Induction of Cytochromes P450 1 and P450 2 by Xenobiotics

  • E. Bresnick
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 105)


It has long been known that metabolic activation of a number of xenobiotics including the polycyclic aromatic hydrocarbons is required prior to eliciting mutagenic, teratogenic or carcinogenic properties. This activation is conducted in part by cytochrome P450 mediated pathways.


CYP2B2 Gene Polycyclic Hydrocarbon Aryl Hydrocarbon Hydroxylase Hepatic Microsomal Cytochrome Phenobarbital Induction 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Atchison M, Adesnik M (1986) Gene conversion in a cytochrome P-450 gene family. Proc Natl Acad Sci USA 83: 2300–2304PubMedCrossRefGoogle Scholar
  2. Beato M (1989) Gene regulation by steriod hormones. Cell 56: 335–344PubMedCrossRefGoogle Scholar
  3. Bradfield CA, Giover E, Poland A (1991) Purification and N-terminal amino acid sequence of the Ah receptor from the C57BL/6J mouse. Mol Pharmacol 39: 13–19PubMedGoogle Scholar
  4. Bresnick E, Siegel LI, Houser WH (1988) The 4S binding protein acts as a trans- regulator of the polycyclic hydrocarbon-inducible cytochrome P450. Cancer Metastasis Rev 7: 51–65PubMedCrossRefGoogle Scholar
  5. Brown RR, Miller JA, Miller EC (1965) The metabolism of methylated aminoazo dyes: IV. Dietary factors enhancing demethylation in vitro. J Biol Chem 209: 211–222.Google Scholar
  6. Collins S, Marietta MA (1984) Carcinogen-binding proteins: high-affinity binding sites for benzo(a)pyrene in mouse liver distinct from the Ah receptor. Mol Pharmacol 26: 353–359PubMedGoogle Scholar
  7. Conney AH (1966) Pharmacological implications of microsomal enzyme induction. Pharmacol Rev 19: 317–366Google Scholar
  8. Conney AH, Gilman AG (1963) Puromycin inhibition of enzyme induction by 3-methylcholanthrene. J Biol Chem 238: 3682–3685PubMedGoogle Scholar
  9. Conney AH, Miller EC, Miller J A (1956) The metabolism of methylated aminoazo dyes. Cancer Res 16: 450PubMedGoogle Scholar
  10. Cutroneo KR, Bresnick E (1973) Induction of benzpyrene hydroxylase in fetal liver expiants by flavones and phénobarbital. Biochem Pharmacol 22: 675–686PubMedCrossRefGoogle Scholar
  11. Denis M, Cuthill S, Wikstrom A-C, Poellinger L, Gustafsson J-A (1988) Association of the dioxin receptor with Mr 90000 heat shock protein: a structural kinship with the glucocorticoid receptor. Biochem Biophys Res Commun 155: 801–807PubMedCrossRefGoogle Scholar
  12. Denison MS, Vella LM, Okey AB (1986) Structure and function of the Ah receptor for 2,3,7,8-tetrachlorodibenzo-p-dioxin. Species differences in molecular properties of the receptors from mouse and rat hepatic cytosols. J Biol Chem 261: 3987–3995PubMedGoogle Scholar
  13. Denison MS, Fisher JM, Whitlock JP Jr (1989) Protein-DNA interactions at recognition sites for the dioxin-Ah receptor complex. J Biol Chem 264: 16478–16482PubMedGoogle Scholar
  14. Dunn TJ, Koleske AJ, Lindahl R, Pitot HC (1989) Phenobarbital-inducible aidehyde dehydrogenase in the rat. cDNA sequence and regulation of the mRNA by phénobarbital in responsive rats. J Biol Chem 264: 13057–13065PubMedGoogle Scholar
  15. Elferink CJ, Whitlock JP Jr (1990) 2,3,7,8-Tetrachlorodibenzo-p-dioxin-inducible, Ah receptor-mediated bending of enhancer DNA. J Biol Chem 265: 5718–5721PubMedGoogle Scholar
  16. Fagan JB, Pastewka JV, Park SS, Guengerich FP, Gelboin HV (1982) Identification and quantitation of a 2.0-kilobase messenger ribonucleic acid coding for 3-methylcholanthrene-induced cytochrome P-450 using cloned cytochrome P-450 complementary deoxyribonucleic acid. Biochemistry 21: 6574–6580PubMedCrossRefGoogle Scholar
  17. Fisher JM, Wu L, Denison MS, Whitlock JP Jr (1990) Organization and function of a dioxin-responsive enhancer. J Biol Chem 265: 9676–9681PubMedGoogle Scholar
  18. Foldes RL, Hines RN, Ho K-L, Shen M-L, Nagel KB, Bresnick E (1985) 3-Methylcholanthrene-induced expression of the cytochrome P-450c gene. Arch Biochem Biophys 239: 137–146Google Scholar
  19. Fujisawa-Sehara A, Sogawa K, Yamane M, Fujil-Kurlyama Y (1987) Characterization of xenobiotic responsive elements upstream from the drug-metabolizing cytochrome P-450c gene: a similarity to glucocorticoid regulatory elements. Nucleic Acids Res 15: 4179–4191PubMedCrossRefGoogle Scholar
  20. Fulco AJ (1991) P450 BM-3 and other inducible bacterial P450 cytochromes: biochemistry and regulation. Annu Rev Pharmacol Toxicol 31: 177–203PubMedCrossRefGoogle Scholar
  21. Gasiewicz IA, Elterink CJ, Henry EC (1991) Characterization of multiple forms of the Ah receptor: recognition of a dioxin-responsive enhancer involves heteromer formation. Biochemistry 30: 2909–2916PubMedCrossRefGoogle Scholar
  22. Gelboin HV, Blackburn NR (1963) The stimulatory effect of 3-methylcholanthrene on microsomal amino acid incorporation and benzpyrene hydroxylase activity and its inhibition by actinomycin D. Biochim Biophys Acta 72: 657–660PubMedCrossRefGoogle Scholar
  23. Gelboin HV, Blackburn NR (1964) The stimulatory effect of 3-methylcholanthrene on benzpyrene hydroxylase activity in several rat tissues: Inhibition by actinomycin D and puromycin. Cancer Res 24: 356–360PubMedGoogle Scholar
  24. Gelboin HV, Sokoloff L (1961) Effects of 3-methylcholanthrene and phenobarbital on amino acid incorporation into protein. Science 134: 611–612PubMedCrossRefGoogle Scholar
  25. Gelboin HV, Sokoloff L (1964) Studies on the mechanism of methylcholanthrene induction of enzyme activities of rat liver. Biochim Biophys Acta 91: 122–129PubMedGoogle Scholar
  26. Gelboin HV, Miller JA, Miller EC (1958) The formation in vitro of protein-bound derivatives of aminoazo dyes by rat liver and its enhancement by benzpyrene treatment. Biochim Biophys Acta 27: 655PubMedCrossRefGoogle Scholar
  27. Giachelli CM, Omiecinski CJ (1987) Developmental regulation of cytochrome P-450 genes in the rat. Mol Pharmacol 31: 477–484PubMedGoogle Scholar
  28. Goldstein JA, Safe S (1989) Mechanism of action and structure-activity relationships for the chlorinated dibenzo-p-dioxins and related compounds. In: Kimbrough RD, Jensen N (eds) Halogenated biphenyls, terphenyls, naphthalenes, dibenzodioxins and related products. Elsevier, Amsterdam, pp 239–293Google Scholar
  29. Gonzalez FJ (1988) The molecular biology of cytochrome P450s. Pharmacol Rev 40: 243–288PubMedGoogle Scholar
  30. Gonzalez FJ, Nebert DW (1990) Evolution of the P450 gene superfamily: animal-plant warfare; molecular drive and human genetic differences in drug oxidation. Trends Genet 6: 182–186PubMedCrossRefGoogle Scholar
  31. Gonzalez FJ, Tukey RH, Nebert DW (1984) Structural gene products of the Ah locus. Transcriptional regulation of cytochrome Pl-450 and P3-450 mRNA levels by 3-methylcholanthrene. Mol Pharmacol 26: 117–121PubMedGoogle Scholar
  32. Greenlee WF, Poland A (1979) Nuclear uptake of 2,3,7,8-tetrachlorodibenzo-p-dioxin in C57BL/6J and DBA/2J mice. J Biol Chem 254: 9814–9821PubMedGoogle Scholar
  33. Hankinson O (1979) Single-step selection of clones of a mouse hepatoma line deficient in aryl hydrocarbon hydroxylase. Proc Natl Acad Sci USA 76: 373–376PubMedCrossRefGoogle Scholar
  34. Hardwick JP, Gonzalez FJ, Kasper CB (1983) Transcriptional regulation of rat liver epoxide hydratase, NADPH-cytochrome P-450 oxidoreductase, and cytochrome P-450b gene by phenobarbital. J Biol Chem 258: 8081–8085PubMedGoogle Scholar
  35. He J-S, Fulco A J (1991) A barbiturate-regulated protein binding to a common sequence in the cytochrome P450 genes of rodents and bacteria. J Biol Chem 266: 7864–7869PubMedGoogle Scholar
  36. Heintz NJ, Tierney B, Bresnick E, Schaeffer WI (1981) Correlation of induction of aryl hydrocarbon hydroxylase in cultured rat hepatocytes with saturable high-affinity binding of 3-methylcholanthrene to a 4S cytoplasmic protein. Cancer Res 41: 1794–1802PubMedGoogle Scholar
  37. Hines RN, Levy JB, Conrad RD, Iversen PL, Shen M-L, Renli A, Bresnick E (1985) Gene structure and nucleotide sequence for rat cytochrome P-450c. Arch Biochem Biophys 237: 465–476PubMedCrossRefGoogle Scholar
  38. Hoffman EC, Reyes H, Chu F-F, Sander F, Conley LH, Brooks BA, Hankinson O (1991) Cloning of a factor required for activity of the Ah (dioxin) receptor. Science 252: 954–958PubMedCrossRefGoogle Scholar
  39. Holder GM, Tierney B, Bresnick E (1981) Nuclear uptake and subsequent nuclear metabolism of benzo(a)pyrene complexed to cytosolic proteins. Cancer Res 41: 4408–4414PubMedGoogle Scholar
  40. Hong J, Pan J, Gonzalez FJ, Gelboin HV, Yang CS (1987) The induction of a specific form of cytochrome P-450 (P-450j) by fasting. Biochem Biophys Res Commun 142: 1077–1083PubMedCrossRefGoogle Scholar
  41. Houser WH, Hines RN, Bresnick E (1985) Implication of the ‘4S’ polycyclic aromatic hydrocarbon binding protein in the transregulation of rat cytochrome P-450c expression. Biochemistry 24: 7839–7845PubMedCrossRefGoogle Scholar
  42. Houser WH, Zielinski R, Bresnick E (1986) Further characterization of the polycyclic aromatic hydrocarbon binding properties of the 4S protein. Arch Biochem Biophys 251: 361–368PubMedCrossRefGoogle Scholar
  43. Houser WH, Cunningham CK, Hines RN, Schaeffer WI, Bresnick E (1987) Interaction of the 4S polycyclic aromatic hydrocarbon-binding protein with the cytochrome P-450c gene. Arch Biochem Biophys 15: 215–223CrossRefGoogle Scholar
  44. Ikeya K, Jaiswal AK, Owens RA, Jones JE, Nebert DW, Kimura S (1989) Human CYP1A2: sequence, gene structure, comparison with the mouse and rat orthologous gene, and genetic differences in liver 1A2 mRNA concentrations. Mol Endocrinol 3: 1399–1408PubMedCrossRefGoogle Scholar
  45. Ioannides C, Parke DV (1990) The cytochrome P450 I gene family of microsomal hemoproteins and their role in the metabolic activation of chemicals. Drug Metab Rev 22: 1–85PubMedCrossRefGoogle Scholar
  46. Israel DI, Whitlock JP Jr (1984) Regulation of cytochrome Pl-450 gene transcription by 2,3,7,8-tetrachlorodlbenzo-p-dioxin in wild type and variant mouse hepatoma cells. J Biol Chem 259: 5400–5402PubMedGoogle Scholar
  47. Jacob ST, Schars MB, Vesell ES (1974) Role of RNA in induction of hepatic microsomal mixed-function oxidase. Proc Natl Acad Sci USA 71: 704–707PubMedCrossRefGoogle Scholar
  48. Jaiswal AK, Gonzalez FJ, Nebert DW (1985) Human Pl-450 gene differences in benzo(a)pyrene metabolism. Nucleic Acids Res 13: 4503–4519PubMedCrossRefGoogle Scholar
  49. Jaiswal AK, Nebert DW, Gonzalez FJ (1986) Human P3450: cDNA and complete amino acid sequence. Nucleic Acids Res 14: 6773–6774PubMedCrossRefGoogle Scholar
  50. Jaiswal AK, Haaparanta T, Luc P-V, Schembri J, Adesnik M (1990) Glucocorticoid regulation of a phenobarbital-inducible cytochrome P-450 gene: the presence of a functional glucocorticoid response element in the 5′-flanking region of the CYP2B2 gene. Nucleic Acids Res 18: 4237–4242PubMedCrossRefGoogle Scholar
  51. Jervell KR, Cristoffersen T, Morland J (1965) Studies on 3-methylcholanthrene induction and carbohydrate repression of rat liver dimethylaminoazobenzene reductase. Arch Biochem Biophys 111: 15–22PubMedCrossRefGoogle Scholar
  52. Karin M, Haslinger A, Holtgreve H, Richards RI, Krauter P, Westphal HM, Beato M (1984) Characterization of DNA sequences through which cadmium and glucocorticoid hormones induce human metallothionein-IIA. Nature 308: 513–519PubMedCrossRefGoogle Scholar
  53. Kawajiri K, Gotoh O, Tagashira Y, Sogawa K, Fujil-Kuriyama Y (1984) Titration of mRNAs for cytochrome P-450c and P-450d under drug-inductive conditions in rat livers by their specific probes of cloned DNAs. J Biol Chem 259: 10145–10149PubMedGoogle Scholar
  54. Kawajiri K, Watanabe J, Gotoh O, Tagashiri Y, Sogawa K, Fujil-Kurlyama Y (1986) Structure and drug inducibility of the human cytochrome P-450c gene. Eur J Biochem 159: 219–225PubMedCrossRefGoogle Scholar
  55. Kimura S, Gonzalez FJ, Nebert DW (1986) Tissue-specific expression of the mouse dioxin-inducible P1450 and P3450 genes: differential transcriptional activation and mRNA stability in liver and extrahepatic tissues. Mol Cell Biol 6: 1471–1477PubMedGoogle Scholar
  56. Koop DR, Crump BL, Nordblom GD, Coon MJ (1985) Immunochemical evidence for induction of the alcohol-oxidizing cytochrome P-450 of rabbit liver microsomes by diverse agents: ethanol, imidazole, trichloroethylene, acetone, pyrazole, and isoniazid. Proc Natl Acad Sci USA 82: 4065–4069PubMedCrossRefGoogle Scholar
  57. Kumar V, Chambon P (1988) The estrogen receptor binds tightly to its responsive element as a ligand induced homodimer. Cell 55: 145–166PubMedCrossRefGoogle Scholar
  58. Lacassagne A, Buu-Hoi NP, Rudali G (1945) Inhibition of the carcinogenic action produced by a weakly carcinogenic hydrocarbon on a highly active carcinogenic hydrocarbon Br J Exp Pathol 26: 5–12Google Scholar
  59. Legraverend C, Hannah RR, Eisen HJ, Owens IS, Nebert DW, Hankinson O (1982) “Regulatory gene product of the ah locus”. Characterization of receptor mutants among mouse hepatoma clones. J Biol Chem 257: 6402–6407PubMedGoogle Scholar
  60. Lieber CS, DeCarli LM (1968) Ethanol oxidation by hepatic microsomes: adaptive increase after ethanol feeding. Science 162: 917–918PubMedCrossRefGoogle Scholar
  61. Loeb LA, Gelboin HV (1963) Stimulation of amino acid incorporation by nuclear ribonucleic acid from normal and methylcholanthrene treated rats. Nature 199: 809–810PubMedCrossRefGoogle Scholar
  62. Mason ME, Okey AB (1982) Cytosolic and nuclear binding of 2,3,7,8- tetrachlorodibenzo-p-dioxin to the Ah receptor in extrahepatic tissues of rats and mice. Eur J Biochem 123: 209–215PubMedCrossRefGoogle Scholar
  63. Miller EC, Miller JA, Brown RR (1952) On the Inhibitory action of certain polycyclic hydrocarbons on azo dye carcinogenesis. Cancer Res 12: 282–283Google Scholar
  64. Nebert DW (1988) Genes encoding drug metabolizing enzymes: Possible role in human disease. In: Woodhead AD, Bender MA, Leonard RC (eds) Phenotypic variation in populations. Plenum, New York, pp 45–64Google Scholar
  65. Nebert DW, Gonzalez FJ (1987) P450 genes: structure, evolution and regulation. Annu Rev Biochem 56: 945–993PubMedCrossRefGoogle Scholar
  66. Nebert DW, Jones JE (1989) Regulation of the mammalian cytochrome P1450 (CYPIA1) gene. Int J Biochem 21: 243–252PubMedCrossRefGoogle Scholar
  67. Nebert DW, Goujon FM, Gielen JE (1972) Aryl hydrocarbon hydroxylase induction by polycyclic hydrocarbons: simple autosomal dominant trait in the mouse. Nature 236: 107–110Google Scholar
  68. Nebert DW, Nelson DR, Coon MJ, Estabrook RW, Feyereisen R, Fujii-Kuriyama Y, Gonzalez FJ, Guengerich FP, Gunsalus IC, Johnson EF, Loper JC, Sato R, Waterman MR, Waxman DJ (1991) The P450 superfamily: update on new sequences gene mapping and recommended nomenclature. DNA Cell Biol 10: 1–14PubMedCrossRefGoogle Scholar
  69. Neuhold LA, Gonzalez FJ, Jaiswal AK, Nebert DW (1986) Regulation of mouse CYPIA1 gene expression by dioxin: requirement of two cis-acting elements during induction. DNA 5: 403–411PubMedCrossRefGoogle Scholar
  70. Neuhold LA, Shirayoshi Y, Ozato K, Jones JE, Nebert DW (1989) Regulation of mouse CYPIA1 gene expression by dioxin: requirement of two cw-acting elements during induction. Mol Cell Biol 9: 2378–2386PubMedGoogle Scholar
  71. Okey AB, Bondy GP, Mason ME, Kahl GF, Eisen HJ, Guenthner TM, Nebert DW (1979) Regulatory gene products of the Ah locus. Characterization of the cytosolic inducer receptor complex and evidence for tis nuclear translocation. J Biol Chem 254: 11636–11648PubMedGoogle Scholar
  72. Okey AB, Bondy GP, Mason ME, Nebert DW, Forster-Gibson CJ, Muncan J, Dufresne MJ (1980) Temperature-dependent cytosol-to-nucleus translocation of the Ah receptor for 2,3,7,8-tetrachlorodibenzo-p-dioxin in continuous cell culture lines. J Biol Chem 255: 11415–11422PubMedGoogle Scholar
  73. Omiecinski CJ, Walz FG Jr, Vlasuk GP (1985) Phenobarbital induction of rat liver cytochromes P-450b and P-450e. Quantitation of specific mRNAs by hybridization to synthetic oligo deoxyribonucleotide probes. J Biol Chem 260: 3247–3250PubMedGoogle Scholar
  74. Pasco DS, Boyum KW, Merchant SN, Chalberg SC, Fagan JB (1988) Transcriptional and post-transcriptional regulation of the genes encoding cytochromes P-450c and P-450d in vivo and in primary hepatocyte cultures. J Biol Chem 263: 8671–8676PubMedGoogle Scholar
  75. Past MR, Cook DE (1982) Effect of diabetes on rat liver cytochrome P-450. Biochem Pharmacol 31: 3329–3334PubMedCrossRefGoogle Scholar
  76. Peng RP, Tennant PO, Lorr NA, Yang CS (1983) Alterations of microsomal monooxygenase system and carcinogen metagbolism by streptozotocin-induced diabetes in rats. Carcinogenesis 4: 703–708PubMedCrossRefGoogle Scholar
  77. Perdew GH (1988) Association of the Ah receptor with the 90-kDa heat shock protein. J Biol Chem 263: 13802–13805PubMedGoogle Scholar
  78. Petersen DP, McKinney CE, Ikeya K, Smith HN, Bale AE, McBride DW, Nebert DW (1991) Human CYPIA1 gene: cosegregation of the enzyme inducibility phenotype and ARFLP. Am J Hum Genet 48: 720–725PubMedGoogle Scholar
  79. Pickett CB, Lu AYH (1989) Glutathione S-transferases: gene structure, regulation and biological function. Annu Rev Biochem 58: 743–764PubMedCrossRefGoogle Scholar
  80. Poland A, Glover E (1974) Comparison of 2,3,7,8-tetrachlorodibenzo-p-dioxin, a potent inducer of aryl hydrocarbon hydroxylase with 3-methylcholanthrene. Mol Pharmacol 10: 349–359PubMedGoogle Scholar
  81. Poland A, Glover E (1975) Genetic expression of aryl hydrocarbon hydroxylase by 2,3,7,8-tetrachlorodibenzo-p-dioxin: evidence for a receptor mutation in genetically non-responsive mice. Mol Pharmacol 11: 389–398Google Scholar
  82. Poland A, Glover E (1988) Ca+2-dependent proteolysis of the Ah receptor. Arch Biochem Biophys 261: 103–111PubMedCrossRefGoogle Scholar
  83. Poland A, Knutson JC (1982) 2,3,7,8-Tetrachlorodibenzo-p-dioxin and related halogenated aromatic hydrocarbons: examination of the mechanism of toxicity. Annu Rev Pharmacol Toxicol 22: 517–524Google Scholar
  84. Poland A, Glover E, Kende AS (1976) Stereospecific, high affinity binding of 2,3,7,8-tetrachlorodibenzo-p-dioxin by hepatic cytosol. J Biol Chem 251: 4926–4946Google Scholar
  85. Poland A, Glover E, Ebetino FH, Kende As (1968) Photoaffinity labelling of the AH receptor. J Biol Chem 261: 6352–6365Google Scholar
  86. Pratt WB (1990) Interaction of hsp90 with steroid receptors: organizing some diverse observations and presenting the newest concepts. Mol Cell Endocrinol 74: C69–C76PubMedCrossRefGoogle Scholar
  87. Prokipcak RD, Okey AB (1990) Equivalent molecular mass of cytosolic and nuclear forms of Ah receptor from HePA-1 cells determined by photoaffinity labeling with 2,3,7,8-[3H]-tetrachlorodibenzo-p-dioxin. Biochem Biophys Res Commun 172: 698–704PubMedCrossRefGoogle Scholar
  88. Quattrochi LC, Okino ST, Pendurthi UR, Tukey RH (1985) Cloning and isolation of human cytochrome P-450 cDNAs homologous to dioxin-inducible rabbit mRNAs encoding P-450 4 and P-450 6. DNA 4: 395–400PubMedCrossRefGoogle Scholar
  89. Quattrochi LC, Pendurthi UR, Okino ST, Potenza C, Tukey RH (1986) Human cytochrome P-450 4 mRNA and gene: part of a multigene family that contains Alu sequences in its mRNA. Proc Natl Acad Sci USA 83: 6731–6735PubMedCrossRefGoogle Scholar
  90. Raha A, Reddy V, Houser W, Bresnick E (1990) Binding characteristics of 4S PAH-binding and Ah receptor from rats and mice. J Toxicol Environ Health 29: 339–355PubMedCrossRefGoogle Scholar
  91. Rao MV, Rangarajan PN, Padmanaban G (1990) Dexamethasone negatively regulates phenobarbitone-activated transcription but synergistically enhances cytoplasmic levels of cytochrome P-450b/e messenger RNA. J Biol Chem 265: 5617–5622PubMedGoogle Scholar
  92. Raval P, Iversen PL, Bresnick E (1991) Induction of cytochromes P450IA1 and IA2 as determined by solution hybridization. Biochem Pharmacol 41: 1719–1723PubMedCrossRefGoogle Scholar
  93. Remmer H (1957) The acceleration of evipan oxidation and the demethylation of methylaminopyrine by barbiturates. Arch Exp Pathol Pharmacol 237: 296–307Google Scholar
  94. Remmer H, Merker HJ (1963) Drug-induced changes in the liver endoplasmic reticulum: association with drug-metabolizing enzymes. Science 14: 1657–1658CrossRefGoogle Scholar
  95. Richardson HL, Cunningham L (1951) The inhibitory action of methylcholanthrene on rats fed the azo dye 3′-methyl-4-dimethyl-aminoazobenzene. Cancer Res 11: 274Google Scholar
  96. Ryan DE, Levin W (1990) Purification and characterization of hepatic microsomal cytochrome P-450. Pharmacol Ther 45: 153–239PubMedCrossRefGoogle Scholar
  97. Ryan DE, Thomas PE, Levin W (1982) Purification and characterization of a minor form of hepatic microsomal cytochrome P-450 from rats treated with polychlorinated biphenyls. Arch Biochem Biophys 216: 272–288PubMedCrossRefGoogle Scholar
  98. Ryan DE, Ramanathan L, Lida S, Thomas PE, Haniu M, Shively JE, Lieber CS, Levin W (1985) Characterization of a major form of rat hepatic microsomal cytochrome P-450 induced by isoniazid. J Biol Chem 260: 6385–6393PubMedGoogle Scholar
  99. Saatcioglu F, Perry DJ, Pasco DS, Fagan JB (1990) Multiple DNA-binding factors interact with overlapping specificities at the aryl hydrocarbon response element of the cytochrome P450IA1 gene. Mol Cell Biol 10: 6408–6416PubMedGoogle Scholar
  100. Scatchard G (1949) The attractions of proteins for small molecules and ions. Ann NY Acad Sci 51: 660–672CrossRefGoogle Scholar
  101. Seidegard J, DePierre JW (1983) Microsomal epoxide hydrolase. Biochim Biophys Acta 695: 251–270PubMedGoogle Scholar
  102. Silver G, Krauter KS (1988) Expression of cytochromes P-450c and P-450d mRNAs in cultured rat hepatocytes. 3-Methylcholanthrene induction is regulated primarily at the post-transcriptional level. J Biol Chem 263: 11802–11807PubMedGoogle Scholar
  103. Soderqvist P, Poellinger L, Toftgard R, Gustafsson J-A (1988) Differential expression of the cytochrome P-450c and P-450d genes in the rat ventral prostate and liver. Cancer Res 48: 3045–3049Google Scholar
  104. Sogawa K, Gotoh O, Kawajiri K, Fujii-Kuriyama Y (1984) Distinct organization of methylcholanthrene- and phenobarbital-inducible cytochrome P450 genes in the rat. Proc Natl Acad Sci USA 81: 5066–5070PubMedCrossRefGoogle Scholar
  105. Sogawa K Fujisawa-Sehara A, Yamane M, Fuji-Kuriyama Y (1986) Location of regulatory elements responsible for drug induction in the rat cytochrome P-450c gene. Proc Natl Acad Sci USA 83: 8044–8046PubMedCrossRefGoogle Scholar
  106. Song B-J, Gelboin HV, Park S-S, Yang CS, Gonzalez FJ (1986) Complementary DNA and protein sequences of ethanol-inducible rat and human P-450s: transcriptional and post-transcriptional regulation of the rat enzyme. J Biol Chem 261: 16689–16697PubMedGoogle Scholar
  107. Song BJ, Matsunaga T, Hardwick JP, Park SS, Veech RL, Yang CS, Gelboin HV, Gonzalez FJ (1987) Stabilization of cytochrome P450j messenger ribonucleic acid in the diabetic rat. Mol Endocrinol 8: 542–547CrossRefGoogle Scholar
  108. Song BJ, Veech RL, Park SS, Gelboin HV, Gonzalez FJ (1989) Induction of rat hepatic N-nitrosodimethylamine demethylase by acetone is due to protein stabilization. J Biol Chem 264: 3568–3572PubMedGoogle Scholar
  109. Suwa Y, Mizukami Y, Sogawa K, Fujii-Kuriyama Y (1985) Gene structure of a major form of phenobarbital-inducible cytochrome P450 in rat liver. J Biol Chem 260: 7980–7984PubMedGoogle Scholar
  110. Thomas DE, Kouri RE, Hutton JJ (1972) The genetics of aryl hydrocarbon hydroxylase induction in mice: a single gene difference between C57BL/6J and DBA/2J. Biochem Genet 6: 157–168PubMedCrossRefGoogle Scholar
  111. Tierney B, Bresnick E (1981) Differences in the binding of 3-methylcholanthrene and phenobarbital to rat liver cytosolic and nuclear protein fractions. Arch Biochem Biophys 210: 729–739PubMedCrossRefGoogle Scholar
  112. Tierney B, Weaver D, Heintz NH, Schaeffer WI, Bresnick E (1980) The identity and nuclear uptake of a cytosolic binding protein for 3-methylcholanthrene. Arch Biochem Biophys 200: 513–523PubMedCrossRefGoogle Scholar
  113. Tu Y, Yang CS (1983) High-affinity nitrosamine dealkylase system in rat liver microsomes and its induction by fasting. Cancer Res 43: 623–629PubMedGoogle Scholar
  114. Tukey RH, Negishi M, Nebert DW (1981) Structural gene product of the Ah complex. Evidence for transcriptional control of cytochrome Pl-450 induction by use of a cloned DNA sequence. J Biol Chem 256: 6969–6974PubMedGoogle Scholar
  115. Waxman DJ, Azaroff L (1992) Phenobarbital induction of cytochrome P450 gene expression. Biochem J (submitted)Google Scholar
  116. Whitlock JP Jr (1987) The regulation of cytochrome P-450 gene expression. Pharmacol Rev 39: 147–161PubMedGoogle Scholar
  117. Whitlock JP Jr (1990) The regulation of cytochrome P-450 gene expression. Annu Rev Pharmacol Toxicol 30: 251–277PubMedCrossRefGoogle Scholar
  118. Wilhelmsson A, Wikstrom A-C, Poellinger L (1986) Polyanionic-binding properties of the receptor for 2,3,7,8-tetrachlorodibenzo-p-dioxin. J Biol Chem 261: 13456–13463PubMedGoogle Scholar
  119. Xu L-C, Bresnick E (1990) Induction of cytochrome P450IA1 in rat hepatoma cells by polycyclic hydrocarbons and a dioxin. Biochem Pharmacol 4: 1399–1403Google Scholar
  120. Yabusaki Y, Shimizu M, Murakami H, Nakamura K, Ceda K, Ohkawa H (1984) Nucleotide sequence of a full-length cDNA coding for 3-methylcholanthrene- and phenobarbital-inducible cytochrome P450 genes in the rat. Nucleic Acids Res 12: 2929–2938PubMedCrossRefGoogle Scholar
  121. Yang CS, Tu YY, Koop DR, Coon MJ (1985) Metabolism of nitrosamines by purified rabbit liver cytochrome P450 isozymes. Cancer Res 45: 11140–1145Google Scholar
  122. Zytkovicz TH (1982) Identification and characterization of a high-affinity saturable binding protein for the carcinogene benzo(a)pyrene. Cancer Res 42: 4387–4393PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1993

Authors and Affiliations

  • E. Bresnick

There are no affiliations available

Personalised recommendations