Oxidative stress and metabolic reprogramming in Cr(VI) carcinogenesis

Marco Clementino, Xianglin Shi, Zhuo Zhang

Research output: Contribution to journalReview articlepeer-review

31 Scopus citations


Cr(VI)-containing compounds are well-established lung carcinogens. Chronic exposure of the normal human epithelial cells is able to induce malignant cell transformation, the first stage of metal carcinogenesis. These Cr(VI)-transformed cells exhibit increased level of antioxidants, reduced capacity of generating reactive oxygen species (ROS), and development of apoptosis resistance, promoting tumorigenesis of Cr(VI)-transformed cells, the second stage of metal carcinogenesis. The mechanism of Cr(VI) induced carcinogenesis is still under investigation. Recent studies indicate that ROS play a positive role in the first stage while a negative role in the second stage. Transformed cells adapt metabolism to support tumor initiation and progression. Altered metabolic activities directly participate in the process of cell transformation or support a large requirement for nucleotides, amino acids, and lipids for tumor growth. In malignantly Cr(VI)-transformed cells, mitochondrial oxidative phosphorylation is defective, and pentose phosphate pathway, glycolysis, and glutaminolysis are upregulated. These metabolic reprogramming supports rapid cell proliferation and contributes to tumorigenesis of Cr(VI)-transformed cells. This article summarizes the current progress in the studies of metabolic reprogramming and Cr(VI) carcinogenesis with emphasis on the metabolic enzymes and oxidative stress related major oncogenic pathways.

Original languageEnglish
Pages (from-to)20-27
Number of pages8
JournalCurrent Opinion in Toxicology
StatePublished - Apr 2018

Bibliographical note

Funding Information:
This work is supported by National Institute of Health R01ES021771 and R01ES025515 to Shi X and Zhang Z and P30ES026529 to Shi X.

Publisher Copyright:
© 2017 Elsevier B.V.


  • Carcinogenesis
  • Chromium (VI)
  • Metabolic reprogramming
  • Oxidative stress

ASJC Scopus subject areas

  • Toxicology


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