Entry
Name
Chemical carcinogenesis - reactive oxygen species
Description
It is well established that cancer is a multi-step process which involves initiation, promotion and progression. Chemical carcinogens can alter any of these processes to induce their carcinogenic effects. In the majority of instances, chemical carcinogens, directly or after xenobiotic metabolism, induce DNA damage and act in a 'genotoxic' manner. There is, however, a group of carcinogens that induce cancer via nongenotoxic mechanisms. The biochemical modes of action for nongenotoxic carcinogens are diverse, one example of which is induction of oxidative stress. Trace metals and organic xenobiotics are typical classes of environmental pollutants with prooxidant effects. Trace metals generate reactive oxygen species (ROS) depending on their ability to lose electrons and catalyze Haber Weiss and Fenton reactions. ROS are also generated due to induction of various cytochrome P450 isoenzymes during detoxification of chemical carcinogens. Increased ROS generation often has been linked to DNA damage that can lead to mutations and may, therefore, play an important role in the initiation and progression of multistage carcinogenesis. Besides causing DNA damage, ROS further induce multiple intracellular signaling pathways, notably NF-kappa B, JNK/SAPK/p38, as well as Erk/MAPK. These signaling routes can lead to transcriptional induction of target genes that could promote proliferation or confer apoptosis resistance to exposed cells.
Class
Human Diseases; Cancer: overview
BRITE hierarchy
Pathway map
map05208 Chemical carcinogenesis - reactive oxygen species
Reference
Authors
Henkler F, Brinkmann J, Luch A
Title
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Journal
Reference
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Title
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Authors
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Title
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Journal
Reference
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Arsenic and Human Health: Genotoxicity, Epigenomic Effects, and Cancer Signaling.
Journal
Reference
Authors
Hubaux R, Becker-Santos DD, Enfield KS, Rowbotham D, Lam S, Lam WL, Martinez VD
Title
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Journal
Reference
Authors
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Title
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Journal
Reference
Authors
Faita F, Cori L, Bianchi F, Andreassi MG
Title
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Reference
Authors
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Title
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Journal
Reference
Authors
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Title
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Reference
Authors
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Title
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Journal
Reference
Authors
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Title
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Reference
Authors
Wang Y, Su H, Gu Y, Song X, Zhao J
Title
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Reference
Authors
Jin X, Chen M, Song L, Li H, Li Z
Title
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Reference
Authors
Liou GY, Storz P
Title
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Journal
Reference
Authors
Murata M, Tamura A, Tada M, Kawanishi S
Title
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Reference
Authors
Title
Journal
Pentachlorophenol and Some Related Compounds (2019)
Reference
Authors
Zhu BZ, Shan GQ
Title
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Journal
Reference
Authors
McHale CM, Zhang L, Smith MT
Title
Current understanding of the mechanism of benzene-induced leukemia in humans: implications for risk assessment.
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Reference
Authors
Scharf P, Broering MF, Oliveira da Rocha GH, Farsky SHP
Title
Cellular and Molecular Mechanisms of Environmental Pollutants on Hematopoiesis.
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Reference
Authors
Snyder R
Title
Leukemia and benzene.
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Reference
Authors
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Title
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Reference
Authors
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Title
The role of metals in site-specific DNA damage with reference to carcinogenesis.
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Title
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Reference
Authors
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Title
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Journal
Reference
Authors
Penning TM
Title
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Journal
Reference
Authors
Burczynski ME, Penning TM
Title
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Journal
Cancer Res 60:908-15 (2000)
Reference
Authors
Xue W, Warshawsky D
Title
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Reference
Authors
Chen ZH, Hurh YJ, Na HK, Kim JH, Chun YJ, Kim DH, Kang KS, Cho MH, Surh YJ
Title
Resveratrol inhibits TCDD-induced expression of CYP1A1 and CYP1B1 and catechol estrogen-mediated oxidative DNA damage in cultured human mammary epithelial cells.
Journal
Reference
Authors
Rifkind AB
Title
CYP1A in TCDD toxicity and in physiology-with particular reference to CYP dependent arachidonic acid metabolism and other endogenous substrates.
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Reference
Authors
Cavalieri EL, Stack DE, Devanesan PD, Todorovic R, Dwivedy I, Higginbotham S, Johansson SL, Patil KD, Gross ML, Gooden JK, Ramanathan R, Cerny RL, Rogan EG
Title
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Journal
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Title
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McKillop IH, Schrum LW
Title
Role of alcohol in liver carcinogenesis.
Journal
Reference
Authors
Gonzalez FJ
Title
Role of cytochromes P450 in chemical toxicity and oxidative stress: studies with CYP2E1.
Journal
Reference
Authors
Montalbano AM, Albano GD, Anzalone G, Moscato M, Gagliardo R, Di Sano C, Bonanno A, Ruggieri S, Cibella F, Profita M
Title
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Reference
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Sun HN, Ren CX, Gong YX, Xie DP, Kwon T
Title
Regulatory function of peroxiredoxin I on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced lung cancer development.
Journal
Reference
Authors
Pluchino LA, Wang HC
Title
Chronic exposure to combined carcinogens enhances breast cell carcinogenesis with mesenchymal and stem-like cell properties.
Journal
Reference
Authors
Pluchino LA, Liu AK, Wang HC
Title
Reactive oxygen species-mediated breast cell carcinogenesis enhanced by multiple carcinogens and intervened by dietary ergosterol and mimosine.
Journal
Reference
Authors
Moldogazieva NT, Lutsenko SV, Terentiev AA
Title
Reactive Oxygen and Nitrogen Species-Induced Protein Modifications: Implication in Carcinogenesis and Anticancer Therapy.
Journal
Reference
Authors
Kirtonia A, Sethi G, Garg M
Title
The multifaceted role of reactive oxygen species in tumorigenesis.
Journal
Reference
Authors
Kumari S, Badana AK, G MM, G S, Malla R
Title
Reactive Oxygen Species: A Key Constituent in Cancer Survival.
Journal
Reference
Authors
Gao X, Schottker B
Title
Reduction-oxidation pathways involved in cancer development: a systematic review of literature reviews.
Journal
Reference
Authors
Storz P
Title
Reactive oxygen species in tumor progression.
Journal
Reference
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Title
The differential role of reactive oxygen species in early and late stages of cancer.
Journal
Reference
Authors
Storz P, Doppler H, Toker A
Title
Protein kinase Cdelta selectively regulates protein kinase D-dependent activation of NF-kappaB in oxidative stress signaling.
Journal
Reference
Authors
Nourazarian AR, Kangari P, Salmaninejad A
Title
Roles of oxidative stress in the development and progression of breast cancer.
Journal
Reference
Authors
Zheng F, Goncalves FM, Abiko Y, Li H, Kumagai Y, Aschner M
Title
Redox toxicology of environmental chemicals causing oxidative stress.
Journal
Related pathway
map00980 Metabolism of xenobiotics by cytochrome P450
map05207 Chemical carcinogenesis - receptor activation
KO pathway