Progress and Prospects of Reactive Oxygen Species in Metal Carcinogenesis

Lei Wang, James T.F. Wise, Zhuo Zhang, Xianglin Shi

Research output: Contribution to journalReview articlepeer-review

31 Scopus citations


Carcinogenesis induced by environmental metal exposure is a major public health concern. The exact mechanisms underlying metal carcinogenesis remain elusive. In the past few decades, the relationship between metal-induced generation of reactive oxygen species (ROS) and the mechanism of metal carcinogenesis has been established. The carcinogenic process is a very complex one. In the early stage of metal carcinogenesis or cell transformation, high levels of ROS are oncogenic by causing DNA damage, genetic instability, epigenetic alteration, and metabolic reprogramming, leading to malignant transformation. In the second stage of metal carcinogenesis or the cancer development of metal-transformed cells, low levels of ROS are carcinogenic by promoting apoptosis resistance. The metal-transformed cells have the property of autophagy deficiency, resulting in accumulation of p62 and constitutive activation of NF-E2-related factor 2 (Nrf2) and leading to higher levels of antioxidants, decreased levels of ROS, apoptosis resistance, inflammation, and angiogenesis. This review summarizes the most recent development in the field of metal carcinogenesis with emphasis on the difference in cellular events between early (cell transformation) and late (after cell transformation) stages of metal carcinogenesis.

Original languageEnglish
Pages (from-to)178-186
Number of pages9
JournalCurrent Pharmacology Reports
Issue number4
StatePublished - Aug 1 2016

Bibliographical note

Funding Information:
This work was supported by the National Institutes of Health [R01ES021771, R01ES025515, R01ES020870, and R01ES017244].

Publisher Copyright:
© 2016, Springer International Publishing AG.


  • Carcinogenesis
  • Metal
  • Nrf2
  • Reactive oxygen species (ROS)
  • Tumorigenesis

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Pharmacology
  • Drug Discovery


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