The role of oxidative stress in carcinogenesis

Chemical carcinogenesis follows a multistep process involving both mutation and increased cell proliferation. Oxidative stress can occur through overproduction of reactive oxygen and nitrogen species through either endogenous or exogenous insults. Important to carcinogenesis, the unregulated or prol...

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Bibliographic Details
Published in:Annual review of pharmacology and toxicology 2004-01, Vol.44 (1), p.239-267
Main Authors: KLAUNIG, James E, KAMENDULIS, Lisa M
Format: Article
Language:English
Subjects:
Antioxidants - physiology
Biological and medical sciences
Carcinogenesis, carcinogens and anticarcinogens
Cell Division - physiology
DNA Damage
DNA Methylation
DNA, Mitochondrial - genetics
DNA, Mitochondrial - metabolism
Gene Expression Regulation
General aspects
Humans
Medical sciences
Mutation
Neoplasms - chemically induced
Neoplasms - metabolism
Oxidative Stress
Reactive Nitrogen Species - metabolism
Reactive Oxygen Species - metabolism
Signal Transduction
Tumors
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Summary:Chemical carcinogenesis follows a multistep process involving both mutation and increased cell proliferation. Oxidative stress can occur through overproduction of reactive oxygen and nitrogen species through either endogenous or exogenous insults. Important to carcinogenesis, the unregulated or prolonged production of cellular oxidants has been linked to mutation (induced by oxidant-induced DNA damage), as well as modification of gene expression. In particular, signal transduction pathways, including AP-1 and NFkappaB, are known to be activated by reactive oxygen species, and they lead to the transcription of genes involved in cell growth regulatory pathways. This review examines the evidence of cellular oxidants' involvement in the carcinogenesis process, and focuses on the mechanisms for production, cellular damage produced, and the role of signaling cascades by reactive oxygen species.
ISSN:0362-1642
1545-4304
DOI:10.1146/annurev.pharmtox.44.101802.121851