Entry Name Chemical carcinogenesis - DNA adducts - Homo sapiens (human)
Description It has been estimated that exposure to environmental chemical carcinogens may contribute significantly to the causation of a sizable fraction, perhaps a majority, of human cancers. Human carcinogens act through a variety of genotoxic and non-genotoxic mechanisms. Genotoxic carcinogens can attack biological macromolecules such as DNA and RNA either directly or indirectly through metabolism, resulting in the formation of adducts with these macromolecules. If DNA adducts escape cellular repair mechanisms and persist, they may lead to miscoding, resulting in permanent mutations. Mutations cause an undefined number of cell changes, translated into aberrant protein expression and in changes in cell cycle control.
Class Human Diseases; Cancer: overviewBRITE hierarchy
Pathway map hsa05204 Chemical carcinogenesis - DNA adducts
Ortholog table Network Element N01376 Melphalan to DNA adducts/cross-links
N01377 Thiotepa to DNA adducts/cross-links
N01387 SM to DNA adducts/cross-links
Organism Homo sapiens (human) [GN:
hsa ]
Gene 1548 CYP2A6; cytochrome P450 family 2 subfamily A member 6 [KO:K17683 ] [EC:1.14.14.-]
1549 CYP2A7; cytochrome P450 family 2 subfamily A member 7 [KO:K17683 ] [EC:1.14.14.-]
10941 UGT2A1; UDP glucuronosyltransferase family 2 member A1 complex locus [KO:K00699 ] [EC:2.4.1.17 ]
1571 CYP2E1; cytochrome P450 family 2 subfamily E member 1 [KO:K07415 ] [EC:1.14.14.-]
Compound C03621 N-Acetoxy-4-aminobiphenyl
C03622 N-Hydroxy-4-aminobiphenyl
C14556 9-Hydroxybenzo[a]pyrene
C14849 Benzo[a]pyrene-9,10-oxide
C14850 Benzo[a]pyrene-7,8-oxide
C14851 Benzo[a]pyrene-4,5-oxide
C14852 Benzo[a]pyrene-7,8-dihydrodiol
C14853 Benzo[a]pyrene-7,8-dihydrodiol-9,10-oxide
C14854 9-Hydroxybenzo[a]pyrene-4,5-oxide
C14855 4,5-Dihydro-4-hydroxy-5-S-glutathionyl-benzo[a]pyrene
C14856 7,8-Dihydro-7-hydroxy-8-S-glutathionyl-benzo[a]pyrene
C14874 Glutathione episulfonium ion
C16038 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine
C16453 4-(N-Nitrosomethylamino)-1-(3-pyridyl)-1-butanone
C19180 2-Amino-3-methylimidazo[4,5-f]quinoline
C19488 7,12-Dimethylbenz[a]anthracene
C19489 1a,11b-Dihydro-4,9-dimethylbenz[a]anthra[3,4-b]oxirene
C19490 trans-3,4-Dihydro-3,4-dihydroxy-7,12-dimethylbenz[a]anthracene
C19559 (1aalpha,2beta,3alpha,11calpha)-1a,2,3,11c-Tetrahydro-6,11-dimethylbenzo[6,7]phenanthro[3,4-b]oxirene-2,3-diol
C19561 7-Hydroxymethyl-12-methylbenz[a]anthracene
C19562 7-Hydroxymethyl-12-methylbenz[a]anthracene sulfate
C19563 4-[(Hydroxymethyl)nitrosoamino]-1-(3-pyridinyl)-1-butanone
C19564 4-(Nitrosoamino)-1-(3-pyridinyl)-1-butanone
C19565 4-Hydroxy-1-(3-pyridinyl)-1-butanone
C19566 4-Hydroxy-4-(methylnitrosoamino)-1-(3-pyridinyl)-1-butanone
C19567 4-Oxo-1-(3-pyridyl)-1-butanone
C19574 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol
C19577 1-(Methylnitrosoamino)-4-(3-pyridinyl)-1,4-butanediol
C19578 5-(3-Pyridyl)-2-hydroxytetrahydrofuran
C19579 gamma-Hydroxy-3-pyridinebutanoate
C19580 alpha-[3-[(Hydroxymethyl)nitrosoamino]propyl]-3-pyridinemethanol
C19581 alpha-[3-(Nitrosoamino)propyl]-3-pyridinemethanol
C19582 1-(3-Pyridinyl)-1,4-butanediol
C19586 Aflatoxin B1-exo-8,9-epoxide
C19602 4-(Methylnitrosamino)-1-(1-oxido-3-pyridinyl)-1-butanone
C19603 4-(Methylnitrosamino)-1-(3-pyridyl-N-oxide)-1-butanol
C19605 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol glucuronide
C20280 1-Phenylazo-2,6-dihydroxynaphthalene
C20281 1-(4-Hydroxyphenylazo)-2-naphthol
C20282 1-(4-Hydroxyphenylazo)-naphthalene-2,6-diol
C20283 1-(3,4-Dihydroxyphenylazo)-2-naphthol
C20286 2-Hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine
C20287 2-Acetoxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine
C20304 S-(2-Chloroethyl)glutathione
Reference Authors Luch A.
Title Nature and nurture - lessons from chemical carcinogenesis.
Journal Reference Authors Hecht SS
Title Tobacco carcinogens, their biomarkers and tobacco-induced cancer.
Journal Reference Authors Oliveira PA, Colaco A, Chaves R, Guedes-Pinto H, De-La-Cruz P LF, Lopes C
Title Chemical carcinogenesis.
Journal Reference Authors Wogan GN, Hecht SS, Felton JS, Conney AH, Loeb LA.
Title Environmental and chemical carcinogenesis.
Journal Reference Authors Hang B
Title Formation and repair of tobacco carcinogen-derived bulky DNA adducts.
Journal Reference Authors Tsuneoka Y, Dalton TP, Miller ML, Clay CD, Shertzer HG, Talaska G, Medvedovic M, Nebert DW
Title 4-aminobiphenyl-induced liver and urinary bladder DNA adduct formation in Cyp1a2(-/-) and Cyp1a2(+/+) mice.
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 Patterson AD, Gonzalez FJ, Idle JR
Title Xenobiotic metabolism: a view through the metabolometer.
Journal Reference Authors Turesky RJ, Box RM, Markovic J, Gremaud E, Snyderwine EG
Title Formation and persistence of DNA adducts of 2-amino-3-methylimidazo[4,5-f]quinoline in the rat and nonhuman primates.
Journal Reference Authors Immonen E, Kummu M, Petsalo A, Pihlaja T, Mathiesen L, Nielsen JK, Knudsen LE, Vahakangas K, Myllynen P
Title Toxicokinetics of the food-toxin IQ in human placental perfusion is not affected by ABCG2 or xenobiotic metabolism.
Journal Reference Authors Solomon MS, Morgenthaler PM, Turesky RJ, Essigmann JM
Title Mutational and DNA binding specificity of the carcinogen 2-amino-3, 8-dimethylimidazo[4,5-f]quinoxaline.
Journal Reference Authors Nauwelaers G, Bessette EE, Gu D, Tang Y, Rageul J, Fessard V, Yuan JM, Yu MC, Langouet S, Turesky RJ
Title DNA adduct formation of 4-aminobiphenyl and heterocyclic aromatic amines in human hepatocytes.
Journal Reference Authors Title The Health Consequences of Involuntary Exposure to Tobacco Smoke: A Report of the Surgeon General.
Journal The Health Consequences of Involuntary Exposure to Tobacco Smoke: A Report of the (2006)
Reference Authors Singh R, Sram RJ, Binkova B, Kalina I, Popov TA, Georgieva T, Garte S, Taioli E, Farmer PB
Title The relationship between biomarkers of oxidative DNA damage, polycyclic aromatic hydrocarbon DNA adducts, antioxidant status and genetic susceptibility following exposure to environmental air pollution in humans.
Journal Reference Authors Lodovici M, Luceri C, Guglielmi F, Bacci C, Akpan V, Fonnesu ML, Boddi V, Dolara P.
Title Benzo(a)pyrene diolepoxide (BPDE)-DNA adduct levels in leukocytes of smokers in relation to polymorphism of CYP1A1, GSTM1, GSTP1, GSTT1, and mEH.
Journal Cancer Epidemiol Biomarkers Prev 13:1342-8 (2004)
Reference Authors Androutsopoulos VP, Tsatsakis AM, Spandidos DA
Title Cytochrome P450 CYP1A1: wider roles in cancer progression and prevention.
Journal Reference Authors Gonzalez FJ, Kimura S
Title Understanding the role of xenobiotic-metabolism in chemical carcinogenesis using gene knockout mice.
Journal Reference Authors Banoglu E
Title Current status of the cytosolic sulfotransferases in the metabolic activation of promutagens and procarcinogens.
Journal Reference Authors Lehner AF, Horn J, Flesher JW
Title Mass spectrometric analysis of 7-sulfoxymethyl-12-methylbenz[a]anthracene and related electrophilic polycyclic aromatic hydrocarbon metabolites.
Journal Reference Authors Stiborova M, Martinek V, Semanska M, Hodek P, Dracinsky M, Cvacka J, Schmeiser HH, Frei E
Title Oxidation of the carcinogenic non-aminoazo dye 1-phenylazo-2-hydroxy-naphthalene (Sudan I) by cytochromes P450 and peroxidases: a comparative study.
Journal Reference Authors Maanen MJ, Smeets CJ, Beijnen JH
Title Chemistry, pharmacology and pharmacokinetics of N,N',N" -triethylenethiophosphoramide (ThioTEPA).
Journal Reference Authors Hoes I, Van Dongen W, Lemiere F, Esmans EL, Van Bockstaele D, Berneman ZN
Title Comparison between capillary and nano liquid chromatography-electrospray mass spectrometry for the analysis of minor DNA-melphalan adducts.
Journal Reference Authors Lee JC, Son YO, Pratheeshkumar P, Shi X
Title Oxidative stress and metal carcinogenesis.
Journal Reference Authors Wild CP, Turner PC
Title The toxicology of aflatoxins as a basis for public health decisions.
Journal Reference Authors Kobertz WR, Wang D, Wogan GN, Essigmann JM
Title An intercalation inhibitor altering the target selectivity of DNA damaging agents: synthesis of site-specific aflatoxin B1 adducts in a p53 mutational hotspot.
Journal Reference Authors Bailey EA, Iyer RS, Harris TM, Essigmann JM
Title A viral genome containing an unstable aflatoxin B1-N7-guanine DNA adduct situated at a unique site.
Journal Reference Authors Chiang HC, Wang CY, Lee HL, Tsou TC
Title Metabolic effects of CYP2A6 and CYP2A13 on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced gene mutation--a mammalian cell-based mutagenesis approach.
Journal Reference Authors Bhat SH, Gelhaus SL, Mesaros C, Vachani A, Blair IA
Title A new liquid chromatography/mass spectrometry method for 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) in urine.
Journal Reference Authors Maertens LA, Upadhyaya P, Hecht SS, Zimmerman CL
Title Formation and distribution of NNK metabolites in an isolated perfused rat lung.
Journal Reference Authors Lee VM, Keefer LK, Archer MC
Title An evaluation of the roles of metabolic denitrosation and alpha-hydroxylation in the hepatotoxicity of N-Nitrosodimethylamine.
Journal Reference Authors Swenberg JA, Lu K, Moeller BC, Gao L, Upton PB, Nakamura J, Starr TB
Title Endogenous versus exogenous DNA adducts: their role in carcinogenesis, epidemiology, and risk assessment.
Journal Reference Authors Yang Y, Nair J, Barbin A, Bartsch H
Title Immunohistochemical detection of 1,N(6)-ethenodeoxyadenosine, a promutagenic DNA adduct, in liver of rats exposed to vinyl chloride or an iron overload.
Journal Reference Authors Bartsch H, Nair J
Title Oxidative stress and lipid peroxidation-derived DNA-lesions in inflammation driven carcinogenesis.
Journal Reference Authors Kehe K, Szinicz L
Title Medical aspects of sulphur mustard poisoning.
Journal Reference Authors Matijasevic Z, Volkert MR
Title Base excision repair sensitizes cells to sulfur mustard and chloroethyl ethyl sulfide.
Journal Related hsa00980 Metabolism of xenobiotics by cytochrome P450
KO pathway LinkDB All DBs
