Progress and prospects of reactive oxygen species in metal carcinogenesis.
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 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.
Center for Research on Environmental Disease, College of Medicine, University of Kentucky, Lexington, KY 40536, USA; Toxicology and Cancer Biology, College of Medicine, University of Kentucky, Lexington, KY 40536, USA.
Lei
L
Wang
Pharmacology and Nutritional Sciences, College of Medicine, University of Kentucky, Lexington, KY 40536, USA.
James T F
JT
Wise
Toxicology and Cancer Biology, College of Medicine, University of Kentucky, Lexington, KY 40536, USA.
Zhuo
Z
Zhang
Center for Research on Environmental Disease, College of Medicine, University of Kentucky, Lexington, KY 40536, USA; Toxicology and Cancer Biology, College of Medicine, University of Kentucky, Lexington, KY 40536, USA.
Xianglin
X
Shi
Nrf2; carcinogenesis; metal; reactive oxygen species (ROS); tumorigenesis