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Gene Review

Cyp1a1  -  cytochrome P450, family 1, subfamily a,...

Mus musculus

Synonyms: AHH, AHRR, CP11, CYPIA1, Cyp1a-1, ...
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Disease relevance of Cyp1a1

  • We have shown previously that exposure of mouse hepatoma Hepa-1 cells to chromate inhibits the induction of the Cyp1a1 and Nqo1 genes by dioxin [1].
  • The incidence of cleft palate and hydronephrosis was not significantly different in fetuses from Cyp1a1(-/-), Cyp1b1(-/-), and Cyp1(+/+) wild-type mice [2].
  • In order to test this hypothesis, we undertook to examine the effect of hypoxia on Cyp1a1 transcription in Hepa-I cells [3].
  • Cyp1a1(-/-) male mice: protection against high-dose TCDD-induced lethality and wasting syndrome, and resistance to intrahepatocyte lipid accumulation and uroporphyria [4].
  • The slower elimination of CPA in CL-LCN mice compared with LCN mice suggests a role for extrahepatic P450 in the in vivo metabolism of CPA and demonstrates the utility of the CL-LCN model in determining the role of extrahepatic P450 enzymes in drug metabolism and chemical toxicity [5].
  • We have confirmed the essential role of pulmonary P450-mediated metabolic activation in NNK-induced lung cancer, and our mouse models should be applicable to studies on other procarcinogens that require P450-mediated metabolic activation [6].

Psychiatry related information on Cyp1a1

  • The effect of circulating oestrogen deficiency on sleep regulation and locomotor activity was investigated in aromatase cytochrome P450 deficient mice (ArKO) and wild-type (WT) controls [7].

High impact information on Cyp1a1

  • Mutations of POR also affect drug-metabolizing P450 enzymes, explaining the association of ABS with maternal fluconazole ingestion [8].
  • As a family of structurally-related enzymes, cytochrome P450 (P450) monooxygenases exhibit paradoxical characteristics: although collectively the enzymes display a broad range of substrate specificities, individually they are characterized by a high degree of substrate and product selectivity [9].
  • C/EBP beta-deficient ovaries lack corpora lutea and fail to down-regulate expression of the prostaglandin endoperoxidase synthase 2 and P450 aromatase genes in response to gonadotropins [10].
  • It is thought that potency to bind to intracellular histamine receptors (HIC), some of which are on cytochromes P450, may correlate with tumor growth-promoting activity [11].
  • When cytochrome P-450 levels were induced by four successive daily treatments of MCA or PB and when poly l X poly C was given on only the 1st day, induction of P-450's was completely suppressed for 24 hours and obtainment of the maximal P-450 level was delayed by 72-96 hours [12].

Chemical compound and disease context of Cyp1a1


Biological context of Cyp1a1


Anatomical context of Cyp1a1


Associations of Cyp1a1 with chemical compounds


Physical interactions of Cyp1a1

  • Interaction of the regulatory domains of the murine Cyp1a1 gene with two DNA-binding proteins in addition to the Ah receptor and the Ah receptor nuclear translocator (ARNT) [27].
  • Amino acid sequence analysis of tryptic peptides revealed significant similarity to the NADPH binding region of plant and animal NADPH-cytochrome P450 reductases and Bacillus megaterium cytochrome P450:NADPH-cytochrome P450 reductase [28].
  • The effect of established inducers of microsomal P-450 caused complex changes in apparent rates of alpha-hydroxylation of NPYR which made interpretation of responses to inducer pretreatment difficult and suggested the participation of multiple cytochrome P-450 isozymes in the metabolism of NPYR [29].

Enzymatic interactions of Cyp1a1

  • The distribution of cytochromes P-450 that catalyze aryl hydrocarbon hydroxylase and 7-ethoxycoumarin O-deethylase were studied with monoclonal antibody (MAb) 1-7-1 which completely inhibits these activities of a purified 3-methylcholanthrene-induced rat liver cytochrome P-450 [30].
  • CCl4-mediated malondialdehyde (MDA) formation was increased in rifampicin-treated liver microsomes, demonstrating that rifampicin was capable of increasing the NADPH-dependent metabolism of CCl4 catalyzed by P-450 2E1 to produce free radicals [31].

Co-localisations of Cyp1a1


Regulatory relationships of Cyp1a1

  • Previously identified functional DREs in well-characterized AhR-regulated genes including Cyp1a1 and Cyp1b1 were corroborated [33].
  • However, normal levels of Cyp1a-1 induction occurred in the livers of the same mice. induction of Cyp1a-1 by TCDD was also suppressed (more than 98%) in chemically induced skin papillomas having Ha-ras mutations, relative to uninvolved surrounding skin [34].
  • Cadmium or arsenic did not change Cyp1a1 mRNA levels but did enhance TCDD-inducible levels of Nqo1 mRNA, an effect that paralleled the ability of these metals to activate a beta-galactosidase gene reporter system regulated by an electrophile response promoter element [14].
  • These results indicate that trans-resveratrol and tannic acid may modulate cytochrome P450 2E1 and influence the metabolic activation of xenobiotics mediated by this P450 isoform [35].
  • In reconstituted systems containing phospholipid and NADPH-cytochrome P-450 reductase, MAb 1-91-3 inhibited aniline p-hydroxylase activity of purified ethanol-induced P-450et and acetone-induced P-450 by more than 90% [36].

Other interactions of Cyp1a1

  • Moreover, mRNA levels of Cyp1a1, the other gene in the same subfamily, appear unaffected by loss of the Cyp1a2 gene [37].
  • Western blot analysis confirmed that Socs2 and Cyp1a1 protein levels were also induced in CH12.LX cells [38].
  • We were unable to detect significant coinduction of MDR1, MDR2, or MDR3 mRNA with CYP1A1 mRNA or with Cyp1a-1 or Nmo-1 transcription under any conditions [39].
  • Acute sodium arsenite treatment induces Cyp2a5 but not Cyp1a1 in the C57Bl/6 mouse in a tissue (kidney) selective manner [40].
  • Hypoxic inhibition of 3-methylcholanthrene-induced CYP1A1 expression is independent of HIF-1alpha [41].

Analytical, diagnostic and therapeutic context of Cyp1a1


  1. Chromium inhibits transcription from polycyclic aromatic hydrocarbon-inducible promoters by blocking the release of histone deacetylase and preventing the binding of p300 to chromatin. Wei, Y.D., Tepperman, K., Huang, M.Y., Sartor, M.A., Puga, A. J. Biol. Chem. (2004) [Pubmed]
  2. For dioxin-induced birth defects, mouse or human CYP1A2 in maternal liver protects whereas mouse CYP1A1 and CYP1B1 are inconsequential. Dragin, N., Dalton, T.P., Miller, M.L., Shertzer, H.G., Nebert, D.W. J. Biol. Chem. (2006) [Pubmed]
  3. Inhibition of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-stimulated Cyp1a1 promoter activity by hypoxic agents. Kim, J.E., Sheen, Y.Y. Biochem. Pharmacol. (2000) [Pubmed]
  4. Cyp1a1(-/-) male mice: protection against high-dose TCDD-induced lethality and wasting syndrome, and resistance to intrahepatocyte lipid accumulation and uroporphyria. Uno, S., Dalton, T.P., Sinclair, P.R., Gorman, N., Wang, B., Smith, A.G., Miller, M.L., Shertzer, H.G., Nebert, D.W. Toxicol. Appl. Pharmacol. (2004) [Pubmed]
  5. A Mouse Model with Liver-Specific Deletion and Global Suppression of the NADPH-Cytochrome P450 Reductase Gene: Characterization and Utility for in Vivo Studies of Cyclophosphamide Disposition. Gu, J., Chen, C.S., Wei, Y., Fang, C., Xie, F., Kannan, K., Yang, W., Waxman, D.J., Ding, X. J. Pharmacol. Exp. Ther. (2007) [Pubmed]
  6. Determination of the role of target tissue metabolism in lung carcinogenesis using conditional cytochrome P450 reductase-null mice. Weng, Y., Fang, C., Turesky, R.J., Behr, M., Kaminsky, L.S., Ding, X. Cancer Res. (2007) [Pubmed]
  7. Sleep and rest regulation in young and old oestrogen-deficient female mice. Vyazovskiy, V.V., Kopp, C., Wigger, E., Jones, M.E., Simpson, E.R., Tobler, I. J. Neuroendocrinol. (2006) [Pubmed]
  8. Mutant P450 oxidoreductase causes disordered steroidogenesis with and without Antley-Bixler syndrome. Flück, C.E., Tajima, T., Pandey, A.V., Arlt, W., Okuhara, K., Verge, C.F., Jabs, E.W., Mendonça, B.B., Fujieda, K., Miller, W.L. Nat. Genet. (2004) [Pubmed]
  9. Alteration of mouse cytochrome P450coh substrate specificity by mutation of a single amino-acid residue. Lindberg, R.L., Negishi, M. Nature (1989) [Pubmed]
  10. An essential role for C/EBPbeta in female reproduction. Sterneck, E., Tessarollo, L., Johnson, P.F. Genes Dev. (1997) [Pubmed]
  11. Enhanced cancer growth in mice administered daily human-equivalent doses of some H1-antihistamines: predictive in vitro correlates. Brandes, L.J., Warrington, R.C., Arron, R.J., Bogdanovic, R.P., Fang, W., Queen, G.M., Stein, D.A., Tong, J., Zaborniak, C.L., LaBella, F.S. J. Natl. Cancer Inst. (1994) [Pubmed]
  12. Kinetics of depression and recovery of murine hepatic cytochrome P-450 levels after treatment with the interferon inducer polyriboinosinic-polyribocytidylic acid. Crowe, D.O., Reiners, J.J., Nerland, D.E., Sonnenfeld, G. J. Natl. Cancer Inst. (1986) [Pubmed]
  13. Induction of cytochrome P450 1A1 gene expression by a vitamin K3 analog in mouse hepatoma Hepa-1c1c7 cells. Chun, Y.J., Lee, B.Y., Yang, S.A., Ryu, C.K., Kim, M.Y. Mol. Cells (2001) [Pubmed]
  14. Disruption of dioxin-inducible phase I and phase II gene expression patterns by cadmium, chromium, and arsenic. Maier, A., Dalton, T.P., Puga, A. Mol. Carcinog. (2000) [Pubmed]
  15. Regulation of [Ah] gene battery enzymes and glutathione levels by 5,10-dihydroindeno[1,2-b]indole in mouse hepatoma cell lines. Liu, R.M., Vasiliou, V., Zhu, H., Duh, J.L., Tabor, M.W., Puga, A., Nebert, D.W., Sainsbury, M., Shertzer, H.G. Carcinogenesis (1994) [Pubmed]
  16. The role of the Ah locus in hexachlorobenzene-induced porphyria. Studies in congenic C57BL/6J mice. Hahn, M.E., Gasiewicz, T.A., Linko, P., Goldstein, J.A. Biochem. J. (1988) [Pubmed]
  17. Down-regulation of murine Cyp1a-1 in mouse hepatoma Hepa-1c1c7 cells by bisphenol A. Jeong, H.G., Kimand, J.Y., Choi, C.Y. Biochem. Biophys. Res. Commun. (2000) [Pubmed]
  18. The murine Cyp1a1 gene is expressed in a restricted spatial and temporal pattern during embryonic development. Campbell, S.J., Henderson, C.J., Anthony, D.C., Davidson, D., Clark, A.J., Wolf, C.R. J. Biol. Chem. (2005) [Pubmed]
  19. Suppression by p38 MAP kinase inhibitors (pyridinyl imidazole compounds) of Ah receptor target gene activation by 2,3,7,8-tetrachlorodibenzo-p-dioxin and the possible mechanism. Shibazaki, M., Takeuchi, T., Ahmed, S., Kikuchi, H. J. Biol. Chem. (2004) [Pubmed]
  20. Cyp1a2 protects against reactive oxygen production in mouse liver microsomes. Shertzer, H.G., Clay, C.D., Genter, M.B., Schneider, S.N., Nebert, D.W., Dalton, T.P. Free Radic. Biol. Med. (2004) [Pubmed]
  21. Oral benzo[a]pyrene in Cyp1 knockout mouse lines: CYP1A1 important in detoxication, CYP1B1 metabolism required for immune damage independent of total-body burden and clearance rate. Uno, S., Dalton, T.P., Dragin, N., Curran, C.P., Derkenne, S., Miller, M.L., Shertzer, H.G., Gonzalez, F.J., Nebert, D.W. Mol. Pharmacol. (2006) [Pubmed]
  22. Leukocyte activation induces aryl hydrocarbon receptor up-regulation, DNA binding, and increased Cyp1a1 expression in the absence of exogenous ligand. Crawford, R.B., Holsapple, M.P., Kaminski, N.E. Mol. Pharmacol. (1997) [Pubmed]
  23. Cell-density-dependent expression of Cyp1a2 gene in monolayer-cultured adult mouse hepatocytes. Nemoto, N., Sakurai, J. Jpn. J. Cancer Res. (1993) [Pubmed]
  24. Marked increases in hepatic NAD(P)H:oxidoreductase gene transcription and mRNA levels correlated with a mouse chromosome 7 deletion. Petersen, D.D., Gonzalez, F.J., Rapic, V., Kozak, C.A., Lee, J.Y., Jones, J.E., Nebert, D.W. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  25. Mitochondrial reactive oxygen production is dependent on the aromatic hydrocarbon receptor. Senft, A.P., Dalton, T.P., Nebert, D.W., Genter, M.B., Puga, A., Hutchinson, R.J., Kerzee, J.K., Uno, S., Shertzer, H.G. Free Radic. Biol. Med. (2002) [Pubmed]
  26. Aryl hydrocarbon receptor-dependent induction of cyp1a1 by bilirubin in mouse hepatoma hepa 1c1c7 cells. Sinal, C.J., Bend, J.R. Mol. Pharmacol. (1997) [Pubmed]
  27. Interaction of the regulatory domains of the murine Cyp1a1 gene with two DNA-binding proteins in addition to the Ah receptor and the Ah receptor nuclear translocator (ARNT). Carrier, F., Chang, C.Y., Duh, J.L., Nebert, D.W., Puga, A. Biochem. Pharmacol. (1994) [Pubmed]
  28. Purification and partial characterization of NADPH-cytochrome c reductase from Petunia hybrida flowers. Menting, J.G., Cornish, E., Scopes, R.K. Plant Physiol. (1994) [Pubmed]
  29. Reconstitution of rabbit liver microsomal N-nitrosopyrrolidine alpha-hydroxylase activity. McCoy, G.D., Koop, D.R. Cancer Res. (1988) [Pubmed]
  30. Monoclonal antibody-directed phenotyping of cytochrome P-450-dependent aryl hydrocarbon hydroxylase and 7-ethoxycoumarin deethylase in mammalian tissues. Fujino, T., West, D., Park, S.S., Gelboin, H.V. J. Biol. Chem. (1984) [Pubmed]
  31. Protective effect of rifampicin against acute liver injury induced by carbon tetrachloride in mice. Huang, R., Okuno, H., Takasu, M., Shiozaki, Y., Inoue, K. Jpn. J. Pharmacol. (1995) [Pubmed]
  32. Cytochrome P4502A-mediated coumarin 7-hydroxylation and testosterone hydroxylation in mouse and rat lung. Honkakoski, P., Mäenpää, J., Leikola, J., Pasanen, M., Juvonen, R., Lang, M.A., Pelkonen, O., Raunio, H. Pharmacol. Toxicol. (1993) [Pubmed]
  33. Comparative analysis of dioxin response elements in human, mouse and rat genomic sequences. Sun, Y.V., Boverhof, D.R., Burgoon, L.D., Fielden, M.R., Zacharewski, T.R. Nucleic Acids Res. (2004) [Pubmed]
  34. Downregulation of aryl hydrocarbon receptor function and cytochrome P450 1A1 induction by expression of Ha-ras oncogenes. Reiners, J.J., Jones, C.L., Hong, N., Clift, R.E., Elferink, C. Mol. Carcinog. (1997) [Pubmed]
  35. Effect of natural phenols on the catalytic activity of cytochrome P450 2E1. Mikstacka, R., Gnojkowski, J., Baer-Dubowska, W. Acta Biochim. Pol. (2002) [Pubmed]
  36. Monoclonal antibodies to ethanol-induced rat liver cytochrome P-450 that metabolizes aniline and nitrosamines. Ko, I.Y., Park, S.S., Song, B.J., Patten, C., Tan, Y.Z., Hah, Y.C., Yang, C.S., Gelboin, H.V. Cancer Res. (1987) [Pubmed]
  37. Cyp1a2(-/-) null mutant mice develop normally but show deficient drug metabolism. Liang, H.C., Li, H., McKinnon, R.A., Duffy, J.J., Potter, S.S., Puga, A., Nebert, D.W. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  38. 2,3,7,8-Tetrachlorodibenzo-p-dioxin induces suppressor of cytokine signaling 2 in murine B cells. Boverhof, D.R., Tam, E., Harney, A.S., Crawford, R.B., Kaminski, N.E., Zacharewski, T.R. Mol. Pharmacol. (2004) [Pubmed]
  39. Murine mdr-1, mdr-2, and mdr-3 gene expression: no coinduction with the Cyp1a-1 and Nmo-1 genes in liver by 2,3,7,8-tetrachlorodibenzo-p-dioxin. Teeter, L.D., Petersen, D.D., Nebert, D.W., Kuo, M.T. DNA Cell Biol. (1991) [Pubmed]
  40. Acute sodium arsenite treatment induces Cyp2a5 but not Cyp1a1 in the C57Bl/6 mouse in a tissue (kidney) selective manner. Seubert, J.M., Webb, C.D., Bend, J.R. J. Biochem. Mol. Toxicol. (2002) [Pubmed]
  41. Hypoxic inhibition of 3-methylcholanthrene-induced CYP1A1 expression is independent of HIF-1alpha. Allen, J.W., Johnson, R.S., Bhatia, S.N. Toxicol. Lett. (2005) [Pubmed]
  42. Determination of murine fetal Cyp1a1 and 1b1 expression by real-time fluorescence reverse transcription-polymerase chain reaction. Xu, M., Miller, M.S. Toxicol. Appl. Pharmacol. (2004) [Pubmed]
  43. In situ hybridization of Cyp1a1, Cyp1a2 and Ah receptor mRNAs expressed in murine ocular tissues. McAvoy, M., Singh, A.K., Shichi, H. Exp. Eye Res. (1996) [Pubmed]
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