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Gene Review

Cyp1a2  -  cytochrome P450, family 1, subfamily a,...

Rattus norvegicus

Synonyms: CYPD45, CYPIA2, Cyp1a-2, Cytochrome P-448, Cytochrome P-450d, ...
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Disease relevance of Cyp1a2


High impact information on Cyp1a2

  • Polychlorinated biphenyls (PCB) are potent inducers of hepatic microsomal CO-binding hemoprotein P-448 (P1-450) and of delta-aminolevulinate synthetase (ALAS) activity [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 [6].
  • Rats pretreated with three agents known to stimulate cytochrome P-448-associated enzymes, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 3-methylcholanthrene (3MC), and Aroclor 1254 were studied with a 14CO2 breath analysis technique after administration of [14C-dimethyl]aminoazobenzene (DMAB) [7].
  • Detection of carcinogen-induced stimulation of cytochrome P-448-associated enzymes by 14CO2 breath analysis studies using dimethylaminoazobenzene [7].
  • Coding nucleotide sequence of 3-methylcholanthrene-inducible cytochrome P-450d cDNA from rat liver [8].

Chemical compound and disease context of Cyp1a2


Biological context of Cyp1a2


Anatomical context of Cyp1a2

  • The CYP1A2-preferential activity MROD was 3-fold higher in the cerebellum than in the cerebral cortex, and was repressed 2.2-fold in the cerebellum but induced 3.7-fold in the cerebral cortex following beta-NF treatment [18].
  • The primary structure of cytochrome P-450d purified from rat liver microsomes: prediction of helical regions and domain analysis [19].
  • On the other hand, microsomes from uninduced LEC rat liver had more 3-methylcholanthrene (MC) inducible P450MC, mainly P450c and P450d, than microsomes from LEA rat liver and these isozymes in the LEC were markedly induced by 3-methylcholanthrene treatment [20].
  • Until now, these hepatocytes were believed to produce only one single cytochrome P-450 species, namely the cytochrome P1-450 (or P-448) [21].
  • The mRNA was translated in an in vitro rabbit reticulocyte lysate system, and assayed for the synthesis of MC-inducible forms of cytochrome P-450 (cytochrome P-450MC) using anti-cytochrome P-450c antibody which reacted with two types of cytochrome P-450MC, P-450c, and P-450d [22].

Associations of Cyp1a2 with chemical compounds


Other interactions of Cyp1a2

  • The other two proteins did not correspond to cytochromes P450b, P450e, or P450f (as might be expected if the antibody were incompletely immunoabsorbed), nor did they correspond to cytochromes P450c, P450d, P450g, P450h, P450i, P450j, P450k, or P450p [28].
  • In contrast, comparison of isozyme 4 with rat cytochrome P-450d, which is also induced by isosafrole and for which the sequence has recently been deduced from cDNA [Kawajiri, K., Gotoh, O., Sogawa, K., Tagashira, Y., Muramatsu, M. & Fujii-Kuriyama, Y. (1984) Proc. Natl. Acad. Sci. USA 81, 1649-1653], showed about 70% homology [29].
  • In contrast, the 8-MeBaA trans-8,9-dihydrodiol formed either by liver microsomes from 3-methylcholanthrene-treated rats or by the reconstituted rat liver enzyme system containing cytochrome P-448 and epoxide hydrolase was enriched with the (-)enantiomer [30].
  • Metabolism and activation of aflatoxin B1, a potent hepatocarcinogenic and mutagenic mycotoxin of Aspergillus flavus, were investigated in the reconstituted enzyme system composed of purified NADPH-cytochrome P-450 reductase and cytochrome P-450 or P-448 of rat liver [31].
  • Further, addition of methimazole, a high affinity substrate for the flavin-containing monooxygenase, reduced the residual mutagenicity in the systems containing antibody to P-450d and cytochrome P-450 reductase to 9% and 19%, respectively, of the appropriate control values [32].

Analytical, diagnostic and therapeutic context of Cyp1a2


  1. Halogenated biphenyls as AHH inducers: effects of different halogen substituents. Bandiera, S., Sawyer, T., Campbell, M.A., Robertson, L., Safe, S. Life Sci. (1982) [Pubmed]
  2. Upregulation of cytochrome P450 1A2 in chronic renal failure: does oxidized tryptophan play a role? Sindhu, R.K., Vaziri, N.D. Adv. Exp. Med. Biol. (2003) [Pubmed]
  3. Metabolic activation of mutagenic heterocyclic aromatic amines from protein pyrolysates. Kato, R. Crit. Rev. Toxicol. (1986) [Pubmed]
  4. Effects of model traumatic injury on hepatic drug metabolism in the rat. VI. Major detoxification/toxification pathways. Griffeth, L.K., Rosen, G.M., Rauchman, E.J. Drug Metab. Dispos. (1987) [Pubmed]
  5. Polychlorinated dibenzofurans (PCDFs): effects of structure on binding to the 2,3,7,8-TCDD cytosolic receptor protein, AHH induction and toxicity. Bandiera, S., Sawyer, T., Romkes, M., Zmudzka, B., Safe, L., Mason, G., Keys, B., Safe, S. Toxicology (1984) [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. Detection of carcinogen-induced stimulation of cytochrome P-448-associated enzymes by 14CO2 breath analysis studies using dimethylaminoazobenzene. Hepner, G.W., Piken, E.P. Gastroenterology (1979) [Pubmed]
  8. Coding nucleotide sequence of 3-methylcholanthrene-inducible cytochrome P-450d cDNA from rat liver. Kawajiri, K., Gotoh, O., Sogawa, K., Tagashira, Y., Muramatsu, M., Fujii-Kuriyama, Y. Proc. Natl. Acad. Sci. U.S.A. (1984) [Pubmed]
  9. Inhibition of 2-aminofluorene mutagenesis in bacteria by inducers of cytochrome P-450d. Miller, D.M., Aust, A.E., Voorman, R., Aust, S.D. Carcinogenesis (1988) [Pubmed]
  10. Restoration of hydroperoxide-dependent lipid peroxidation by 3-methylcholanthrene induction of cytochrome P-448 in hepatoma microsomes. Borrello, S., Galeotti, T., Palombini, G., Minotti, G. FEBS Lett. (1986) [Pubmed]
  11. Identification of the hepatic cytochrome P-450 isozymes induced and decreased by picloram. Reidy, G.F., Murray, M., Rose, H.A., Bonin, A.M., Baker, R.S., Stacey, N.H. Biochem. Pharmacol. (1988) [Pubmed]
  12. Induction of cytochrome P-448 isozyme(s) in primary cultured rat hepatocytes by drugs which induce different isozymes in vivo. Hishinuma, T., Degawa, M., Masuko, T., Hashimoto, Y. Biochem. Biophys. Res. Commun. (1987) [Pubmed]
  13. Evidence for the involvement of cytochrome P-450-dependent monooxygenase(s) in the formation of genotoxic metabolites from N-hydroxyurea. Andrae, U. Biochem. Biophys. Res. Commun. (1984) [Pubmed]
  14. A mechanistic model of effects of dioxin on gene expression in the rat liver. Kohn, M.C., Lucier, G.W., Clark, G.C., Sewall, C., Tritscher, A.M., Portier, C.J. Toxicol. Appl. Pharmacol. (1993) [Pubmed]
  15. Complete nucleotide sequence of a methylcholanthrene-inducible cytochrome P-450 (P-450d) gene in the rat. Sogawa, K., Gotoh, O., Kawajiri, K., Harada, T., Fujii-Kuriyama, Y. J. Biol. Chem. (1985) [Pubmed]
  16. Identification of cytochrome P-450 isozymes involved in the hydroxylation of dantrolene by rat liver microsomes. Jayyosi, Z., Villoutreix, J., Ziegler, J.M., Batt, A.M., De Maack, F., Siest, G., Thomas, P.E. Drug Metab. Dispos. (1993) [Pubmed]
  17. Expression of cytochrome P-450s and glutathione S-transferases in the rat liver during water deprivation: effects of glucose supplementation. Kim, S.G., Kim, E.J., Kim, Y.G., Lee, M.G. Journal of applied toxicology : JAT. (2001) [Pubmed]
  18. Constitutive and inducible levels of CYP1A1 and CYP1A2 in rat cerebral cortex and cerebellum. Iba, M.M., Storch, A., Ghosal, A., Bennett, S., Reuhl, K.R., Lowndes, H.E. Arch. Toxicol. (2003) [Pubmed]
  19. The primary structure of cytochrome P-450d purified from rat liver microsomes: prediction of helical regions and domain analysis. Haniu, M., Ryan, D.E., Levin, W., Shively, J.E. Arch. Biochem. Biophys. (1986) [Pubmed]
  20. Selective expression and induction of cytochrome P450PB and P450MC during the development of hereditary hepatitis and hepatoma of LEC rats. Sugiyama, T., Suzuki, K., Ookawara, T., Kurosawa, T., Taniguchi, N. Carcinogenesis (1989) [Pubmed]
  21. Multiplicity of cytochrome P-450 in primary fetal hepatocytes in culture. Kremers, P., Goujon, F., De Graeve, J., Van Cantfort, J., Gielen, J.E. Eur. J. Biochem. (1981) [Pubmed]
  22. Molecular cloning of a complementary DNA to 3-methylcholanthrene-inducible cytochrome P-450 mRNA from rat liver. Kawajiri, K., Sogawa, K., Gotoh, O., Tagashira, Y., Muramatsu, M., Fujii-Kuriyama, Y. J. Biochem. (1983) [Pubmed]
  23. 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]
  24. Amino-terminal and carboxy-terminal sequence of hepatic microsomal cytochrome P-450d, a unique hemoprotein from rats treated with isosafrole. Botelho, L.H., Ryan, D.E., Yuan, P.M., Kutny, R., Shively, J.E., Levin, W. Biochemistry (1982) [Pubmed]
  25. Modification of cytochrome P450 1A2 enzymes by the mechanism-based inactivator 2-ethynylnaphthalene and the photoaffinity label 4-azidobiphenyl. Yun, C.H., Hammons, G.J., Jones, G., Martin, M.V., Hopkins, N.E., Alworth, W.L., Guengerich, F.P. Biochemistry (1992) [Pubmed]
  26. Ethanol interferes with regeneration-associated changes in biotransforming enzymes: a potential mechanism underlying ethanol's carcinogenicity? Diehl, A.M., Bisgaard, H.C., Kren, B.T., Steer, C.J. Hepatology (1991) [Pubmed]
  27. Dihydralazine-induced inactivation of cytochrome P450 enzymes in rat liver microsomes. Masubuchi, Y., Horie, T. Drug Metab. Dispos. (1998) [Pubmed]
  28. Purification of two isozymes of rat liver microsomal cytochrome P450 with testosterone 7 alpha-hydroxylase activity. Arlotto, M.P., Greenway, D.J., Parkinson, A. Arch. Biochem. Biophys. (1989) [Pubmed]
  29. On the amino acid sequence of cytochrome P-450 isozyme 4 from rabbit liver microsomes. Fujita, V.S., Black, S.D., Tarr, G.E., Koop, D.R., Coon, M.J. Proc. Natl. Acad. Sci. U.S.A. (1984) [Pubmed]
  30. Epoxidation reactions catalyzed by rat liver cytochromes P-450 and P-448 occur at different faces of the 8,9-double bond of 8-methylbenz[a]anthracene. Yang, S.K., Chou, M.W., Fu, P.P., Wislocki, P.G., Lu, A.H. Proc. Natl. Acad. Sci. U.S.A. (1982) [Pubmed]
  31. Metabolism and activation of aflatoxin B1 by reconstituted cytochrome P-450 system of rat liver. Yoshizawa, H., Uchimaru, R., Kamataki, T., Kato, R., Ueno, Y. Cancer Res. (1982) [Pubmed]
  32. Activation of 3,3'-dichlorobenzidine in rat liver microsomes to mutagens: involvement of cytochrome P-450d. Iba, M.M., Thomas, P.E. Carcinogenesis (1988) [Pubmed]
  33. Induction of cytochrome P450 1A2 by musk analogues and other inducing agents in rat liver. Iwata, N., Suzuki, K., Minegishi, K., Kawanishi, T., Hara, S., Endo, T., Takahashi, A. Eur. J. Pharmacol. (1993) [Pubmed]
  34. Differential effects of nonhydroxylated flavonoids as inducers of cytochrome P450 1A and 2B isozymes in rat liver. Canivenc-Lavier, M.C., Bentejac, M., Miller, M.L., Leclerc, J., Siess, M.H., Latruffe, N., Suschetet, M. Toxicol. Appl. Pharmacol. (1996) [Pubmed]
  35. The influence of age on the inducibility of rat liver cytochrome P450IA1 (CYPIA1) and P450IA2 (CYPIA2) mRNAs. Horbach, G.J., Van Asten, J.G., Van Bezooijen, C.F. Mutat. Res. (1990) [Pubmed]
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