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Gene Review

CYP1A1  -  cytochrome P450, family 1, subfamily A,...

Homo sapiens

Synonyms: AHH, AHRR, CP11, CYP1, CYPIA1, ...
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Disease relevance of CYP1A1


Psychiatry related information on CYP1A1


High impact information on CYP1A1


Chemical compound and disease context of CYP1A1


Biological context of CYP1A1

  • The CYP1A1*2B allele may predispose to the development of these subgroups of AML by augmented phase 1 metabolism to highly reactive intermediates of CYP1A1 substrates, including polycyclic aromatic hydrocarbons, or by generation of oxidative stress as a metabolic by-product [18].
  • RNA interference studies with T47D cells support a role for ERalpha in TCDD-dependent CYP1A1 expression [19].
  • The CYP1A1 (m) "variant" genotype, which contains at least one copy of the CYP1A1 variant alleles, was found to be associated with a 2.1-fold [95% confidence interval (CI), 1.1-3.9] increase in the risk of RCC [20].
  • These data underline the major importance of the CYP1A1 inducibility phenotype associated with the homozygous GSTM1 null genotype in chemically induced cancers [21].
  • Thus, methoxyestrogens exert feedback inhibition on CYP1A1- and CYP1B1-mediated oxidative estrogen metabolism, thereby reducing the potential for estrogen-induced DNA damage [22].

Anatomical context of CYP1A1

  • There was an inverse correlation between the level of peripheral polycyclic aromatic hydrocarbon DNA adducts measured on day 11 and both liver CYP1A2 activity (P = 0.027) and enterocyte CYP1A1 protein concentration (P = 0.046) [23].
  • These results show that xenoestrogens, by altering the ratio of CYP1B1/CYP1A1, could redirect estradiol metabolism in a more toxic pathway in the breast cell line MCF-7 [3].
  • Association of CYP1A1 germ line polymorphisms with mutations of the p53 gene in lung cancer [24].
  • Because CYP1A1 is one of the primary carcinogen-activating enzymes in oral mucosa, the use of curcumin as an oral cavity chemopreventive agent could have significant clinical impact via its ability to inhibit carcinogen bioactivation [25].
  • Results of our metabolism studies showed that curcumin significantly inhibited CYP1A1-mediated benzo(a)pyrene diol bioactivation in both oral SCC cells and intact oral mucosa [25].

Associations of CYP1A1 with chemical compounds


Physical interactions of CYP1A1


Enzymatic interactions of CYP1A1

  • CYP1B1 catalyzed benzo[a]pyrene 3-hydroxylation at rates lower than those of CYP1A1 but higher than those of CYP1A2 [33].
  • In vitro and whole-cell metabolic activity studies showed that the periplasmically-located CYP1A1 competently catalysed NADPH-dependent benzo[a]pyrene 3-hydroxylation and 7-ethoxyresorufin O-deethylation [34].

Regulatory relationships of CYP1A1

  • Polyinosinic acid-polycytidylic acid down regulated the constitutive and pyridine-induced expression of CYP2E1 and the pyridine- and beta-naphthoflavone-induced expression of CYP1A1 as demonstrated by metabolic activity and immunoblot analyses [35].
  • CYP1B1 mRNA was consistently expressed in both normal and neoplastic kidney while CYP1A1 was present in the majority of normal and neoplastic whereas CYP1A2 was infrequently expressed [36].
  • Like other groups we found that 10 nM TCDD inhibits cell growth and induces cytochrome P450 1A1 (CYP1A1)-associated 7-ethoxyresorufin-O-deethylase (EROD) activity in MCF-7 cells expressing the estradiol receptor (ER) [37].
  • In transiently transfected MCF-7 human breast cancer cells, overexpression of COUP-TFI inhibited TCDD-activated reporter gene activity from the CYP1A1 promoter [38].
  • In addition, the hAhR/L678A failed to activate CYP1A1 gene transcription in transfected BP-8 cells and exhibited reduced binding to RIP140 in vitro [39].

Other interactions of CYP1A1

  • Evidence for a new human CYP1A1 regulation pathway involving PPAR-alpha and 2 PPRE sites [32].
  • Treatment of the colon cell line with ICZ or SUL caused increases in the levels of mRNA for CYP1A1, AKR1C1, and NQO1 that were consistent with the enzyme data [26].
  • There was also a higher risk of RCC for subjects with the CYP1A1 (m) variant genotype combined with any of the following genotypes: GSTT1 (+) "active" [odds ratio (OR), 2.3; 95% CI, 1.2-4.5], GSTP1 (m) variant (OR, 2.4; 95% CI, 1.0-5.4), or NAT2 (-) "slow acetylator" (OR, 2.5; 95% CI, 1.1-5.5) [20].
  • CYP2C19 may have a role in bladder cancer risk, but polymorphisms in CYP1A1 and 2E1 had no statistically significant impact [40].
  • Thus, we conclude that (a) CYP3A4 and CYP1A1 are the predominant cytochrome P450 enzymes that catalyze BPU metabolism, (b) BPU is metabolized to two cytotoxic and four noncytotoxic metabolites, and (c) ritonavir inhibits BPU metabolism to improve the systemic exposure to BPU without altering cumulative exposure to BPU and the cytotoxic metabolites [41].

Analytical, diagnostic and therapeutic context of CYP1A1


  1. Environmental tobacco smoke, genetic susceptibility, and risk of lung cancer in never-smoking women. Bennett, W.P., Alavanja, M.C., Blomeke, B., Vähäkangas, K.H., Castrén, K., Welsh, J.A., Bowman, E.D., Khan, M.A., Flieder, D.B., Harris, C.C. J. Natl. Cancer Inst. (1999) [Pubmed]
  2. A population-based, case-control study of polymorphisms in carcinogen-metabolizing genes, smoking, and pancreatic adenocarcinoma risk. Duell, E.J., Holly, E.A., Bracci, P.M., Liu, M., Wiencke, J.K., Kelsey, K.T. J. Natl. Cancer Inst. (2002) [Pubmed]
  3. Differential regulation of cytochrome P450 1A1 and 1B1 by a combination of dioxin and pesticides in the breast tumor cell line MCF-7. Coumoul, X., Diry, M., Robillot, C., Barouki, R. Cancer Res. (2001) [Pubmed]
  4. Associations between breast cancer susceptibility gene polymorphisms and clinicopathological features. Han, W., Kang, D., Park, I.A., Kim, S.W., Bae, J.Y., Chung, K.W., Noh, D.Y. Clin. Cancer Res. (2004) [Pubmed]
  5. Genotoxic profiling of MCF-7 breast cancer cell line elucidates gene expression modifications underlying toxicity of the anticancer drug 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole. Monks, A., Harris, E., Hose, C., Connelly, J., Sausville, E.A. Mol. Pharmacol. (2003) [Pubmed]
  6. Genetic polymorphisms of drug-metabolizing enzymes and lung cancer susceptibility. Kawajiri, K., Watanabe, J., Eguchi, H., Hayashi, S. Pharmacogenetics (1995) [Pubmed]
  7. Aromatic DNA adducts in foundry workers in relation to exposure, life style and CYP1A1 and glutathione transferase M1 genotype. Hemminki, K., Dickey, C., Karlsson, S., Bell, D., Hsu, Y., Tsai, W.Y., Mooney, L.A., Savela, K., Perera, F.P. Carcinogenesis (1997) [Pubmed]
  8. Genetic susceptibility and environmental factors of esophageal cancer in Xi'an. Wang, A.H., Sun, C.S., Li, L.S., Huang, J.Y., Chen, Q.S., Xu, D.Z. World J. Gastroenterol. (2004) [Pubmed]
  9. Effects of dietary habits and CYP1A1 polymorphisms on blood dioxin concentrations in Japanese men. Tsuchiya, Y., Nakai, S., Nakamura, K., Hayashi, K., Nakanishi, J., Yamamoto, M. Chemosphere (2003) [Pubmed]
  10. Sex steroid hormone pathway genes and health-related measures in women of 4 races/ethnicities: the Study of Women's Health Across the Nation (SWAN). Sowers, M.R., Wilson, A.L., Karvonen-Gutierrez, C.A., Kardia, S.R. Am. J. Med. (2006) [Pubmed]
  11. Human dioxin-inducible cytochrome P1-450: complementary DNA and amino acid sequence. Jaiswal, A.K., Gonzalez, F.J., Nebert, D.W. Science (1985) [Pubmed]
  12. Induction of cytochrome P4501A1. Whitlock, J.P. Annu. Rev. Pharmacol. Toxicol. (1999) [Pubmed]
  13. Maternal cigarette smoking, metabolic gene polymorphism, and infant birth weight. Wang, X., Zuckerman, B., Pearson, C., Kaufman, G., Chen, C., Wang, G., Niu, T., Wise, P.H., Bauchner, H., Xu, X. JAMA (2002) [Pubmed]
  14. Effect of transforming growth factor-beta1 on expression of aryl hydrocarbon receptor and genes of Ah gene battery: clues for independent down-regulation in A549 cells. Döhr, O., Sinning, R., Vogel, C., Münzel, P., Abel, J. Mol. Pharmacol. (1997) [Pubmed]
  15. Inhibition of aryl hydrocarbon-induced cytochrome P-450 1A1 enzyme activity and CYP1A1 expression by resveratrol. Ciolino, H.P., Yeh, G.C. Mol. Pharmacol. (1999) [Pubmed]
  16. Dietary flavonols quercetin and kaempferol are ligands of the aryl hydrocarbon receptor that affect CYP1A1 transcription differentially. Ciolino, H.P., Daschner, P.J., Yeh, G.C. Biochem. J. (1999) [Pubmed]
  17. Germ line polymorphisms in cytochrome-P450 1A1 (C4887 CYP1A1) and methylenetetrahydrofolate reductase (MTHFR) genes and endometrial cancer susceptibility. Esteller, M., Garcia, A., Martinez-Palones, J.M., Xercavins, J., Reventos, J. Carcinogenesis (1997) [Pubmed]
  18. CYP1A1*2B (Val) allele is overrepresented in a subgroup of acute myeloid leukemia patients with poor-risk karyotype associated with NRAS mutation, but not associated with FLT3 internal tandem duplication. Bowen, D.T., Frew, M.E., Rollinson, S., Roddam, P.L., Dring, A., Smith, M.T., Langabeer, S.E., Morgan, G.J. Blood (2003) [Pubmed]
  19. Aryl hydrocarbon receptor-mediated transcription: ligand-dependent recruitment of estrogen receptor alpha to 2,3,7,8-tetrachlorodibenzo-p-dioxin-responsive promoters. Matthews, J., Wihlén, B., Thomsen, J., Gustafsson, J.A. Mol. Cell. Biol. (2005) [Pubmed]
  20. Candidate genetic modifiers of individual susceptibility to renal cell carcinoma: a study of polymorphic human xenobiotic-metabolizing enzymes. Longuemaux, S., Deloménie, C., Gallou, C., Méjean, A., Vincent-Viry, M., Bouvier, R., Droz, D., Krishnamoorthy, R., Galteau, M.M., Junien, C., Béroud, C., Dupret, J.M. Cancer Res. (1999) [Pubmed]
  21. Human glutathione S-transferase M1 null genotype is associated with a high inducibility of cytochrome P450 1A1 gene transcription. Vaury, C., Lainé, R., Noguiez, P., de Coppet, P., Jaulin, C., Praz, F., Pompon, D., Amor-Guéret, M. Cancer Res. (1995) [Pubmed]
  22. Methoxyestrogens exert feedback inhibition on cytochrome P450 1A1 and 1B1. Dawling, S., Roodi, N., Parl, F.F. Cancer Res. (2003) [Pubmed]
  23. Effects of a chargrilled meat diet on expression of CYP3A, CYP1A, and P-glycoprotein levels in healthy volunteers. Fontana, R.J., Lown, K.S., Paine, M.F., Fortlage, L., Santella, R.M., Felton, J.S., Knize, M.G., Greenberg, A., Watkins, P.B. Gastroenterology (1999) [Pubmed]
  24. Association of CYP1A1 germ line polymorphisms with mutations of the p53 gene in lung cancer. Kawajiri, K., Eguchi, H., Nakachi, K., Sekiya, T., Yamamoto, M. Cancer Res. (1996) [Pubmed]
  25. Curcumin activates the aryl hydrocarbon receptor yet significantly inhibits (-)-benzo(a)pyrene-7R-trans-7,8-dihydrodiol bioactivation in oral squamous cell carcinoma cells and oral mucosa. Rinaldi, A.L., Morse, M.A., Fields, H.W., Rothas, D.A., Pei, P., Rodrigo, K.A., Renner, R.J., Mallery, S.R. Cancer Res. (2002) [Pubmed]
  26. Dietary indoles and isothiocyanates that are generated from cruciferous vegetables can both stimulate apoptosis and confer protection against DNA damage in human colon cell lines. Bonnesen, C., Eggleston, I.M., Hayes, J.D. Cancer Res. (2001) [Pubmed]
  27. Diosmin and diosmetin are agonists of the aryl hydrocarbon receptor that differentially affect cytochrome P450 1A1 activity. Ciolino, H.P., Wang, T.T., Yeh, G.C. Cancer Res. (1998) [Pubmed]
  28. Is CYP1A1 induction always related to AHR signaling pathway? Delescluse, C., Lemaire, G., de Sousa, G., Rahmani, R. Toxicology (2000) [Pubmed]
  29. Functional role of AhR in the expression of toxic effects by TCDD. Mimura, J., Fujii-Kuriyama, Y. Biochim. Biophys. Acta (2003) [Pubmed]
  30. The binding of aristolochic acid I to the active site of human cytochromes P450 1A1 and 1A2 explains their potential to reductively activate this human carcinogen. Stiborová, M., Sopko, B., Hodek, P., Frei, E., Schmeiser, H.H., Hudecek, J. Cancer Lett. (2005) [Pubmed]
  31. Modulation of CYP1A1-mediated oxidation of carcinogenic azo dye Sudan I and its binding to DNA by cytochrome b5. Stiborova, M., Martinek, V., Schmeiser, H.H., Frei, E. Neuro Endocrinol. Lett. (2006) [Pubmed]
  32. Evidence for a new human CYP1A1 regulation pathway involving PPAR-alpha and 2 PPRE sites. Sérée, E., Villard, P.H., Pascussi, J.M., Pineau, T., Maurel, P., Nguyen, Q.B., Fallone, F., Martin, P.M., Champion, S., Lacarelle, B., Savouret, J.F., Barra, Y. Gastroenterology (2004) [Pubmed]
  33. Oxidation of xenobiotics by recombinant human cytochrome P450 1B1. Shimada, T., Gillam, E.M., Sutter, T.R., Strickland, P.T., Guengerich, F.P., Yamazaki, H. Drug Metab. Dispos. (1997) [Pubmed]
  34. Targeting of active human cytochrome P4501A1 (CYP1A1) to the periplasmic space of Escherichia coli. Kaderbhai, M.A., Ugochukwu, C.C., Lamb, D.C., Kelly, S.L. Biochem. Biophys. Res. Commun. (2000) [Pubmed]
  35. Regulation of cytochrome P-4501A and cytochrome P-4502E induction in the rat during the production of interferon alpha/beta. Cribb, A.E., Delaporte, E., Kim, S.G., Novak, R.F., Renton, K.W. J. Pharmacol. Exp. Ther. (1994) [Pubmed]
  36. Differential expression of CYP1A1, CYP1A2, CYP1B1 in human kidney tumours. Cheung, Y.L., Kerr, A.C., McFadyen, M.C., Melvin, W.T., Murray, G.I. Cancer Lett. (1999) [Pubmed]
  37. Different response of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-sensitive genes in human breast cancer MCF-7 and MDA-MB 231 cells. Döhr, O., Vogel, C., Abel, J. Arch. Biochem. Biophys. (1995) [Pubmed]
  38. The aryl hydrocarbon receptor interacts with estrogen receptor alpha and orphan receptors COUP-TFI and ERRalpha1. Klinge, C.M., Kaur, K., Swanson, H.I. Arch. Biochem. Biophys. (2000) [Pubmed]
  39. The Q-rich subdomain of the human Ah receptor transactivation domain is required for dioxin-mediated transcriptional activity. Kumar, M.B., Ramadoss, P., Reen, R.K., Vanden Heuvel, J.P., Perdew, G.H. J. Biol. Chem. (2001) [Pubmed]
  40. Combined analysis of inherited polymorphisms in arylamine N-acetyltransferase 2, glutathione S-transferases M1 and T1, microsomal epoxide hydrolase, and cytochrome P450 enzymes as modulators of bladder cancer risk. Brockmöller, J., Cascorbi, I., Kerb, R., Roots, I. Cancer Res. (1996) [Pubmed]
  41. In vitro and in vivo clinical pharmacology of dimethyl benzoylphenylurea, a novel oral tubulin-interactive agent. Rudek, M.A., Zhao, M., Smith, N.F., Robey, R.W., He, P., Hallur, G., Khan, S., Hidalgo, M., Jimeno, A., Colevas, A.D., Messersmith, W.A., Wolff, A.C., Baker, S.D. Clin. Cancer Res. (2005) [Pubmed]
  42. Piperonyl butoxide and acenaphthylene induce cytochrome P450 1A2 and 1B1 mRNA in aromatic hydrocarbon-responsive receptor knock-out mouse liver. Ryu, D.Y., Levi, P.E., Fernandez-Salguero, P., Gonzalez, F.J., Hodgson, E. Mol. Pharmacol. (1996) [Pubmed]
  43. Requirement of Aryl Hydrocarbon Receptor Overexpression for CYP1B1 Up-Regulation and Cell Growth in Human Lung Adenocarcinomas. Chang, J.T., Chang, H., Chen, P.H., Lin, S.L., Lin, P. Clin. Cancer Res. (2007) [Pubmed]
  44. Cytochromes P450 in cynomolgus monkeys mutagenically activate 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) but not 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx). Sadrieh, N., Snyderwine, E.G. Carcinogenesis (1995) [Pubmed]
  45. Variation in induced CYP1A1 levels: relationship to CYP1A1, Ah receptor and GSTM1 polymorphisms. Smart, J., Daly, A.K. Pharmacogenetics (2000) [Pubmed]
  46. CYP1A1 and GSTM1 polymorphisms affect urinary 1-hydroxypyrene levels after PAH exposure. Alexandrie, A.K., Warholm, M., Carstensen, U., Axmon, A., Hagmar, L., Levin, J.O., Ostman, C., Rannug, A. Carcinogenesis (2000) [Pubmed]
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