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Citation
Tags
HERO ID
5879721
Reference Type
Journal Article
Title
Investigating the Role of Mitochondrial Respiratory Dysfunction during Hexavalent Chromium-Induced Lung Carcinogenesis
Author(s)
Wise, JTF; Wang, L; Alstott, MC; Ngalame, NNO; Wang, Y; Zhang, Z; Shi, X
Year
2018
Is Peer Reviewed?
Yes
Journal
Journal of Environmental Pathology, Toxicology and Oncology
ISSN:
0731-8898
EISSN:
2162-6537
Volume
37
Issue
4
Page Numbers
317-329
Language
English
PMID
30806238
DOI
10.1615/JEnvironPatholToxicolOncol.2018028689
Web of Science Id
WOS:000447381600004
Abstract
Hexavalent chromium [Cr(VI)] is a lung carcinogen and its complete mechanism of action remains to be investigated. Metabolic reprogramming of key energy metabolism pathways (e.g., increased anaerobic glycolysis in the presence of oxygen or "Warburg effect", dysregulated mitochondrial function, and lipogenesis) are important to cancer cell and tumor survival and growth. In our current understanding of Cr(VI)-induced carcinogenesis, the role for metabolic reprogramming remains unclear. In this study, we treated human lung epithelial cells (BEAS-2B) with Cr(VI) for 6 months and obtained malignantly transformed cells from an isolated colony grown in soft agar. We also used Cr(VI)-transformed cells from two other human lung cell lines (BEP2D and WTHBF-6 cells). Overall, we found that all the Cr(VI)-transformed cells had no changes in their mitochondrial respiratory functions (measured by the Seahorse Analyzer) compared with passaged-matched control cells. Using a xenograft tumor growth model, we generated tumors from these transformed cells in Nude mice. Using cells obtained from the xenograft tumor tissues, we observed that these cells had decreased maximal mitochondrial respiration, spare respiratory capacity, and coupling efficiency. These results provide evidence that, although mitochondrial dysfunction does not occur during Cr(VI)-induced transformation of lung cells, it does occur during tumor development.
Tags
IRIS
•
Chromium VI
Considered
Potentially Relevant Supplemental Material
Mechanistic
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May 2018 - October 2019
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