Metal-induced oxidative stress and signal transduction

Stephen S. Leonard, Gabriel K. Harris, Xianglin Shi

Research output: Contribution to journalReview articlepeer-review

545 Scopus citations


Occupational and environmental exposures to metals are associated with the development of various cancers. Although carcinogenesis caused by metals has been intensively investigated, the mechanisms of action, especially at the molecular level, are still unclear. Accumulating evidence indicates that reactive oxygen species generated by metals may play an important role in the etiology of disease. This review covers recent advances in (1) metal-induced generation of reactive oxygen species; (2) the receptors, kinases, and nuclear transcription factors affected by metals and metal-induced oxidative stress, including growth factor receptors, src kinase, ras signaling, mitogen-activated protein kinases, the phosphoinositide 3-phosphate/Akt pathway, nuclear transcription factor κB, activator protein 1, p53, nuclear factor of activated T cells, and hypoxia-inducible factor 1; and (3) global cellular phenomena (signal transduction, cell cycle regulation, and apoptosis) associated with metal-induced ROS production and gene expression.

Original languageEnglish
Pages (from-to)1921-1942
Number of pages22
JournalFree Radical Biology and Medicine
Issue number12
StatePublished - Dec 15 2004


  • Carcinogenesis
  • Free radicals
  • Metals
  • Reactive oxygen species
  • Signal transduction

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)


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