mechanistic event in metal carcinogenesis

Constitutive Activation of Epidermal Growth Factor Receptor Promotes Tumorigenesis of Cr(VI)-transformed Cells through Decreased Reactive Oxygen Species and Apoptosis Resistance Development

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