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Gene Review

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

Rattus norvegicus

Synonyms: AHH, AHRR, CP11, CYP1, CYP1A1, ...
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Disease relevance of Cyp1a1


High impact information on Cyp1a1

  • Polychlorinated biphenyls (PCB) are potent inducers of hepatic microsomal CO-binding hemoprotein P-448 (P1-450) and of delta-aminolevulinate synthetase (ALAS) activity [6].
  • Two CYP1A forms were detected by Western blot analysis in the small intestine with electrophoretic mobilities corresponding to hepatic CYP1A1 and CYP1A2 [7].
  • We have investigated the sites of N-terminally truncated cytochrome P4501A1 targeted to mitochondria (P450MT2) which interact with adrenodoxin (Adx), cytochrome P450 reductase (CPR) and bacterial flavodoxin (Fln) [8].
  • Targeting of NH2-terminal-processed microsomal protein to mitochondria: a novel pathway for the biogenesis of hepatic mitochondrial P450MT2 [9].
  • The correlation between AH receptor DNA-binding activity, intensity of in vivo footprints at xenobiotic response elements, and CYP1A1 transcription rate implies that down-regulation of AH receptor DNA-binding activity is important in regulating CYP1A1 transcription and that receptor is required continuously to maintain transcription [10].

Chemical compound and disease context of Cyp1a1


Biological context of Cyp1a1


Anatomical context of Cyp1a1


Associations of Cyp1a1 with chemical compounds

  • Indolo[3,2-b]carbazole increased the Cyp1a1, Cyp1a2 and Cyp1b1 mRNA levels concurrently with an increase in 7-ethoxyresorufin O-deethylase (EROD) activities [22].
  • Beta-naphthoflavone induced the expression of Cyp1a1 and Cyp1b1 transcripts, two well-characterized AHR-inducible genes that code for hydroxylases that metabolize estradiol to catecholestrogens [23].
  • Treatment of rats with omeprazole, an atypical nonligand activator of the AHR, caused a zone-specific induction of CYP1A1 in the centrilobular region similar to that seen after pretreatment with the AHR ligand 3-methylcholanthrene [24].
  • We have investigated the interaction of four furocoumarins angelicin, bergamottin, isopimpinellin, and 8-methoxypsoralen with the expression and activity of aryl hydrocarbon receptor (AhR)-regulated CYP1A1 in rat hepatocytes in primary culture, both in the presence and absence of light [1].
  • Recently, we reported that lipophilic cytochrome P450 inducers, beta-naphthoflavone (BNF), phenobarbital, and dexamethasone, induced CYP1, CYP2B, and CYP3A enzymes, respectively, in rat epididymal white adipose tissue (WAT) at both mRNA and protein levels [25].

Physical interactions of Cyp1a1


Enzymatic interactions of Cyp1a1


Regulatory relationships of Cyp1a1

  • It has been previously reported that in vivo treatment with CYP1A1 inducer 3-methylcholanthrene (3-MC) suppresses rat hepatic HST-a mRNA expression in a dose-dependent manner [29].
  • In contrast to the P-450s, microsomal epoxide hydrolase mRNAs were expressed at relative homogeneous amounts throughout the brain. beta-Naphthoflavone markedly increased the CYP1A1 and CYP1A2 mRNA contents of each brain region investigated, although this agent did not affect levels of epoxide hydrolase [30].

Other interactions of Cyp1a1

  • Maximum EROD activity and Cyp1a1 mRNA levels were observed after approximately 12 h, whereas Cyp1a2 and Cyp1b1 mRNA levels peaked after 48 h [22].
  • Though supplementary vanadium had little or no influence on the contents of cytochrome P450 and b5 and activities of CYP2E1 and AHH in HNs and NNSP, it substantially elevated the UDPGT activity in both HNs and NNSP liver areas [31].
  • A significant increase in CYP1A1 mRNA was also detected in all the brain regions examined including olfactory bulb, striatum-caudate, hypothalamus, hippocampus, cortex, cerebellum, and substantia nigra [32].
  • These results are consistent with the implication of a tyrosine kinase, most probably the Src tyrosine kinase, in the mechanism of CYP1A1 induction in rat hepatocytes [33].
  • Increase in CYP1A1 and decrease in CCKAR expressions in vacuolated acinar cells may be involved in the pathogenesis of pancreatic lesions [34].

Analytical, diagnostic and therapeutic context of Cyp1a1

  • Sequence analysis of the cDNA insert revealed that the amino acid sequence of cytochrome P-450MC was composed of 523 amino acid residues, including the initial 22 N-terminal amino acids whose sequence was determined with the purified protein [16].
  • By Western blotting, only the ventral and dorsolateral prostates exhibited significant induction of CYP1A1 [17].
  • Quantitative real-time RT-PCR analysis revealed that the 7.5 microg group showed a significantly higher level of CYP1A1 mRNA, and that the 250 ng group showed significantly higher levels of CYP1B1 mRNA [35].
  • Radioimmunoassay data revealed a maximum induction of 200-fold for CYP1A1 and 10-fold for CYP1A2 and there were no statistically significant differences between initiated and noninitiated rats [36].
  • The level of induction of CYP1A1 mRNA and apoprotein was lower in rats fed soy diets than in rats fed casein diets (P < 0.05), and the level of induced CYP1A2 mRNA was lower in rats fed soy or whey (P < 0.05) after treatment with the aryl hydrocarbon (Ah) receptor-dependent inducer 3-MC [37].


  1. Natural furocoumarins as inducers and inhibitors of cytochrome P450 1A1 in rat hepatocytes. Baumgart, A., Schmidt, M., Schmitz, H.J., Schrenk, D. Biochem. Pharmacol. (2005) [Pubmed]
  2. Induction of cytochrome CYPIA1 and formation of toxic metabolites of benzo[a]pyrene by rat aorta: a possible role in atherogenesis. Thirman, M.J., Albrecht, J.H., Krueger, M.A., Erickson, R.R., Cherwitz, D.L., Park, S.S., Gelboin, H.V., Holtzman, J.L. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  3. In vivo up-regulation of aryl hydrocarbon receptor expression by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in a dioxin-resistant rat model. Franc, M.A., Pohjanvirta, R., Tuomisto, J., Okey, A.B. Biochem. Pharmacol. (2001) [Pubmed]
  4. Cooperation of the inducible nitric oxide synthase and cytochrome P450 1A1 in mediating lung inflammation and mutagenicity induced by diesel exhaust particles. Zhao, H., Barger, M.W., Ma, J.K., Castranova, V., Ma, J.Y. Environ. Health Perspect. (2006) [Pubmed]
  5. Comparative assessment of metabolic enzyme levels in macrophage populations of the F344 rat. Germolec, D.R., Adams, N.H., Luster, M.I. Biochem. Pharmacol. (1995) [Pubmed]
  6. Evidence for the catabolism of polychlorinated biphenyl-induced cytochrome P-448 by microsomal heme oxygenase, and the inhibition of delta-aminolevulinate dehydratase by polychlorinated biphenyls. Maines, M.D. J. Exp. Med. (1976) [Pubmed]
  7. Effects of enteral nutrition and ethanol on cytochrome P450 distribution in small intestine of male rats. Hakkak, R., Ronis, M.J., Badger, T.M. Gastroenterology (1993) [Pubmed]
  8. Evolutionarily divergent electron donor proteins interact with P450MT2 through the same helical domain but different contact points. Anandatheerthavarada, H.K., Amuthan, G., Biswas, G., Robin, M.A., Murali, R., Waterman, M.R., Avadhani, N.G. EMBO J. (2001) [Pubmed]
  9. Targeting of NH2-terminal-processed microsomal protein to mitochondria: a novel pathway for the biogenesis of hepatic mitochondrial P450MT2. Addya, S., Anandatheerthavarada, H.K., Biswas, G., Bhagwat, S.V., Mullick, J., Avadhani, N.G. J. Cell Biol. (1997) [Pubmed]
  10. Down-regulation of nuclear aryl hydrocarbon receptor DNA-binding and transactivation functions: requirement for a labile or inducible factor. Reick, M., Robertson, R.W., Pasco, D.S., Fagan, J.B. Mol. Cell. Biol. (1994) [Pubmed]
  11. Signal transduction-mediated activation of the aryl hydrocarbon receptor in rat hepatoma H4IIE cells. Backlund, M., Johansson, I., Mkrtchian, S., Ingelman-Sundberg, M. J. Biol. Chem. (1997) [Pubmed]
  12. alpha-Naphthoflavone-induced CYP1A1 gene expression and cytosolic aryl hydrocarbon receptor transformation. Santostefano, M., Merchant, M., Arellano, L., Morrison, V., Denison, M.S., Safe, S. Mol. Pharmacol. (1993) [Pubmed]
  13. Probing the control elements of the CYP1A1 switching module in H4IIE hepatoma cells. Broccardo, C.J., Billings, R.E., Andersen, M.E., Hanneman, W.H. Toxicol. Sci. (2005) [Pubmed]
  14. Comparison of expression of aldehyde dehydrogenase 3 and CYP1A1 in dominant and recessive aryl hydrocarbon hydroxylase-deficient mutant mouse hepatoma cells. Korkalainen, M.K., Törrönen, A.R., Kärenlampi, S.O. Chem. Biol. Interact. (1995) [Pubmed]
  15. Accumulation of mitochondrial P450MT2, NH(2)-terminal truncated cytochrome P4501A1 in rat brain during chronic treatment with beta-naphthoflavone. A role in the metabolism of neuroactive drugs. Boopathi, E., Anandatheerthavarada, H.K., Bhagwat, S.V., Biswas, G., Fang, J.K., Avadhani, N.G. J. Biol. Chem. (2000) [Pubmed]
  16. Nucleotide sequence of a full-length cDNA coding for 3-methylcholanthrene-induced rat liver cytochrome P-450MC. Yabusaki, Y., Shimizu, M., Murakami, H., Nakamura, K., Oeda, K., Ohkawa, H. Nucleic Acids Res. (1984) [Pubmed]
  17. Responsiveness of the adult male rat reproductive tract to 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure: Ah receptor and ARNT expression, CYP1A1 induction, and Ah receptor down-regulation. Roman, B.L., Pollenz, R.S., Peterson, R.E. Toxicol. Appl. Pharmacol. (1998) [Pubmed]
  18. Characterization of in vitro metabolites of the aryl hydrocarbon receptor ligand 6-formylindolo[3,2-b]carbazole by liquid chromatography-mass spectrometry and NMR. Bergander, L., Wahlström, N., Alsberg, T., Bergman, J., Rannug, A., Rannug, U. Drug Metab. Dispos. (2003) [Pubmed]
  19. Biodegradation of polychlorinated dibenzo-p-dioxins by recombinant yeast expressing rat CYP1A subfamily. Sakaki, T., Shinkyo, R., Takita, T., Ohta, M., Inouye, K. Arch. Biochem. Biophys. (2002) [Pubmed]
  20. Induction of CYP1A1 and ALDH-3 in lymphoid tissues from Fisher 344 rats exposed to 2,3,7,8-tetrachlorodibenzodioxin (TCDD). Germolec, D.R., Henry, E.C., Maronpot, R., Foley, J.F., Adams, N.H., Gasiewicz, T.A., Luster, M.I. Toxicol. Appl. Pharmacol. (1996) [Pubmed]
  21. Reversible stepwise negative regulation of CYP1A1 in cultured rat epidermal cells. Monk, S.A., Denison, M.S., Rice, R.H. Arch. Biochem. Biophys. (2003) [Pubmed]
  22. Indolo[3,2-b]carbazole inhibits gap junctional intercellular communication in rat primary hepatocytes and acts as a potential tumor promoter. Herrmann, S., Seidelin, M., Bisgaard, H.C., Vang, O. Carcinogenesis (2002) [Pubmed]
  23. An aryl hydrocarbon receptor agonist amplifies the mitogenic actions of estradiol in granulosa cells: evidence of involvement of the cognate receptors. Bussmann, U.A., Bussmann, L.E., Barañao, J.L. Biol. Reprod. (2006) [Pubmed]
  24. Selective centrilobular expression of the aryl hydrocarbon receptor in rat liver. Lindros, K.O., Oinonen, T., Johansson, I., Ingelman-Sundberg, M. J. Pharmacol. Exp. Ther. (1997) [Pubmed]
  25. Induction of detoxifying enzymes in rodent white adipose tissue by aryl hydrocarbon receptor agonists and antioxidants. Yoshinari, K., Okino, N., Sato, T., Sugatani, J., Miwa, M. Drug Metab. Dispos. (2006) [Pubmed]
  26. Regulation of CYP1A1 transcription via the metabolism of the tryptophan-derived 6-formylindolo[3,2-b]carbazole. Wei, Y.D., Bergander, L., Rannug, U., Rannug, A. Arch. Biochem. Biophys. (2000) [Pubmed]
  27. Ligand/receptor binding for 2,3,7,8-TCDD: implications for risk assessment. Portier, C., Tritscher, A., Kohn, M., Sewall, C., Clark, G., Edler, L., Hoel, D., Lucier, G. Fundamental and applied toxicology : official journal of the Society of Toxicology. (1993) [Pubmed]
  28. Involvement of cytochrome b5 in the metabolism of tetrachlorobiphenyls catalyzed by CYP2B1 and CYP1A1. Matsusue, K., Ariyoshi, N., Oguri, K., Koga, N., Yoshimura, H. Chemosphere (1996) [Pubmed]
  29. Regulation of sulfotransferase gene expression by glucocorticoid hormones and xenobiotics in primary rat hepatocyte culture. Runge-Morris, M. Chem. Biol. Interact. (1998) [Pubmed]
  30. Regional distribution and expression modulation of cytochrome P-450 and epoxide hydrolase mRNAs in the rat brain. Schilter, B., Omiecinski, C.J. Mol. Pharmacol. (1993) [Pubmed]
  31. Characterization of selective induction and alteration of xenobiotic biotransforming enzymes by vanadium during diethylnitrosamine-induced chemical rat liver carcinogenesis. Bishayee, A., Roy, S., Chatterjee, M. Oncol. Res. (1999) [Pubmed]
  32. Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on the expression of cytochrome P450 1A1, the aryl hydrocarbon receptor, and the aryl hydrocarbon receptor nuclear translocator in rat brain and pituitary. Huang, P., Rannug, A., Ahlbom, E., Håkansson, H., Ceccatelli, S. Toxicol. Appl. Pharmacol. (2000) [Pubmed]
  33. The role of protein tyrosine kinases in CYP1A1 induction by omeprazole and thiabendazole in rat hepatocytes. Lemaire, G., Delescluse, C., Pralavorio, M., Ledirac, N., Lesca, P., Rahmani, R. Life Sci. (2004) [Pubmed]
  34. Mechanisms of exocrine pancreatic toxicity induced by oral treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin in female Harlan Sprague-Dawley Rats. Yoshizawa, K., Marsh, T., Foley, J.F., Cai, B., Peddada, S., Walker, N.J., Nyska, A. Toxicol. Sci. (2005) [Pubmed]
  35. CYP1 and AhR expression in 7,12-dimethylbenz[a]anthracene-induced mammary carcinoma of rats prenatally exposed to 3,3',4,4',5-pentachlorobiphenyl. Wakui, S., Yokoo, K., Takahashi, H., Muto, T., Suzuki, Y., Kanai, Y., Hano, H., Furusato, M., Endou, H. Toxicology (2005) [Pubmed]
  36. Dose-response relationships for chronic exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin in a rat tumor promotion model: quantification and immunolocalization of CYP1A1 and CYP1A2 in the liver. Tritscher, A.M., Goldstein, J.A., Portier, C.J., McCoy, Z., Clark, G.C., Lucier, G.W. Cancer Res. (1992) [Pubmed]
  37. Inducibility of hepatic CYP1A enzymes by 3-methylcholanthrene and isosafrole differs in male rats fed diets containing casein, soy protein isolate or whey from conception to adulthood. Ronis, M.J., Rowlands, J.C., Hakkak, R., Badger, T.M. J. Nutr. (2001) [Pubmed]
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