KEGG   PATHWAY: map05208
Entry
map05208                    Pathway                                
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
Pathway map
map05208  Chemical carcinogenesis - reactive oxygen species
map05208

Reference
  Authors
Henkler F, Brinkmann J, Luch A
  Title
The role of oxidative stress in carcinogenesis induced by metals and xenobiotics.
  Journal
Cancers (Basel) 2:376-96 (2010)
DOI:10.3390/cancers2020376
Reference
  Authors
Lee JC, Son YO, Pratheeshkumar P, Shi X
  Title
Oxidative stress and metal carcinogenesis.
  Journal
Free Radic Biol Med 53:742-57 (2012)
DOI:10.1016/j.freeradbiomed.2012.06.002
Reference
  Authors
Hu Y, Li J, Lou B, Wu R, Wang G, Lu C, Wang H, Pi J, Xu Y
  Title
The Role of Reactive Oxygen Species in Arsenic Toxicity.
  Journal
Biomolecules 10:E240 (2020)
DOI:10.3390/biom10020240
Reference
  Authors
Ozturk M, Metin M, Altay V, Bhat RA, Ejaz M, Gul A, Unal BT, Hasanuzzaman M, Nibir L, Nahar K, Bukhari A, Dervash MA, Kawano T
  Title
Arsenic and Human Health: Genotoxicity, Epigenomic Effects, and Cancer Signaling.
  Journal
Biol Trace Elem Res 10.1007/s12011-021-02719-w (2021)
DOI:10.1007/s12011-021-02719-w
Reference
  Authors
Hubaux R, Becker-Santos DD, Enfield KS, Rowbotham D, Lam S, Lam WL, Martinez VD
  Title
Molecular features in arsenic-induced lung tumors.
  Journal
Mol Cancer 12:20 (2013)
DOI:10.1186/1476-4598-12-20
Reference
  Authors
Naranmandura H, Xu S, Sawata T, Hao WH, Liu H, Bu N, Ogra Y, Lou YJ, Suzuki N
  Title
Mitochondria are the main target organelle for trivalent monomethylarsonous acid (MMA(III))-induced cytotoxicity.
  Journal
Chem Res Toxicol 24:1094-103 (2011)
DOI:10.1021/tx200156k
Reference
  Authors
Faita F, Cori L, Bianchi F, Andreassi MG
  Title
Arsenic-induced genotoxicity and genetic susceptibility to arsenic-related pathologies.
  Journal
Int J Environ Res Public Health 10:1527-46 (2013)
DOI:10.3390/ijerph10041527
Reference
  Authors
Sage AP, Minatel BC, Ng KW, Stewart GL, Dummer TJB, Lam WL, Martinez VD
  Title
Oncogenomic disruptions in arsenic-induced carcinogenesis.
  Journal
Oncotarget 8:25736-25755 (2017)
DOI:10.18632/oncotarget.15106
Reference
  Authors
Jomova K, Valko M
  Title
Advances in metal-induced oxidative stress and human disease.
  Journal
Toxicology 283:65-87 (2011)
DOI:10.1016/j.tox.2011.03.001
Reference
  Authors
Valko M, Rhodes CJ, Moncol J, Izakovic M, Mazur M
  Title
Free radicals, metals and antioxidants in oxidative stress-induced cancer.
  Journal
Chem Biol Interact 160:1-40 (2006)
DOI:10.1016/j.cbi.2005.12.009
Reference
  Authors
Tumolo M, Ancona V, De Paola D, Losacco D, Campanale C, Massarelli C, Uricchio VF
  Title
Chromium Pollution in European Water, Sources, Health Risk, and Remediation Strategies: An Overview.
  Journal
Int J Environ Res Public Health 17:E5438 (2020)
DOI:10.3390/ijerph17155438
Reference
  Authors
Wang Y, Su H, Gu Y, Song X, Zhao J
  Title
Carcinogenicity of chromium and chemoprevention: a brief update.
  Journal
Onco Targets Ther 10:4065-4079 (2017)
DOI:10.2147/OTT.S139262
Reference
  Authors
Jin X, Chen M, Song L, Li H, Li Z
  Title
The evaluation of p,p'-DDT exposure on cell adhesion of hepatocellular carcinoma.
  Journal
Toxicology 322:99-108 (2014)
DOI:10.1016/j.tox.2014.05.002
Reference
  Authors
Liou GY, Storz P
  Title
Reactive oxygen species in cancer.
  Journal
Free Radic Res 44:479-96 (2010)
DOI:10.3109/10715761003667554
Reference
  Authors
Murata M, Tamura A, Tada M, Kawanishi S
  Title
Mechanism of oxidative DNA damage induced by carcinogenic 4-aminobiphenyl.
  Journal
Free Radic Biol Med 30:765-73 (2001)
DOI:10.1016/S0891-5849(01)00463-4
Reference
  Authors
  Title
  Journal
Pentachlorophenol and Some Related Compounds (2019)
Reference
  Authors
Zhu BZ, Shan GQ
  Title
Potential mechanism for pentachlorophenol-induced carcinogenicity: a novel mechanism for metal-independent production of hydroxyl radicals.
  Journal
Chem Res Toxicol 22:969-77 (2009)
DOI:10.1021/tx900030v
Reference
  Authors
McHale CM, Zhang L, Smith MT
  Title
Current understanding of the mechanism of benzene-induced leukemia in humans: implications for risk assessment.
  Journal
Carcinogenesis 33:240-52 (2012)
DOI:10.1093/carcin/bgr297
Reference
  Authors
Scharf P, Broering MF, Oliveira da Rocha GH, Farsky SHP
  Title
Cellular and Molecular Mechanisms of Environmental Pollutants on Hematopoiesis.
  Journal
Int J Mol Sci 21:E6996 (2020)
DOI:10.3390/ijms21196996
Reference
  Authors
Snyder R
  Title
Leukemia and benzene.
  Journal
Int J Environ Res Public Health 9:2875-93 (2012)
DOI:10.3390/ijerph9082875
Reference
PMID:9118888
  Authors
Snyder R, Hedli CC
  Title
An overview of benzene metabolism.
  Journal
Environ Health Perspect 104 Suppl 6:1165-71 (1996)
DOI:10.1289/ehp.961041165
Reference
  Authors
Kawanishi S, Hiraku Y, Murata M, Oikawa S
  Title
The role of metals in site-specific DNA damage with reference to carcinogenesis.
  Journal
Free Radic Biol Med 32:822-32 (2002)
DOI:10.1016/S0891-5849(02)00779-7
Reference
  Authors
Das DN, Panda PK, Naik PP, Mukhopadhyay S, Sinha N, Bhutia SK
  Title
Phytotherapeutic approach: a new hope for polycyclic aromatic hydrocarbons induced cellular disorders, autophagic and apoptotic cell death.
  Journal
Toxicol Mech Methods 27:1-17 (2017)
DOI:10.1080/15376516.2016.1268228
Reference
  Authors
Shultz CA, Quinn AM, Park JH, Harvey RG, Bolton JL, Maser E, Penning TM.
  Title
Specificity of human aldo-keto reductases, NAD(P)H:quinone oxidoreductase, and carbonyl reductases to redox-cycle polycyclic aromatic hydrocarbon diones and 4-hydroxyequilenin-o-quinone.
  Journal
Chem Res Toxicol 24:2153-66 (2011)
DOI:10.1021/tx200294c
Reference
  Authors
Penning TM
  Title
Human aldo-keto reductases and the metabolic activation of polycyclic aromatic hydrocarbons.
  Journal
Chem Res Toxicol 27:1901-17 (2014)
DOI:10.1021/tx500298n
Reference
  Authors
Burczynski ME, Penning TM
  Title
Genotoxic polycyclic aromatic hydrocarbon ortho-quinones generated by aldo-keto reductases induce CYP1A1 via nuclear translocation of the aryl hydrocarbon receptor.
  Journal
Cancer Res 60:908-15 (2000)
Reference
  Authors
Xue W, Warshawsky D
  Title
Metabolic activation of polycyclic and heterocyclic aromatic hydrocarbons and DNA damage: a review.
  Journal
Toxicol Appl Pharmacol 206:73-93 (2005)
DOI:10.1016/j.taap.2004.11.006
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
Carcinogenesis 25:2005-13 (2004)
DOI:10.1093/carcin/bgh183
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.
  Journal
Drug Metab Rev 38:291-335 (2006)
DOI:10.1080/03602530600570107
Reference
PMID:9380738
  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
Molecular origin of cancer: catechol estrogen-3,4-quinones as endogenous tumor initiators.
  Journal
Proc Natl Acad Sci U S A 94:10937-42 (1997)
DOI:10.1073/pnas.94.20.10937
Reference
PMID:9472688
  Authors
Zhu BT, Conney AH
  Title
Functional role of estrogen metabolism in target cells: review and perspectives.
  Journal
Carcinogenesis 19:1-27 (1998)
DOI:10.1093/carcin/19.1.1
Reference
  Authors
McKillop IH, Schrum LW
  Title
Role of alcohol in liver carcinogenesis.
  Journal
Semin Liver Dis 29:222-32 (2009)
DOI:10.1055/s-0029-1214377
Reference
  Authors
Gonzalez FJ
  Title
Role of cytochromes P450 in chemical toxicity and oxidative stress: studies with CYP2E1.
  Journal
Mutat Res 569:101-10 (2005)
DOI:10.1016/j.mrfmmm.2004.04.021
Reference
  Authors
Montalbano AM, Albano GD, Anzalone G, Moscato M, Gagliardo R, Di Sano C, Bonanno A, Ruggieri S, Cibella F, Profita M
  Title
Cytotoxic and genotoxic effects of the flame retardants (PBDE-47, PBDE-99 and PBDE-209) in human bronchial epithelial cells.
  Journal
Chemosphere 245:125600 (2020)
DOI:10.1016/j.chemosphere.2019.125600
Reference
  Authors
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
Oncol Lett 21:465 (2021)
DOI:10.3892/ol.2021.12726
Reference
  Authors
Pluchino LA, Wang HC
  Title
Chronic exposure to combined carcinogens enhances breast cell carcinogenesis with mesenchymal and stem-like cell properties.
  Journal
PLoS One 9:e108698 (2014)
DOI:10.1371/journal.pone.0108698
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
Free Radic Biol Med 80:12-26 (2015)
DOI:10.1016/j.freeradbiomed.2014.12.015
Reference
  Authors
Moldogazieva NT, Lutsenko SV, Terentiev AA
  Title
Reactive Oxygen and Nitrogen Species-Induced Protein Modifications: Implication in Carcinogenesis and Anticancer Therapy.
  Journal
Cancer Res 78:6040-6047 (2018)
DOI:10.1158/0008-5472.CAN-18-0980
Reference
  Authors
Kirtonia A, Sethi G, Garg M
  Title
The multifaceted role of reactive oxygen species in tumorigenesis.
  Journal
Cell Mol Life Sci 77:4459-4483 (2020)
DOI:10.1007/s00018-020-03536-5
Reference
  Authors
Kumari S, Badana AK, G MM, G S, Malla R
  Title
Reactive Oxygen Species: A Key Constituent in Cancer Survival.
  Journal
Biomark Insights 13:1177271918755391 (2018)
DOI:10.1177/1177271918755391
Reference
  Authors
Gao X, Schottker B
  Title
Reduction-oxidation pathways involved in cancer development: a systematic review of literature reviews.
  Journal
Oncotarget 8:51888-51906 (2017)
DOI:10.18632/oncotarget.17128
Reference
  Authors
Storz P
  Title
Reactive oxygen species in tumor progression.
  Journal
Front Biosci 10:1881-96 (2005)
DOI:10.2741/1667
Reference
  Authors
Assi M
  Title
The differential role of reactive oxygen species in early and late stages of cancer.
  Journal
Am J Physiol Regul Integr Comp Physiol 313:R646-R653 (2017)
DOI:10.1152/ajpregu.00247.2017
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
Mol Cell Biol 24:2614-26 (2004)
DOI:10.1128/MCB.24.7.2614-2626.2004
Reference
  Authors
Nourazarian AR, Kangari P, Salmaninejad A
  Title
Roles of oxidative stress in the development and progression of breast cancer.
  Journal
Asian Pac J Cancer Prev 15:4745-51 (2014)
DOI:10.7314/apjcp.2014.15.12.4745
Reference
  Authors
Zheng F, Goncalves FM, Abiko Y, Li H, Kumagai Y, Aschner M
  Title
Redox toxicology of environmental chemicals causing oxidative stress.
  Journal
Redox Biol 34:101475 (2020)
DOI:10.1016/j.redox.2020.101475
Related
pathway
map00190  Oxidative phosphorylation
map00980  Metabolism of xenobiotics by cytochrome P450
map04010  MAPK signaling pathway
map04064  NF-kappa B signaling pathway
map04066  HIF-1 signaling pathway
map04151  PI3K-Akt signaling pathway
map04370  VEGF signaling pathway
map05207  Chemical carcinogenesis - receptor activation
map05211  Renal cell carcinoma
map05215  Prostate cancer
map05219  Bladder cancer
map05221  Acute myeloid leukemia
map05222  Small cell lung cancer
map05223  Non-small cell lung cancer
map05224  Breast cancer
map05225  Hepatocellular carcinoma
KO pathway
ko05208   
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