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Cytochrome P450 in Primary and Permanent Liver Cell Cultures

  • L. R. Schwarz
  • F. J. Wiebel
Chapter
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 105)

Abstract

Liver cell cultures are of great interest in pharmacological and toxicological research (Schwarz and Greim 1981; Guillouzo 1988). They are ideal instruments for analyzing the metabolism of xenobiotics or the regulation of xenobiotic-metabolizing enzymes. The initial high expectations regarding this in vitro system were soon greatly reduced by the finding that hepatocytes, when isolated and kept in culture, rapidly lost cytochrome P450 activities along with other liver-specific functions (Guzelian et al. 1977; Schwarz et al. 1979; Sirica and Pitot 1980). Equally disappointing were the observations that permanent, “immortalized,” cell lines derived from liver possessed none, or only a few, of the properties of adult liver. Considering the potential usefulness of metabolically competent liver cell cultures, intensive efforts were made to establish culture conditions that would help maintaining cytochrome P450 activities in this cell system. Likewise, many attempts were made to find or develop permanent liver cell lines that mimic, at least in some respects, adult hepatocytes. The following reviews the progress which has been made during the last decade. For most of the older reports the reader is referred to earlier reviews (Fry and Bridges 1977; Sirica and Pitot 1980; Schwarz and Greim 1981).

Keywords

Liver Cell Culture Primary Hepatocyte Culture Cytochrome P450 Activity Cytochrome P450 Isozyme Primary Monolayer Culture 
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.

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References

  1. Abe S, Nemoto N, Sasaki M (1983) Sister-chromatid exchange induction by indirect mutagens/carcinogens, aryl hydrocarbon hydroxylase activity and benz[a]pyrene metabolism in cultured human hepatoma cells. Mutat Res 109: 83–90PubMedGoogle Scholar
  2. Aden DP, Fogel A, Plotkin S, Damjanow I, Knowles BB (1979) Controlled synthesis of HBsAg in a differentiated human liver carcinoma-derived cell line. Nature 282: 615–616PubMedGoogle Scholar
  3. Althaus FR, Sinclair JF, Sinclair RR, Meyer UA (1979) Drug-mediated induction of cytochrome(S) P-450 and drug metabolism in cultured hepatocytes maintained in chemically defined medium. J Biol Chem 254: 2148–2153PubMedGoogle Scholar
  4. Bars RG, Mitchell AM, Wolf CR, Elcombe CR (1989) Induction of cytochrome P-450 in cultured rat hepatocytes. The heterogeneous localization of specific isoenzymes using immunocytochemistry. Biochem J 262: 151–158PubMedGoogle Scholar
  5. Begue JM, Guguen-Guillouzo C, Pasdeloup N, Guillouzo A (1984) Prolonged maintenance of active cytochrome P-450 in adult rat hepatocytes co-cultured with another liver cell type. Hepatology 4: 839–842PubMedGoogle Scholar
  6. Bieri F, Meier V, Staubli W, Muakkassah-Kelly SF, Waechter F, Sagelsdorff P, Bentley P (1991) Studies on the mechanism of induction of microsomal cytochrome P-452 and peroxisomal bifunctional enzyme mRNAs by nafenopin in primary cultures of adult rat hepatocytes. Biochem Pharmacol 41: 310–312PubMedGoogle Scholar
  7. Bissell DM, Guzelian PS (1979) Ascorbic acid deficiency and cytochrome P-450 in adult rat hepatocytes in primary monolayer culture. Arch Biochem Biophys 192: 569–576PubMedGoogle Scholar
  8. Bissell DM, Arenson DM, Maher JJ, Roll FJ (1987) Support of cultured hepatocytes by a laminin-rich gel. Evidence for a functionally significant subendothelial matrix in normal rat liver. J Clin Invest 79: 801–812PubMedGoogle Scholar
  9. Burger H-J, Schuetz EG, Schuetz JD, Guzelian PS (1990) Divergent effects of cycloheximide on the induction of class II and class III cytochrome P-450 mRNAs in cultures of adult rat hepatocytes. Arch Biochem Biophys 281: 204–211PubMedGoogle Scholar
  10. Clayton DF, Darnell JE (1983) Changes in liver specific compared to common gene transcription during primary culture of mouse hepatocytes. Mol Cell Biol 3: 1552–1561PubMedGoogle Scholar
  11. Corcos L, Weiss MC (1988) Phenobarbital, dexamethasone and benzanthracene induce several cytochrome P450 mRNAs in rat hepatoma cells. FEBS Lett 233 /1: 37–40PubMedGoogle Scholar
  12. Corcos L, Rechenmann C, Weiss MC, Pompon D (1989) Establishment of mouse and rat hepatoma cell clones showing stable expression of rabbit cytochrome P450 1A2. FEBS Lett 259: 175–180PubMedGoogle Scholar
  13. Corcos L, Rousset J-P, Kiefer F, Wiebel FJ, Weiss M (1990) Genetic analysis of aflatoxin B1 activation in rat hepatoma cells. Mol Gen Genet 222: 291–296PubMedGoogle Scholar
  14. Daujat M, Pichard L, Dalet C, Larroque C, Bonfils C, Pompon D, Li D, Guzelian PS, Maurel P (1987) Expression of five forms of microsomal cytochrome P-450 in primary cultures of rabbit hepatocytes treated with various classes of inducers. Biochem Pharmacol 36: 3597–3606PubMedGoogle Scholar
  15. Daujat M, Clair P, Astier C, Fabre I, Pineau T, Yerle M, Gellin J, Maurel P (1991) Induction, regulation and messenger half-life of cytochromes P450 IA1, IA2 and IIIA6 in primary cultures of rabbit hepatocytes. Eur J Biochem 200: 501–510PubMedGoogle Scholar
  16. Dawson JR, Adams DJ, Wolf CR (1985) Induction of drug metabolizing enzymes in human liver cell line Hep G2. FEBS Lett 183: 219–222PubMedGoogle Scholar
  17. Dearfield KL, Jacobson-Kram D, Brown NA, Williams JR (1983) Evaluation of a human hepatoma cell line as a target cell in genetic toxicology. Mutat Res 108: 437–449PubMedGoogle Scholar
  18. Dearfield KL, Jacobson-Kram D, Huber BE, Williams JR (1986) Induction of sister chromatid exchanges in human and rat hepatoma cell lines by cyclophosphamide and phosphoramide mustard and the effects of cytochrome P-450 inhibitors. Biochem Pharmacol 35: 2199–2205PubMedGoogle Scholar
  19. Decad GM, Hsieh DPH, Byard JL (1977) Maintenance of cytochrome P-450 and metabolism of aflatoxin B, in primary hepatocyte cultures. Biochem Biophys Res Commun 78: 279–287PubMedGoogle Scholar
  20. Dickins M, Peterson RE (1980) Effects of a hormone-supplemented medium on cytochrome P-450 content and mono-oxygenase activities of rat hepatocytes in primary culture. Biochem Pharmacol 29: 1231–1238PubMedGoogle Scholar
  21. Donato MT, Gomez-Lechon M, Castell JV (1990) Drug metabolizing enzymes in rat hepatocytes ω-cultured with cell lines. In Vitro 26: 1057–1062Google Scholar
  22. Donato MT, Castell JV, Gomez-Lechon MJ (1991) Co-cultures of hepatocytes with epithelial-like cell lines: expression of drug-biotransformation activities by hepatocytes. J Cell Biol Toxicol 7: 1–14Google Scholar
  23. Doostdar H, Duthie SJ, Burke MD, Melvin WT, Grant MH (1988) The influence of culture medium composition on drug metabolising enzyme activities of the human liver derived HepG2 cell line. FEBS Lett 241: 15–18PubMedGoogle Scholar
  24. Doostdar H, Demoz A, Burke MD, Melvin WT, Grant MH (1990) Variation in drug-metabolizing enzyme activities during growth of human HepG2 hepatoma cells. Xenobiotica 20: 435–441PubMedGoogle Scholar
  25. Doostdar H, Burke MD, Melvin WT, Grant MH (1991) The effects of dimethylsulphoxide and 5-aminolaevulinic acid on the activities of cytochrome P450-dependent mixed function oxidase and UDP-glucuronosyl transferase activities in human HepG2 hepatoma cells. Biochem Pharmacol 42: 1307–1313PubMedGoogle Scholar
  26. Edwards AM, Glistak ML, Lucas CM, Wilson PA (1984) 7-Ethoxycoumarin deethylase activity as a convenient measure of liver drug metabolizing enzymes: regulation in cultured rat hepatocytes. Biochem Pharmacol 33: 1537–1544Google Scholar
  27. Eliasson E, Johansson I, Ingelman-Sundberg M (1988) Ligand-dependent maintenance of ethanol-inducible cytochrome P-450 in primary rat hepatocyte cell cultures. Biochem Biophys Res Commun 150: 436–443PubMedGoogle Scholar
  28. Eliasson E, Johansson I, Ingelman-Sundberg M (1990) Substrate-, hormone-, and cAMP-regulated cytochrome P-450 degradation. Proc Natl Acad Sci USA 87: 3225–3229PubMedGoogle Scholar
  29. Enat R, Jefferson DM, Ruiz-Opazo N, Gatmaitan Z, Leinwand LA, Reid LM (1984) Hepatocyte proliferation in vitro: its dependence on the use of serum-free hormonally defined medium and substrata of extracellular matrix. Proc Natl Acad Sci USA 81: 1411–1415PubMedGoogle Scholar
  30. Engelmann GL, Richardson AG, Fierer JA (1985) Maintenance and induction of cytochrome P-450 in cultured rat hepatocytes. Arch Biochem Biophys 238: 359–367PubMedGoogle Scholar
  31. Fentem JH, Hammond AH, Fry JR (1991) Maintenance of monooxygenase activities and detection of cytochrome P-450-mediated cytotoxicity in Mongolian gerbil hepatocyte cultures. Xenobiotica 21: 1363–1370PubMedGoogle Scholar
  32. Ferro M, Bassi AM, Marinari UM, Nanni G (1984) Induction of cytochrome(s) P450-dependent drug metabolism in cultured MH1C1 hepatoma cells. Cell Biochem Funct 2: 263–268PubMedGoogle Scholar
  33. Forster U, Luippold G, Schwarz LR (1986) Induction of monooxygenase and UDP- glucuronosyltransferase activities in primary cultures of rat hepatocytes. Drug Metab Dispos 14: 353–360PubMedGoogle Scholar
  34. Franzen B, Haaparanta T, Gustafsson J-A, Toftgard R (1988) TCDD receptor ligands present in extracts of urban air particulate matter induce aryl hydrocarbon hydroxylase activity and cytochrome P-450c gene expression in rat hepatoma cells. Carcinogenesis 9: 11–115Google Scholar
  35. Fraslin J-M, Kneip B, Vaulont S, Glaise D, Munnich A, Guguen-Guillouzo C (1985) Dependence of hepatocyte-specific gene expression on cell-cell interactions in primary culture. EMBO J 4: 2487–2491PubMedGoogle Scholar
  36. Fry JR, Birdges JW (1977) The metabolism of xenobiotics in cell suspension and cell cultures. In: Bridges JW, Chasseaud LF (eds) Progress in drug metabolism, vol 2. Wiley, London, p 71Google Scholar
  37. Grant MH, Melvin MAL, Shaw P, Melvin WT, Burke MD (1985) Studies on the maintenance of cytochromes P-450 and b5, monooxygenases and cytochrome reductases in primary cultures of rat hepatocytes. FEBS Lett 190: 99–103PubMedGoogle Scholar
  38. Grant MH, Burke MD, Hawksworth GM, Duthie SJ, Engeset J, Petrie JC (1987) Human adult hepatocytes in primary monolayer culture. Maintenance of mixed function oxidase and conjugation pathways of drug metabolism. Biochem Pharmacol 36: 2311–2316PubMedGoogle Scholar
  39. Gudas JM, Hankinson O (1987) Regulation of cytochrome P-450c in differentiated and dedifferentiated rat hepatoma cells: role of the AH receptor. Somat Cell Mol Genet 13: 513–528PubMedGoogle Scholar
  40. Guguen-Guillouzo C, Guillouzo A (1983) Modulation of functional activities in cultured rat hepatocytes. Mol Cell Biochem 53 /54: 235–56Google Scholar
  41. Guillouzo A (ed) (1988) Liver cells and drugs. INSERM, Paris; Libbey Eurotext, LondonGoogle Scholar
  42. Guillouzo A, Beaune P, Gascoin MN, Begue JM, Campion JP, Guengerich FP, Guguen-Guillouzo C (1985) Maintenance of cytochrome P-450 in cultured adult human hepatocytes. Biochem Pharmacol 34: 2991–2995PubMedGoogle Scholar
  43. Guillouzo A, Gripon P, Ratanasavanh D, Clement B, Guguen-Guillouzo C (1989) Cultured human hepatocytes as a model system for man in pharmacotoxicological research. In: Dayan AD, Paine A J (eds) Advances in applied toxicology. Taylor and Francis, London, p 165Google Scholar
  44. Guzelian PS, Bissell DM (1976) Effect of cobalt on synthesis of heme and cytochrome P-450 in the liver. J Biol Chem 251: 4421–4427PubMedGoogle Scholar
  45. Guzelian PS, Bissell DM, Meyer UA (1977) Drug metabolism in adult rat hepatocytes in primary monolayer culture. Gastroenterology 72: 1232–1239PubMedGoogle Scholar
  46. Guzelian PS, Li D, Schuetz EG, Thomas P, Levin W, Mode A, Gustafsson JA (1988) Sex changes in cytochrome P-450 phenotype by growth hormone treatment of adult rat hepatocytes maintained in a culture system on matrigel. Proc Natl Acad Sci USA 85: 9783–9787PubMedGoogle Scholar
  47. Hammond AH, Fry JR (1990) The in vivo induction of rat hepatic cytochrome P-450-dependent enzyme activities and their maintenance in culture. Biochem Pharmacol 40: 637–642PubMedGoogle Scholar
  48. Hankinson O (1979) Single-step selection of clones of a mouse hepatoma line deficient in aryl hydrocarbon hydroxylase. Proc Natl Acad Sci USA 76: 373–376PubMedGoogle Scholar
  49. Hirota K, Kawanishi T, Sunouchi M, Ohno Y, Takanaka A, Yamazoe Y, Kato R, Murakoshi Y (1989) Induction of cytochrome P-450c and P-450d by metyrapone in the primary culture of rat hepatocytes. Jpn J Pharmacol 51: 136–139PubMedGoogle Scholar
  50. Hishinuma T, Degawa M, Masuko T, Hashimoto Y (1987) Induction of cytochrome P-488 isozyme(s) in primary cultured rat hepatocytes by drugs which induce different isozymes in vivo. Biochem Biophys Res Commun 148: 947–953PubMedGoogle Scholar
  51. Hohne M, Becker-Rabbenstein V, Kahl GF, Taniguchi H (1990) Regulation of cytochrome P-450 CypIAl gene expression and protooncogene expression by growth factors in primary hepatocytes. FEBS Lett 273: 219–222PubMedGoogle Scholar
  52. Isom HC, Secott T, Georgoff I, Woodworth C, Mummaw J (1985) Maintenance of differentiated rat hepatocytes in primary culture. Proc Natl Acad Sci USA 82: 3252–3256PubMedGoogle Scholar
  53. Isom H, Georgoff I, Salditt-Georgieff M, Darnell JE (1987) Persistence of liver-specific messenger RNA in cultured hepatocytes: different regulatory events for different genes. J Cell Biol 105: 2877–2885PubMedGoogle Scholar
  54. Knowles BB, Howe CC, Aden DP (1980) Human hepatocellular carcinoma cell lines secrete the major plasma proeins and hepatitis B surface antigen. Science 209: 497–499PubMedGoogle Scholar
  55. Kocarek TA, Schuetz EG, Guzelian PS (1990) Differentiated induction of cytochrome P-450b/e and P-450p mRNAs by dose of phenobarbital in primary cultures of adult rat hepatocytes Mol Pharmacol 38: 440–444Google Scholar
  56. Krupski G, Kiefer F, Wiebel FJ (1985) Variability in the expression of xenobiotic-metabolizing enzymes during the growth cycle of rat hepatoma cells. Xenobiotica 15: 781–787PubMedGoogle Scholar
  57. Lake BG, Gray TJB, Stubberfield CR, Beamand JA, Gangolli SD (1983) Induction of lauric acid hydroxylation and maintenance of cytochrome P-450 content by clofribrate in primary cultures of rat hepatocytes. Life Sci 33: 249–254PubMedGoogle Scholar
  58. Lambiotte M, Thierry N (1980) Hydroxylation, sulfation, and conjugation of bile acids in rat hepatoma and hepatocyte cultures under the influence of glucocorticoids. J Biol Chem 255: 11324–11331PubMedGoogle Scholar
  59. Maher JJ (1988) Primary hepatocyte culture: is it home away from home? Hepatology 8: 1162–1166PubMedGoogle Scholar
  60. Martin GR, Kleinman HK (1981) Extracellular matrix proteins give new life to cell cultures. Hepatology 1: 264–266PubMedGoogle Scholar
  61. Maslansky CJ, Williams GM (1982) Primary cultures and the levels of cytochrome P-450 in hepatocytes from mouse, rat, hamster, and rabbit liver. In Vitro 18: 683–693Google Scholar
  62. Mennes WC, van Holsteijn CWM, Timmerman A, Noordhoek J, Blaauboer BJ (1991a) Biotransformation of scoparone used to monitor changes in cytochrome P450 activities in primary hepatocyte cultures derived from rats, hamsters and monkeys. Biochem Pharmacol 41: 1203–1208PubMedGoogle Scholar
  63. Mennes WC, van Holsteijn CWM, Noordhoek J, Blaauboer BJ (1991b) Comparative cytotoxicity of bromobenzene in primary cultures of rat and hamster hepatocytes and its relation to biotransformation. Toxic In Vitro 5: 63–70Google Scholar
  64. Miyazaki M, Handa Y, Oda M, Yabe T, Miyano K, Sato J (1985) Long term survival of functional hepatocytes from adult rat in the presence of phenobarbital in primary culture. Exp Cell Res 159: 176–190PubMedGoogle Scholar
  65. Monteith DK, Ding D, Chem YT, Michalopoulos G, Stroms SC (1990) Induction of cytochrome P1450 RNA and benzo[a]pyrene metabolism in primary human hepatocyte cultures with benzanthracene. Toxicol Appl Pharmacol 105: 460–471PubMedGoogle Scholar
  66. Morel F, Beaune PH, Ratanasavanh D, Flinois JP, Yang CS, Guengerich FP, Guillouzo A (1990) Expression of cytochrome P-450 enzymes in cultured human hepatocytes. Eur J Biochem 191: 437–444PubMedGoogle Scholar
  67. Namiki M, Degawa M, Masuko T, Hashimoto Y (1989) Changes in the quantity and activity of cytochrome P-450 isozymes in primary cultured rat hepatocytes. Jpn J Cancer Res 80: 126–131PubMedGoogle Scholar
  68. Nemoto N, Sakurai J, Tazawa A, Ishikawa T (1991) Regulation of mouse Pi 450 gene expression in monolayer-cultured hepatocytes from responsive and non-responsive strains. Carcinogenesis 12: 623–629PubMedGoogle Scholar
  69. Paine AJ (1990) The maintenance of cytochrome P-450 in rat hepatocyte culture: some applications of liver cell cultures to the study of drug metabolism, toxicity and induction of the P-450 systems. Chem Biol Interact 74: 1–31PubMedGoogle Scholar
  70. Paine AJ, Hockin LJ (1980) Nutrient imbalance causes the loss of cytochrome P-450 in liver cell culture: formulation of culture media which maintain cytochrome P-450 at in vivo concentrations. Biochem Pharmacol 29: 3215–3218PubMedGoogle Scholar
  71. 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
  72. Perrot N, Chesne C, De Waziers J, Conner J, Beaune PH, Guillouzo A (1991) Effects of ethanol and Clofibrate on expression of cytochrome P-450 enzymes and epoxide hydrolase in cultures and cocultures of rat hepatocytes. Eur J Biochem 200: 255–261PubMedGoogle Scholar
  73. Pesonen M, Andersson T (1991) Characterization and induction of xenobiotic metabolizing enzyme activities in a primary culture of rainbow trout hepatocytes. Xenobiotica 21: 461–471PubMedGoogle Scholar
  74. Pichard L, Fabre I, Fabre G, Domergue J, Saint Aubert B, Mourad G, Maurel P (1990) Cyclosporin a drug interactions. Drug Metab Dispos 18: 595–606PubMedGoogle Scholar
  75. Rogiers V, Vandenberghe Y, Callaerts A, Sonck W, Vercruysse A (1990) Effects of dimethylsulphoxide on phase I and II biotransformation in cultured rat hepatocytes. Toxic In Vitro 4: 439–442Google Scholar
  76. Roscher E, Wiebel FJ (1988) Mutagenicity, clastogenicity and cytotoxicity of procarcinogens in a rat hepatoma cell line competent for xenobiotic metabolism. Mutagenesis 3: 269–276PubMedGoogle Scholar
  77. Roscher E, Wiebel FJ (1989) H4IIEC3 rat hepatoma cells activate N-nitrosodimethylamine but are resistant to the genotoxic products. Mutagenesis 4: 292–296PubMedGoogle Scholar
  78. Sassa S, Sugita O, Galbraith RA, Kappas A (1987) Drug metabolism by the human hepatoma cell Hep G2. Biochem Biophys Res Commun 143: 52–57PubMedGoogle Scholar
  79. Schuetz EG, Wrighton SA, Barwick JL, Guzelian PS (1984) Induction of cytochrome P-450 by glucocorticoids in rat liver. J Biol Chem 259: 1999–2006PubMedGoogle Scholar
  80. Schuetz EG, Wrighton SA, Safe SH, Guzelian PS (1986) Regulation of cytochrome P-450p by phenobarbital and phenobarbital-like inducers in adult rat hepatocytes in primary monolayer culture and in vivo. Biochemistry 25: 1124–1133PubMedGoogle Scholar
  81. Schuetz EG, Li D, Omiecinski CJ, Muller-Eberhard U, Kleinman HK, Elswick B, Guzelian PS (1988) Regulation of gene expression in adult rat hepatocytes cultured on a basement membrane matrix. J Cell Physiol 134: 309–323PubMedGoogle Scholar
  82. Schuetz EG, Schuetz JD, May B, Guzelian PS (1990) Regulation of cytochrome P-450b/e and P-450p gene expression by growth hormone in adult rat hepatocytes cultured on a reconstituted basement membrane. J Biol Chem 265: 1188–1192PubMedGoogle Scholar
  83. Schwarz LR, Greim H (1981) Isolated hepatocytes: an analytical tool in hepatotoxicology. In: Berk PD, Chalmers TC (eds) Frontiers in liver disease. Thieme-Stratton, New York, p 61Google Scholar
  84. Schwarz LR, Goetz R, Wolff TH, Wiebel FJ (1979) Monooxygenase and glucuronyltransferase activities in short term cultures of isolated rat hepatocytes. FEBS Lett 98: 203–206PubMedGoogle Scholar
  85. Shean K, Paine AJ (1990) Immunochemical quantification of cytochrome P-450IA and IIB subfamilies in the livers of metyrapone-treated rats. Relevance to the ability of metyrapone to prevent the loss of cytochrome P-450 in rat hepatocyte culture. Biochem J 267: 715–719PubMedGoogle Scholar
  86. Silver G, Reid LM, Krauter KS (1990) Dexamethasone-mediated regulation of 3-methylchloanthrene-induced cytochrome P-450d mRNS accumulation in primary rat hepatocyte cultures. J Biol Chem 265: 3134–3138PubMedGoogle Scholar
  87. Sinclair PR, Bement WJ, Haugen SA, Sinclair JF, Guzelian PS (1990a) Induction of cytochrome P-450 and 5-aminolevulinate synthase activities in cultured rat hepatocytes. Cancer Res 50: 5219–5224PubMedGoogle Scholar
  88. Sinclair PR, Bement WJ, Lambrecht RW, Gorman N, Sinclair JF (1990b) Chlorinated biphenyls induce cytochrome P450 IA2 and uroporphyrin accumulation in cultures of mouse hepatocytes. Arch Biochem Biophys 281: 225–232PubMedGoogle Scholar
  89. Sinclair JF, McCaffrey J, Sinclair PR, Bement WJ, Lambrecht LK, Wood SG, Smith EL, Schenkman JB, Guzelian PS, Park SS, Gelboin HV (1991) Ethanol increases cytochromes P-450IIE, IIB1/2, and IIIA in cultured rat hepatocytes. Arch Biochem Biophys 284: 360–365PubMedGoogle Scholar
  90. Sirica AE, Pitot HC (1980) Drug metabolism and effects of carcinogens in cultured hepatic cells. Pharmacol Rev 31: 205–228Google Scholar
  91. Steward AR, Dannan GA, Guzelian PS, Guengerich FP (1985a) Changes in the concentration of seven forms of cytochrome P-450 in primary cultures of adult rat hepatocytes. Mol Pharmacol 27: 125–132PubMedGoogle Scholar
  92. Steward AR, Wrighton SA, Pasco DS, Fagan JB, Li D, Guzelian PS (1985b) Synthesis and degradation of 3-methylcholanthrene-inducible cytochromes P-450 and their mRNAs in primary monolayer cultures of adult rat hepatocytes. Arch Biochem Biophys 241: 494–508PubMedGoogle Scholar
  93. Suolinna E-M, Pitkaranta T (1986) Effect of culture age on drug metabolizing enzymes and their induction in primary cultures of rat hepatocytes. Biochem Pharmacol 35: 2241–2245PubMedGoogle Scholar
  94. Turner NA, Pitot HC (1989) Dependence of the induction of cytochrome P-450 by phenobarbital in primary cultures of adult rat hepatocytes on the composition of the culture medium. Biochem Pharmacol 38: 2247–2251PubMedGoogle Scholar
  95. Turner NA, Wilson NM, Jefcoate CR, Pitot HC (1988) The expression and metabolic activity of cytochrome P-450 isozymes in control and phenobarbital induced primary cultures of rat hepatocytes. Arch Biochem Biophys 263: 204–215PubMedGoogle Scholar
  96. Vessal M, Choun MO, Bissel MJ, Bissell DM (1980) Fructose utilization and altered cytochrome P-450 in cultured hepatocytes from adult rats. Biochim Biophys Acta 633: 201–210PubMedGoogle Scholar
  97. Waxman DJ, Morrissey JJ, Naik S, Jauregui HO (1990) Phenobarbital induction of cytochromes P-450. Biochem J 271: 113–119PubMedGoogle Scholar
  98. Wiebel FJ, Cikryt P (1990) Dexamethasone-mediated potentiation of P450IA1 induction in H4IIEC3/T hepatoma cells is dependent on a time-consuming process and associated with induction of the Ah receptor. Chem Biol Interact 76: 307–320PubMedGoogle Scholar
  99. Wiebel FJ, Gelboin HV, Coon HG (1972) Regulation of aryl hydrocarbon hydroxylase in intraspecific hybrids of human, mouse and hamster cells. Proc Natl Acad Sei USA 69: 3580–3584Google Scholar
  100. Wiebel FJ, Wolff T, Lambiotte M (1980) Presence of cytochrome P-450- and cytochrome P-448-dependent monooxygenase functions in hepatoma cell lines. Biochem Biophys Res Commun 94: 466–472PubMedGoogle Scholar
  101. Wiebel FJ, Park SS, Kiefer F, Gelboin HV (1984a) Expression of cytochromes P-450 in rat hepatoma cells: analysis by monoclonal antibodies specific for cytochromes P-450 from rat liver by 3-metnylcholanthrene- or phenobarbital. Eur J Biochem 145: 455–462PubMedGoogle Scholar
  102. Wiebel FJ, Kiefer F, Murdia U (1984b) Phenobarbital induces cytochrome P-450- and cytochrome P-448-dependent monooxygenases in rat hepatoma cells. Chem Biol Interact 52: 151–162PubMedGoogle Scholar
  103. Wiebel FJ, Lambiotte M, Singh J, Summer KH, Wolff T (1984c) Expression of carcinogen-metabolizing enzymes in continuous cultures of mammalian cells. In: Greim H, Jung R, Kramer M, Marquardt H, Oesch F (eds) Biochemical basis of chemical carcinogenesis. Raven, New York, pp 77–88Google Scholar
  104. Williams JF, Bement WJ, Sinclair JF, Sinclair PR (1991) Effect of interleukin 6 on phenobarbital induction of cytochrome P-450IIB in cultured rat hepatocytes. Biochem Biophys Res Commun 178: 1049–1055PubMedGoogle Scholar
  105. Wölfel D, Platt KL, Dogra S, Glatt HR, Wächter F, Doehmer J (1991) Stable expression of rat cytochrome P450IA2 cDNA in V79 Chinese hamster cells and hydroxylation of 17 ß-estradiol and 2-aminofluorene. Mol Carcinog 4: 489–498PubMedGoogle Scholar
  106. Wolff T, Guengerich FP (1987) Rat liver cytochrome P-450 isoenzymes as catalyst of aldrin epoxidation in reconstituted monooxygenase systems and microsomes. Pharmacology 36: 2581–2588Google Scholar
  107. Wortelboer HM, de Kruij CA, van Iersel AAJ, Falke HE, Noordhoek J, Blaauboer BJ (1990) The isoenzyme pattern of cytochrome P450 in rat hepatocytes in primary cultures, comaparing different enzyme activities in microsomal incubations and in intact monolayers. Biochem Pharmacol 40: 2525–2534Google Scholar
  108. Wortelboer HM, De Kruif CA, van Iersel AAJ, Falke HE, Noordhoek J, Blaauboer BJ (1991) Comparison of cytochrome P450 isoenzyme profiles in rat liver and hepatocyte cultures. Biochem Pharmacol 42: 381–390PubMedGoogle Scholar
  109. Wu DF, Clejan L, Potter B, Cederbaum AI (1990) Rapid decrease of cytochrome P-450IIE1 in primary hepatocyte culture and its maintenance by added 4- methylpyrazole. Hepatology 12: 1379–1389PubMedGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 1993

Authors and Affiliations

  • L. R. Schwarz
  • F. J. Wiebel

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