Entry
Name
Chemical carcinogenesis - reactive oxygen species - Mustela putorius furo (domestic ferret)
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
mpuf05208 Chemical carcinogenesis - reactive oxygen species
Ortholog table
Organism
Mustela putorius furo (domestic ferret) [GN:
mpuf ]
Gene
101679801 NDUFV3; NADH dehydrogenase [ubiquinone] flavoprotein 3, mitochondrial [KO:K03944 ]
101683103 NDUFA1; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 1 [KO:K03945 ]
101681305 NDUFA2; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 2 [KO:K03946 ]
101671885 NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 3-like [KO:K03947 ]
101678258 NDUFA3; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 3 [KO:K03947 ]
101678946 NDUFA4L2; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 4-like 2 [KO:K03948 ]
101688416 NDUFA5; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 5 [KO:K03949 ]
101673253 NDUFA6; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 6 [KO:K03950 ]
101686920 NDUFA7; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 7 [KO:K03951 ]
101675000 NDUFA8; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 8 [KO:K03952 ]
101680168 NDUFA9; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 9, mitochondrial [KO:K03953 ]
101693615 NDUFA10; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 10, mitochondrial [KO:K03954 ]
101684673 NDUFA11; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 11 [KO:K03956 ]
101674482 NDUFA12; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 12 [KO:K11352 ]
101679389 NDUFA13; LOW QUALITY PROTEIN: NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 13 [KO:K11353 ]
101694062 NDUFB1; NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 1 [KO:K03957 ]
101674641 NDUFB2; NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 2, mitochondrial isoform X2 [KO:K03958 ]
101683892 NDUFB3; NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 3 [KO:K03959 ]
101691663 NDUFB4; NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 4 [KO:K03960 ]
101687434 NDUFB5; NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 5, mitochondrial [KO:K03961 ]
101688606 NDUFB6; NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 6 [KO:K03962 ]
101675882 NDUFB7; NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 7 [KO:K03963 ]
101675804 NDUFB8; NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 8, mitochondrial [KO:K03964 ]
101682240 NDUFB9; NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 9 isoform X1 [KO:K03965 ]
101681324 NDUFB10; NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 10 [KO:K03966 ]
101682983 NDUFB11; NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 11, mitochondrial [KO:K11351 ]
101688652 NDUFS2; NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrial [KO:K03935 ] [EC:7.1.1.2 ]
101686313 NDUFS3; NADH dehydrogenase [ubiquinone] iron-sulfur protein 3, mitochondrial [KO:K03936 ] [EC:7.1.1.2 ]
101674933 NDUFS4; NADH dehydrogenase [ubiquinone] iron-sulfur protein 4, mitochondrial [KO:K03937 ]
101684469 NDUFS5; NADH dehydrogenase [ubiquinone] iron-sulfur protein 5 [KO:K03938 ]
101692362 NADH dehydrogenase [ubiquinone] iron-sulfur protein 6, mitochondrial-like [KO:K03939 ]
101688718 NDUFS6; NADH dehydrogenase [ubiquinone] iron-sulfur protein 6, mitochondrial [KO:K03939 ]
101674706 NDUFS7; NADH dehydrogenase [ubiquinone] iron-sulfur protein 7, mitochondrial [KO:K03940 ] [EC:7.1.1.2 ]
101679983 NDUFS8; NADH dehydrogenase [ubiquinone] iron-sulfur protein 8, mitochondrial isoform X1 [KO:K03941 ] [EC:7.1.1.2 ]
101691647 NDUFC1; NADH dehydrogenase [ubiquinone] 1 subunit C1, mitochondrial [KO:K03967 ]
101678731 SDHA; succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial [KO:K00234 ] [EC:1.3.5.1 ]
101692858 SDHB; succinate dehydrogenase [ubiquinone] iron-sulfur subunit, mitochondrial [KO:K00235 ] [EC:1.3.5.1 ]
101685355 LOW QUALITY PROTEIN: succinate dehydrogenase cytochrome b560 subunit, mitochondrial-like [KO:K00236 ]
101680264 SDHC; succinate dehydrogenase cytochrome b560 subunit, mitochondrial [KO:K00236 ]
101694292 SDHD; succinate dehydrogenase [ubiquinone] cytochrome b small subunit, mitochondrial [KO:K00237 ]
101685926 LOW QUALITY PROTEIN: cytochrome b-c1 complex subunit 2, mitochondrial-like [KO:K00415 ]
101681748 cytochrome b-c1 complex subunit 6, mitochondrial isoform X1 [KO:K00416 ]
101680163 cytochrome c oxidase subunit 4 isoform 1, mitochondrial [KO:K02263 ]
101676075 cytochrome c oxidase subunit 4 isoform 2, mitochondrial isoform X1 [KO:K02263 ]
101672219 cytochrome c oxidase subunit 7A-related protein, mitochondrial [KO:K02270 ]
101689814 ATP5C1; ATP synthase subunit gamma, mitochondrial isoform X1 [KO:K02136 ]
101683533 ATP5F1; ATP synthase F(0) complex subunit B1, mitochondrial [KO:K02127 ]
101672934 ATP5G1; ATP synthase F(0) complex subunit C1, mitochondrial isoform X1 [KO:K02128 ]
101673943 ATP5G2; LOW QUALITY PROTEIN: ATP synthase F(0) complex subunit C2, mitochondrial [KO:K02128 ]
106005210 LOW QUALITY PROTEIN: uncharacterized protein LOC106005210 [KO:K02128 ]
106006495 LOW QUALITY PROTEIN: ATP synthase F(0) complex subunit C2, mitochondrial-like [KO:K02128 ]
101690076 ATP5G3; ATP synthase F(0) complex subunit C3, mitochondrial [KO:K02128 ]
101679422 VDAC1; voltage-dependent anion-selective channel protein 1 [KO:K05862 ]
101674296 VDAC2; voltage-dependent anion-selective channel protein 2 isoform X1 [KO:K15040 ]
101687790 VDAC3; voltage-dependent anion-selective channel protein 3 isoform X1 [KO:K15041 ]
101685800 SLC26A9; solute carrier family 26 member 9 isoform X1 [KO:K14706 ]
101682951 EGF; LOW QUALITY PROTEIN: pro-epidermal growth factor [KO:K04357 ]
101680399 PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
101683594 phosphatidylinositol 3-kinase regulatory subunit gamma isoform X2 [KO:K02649 ]
101683710 PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649 ]
101681650 PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
101676567 PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
101684443 PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
101693834 RAC1; ras-related C3 botulinum toxin substrate 1 isoform X1 [KO:K04392 ]
101680542 NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580 ]
101677663 ARNT; aryl hydrocarbon receptor nuclear translocator isoform X1 [KO:K09097 ]
101672411 NFE2L2; nuclear factor erythroid 2-related factor 2 isoform X1 [KO:K05638 ]
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
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Title
The role of oxidative stress in carcinogenesis induced by metals and xenobiotics.
Journal
Reference
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Title
Oxidative stress and metal carcinogenesis.
Journal
Reference
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Title
The Role of Reactive Oxygen Species in Arsenic Toxicity.
Journal
Reference
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Title
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Title
Arsenic-induced genotoxicity and genetic susceptibility to arsenic-related pathologies.
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Title
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Free radicals, metals and antioxidants in oxidative stress-induced cancer.
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Title
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Reference
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Title
Human aldo-keto reductases and the metabolic activation of polycyclic aromatic hydrocarbons.
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Reference
Authors
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Title
Genotoxic polycyclic aromatic hydrocarbon ortho-quinones generated by aldo-keto reductases induce CYP1A1 via nuclear translocation of the aryl hydrocarbon receptor.
Journal
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Reference
Authors
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Title
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Title
Resveratrol inhibits TCDD-induced expression of CYP1A1 and CYP1B1 and catechol estrogen-mediated oxidative DNA damage in cultured human mammary epithelial cells.
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Reference
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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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Title
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Title
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Title
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Title
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Title
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Title
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Title
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Title
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Title
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Title
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Title
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Title
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Title
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Title
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Title
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Journal
Related pathway
mpuf00980 Metabolism of xenobiotics by cytochrome P450
mpuf05207 Chemical carcinogenesis - receptor activation
KO pathway
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