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Journal of Environmental Pathology, Toxicology and Oncology
IF: 1.625 5-Year IF: 1.63 SJR: 0.402 SNIP: 0.613 CiteScore™: 2.3

ISSN Print: 0731-8898
ISSN Online: 2162-6537

Journal of Environmental Pathology, Toxicology and Oncology

DOI: 10.1615/JEnvironPatholToxicolOncol.2018028689
pages 317-329

Investigating the Role of Mitochondrial Respiratory Dysfunction during Hexavalent Chromium-Induced Lung Carcinogenesis

James T. F. Wise
Division of Nutritional Sciences, Department of Pharmacology and Nutritional Sciences, College of Medicine, University of Kentucky, Lexington, KY 40536, USA
Lei Wang
Center for Research on Environmental Disease, College of Medicine, University of Kentucky, Lexington, KY 40536, USA
Michael C. Alstott
Markey Cancer Center, Redox Metabolism Shared Resource Facility, University of Kentucky, Lexington, KY
Ntube N.O. Ngalame
Center for Research on Environmental Disease, College of Medicine, University of Kentucky, Lexington, KY
Yuting Wang
Center for Research on Environmental Disease, College of Medicine, University of Kentucky, Lexington, KY
Zhuo Zhang
Toxicology and Cancer Biology, College of Medicine, University of Kentucky, Lexington, KY
Xianglin Shi
Division of Nutritional Sciences, Pharmacology and Nutritional Sciences, College of Medicine, University of Kentucky, Lexington, KY; Center for Research on Environmental Disease, College of Medicine, University of Kentucky, Lexington, KY; Toxicology and Cancer Biology, College of Medicine, University of Kentucky, Lexington, KY

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.


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