Entry Name Chemical carcinogenesis - reactive oxygen species - Panthera uncia (snow leopard)
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: overviewBRITE hierarchy
Pathway map puc05208 Chemical carcinogenesis - reactive oxygen species
Organism Panthera uncia (snow leopard) [GN:
puc ]
Gene Compound C00019 S-Adenosyl-L-methionine
C00021 S-Adenosyl-L-homocysteine
C03434 Tetrachlorohydroquinone
C03622 N-Hydroxy-4-aminobiphenyl
C05981 Phosphatidylinositol-3,4,5-trisphosphate
C07557 2,3,7,8-Tetrachlorodibenzodioxin
C14209 4-Hydroxy-17beta-estradiol
C14850 Benzo[a]pyrene-7,8-oxide
C14852 Benzo[a]pyrene-7,8-dihydrodiol
C16038 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine
C16453 4-(N-Nitrosomethylamino)-1-(3-pyridyl)-1-butanone
C18205 2,2',4,4'-Tetrabromodiphenyl ether
C22355 Benzo[a]pyrene-7,8-diol
C22356 Benzo[a]pyrene-7,8-dione
C22357 17beta-Estradiol-2,3-quinone
C22381 Reactive oxygen species
Reference Authors Henkler F, Brinkmann J, Luch A
Title The role of oxidative stress in carcinogenesis induced by metals and xenobiotics.
Journal Reference Authors Lee JC, Son YO, Pratheeshkumar P, Shi X
Title Oxidative stress and metal carcinogenesis.
Journal 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 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 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 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 Reference Authors Faita F, Cori L, Bianchi F, Andreassi MG
Title Arsenic-induced genotoxicity and genetic susceptibility to arsenic-related pathologies.
Journal Reference Authors Sage AP, Minatel BC, Ng KW, Stewart GL, Dummer TJB, Lam WL, Martinez VD
Title Oncogenomic disruptions in arsenic-induced carcinogenesis.
Journal Reference Authors Jomova K, Valko M
Title Advances in metal-induced oxidative stress and human disease.
Journal Reference Authors Valko M, Rhodes CJ, Moncol J, Izakovic M, Mazur M
Title Free radicals, metals and antioxidants in oxidative stress-induced cancer.
Journal 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 Reference Authors Wang Y, Su H, Gu Y, Song X, Zhao J
Title Carcinogenicity of chromium and chemoprevention: a brief update.
Journal 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 Reference Authors Liou GY, Storz P
Title Reactive oxygen species in cancer.
Journal Reference Authors Murata M, Tamura A, Tada M, Kawanishi S
Title Mechanism of oxidative DNA damage induced by carcinogenic 4-aminobiphenyl.
Journal 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 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 Reference Authors Scharf P, Broering MF, Oliveira da Rocha GH, Farsky SHP
Title Cellular and Molecular Mechanisms of Environmental Pollutants on Hematopoiesis.
Journal Reference Authors Snyder R
Title Leukemia and benzene.
Journal Reference Authors Snyder R, Hedli CC
Title An overview of benzene metabolism.
Journal 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 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 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 Reference Authors Penning TM
Title Human aldo-keto reductases and the metabolic activation of polycyclic aromatic hydrocarbons.
Journal 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 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.
Journal 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 Molecular origin of cancer: catechol estrogen-3,4-quinones as endogenous tumor initiators.
Journal Reference Authors Zhu BT, Conney AH
Title Functional role of estrogen metabolism in target cells: review and perspectives.
Journal Reference Authors 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 Cytotoxic and genotoxic effects of the flame retardants (PBDE-47, PBDE-99 and PBDE-209) in human bronchial epithelial cells.
Journal 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 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 Authors Assi M
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 puc00980 Metabolism of xenobiotics by cytochrome P450
puc05207 Chemical carcinogenesis - receptor activation
KO pathway
