Skip to main content
NCBI home page
Environmental Health Perspectives logoLink to Environmental Health Perspectives
. 1998 Apr;106(Suppl 2):511–532. doi: 10.1289/ehp.98106511

Liver cell models in in vitro toxicology.

A Guillouzo 1
PMCID: PMC1533385  PMID: 9599700

Abstract

In vitro liver preparations are increasingly used for the study of hepatotoxicity of chemicals. In recent years their actual advantages and limitations have been better defined. The cell models, slices, and mainly primary hepatocyte cultures, appear to be the most powerful in vitro systems, as liver-specific functions and responsiveness to inducers are retained either for a few days or several weeks depending on culture conditions. Maintenance of phase I and phase II xenobiotic metabolizing enzyme activities allows various chemical investigations to be performed, including determination of kinetic parameters, metabolic profile, interspecies comparison, inhibition and induction effects, and drug-drug interactions. In vitro liver cell models also have various applications in toxicology: screening of cytotoxic and genotoxic compounds, evaluation of chemoprotective agents, and determination of characteristic liver lesions and associated biochemical mechanisms induced by toxic compounds. Extrapolation of the results to the in vivo situation remains a matter of debate. Presently, the most convincing applications of liver cell models are the studies on different aspects of metabolism and mechanisms of toxicity. For the future, there is a need for better culture conditions and differentiated hepatocyte cell lines to overcome the limited availability of human liver tissues. In addition, strategies for in vitro analysis of potentially toxic chemicals must be better defined.

Full text

PDF
511

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abdel-Razzak Z., Loyer P., Fautrel A., Gautier J. C., Corcos L., Turlin B., Beaune P., Guillouzo A. Cytokines down-regulate expression of major cytochrome P-450 enzymes in adult human hepatocytes in primary culture. Mol Pharmacol. 1993 Oct;44(4):707–715. [PubMed] [Google Scholar]
  2. Akrawi M., Rogiers V., Vandenberghe Y., Palmer C. N., Vercruysse A., Shephard E. A., Phillips I. R. Maintenance and induction in co-cultured rat hepatocytes of components of the cytochrome P450-mediated mono-oxygenase. Biochem Pharmacol. 1993 Apr 22;45(8):1583–1591. doi: 10.1016/0006-2952(93)90298-b. [DOI] [PubMed] [Google Scholar]
  3. Ames B. N., Mccann J., Yamasaki E. Methods for detecting carcinogens and mutagens with the Salmonella/mammalian-microsome mutagenicity test. Mutat Res. 1975 Dec;31(6):347–364. doi: 10.1016/0165-1161(75)90046-1. [DOI] [PubMed] [Google Scholar]
  4. Amiel S., Health I., Bennett J., Kelley D., Dickinson C., Miller R. Health promotion in general practice. BMJ. 1991 Mar 2;302(6775):527–527. doi: 10.1136/bmj.302.6775.527. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Anundi I., Lindros K. O. Evidence for cytochrome P450 2E1-mediated toxicity of N-nitrosodimethylamine in cultured perivenous hepatocytes from ethanol treated rats. Pharmacol Toxicol. 1992 Jun;70(6 Pt 1):453–458. doi: 10.1111/j.1600-0773.1992.tb00507.x. [DOI] [PubMed] [Google Scholar]
  6. Baffet G., Clément B., Glaise D., Guillouzo A., Guguen-Guillouzo C. Hydrocortisone modulates the production of extracellular material and albumin in long-term cocultures of adult rat hepatocytes with other liver epithelial cells. Biochem Biophys Res Commun. 1982 Nov 30;109(2):507–512. doi: 10.1016/0006-291x(82)91750-8. [DOI] [PubMed] [Google Scholar]
  7. Bartolone J. B., Birge R. B., Sparks K., Cohen S. D., Khairallah E. A. Immunochemical analysis of acetaminophen covalent binding to proteins. Partial characterization of the major acetaminophen-binding liver proteins. Biochem Pharmacol. 1988 Dec 15;37(24):4763–4774. doi: 10.1016/0006-2952(88)90350-4. [DOI] [PubMed] [Google Scholar]
  8. Bayly A. C., Roberts R. A., Dive C. Suppression of liver cell apoptosis in vitro by the non-genotoxic hepatocarcinogen and peroxisome proliferator nafenopin. J Cell Biol. 1994 Apr;125(1):197–203. doi: 10.1083/jcb.125.1.197. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Beamand J. A., Price R. J., Cunninghame M. E., Lake B. G. Culture of precision-cut liver slices: effect of some peroxisome proliferators. Food Chem Toxicol. 1993 Feb;31(2):137–147. doi: 10.1016/0278-6915(93)90127-k. [DOI] [PubMed] [Google Scholar]
  10. Begue J. M., Guguen-Guillouzo C., Pasdeloup N., Guillouzo A. Prolonged maintenance of active cytochrome P-450 in adult rat hepatocytes co-cultured with another liver cell type. Hepatology. 1984 Sep-Oct;4(5):839–842. doi: 10.1002/hep.1840040507. [DOI] [PubMed] [Google Scholar]
  11. Begue J. M., Le Bigot J. F., Guguen-Guillouzo C., Kiechel J. R., Guillouzo A. Cultured human adult hepatocytes: a new model for drug metabolism studies. Biochem Pharmacol. 1983 May 15;32(10):1643–1646. doi: 10.1016/0006-2952(83)90341-6. [DOI] [PubMed] [Google Scholar]
  12. Belinsky S. A., Matsumura T., Kauffman F. C., Thurman R. G. Rates of allyl alcohol metabolism in periportal and pericentral regions of the liver lobule. Mol Pharmacol. 1984 Jan;25(1):158–164. [PubMed] [Google Scholar]
  13. Berry M. N., Friend D. S. High-yield preparation of isolated rat liver parenchymal cells: a biochemical and fine structural study. J Cell Biol. 1969 Dec;43(3):506–520. doi: 10.1083/jcb.43.3.506. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Berthou F., Ratanasavanh D., Alix D., Carlhant D., Riche C., Guillouzo A. Caffeine and theophylline metabolism in newborn and adult human hepatocytes; comparison with adult rat hepatocytes. Biochem Pharmacol. 1988 Oct 1;37(19):3691–3700. doi: 10.1016/0006-2952(88)90402-9. [DOI] [PubMed] [Google Scholar]
  15. Bieri F., Bentley P., Waechter F., Stäubli W. Use of primary cultures of adult rat hepatocytes to investigate mechanisms of action of nafenopin, a hepatocarcinogenic peroxisome proliferator. Carcinogenesis. 1984 Aug;5(8):1033–1039. doi: 10.1093/carcin/5.8.1033. [DOI] [PubMed] [Google Scholar]
  16. Bissell D. M., Arenson D. M., Maher J. J., Roll F. J. Support of cultured hepatocytes by a laminin-rich gel. Evidence for a functionally significant subendothelial matrix in normal rat liver. J Clin Invest. 1987 Mar;79(3):801–812. doi: 10.1172/JCI112887. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Blaauboer B. J., van Holsteijn C. W., Bleumink R., Mennes W. C., van Pelt F. N., Yap S. H., van Pelt J. F., van Iersel A. A., Timmerman A., Schmid B. P. The effect of beclobric acid and clofibric acid on peroxisomal beta-oxidation and peroxisome proliferation in primary cultures of rat, monkey and human hepatocytes. Biochem Pharmacol. 1990 Aug 1;40(3):521–528. doi: 10.1016/0006-2952(90)90551-u. [DOI] [PubMed] [Google Scholar]
  18. Blanc P., Etienne H., Daujat M., Fabre I., Zindy F., Domergue J., Astre C., Saint Aubert B., Michel H., Maurel P. Mitotic responsiveness of cultured adult human hepatocytes to epidermal growth factor, transforming growth factor alpha, and human serum. Gastroenterology. 1992 Apr;102(4 Pt 1):1340–1350. [PubMed] [Google Scholar]
  19. Block G. D., Locker J., Bowen W. C., Petersen B. E., Katyal S., Strom S. C., Riley T., Howard T. A., Michalopoulos G. K. Population expansion, clonal growth, and specific differentiation patterns in primary cultures of hepatocytes induced by HGF/SF, EGF and TGF alpha in a chemically defined (HGM) medium. J Cell Biol. 1996 Mar;132(6):1133–1149. doi: 10.1083/jcb.132.6.1133. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Boobis A. R., Fawthrop D. J., Davies D. S. Mechanisms of cell death. Trends Pharmacol Sci. 1989 Jul;10(7):275–280. doi: 10.1016/0165-6147(89)90027-8. [DOI] [PubMed] [Google Scholar]
  21. Boobis A. R., Tee L. B., Hampden C. E., Davies D. S. Freshly isolated hepatocytes as a model for studying the toxicity of paracetamol. Food Chem Toxicol. 1986 Jun-Jul;24(6-7):731–736. doi: 10.1016/0278-6915(86)90172-9. [DOI] [PubMed] [Google Scholar]
  22. Bourdi M., Gautier J. C., Mircheva J., Larrey D., Guillouzo A., Andre C., Belloc C., Beaune P. H. Anti-liver microsomes autoantibodies and dihydralazine-induced hepatitis: specificity of autoantibodies and inductive capacity of the drug. Mol Pharmacol. 1992 Aug;42(2):280–285. [PubMed] [Google Scholar]
  23. Boyer J. L. Isolated hepatocyte couplets and bile duct units--novel preparations for the in vitro study of bile secretory function. Cell Biol Toxicol. 1997 Jul;13(4-5):289–300. doi: 10.1023/a:1007435408208. [DOI] [PubMed] [Google Scholar]
  24. Butterworth B. E., Smith-Oliver T., Earle L., Loury D. J., White R. D., Doolittle D. J., Working P. K., Cattley R. C., Jirtle R., Michalopoulos G. Use of primary cultures of human hepatocytes in toxicology studies. Cancer Res. 1989 Mar 1;49(5):1075–1084. [PubMed] [Google Scholar]
  25. Bégué J. M., Baffet G., Campion J. P., Guillouzo A. Differential response of primary cultures of human and rat hepatocytes to aflatoxin B1-induced cytotoxicity and protection by the hepatoprotective agent (+)-cyanidanol-3. Biol Cell. 1988;63(3):327–333. doi: 10.1111/j.1768-322x.1988.tb00756.x. [DOI] [PubMed] [Google Scholar]
  26. Campion J. P., Porchet N., Aubert J. P., L'Helgoualc'h A., Clément B. UW-preservation of cultured human gallbladder epithelial cells: phenotypic alterations and differential mucin gene expression in the presence of bile. Hepatology. 1995 Jan;21(1):223–231. [PubMed] [Google Scholar]
  27. Caron J. M. Induction of albumin gene transcription in hepatocytes by extracellular matrix proteins. Mol Cell Biol. 1990 Mar;10(3):1239–1243. doi: 10.1128/mcb.10.3.1239. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Chenery R. J., Ayrton A., Oldham H. G., Standring P., Norman S. J., Seddon T., Kirby R. Diazepam metabolism in cultured hepatocytes from rat, rabbit, dog, guinea pig, and man. Drug Metab Dispos. 1987 May-Jun;15(3):312–317. [PubMed] [Google Scholar]
  29. Chenery R., George M., Krishna G. The effect of ionophore A23187 and calcium on carbon tetrachloride-induced toxicity in cultured rat hepatocytes. Toxicol Appl Pharmacol. 1981 Sep 15;60(2):241–252. doi: 10.1016/0041-008x(91)90228-7. [DOI] [PubMed] [Google Scholar]
  30. Chesné C., Guillouzo A. Cryopreservation of isolated rat hepatocytes: a critical evaluation of freezing and thawing conditions. Cryobiology. 1988 Aug;25(4):323–330. doi: 10.1016/0011-2240(88)90040-5. [DOI] [PubMed] [Google Scholar]
  31. Chesné C., Guyomard C., Fautrel A., Poullain M. G., Frémond B., De Jong H., Guillouzo A. Viability and function in primary culture of adult hepatocytes from various animal species and human beings after cryopreservation. Hepatology. 1993 Aug;18(2):406–414. doi: 10.1002/hep.1840180227. [DOI] [PubMed] [Google Scholar]
  32. Clayton D. F., Darnell J. E., Jr Changes in liver-specific compared to common gene transcription during primary culture of mouse hepatocytes. Mol Cell Biol. 1983 Sep;3(9):1552–1561. doi: 10.1128/mcb.3.9.1552. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Clement B., Guguen-Guillouzo C., Campion J. P., Glaise D., Bourel M., Guillouzo A. Long-term co-cultures of adult human hepatocytes with rat liver epithelial cells: modulation of albumin secretion and accumulation of extracellular material. Hepatology. 1984 May-Jun;4(3):373–380. doi: 10.1002/hep.1840040305. [DOI] [PubMed] [Google Scholar]
  34. Conner J., Vallet-Collom I., Daveau M., Delers F., Hiron M., Lebreton J. P., Guillouzo A. Acute-phase-response induction in rat hepatocytes co-cultured with rat liver epithelial cells. Biochem J. 1990 Mar 15;266(3):683–688. doi: 10.1042/bj2660683. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Conway J. G., Popp J. A., Ji S., Thurman R. G. Effect of size on portal circulation of hepatic nodules from carcinogen-treated rats. Cancer Res. 1983 Jul;43(7):3374–3378. [PubMed] [Google Scholar]
  36. Corlu A., Ilyin G. P., Gérard N., Kneip B., Rissel M., Jégou B., Guguen-Guillouzo C. Tissue distribution of liver regulating protein. Evidence for a cell recognition signal common to liver, pancreas, gonads, and hemopoietic tissues. Am J Pathol. 1994 Sep;145(3):715–727. [PMC free article] [PubMed] [Google Scholar]
  37. Corlu A., Kneip B., Lhadi C., Leray G., Glaise D., Baffet G., Bourel D., Guguen-Guillouzo C. A plasma membrane protein is involved in cell contact-mediated regulation of tissue-specific genes in adult hepatocytes. J Cell Biol. 1991 Oct;115(2):505–515. doi: 10.1083/jcb.115.2.505. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Dahlin D. C., Miwa G. T., Lu A. Y., Nelson S. D. N-acetyl-p-benzoquinone imine: a cytochrome P-450-mediated oxidation product of acetaminophen. Proc Natl Acad Sci U S A. 1984 Mar;81(5):1327–1331. doi: 10.1073/pnas.81.5.1327. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Daujat M., Pichard L., Dalet C., Larroque C., Bonfils C., Pompon D., Li D., Guzelian P. S., Maurel P. Expression of five forms of microsomal cytochrome P-450 in primary cultures of rabbit hepatocytes treated with various classes of inducers. Biochem Pharmacol. 1987 Nov 1;36(21):3597–3606. doi: 10.1016/0006-2952(87)90008-6. [DOI] [PubMed] [Google Scholar]
  40. Deboyser D., Goethals F., Krack G., Roberfroid M. Investigation into the mechanism of tetracycline-induced steatosis: study in isolated hepatocytes. Toxicol Appl Pharmacol. 1989 Mar 1;97(3):473–479. doi: 10.1016/0041-008x(89)90252-4. [DOI] [PubMed] [Google Scholar]
  41. Decad G. M., Hsieh D. P., Byard J. L. Maintenance of cytochrome P-450 and metabolism of aflatoxin B1 in primary hepatocyte cultures. Biochem Biophys Res Commun. 1977 Sep 9;78(1):279–287. doi: 10.1016/0006-291x(77)91251-7. [DOI] [PubMed] [Google Scholar]
  42. Diaz D., Fabre I., Daujat M., Saint Aubert B., Bories P., Michel H., Maurel P. Omeprazole is an aryl hydrocarbon-like inducer of human hepatic cytochrome P450. Gastroenterology. 1990 Sep;99(3):737–747. doi: 10.1016/0016-5085(90)90963-2. [DOI] [PubMed] [Google Scholar]
  43. Dirami G., Papadopoulos V., Kleinman H. K., Defreese D. C., Musto N. A., Dym M. Identification of transferrin and inhibin-like proteins in matrigel. In Vitro Cell Dev Biol Anim. 1995 Jun;31(6):404–411. doi: 10.1007/BF02634247. [DOI] [PubMed] [Google Scholar]
  44. Donato M. T., Castell J. V., Gómez-Lechón M. J. Co-cultures of hepatocytes with epithelial-like cell lines: expression of drug-biotransformation activities by hepatocytes. Cell Biol Toxicol. 1991 Jan;7(1):1–14. doi: 10.1007/BF00121326. [DOI] [PubMed] [Google Scholar]
  45. Dou M., de Sousa G., Lacarelle B., Placidi M., Lechene de la Porte P., Domingo M., Lafont H., Rahmani R. Thawed human hepatocytes in primary culture. Cryobiology. 1992 Aug;29(4):454–469. doi: 10.1016/0011-2240(92)90048-7. [DOI] [PubMed] [Google Scholar]
  46. Dunn J. C., Yarmush M. L., Koebe H. G., Tompkins R. G. Hepatocyte function and extracellular matrix geometry: long-term culture in a sandwich configuration. FASEB J. 1989 Feb;3(2):174–177. doi: 10.1096/fasebj.3.2.2914628. [DOI] [PubMed] [Google Scholar]
  47. Eckl P. M., Strom S. C., Michalopoulos G., Jirtle R. L. Induction of sister chromatid exchanges in cultured adult rat hepatocytes by directly and indirectly acting mutagens/carcinogens. Carcinogenesis. 1987 Aug;8(8):1077–1083. doi: 10.1093/carcin/8.8.1077. [DOI] [PubMed] [Google Scholar]
  48. Eckl P. M., Whitcomb W. R., Michalopoulos G., Jirtle R. L. Effects of EGF and calcium on adult parenchymal hepatocyte proliferation. J Cell Physiol. 1987 Aug;132(2):363–366. doi: 10.1002/jcp.1041320225. [DOI] [PubMed] [Google Scholar]
  49. Ekwall B., Acosta D. In vitro comparative toxicity of selected drugs and chemicals in HeLa cells, Chang liver cells, and rat hepatocytes. Drug Chem Toxicol. 1982;5(3):219–231. doi: 10.3109/01480548209041054. [DOI] [PubMed] [Google Scholar]
  50. Eliasson E., Kenna J. G. Cytochrome P450 2E1 is a cell surface autoantigen in halothane hepatitis. Mol Pharmacol. 1996 Sep;50(3):573–582. [PubMed] [Google Scholar]
  51. Elshourbagy N. A., Barwick J. L., Guzelian P. S. Induction of cytochrome P-450 by pregnenolone-16 alpha-carbonitrile in primary monolayer cultures of adult rat hepatocytes and in a cell-free translation system. J Biol Chem. 1981 Jun 25;256(12):6060–6068. [PubMed] [Google Scholar]
  52. Enat R., Jefferson D. M., Ruiz-Opazo N., Gatmaitan Z., Leinwand L. A., Reid L. M. Hepatocyte proliferation in vitro: its dependence on the use of serum-free hormonally defined medium and substrata of extracellular matrix. Proc Natl Acad Sci U S A. 1984 Mar;81(5):1411–1415. doi: 10.1073/pnas.81.5.1411. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Etienne P. L., Baffet G., Desvergne B., Boisnard-Rissel M., Glaise D., Guguen-Guillouzo C. Transient expression of c-fos and constant expression of c-myc in freshly isolated and cultured normal adult rat hepatocytes. Oncogene Res. 1988;3(3):255–262. [PubMed] [Google Scholar]
  54. Fabre G., Rahmani R., Placidi M., Combalbert J., Covo J., Cano J. P., Coulange C., Ducros M., Rampal M. Characterization of midazolam metabolism using human hepatic microsomal fractions and hepatocytes in suspension obtained by perfusing whole human livers. Biochem Pharmacol. 1988 Nov 15;37(22):4389–4397. doi: 10.1016/0006-2952(88)90622-3. [DOI] [PubMed] [Google Scholar]
  55. Fahl W. E., Michalopoulos G., Sattler G. L., Jefcoate C. R., Pitot H. C. Characteristcs of microsomal enzyme controls in primary cultures of rat hepatocytes. Arch Biochem Biophys. 1979 Jan;192(1):61–72. doi: 10.1016/0003-9861(79)90071-7. [DOI] [PubMed] [Google Scholar]
  56. Fardel O., Morel F., Guillouzo A. P-glycoprotein expression in human, mouse, hamster and rat hepatocytes in primary culture. Carcinogenesis. 1993 Apr;14(4):781–783. doi: 10.1093/carcin/14.4.781. [DOI] [PubMed] [Google Scholar]
  57. Fardel O., Ratanasavanh D., Loyer P., Ketterer B., Guillouzo A. Overexpression of the multidrug resistance gene product in adult rat hepatocytes during primary culture. Eur J Biochem. 1992 Apr 15;205(2):847–852. doi: 10.1111/j.1432-1033.1992.tb16849.x. [DOI] [PubMed] [Google Scholar]
  58. Fautrel A., Joly B., Guyomard C., Guillouzo A. Long-term maintenance of drug-metabolizing enzyme activities in rat hepatocytes after cryopreservation. Toxicol Appl Pharmacol. 1997 Nov;147(1):110–114. doi: 10.1006/taap.1997.8253. [DOI] [PubMed] [Google Scholar]
  59. Fellous R., Coulaud D., el Abed I., Roques B. P., Le Pecq J. B., Delain E., Gouyette A. Cytoplasmic accumulation of ditercalinium in rat hepatocytes and induction of mitochondrial damage. Cancer Res. 1988 Nov 15;48(22):6542–6549. [PubMed] [Google Scholar]
  60. Foliot A., Glaise D., Erlinger S., Guguen-Guillouzo C. Long-term maintenance of taurocholate uptake by adult rat hepatocytes co-cultured with a liver epithelial cell line. Hepatology. 1985 Mar-Apr;5(2):215–219. doi: 10.1002/hep.1840050210. [DOI] [PubMed] [Google Scholar]
  61. Forster U., Luippold G., Schwarz L. R. Induction of monooxygenase and UDP-glucuronosyltransferase activities in primary cultures of rat hepatocytes. Drug Metab Dispos. 1986 May-Jun;14(3):353–360. [PubMed] [Google Scholar]
  62. Fraslin J. M., Kneip B., Vaulont S., Glaise D., Munnich A., Guguen-Guillouzo C. Dependence of hepatocyte-specific gene expression on cell-cell interactions in primary culture. EMBO J. 1985 Oct;4(10):2487–2491. doi: 10.1002/j.1460-2075.1985.tb03960.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Fremond B., Malandain C., Guyomard C., Chesne C., Guillouzo A., Campion J. P. Correction of bilirubin conjugation in the Gunn rat using hepatocytes immobilized in alginate gel beads as an extracorporeal bioartificial liver. Cell Transplant. 1993 Nov-Dec;2(6):453–460. doi: 10.1177/096368979300200603. [DOI] [PubMed] [Google Scholar]
  64. Gautam A., Ng O. C., Boyer J. L. Isolated rat hepatocyte couplets in short-term culture: structural characteristics and plasma membrane reorganization. Hepatology. 1987 Mar-Apr;7(2):216–223. doi: 10.1002/hep.1840070203. [DOI] [PubMed] [Google Scholar]
  65. Gebhardt R., Wegner H., Alber J. Perifusion of co-cultured hepatocytes: optimization of studies on drug metabolism and cytotoxicity in vitro. Cell Biol Toxicol. 1996 Apr;12(2):57–68. doi: 10.1007/BF00143356. [DOI] [PubMed] [Google Scholar]
  66. Gee S. J., Green C. E., Tyson C. A. Comparative metabolism of tolbutamide by isolated hepatocytes from rat, rabbit, dog, and squirrel monkey. Drug Metab Dispos. 1984 Mar-Apr;12(2):174–178. [PubMed] [Google Scholar]
  67. Gillette J. R. A perspective on the role of chemically reactive metabolites of foreign compounds in toxicity. II. Alterations in the kinetics of covalent binding. Biochem Pharmacol. 1974 Nov 1;23(21):2927–2938. doi: 10.1016/0006-2952(74)90267-6. [DOI] [PubMed] [Google Scholar]
  68. Gleiberman A. S., Kudrjavtseva E. I., Sharovskaya YuYu, Abelev G. I. Synthesis of alpha-fetoprotein in hepatocytes is co-ordinately regulated with cell-cell and cell-matrix interactions. Mol Biol Med. 1989 Apr;6(2):95–107. [PubMed] [Google Scholar]
  69. Glende E. A., Jr, Lee P. Y. Isopropanol and chlordecone potentiation of carbon tetrachloride liver injury: retention of potentiating action in hepatocyte suspensions prepared from rats given isopropanol or chlordecone. Exp Mol Pathol. 1985 Apr;42(2):167–174. doi: 10.1016/0014-4800(85)90025-5. [DOI] [PubMed] [Google Scholar]
  70. Goethals F., Krack G., Deboyser D., Vossen P., Roberfroid M. Critical biochemical functions of isolated hepatocytes as sensitive indicators of chemical toxicity. Fundam Appl Toxicol. 1984 Jun;4(3 Pt 1):441–450. doi: 10.1016/0272-0590(84)90201-x. [DOI] [PubMed] [Google Scholar]
  71. Goulet F., Normand C., Morin O. Cellular interactions promote tissue-specific function, biomatrix deposition and junctional communication of primary cultured hepatocytes. Hepatology. 1988 Sep-Oct;8(5):1010–1018. doi: 10.1002/hep.1840080506. [DOI] [PubMed] [Google Scholar]
  72. Grant M. H., Burke M. D., Hawksworth G. M., Duthie S. J., Engeset J., Petrie J. C. Human adult hepatocytes in primary monolayer culture. Maintenance of mixed function oxidase and conjugation pathways of drug metabolism. Biochem Pharmacol. 1987 Jul 15;36(14):2311–2316. doi: 10.1016/0006-2952(87)90596-x. [DOI] [PubMed] [Google Scholar]
  73. Gray T. J., Lake B. G., Beamand J. A., Foster J. R., Gangolli S. D. Peroxisome proliferation in primary cultures of rat hepatocytes. Toxicol Appl Pharmacol. 1983 Jan;67(1):15–25. doi: 10.1016/0041-008x(83)90240-5. [DOI] [PubMed] [Google Scholar]
  74. Green C. E., Dabbs J. E., Tyson C. A. Metabolism and cytotoxicity of acetaminophen in hepatocytes isolated from resistant and susceptible species. Toxicol Appl Pharmacol. 1984 Oct;76(1):139–149. doi: 10.1016/0041-008x(84)90037-1. [DOI] [PubMed] [Google Scholar]
  75. Green C. E., LeValley S. E., Tyson C. A. Comparison of amphetamine metabolism using isolated hepatocytes from five species including human. J Pharmacol Exp Ther. 1986 Jun;237(3):931–936. [PubMed] [Google Scholar]
  76. Guengerich F. P., Gillam E. M., Shimada T. New applications of bacterial systems to problems in toxicology. Crit Rev Toxicol. 1996 Sep;26(5):551–583. doi: 10.3109/10408449609037477. [DOI] [PubMed] [Google Scholar]
  77. Guguen-Guillouzo C., Clement B., Lescoat G., Glaise D., Guillouzo A. Modulation of human fetal hepatocyte survival and differentiation by interactions with a rat liver epithelial cell line. Dev Biol. 1984 Sep;105(1):211–220. doi: 10.1016/0012-1606(84)90276-8. [DOI] [PubMed] [Google Scholar]
  78. Guguen-Guillouzo C., Clément B., Baffet G., Beaumont C., Morel-Chany E., Glaise D., Guillouzo A. Maintenance and reversibility of active albumin secretion by adult rat hepatocytes co-cultured with another liver epithelial cell type. Exp Cell Res. 1983 Jan;143(1):47–54. doi: 10.1016/0014-4827(83)90107-6. [DOI] [PubMed] [Google Scholar]
  79. Guguen-Guillouzo C., Guillouzo A. Modulation of functional activities in cultured rat hepatocytes. Mol Cell Biochem. 1983;53-54(1-2):35–56. doi: 10.1007/BF00225245. [DOI] [PubMed] [Google Scholar]
  80. Guguen C., Guillouzo A., Boisnard M., Le Cam A., Bourel M. Etude ultrastructurale de monocouches d'hépatocytes de rat adulte cultivés en présence d'hémisuccinate d'hydrocortisone. Biol Gastroenterol (Paris) 1975 Jul-Aug;8(3):223–231. [PubMed] [Google Scholar]
  81. Guigoz Y., Werffeli P., Favre D., Juillerat M., Wellinger R., Honegger P. Aggregate cultures of foetal rat liver cells: development and maintenance of liver gene expression. Biol Cell. 1987;60(3):163–171. doi: 10.1111/j.1768-322x.1987.tb00555.x. [DOI] [PubMed] [Google Scholar]
  82. Guillouzo A., Beaune P., Gascoin M. N., Begue J. M., Campion J. P., Guengerich F. P., Guguen-Guillouzo C. Maintenance of cytochrome P-450 in cultured adult human hepatocytes. Biochem Pharmacol. 1985 Aug 15;34(16):2991–2995. doi: 10.1016/0006-2952(85)90027-9. [DOI] [PubMed] [Google Scholar]
  83. Guillouzo A., Bégué J. M., Maurer G., Koch P. Identification of metabolic pathways of pindolol and fluperlapine in adult human hepatocyte cultures. Xenobiotica. 1988 Feb;18(2):131–139. doi: 10.3109/00498258809041649. [DOI] [PubMed] [Google Scholar]
  84. Guillouzo A., Delers F., Clement B., Bernard N., Engler R. Long term production of acute-phase proteins by adult rat hepatocytes co-cultured with another liver cell type in serum-free medium. Biochem Biophys Res Commun. 1984 Apr 30;120(2):311–317. doi: 10.1016/0006-291x(84)91255-5. [DOI] [PubMed] [Google Scholar]
  85. Guyomard C., Chesne C., Meunier B., Fautrel A., Clerc C., Morel F., Rissel M., Campion J. P., Guillouzo A. Primary culture of adult rat hepatocytes after 48-hour preservation of the liver with cold UW solution. Hepatology. 1990 Dec;12(6):1329–1336. doi: 10.1002/hep.1840120613. [DOI] [PubMed] [Google Scholar]
  86. Guyomard C., Rialland L., Fremond B., Chesne C., Guillouzo A. Influence of alginate gel entrapment and cryopreservation on survival and xenobiotic metabolism capacity of rat hepatocytes. Toxicol Appl Pharmacol. 1996 Dec;141(2):349–356. doi: 10.1006/taap.1996.0299. [DOI] [PubMed] [Google Scholar]
  87. Guzelian P. S., Bissell D. M., Meyer U. A. Drug metabolism in adult rat hepatocytes in primary monolayer culture. Gastroenterology. 1977 Jun;72(6):1232–1239. [PubMed] [Google Scholar]
  88. Harman A. W., Mahar S. O., Burcham P. C., Madsen B. W. Level of cytosolic free calcium during acetaminophen toxicity in mouse hepatocytes. Mol Pharmacol. 1992 Apr;41(4):665–670. [PubMed] [Google Scholar]
  89. Hensgens H. E., Meijer A. J. The interrelationship between ureogenesis and protein synthesis in isolated rat-liver cells. Biochim Biophys Acta. 1979 Feb 1;582(3):525–532. doi: 10.1016/0304-4165(79)90143-0. [DOI] [PubMed] [Google Scholar]
  90. Hikino H., Kiso Y., Taguchi H., Ikeya Y. Antihepatotoxic actions of lignoids from Schizandra chinensis fruits. Planta Med. 1984 Jun;50(3):213–218. doi: 10.1055/s-2007-969681. [DOI] [PubMed] [Google Scholar]
  91. Hoerl B. J., Vroman B. T., Kasperbauer J. L., LaRusso N. F., Scott R. E. Biological characteristics of primary cultures of human gallbladder epithelial cells. Lab Invest. 1992 Feb;66(2):243–250. [PubMed] [Google Scholar]
  92. Houssin D., Capron M., Celier C., Cresteil T., Demaugre F., Beaune P. Evaluation of isolated human hepatocytes. Life Sci. 1983 Oct 31;33(18):1805–1809. doi: 10.1016/0024-3205(83)90688-4. [DOI] [PubMed] [Google Scholar]
  93. Howard R. B., Christensen A. K., Gibbs F. A., Pesch L. A. The enzymatic preparation of isolated intact parenchymal cells from rat liver. J Cell Biol. 1967 Dec;35(3):675–684. doi: 10.1083/jcb.35.3.675. [DOI] [PMC free article] [PubMed] [Google Scholar]
  94. Ilyin G. P., Rissel M., Malledant Y., Tanguy M., Guillouzo A. Human hepatocytes express trifluoroacetylated neoantigens after in vitro exposure to halothane. Biochem Pharmacol. 1994 Aug 3;48(3):561–567. doi: 10.1016/0006-2952(94)90286-0. [DOI] [PubMed] [Google Scholar]
  95. Inoue C., Yamamoto H., Nakamura T., Ichihara A., Okamoto H. Nicotinamide prolongs survival of primary cultured hepatocytes without involving loss of hepatocyte-specific functions. J Biol Chem. 1989 Mar 25;264(9):4747–4750. [PubMed] [Google Scholar]
  96. Ismail T., Howl J., Wheatley M., McMaster P., Neuberger J. M., Strain A. J. Growth of normal human hepatocytes in primary culture: effect of hormones and growth factors on DNA synthesis. Hepatology. 1991 Dec;14(6):1076–1082. [PubMed] [Google Scholar]
  97. Isom H. C., Secott T., Georgoff I., Woodworth C., Mummaw J. Maintenance of differentiated rat hepatocytes in primary culture. Proc Natl Acad Sci U S A. 1985 May;82(10):3252–3256. doi: 10.1073/pnas.82.10.3252. [DOI] [PMC free article] [PubMed] [Google Scholar]
  98. Jego P., Hubert N., Morel I., Pasdeloup N., Ocaktan A., Abdallah M., Brissot P., Lescoat G. Inhibition of iron overload toxicity in rat hepatocyte cultures by pyoverdin Pf, the siderophore of Pseudomonas fluorescens. Biochem Pharmacol. 1992 Mar 17;43(6):1275–1280. doi: 10.1016/0006-2952(92)90503-b. [DOI] [PubMed] [Google Scholar]
  99. Jernigan J. D., Pounds J. G., Harbison R. D. Potentiation of chlorinated hydrocarbon toxicity by 2,5-hexanedione in primary cultures of adult rat hepatocytes. Fundam Appl Toxicol. 1983 Jan-Feb;3(1):22–26. doi: 10.1016/s0272-0590(83)80168-7. [DOI] [PubMed] [Google Scholar]
  100. Johansson S., Hök M. Substrate adhesion of rat hepatocytes: on the mechanism of attachment to fibronectin. J Cell Biol. 1984 Mar;98(3):810–817. doi: 10.1083/jcb.98.3.810. [DOI] [PMC free article] [PubMed] [Google Scholar]
  101. Joplin R., Strain A. J., Neuberger J. M. Immuno-isolation and culture of biliary epithelial cells from normal human liver. In Vitro Cell Dev Biol. 1989 Dec;25(12):1189–1192. doi: 10.1007/BF02621273. [DOI] [PubMed] [Google Scholar]
  102. Jung W., Gebhardt R., Robenek H. Primary culture of rat hepatocytes as a model system of canalicular development, biliary secretion, and intrahepatic cholestasis. V. Disturbance of the cellular membrane and bile canalicular ultrastructure induced by chlorpromazine. Virchows Arch B Cell Pathol Incl Mol Pathol. 1985;49(4):349–363. doi: 10.1007/BF02912112. [DOI] [PubMed] [Google Scholar]
  103. Kitani K., Kanai S. Tauroursodeoxycholate prevents taurocholate induced cholestasis. Life Sci. 1982 Feb 7;30(6):515–523. doi: 10.1016/0024-3205(82)90264-8. [DOI] [PubMed] [Google Scholar]
  104. Knook D. L., Blansjaar N., Sleyster E. C. Isolation and characterization of Kupffer and endothelial cells from the rat liver. Exp Cell Res. 1977 Oct 15;109(2):317–329. doi: 10.1016/0014-4827(77)90011-8. [DOI] [PubMed] [Google Scholar]
  105. Kocarek T. A., Schuetz E. G., Guzelian P. S. Expression of multiple forms of cytochrome P450 mRNAs in primary cultures of rat hepatocytes maintained on matrigel. Mol Pharmacol. 1993 Mar;43(3):328–334. [PubMed] [Google Scholar]
  106. Koebe H. G., Pahernik S., Eyer P., Schildberg F. W. Collagen gel immobilization: a useful cell culture technique for long-term metabolic studies on human hepatocytes. Xenobiotica. 1994 Feb;24(2):95–107. doi: 10.3109/00498259409043224. [DOI] [PubMed] [Google Scholar]
  107. Koide N., Sakaguchi K., Koide Y., Asano K., Kawaguchi M., Matsushima H., Takenami T., Shinji T., Mori M., Tsuji T. Formation of multicellular spheroids composed of adult rat hepatocytes in dishes with positively charged surfaces and under other nonadherent environments. Exp Cell Res. 1990 Feb;186(2):227–235. doi: 10.1016/0014-4827(90)90300-y. [DOI] [PubMed] [Google Scholar]
  108. Lacarelle B., Marre F., Durand A., Davi H., Rahmani R. Metabolism of minaprine in human and animal hepatocytes and liver microsomes--prediction of metabolism in vivo. Xenobiotica. 1991 Mar;21(3):317–329. doi: 10.3109/00498259109039472. [DOI] [PubMed] [Google Scholar]
  109. Laishes B. A., Williams G. M. Conditions affecting primary cell cultures of functional adult rat hepatocytes. 1. The effect of insulin. In Vitro. 1976 Jul;12(7):521–532. doi: 10.1007/BF02796495. [DOI] [PubMed] [Google Scholar]
  110. Lake B. G., Gray T. J., Stubberfield C. R., Beamand J. A., Gangolli S. D. Induction of lauric acid hydroxylation and maintenance of cytochrome P-450 content by clofibrate in primary cultures of rat hepatocytes. Life Sci. 1983 Jul 18;33(3):249–254. doi: 10.1016/0024-3205(83)90383-1. [DOI] [PubMed] [Google Scholar]
  111. Landry J., Bernier D., Ouellet C., Goyette R., Marceau N. Spheroidal aggregate culture of rat liver cells: histotypic reorganization, biomatrix deposition, and maintenance of functional activities. J Cell Biol. 1985 Sep;101(3):914–923. doi: 10.1083/jcb.101.3.914. [DOI] [PMC free article] [PubMed] [Google Scholar]
  112. Langouët S., Coles B., Morel F., Becquemont L., Beaune P., Guengerich F. P., Ketterer B., Guillouzo A. Inhibition of CYP1A2 and CYP3A4 by oltipraz results in reduction of aflatoxin B1 metabolism in human hepatocytes in primary culture. Cancer Res. 1995 Dec 1;55(23):5574–5579. [PubMed] [Google Scholar]
  113. Langouët S., Morel F., Meyer D. J., Fardel O., Corcos L., Ketterer B., Guillouzo A. A comparison of the effect of inducers on the expression of glutathione-S-transferases in the liver of the intact rat and in hepatocytes in primary culture. Hepatology. 1996 Apr;23(4):881–887. doi: 10.1002/hep.510230432. [DOI] [PubMed] [Google Scholar]
  114. Larrey D., Funck-Brentano C., Breil P., Vitaux J., Theodore C., Babany G., Pessayre D. Effects of erythromycin on hepatic drug-metabolizing enzymes in humans. Biochem Pharmacol. 1983 Mar 15;32(6):1063–1068. doi: 10.1016/0006-2952(83)90626-3. [DOI] [PubMed] [Google Scholar]
  115. Lavoie L., Tremblay A., Mirault M. E. Distinct oxidoresistance phenotype of human T47D cells transfected by rat glutathione S-transferase Yc expression vectors. J Biol Chem. 1992 Feb 25;267(6):3632–3636. [PubMed] [Google Scholar]
  116. Le Bigot J. F., Begue J. M., Kiechel J. R., Guillouzo A. Species differences in metabolism of ketotifen in rat, rabbit and man: demonstration of similar pathways in vivo and in cultured hepatocytes. Life Sci. 1987 Mar 2;40(9):883–890. doi: 10.1016/0024-3205(87)90037-3. [DOI] [PubMed] [Google Scholar]
  117. Le Bot M. A., Bégué J. M., Kernaleguen D., Robert J., Ratanasavanh D., Airiau J., Riché C., Guillouzo A. Different cytotoxicity and metabolism of doxorubicin, daunorubicin, epirubicin, esorubicin and idarubicin in cultured human and rat hepatocytes. Biochem Pharmacol. 1988 Oct 15;37(20):3877–3887. doi: 10.1016/0006-2952(88)90069-x. [DOI] [PubMed] [Google Scholar]
  118. Le Corre P., Ratanasavanh D., Chevanne F., Gibassier D., Sado P., Le Verge R., Guillouzo A. In vitro assessment of stereoselective hepatic metabolism of disopyramide in humans: comparison with in vivo data. Chirality. 1991;3(5):405–411. doi: 10.1002/chir.530030505. [DOI] [PubMed] [Google Scholar]
  119. Le Rumeur E., Guguen-Guillouzo C., Beaumont C., Saunier A., Guillouzo A. Albumin secretion and protein synthesis by cultured diploid and tetraploid rat hepatocytes separated by elutriation. Exp Cell Res. 1983 Aug;147(1):247–254. doi: 10.1016/0014-4827(83)90293-8. [DOI] [PubMed] [Google Scholar]
  120. Lebreton J. P., Daveau M., Hiron M., Fontaine M., Biou D., Gilbert D., Guguen-Guillouzo C. Long-term biosynthesis of complement component C3 and alpha-1 acid glycoprotein by adult rat hepatocytes in a co-culture system with an epithelial liver cell-type. Biochem J. 1986 Apr 15;235(2):421–427. doi: 10.1042/bj2350421. [DOI] [PMC free article] [PubMed] [Google Scholar]
  121. Lee J., Morgan J. R., Tompkins R. G., Yarmush M. L. Proline-mediated enhancement of hepatocyte function in a collagen gel sandwich culture configuration. FASEB J. 1993 Apr 1;7(6):586–591. doi: 10.1096/fasebj.7.6.8472895. [DOI] [PubMed] [Google Scholar]
  122. Lerche C., Fautrel A., Shaw P. M., Glaise D., Ballet F., Guillouzo A., Corcos L. Regulation of the major detoxication functions by phenobarbital and 3-methylcholanthrene in co-cultures of rat hepatocytes and liver epithelial cells. Eur J Biochem. 1997 Feb 15;244(1):98–106. doi: 10.1111/j.1432-1033.1997.00098.x. [DOI] [PubMed] [Google Scholar]
  123. Lerche C., Le Jossic C., Fautrel A., de Waziers I., Ballet F., Guillouzo A., Corcos L. Rat liver epithelial cells express functional cytochrome P450 2E1. Carcinogenesis. 1996 May;17(5):1101–1106. doi: 10.1093/carcin/17.5.1101. [DOI] [PubMed] [Google Scholar]
  124. Li A. P., Myers C. A., Roque M. A., Kaminski D. L. Epidermal growth factor, DNA synthesis and human hepatocytes. In Vitro Cell Dev Biol. 1991 Nov;27A(11):831–833. doi: 10.1007/BF02630982. [DOI] [PubMed] [Google Scholar]
  125. Liu L., LeCluyse E. L., Liu J., Klaassen C. D. Sulfotransferase gene expression in primary cultures of rat hepatocytes. Biochem Pharmacol. 1996 Nov 22;52(10):1621–1630. doi: 10.1016/s0006-2952(96)00569-2. [DOI] [PubMed] [Google Scholar]
  126. Long R. M., Moore L. Biochemical evaluation of rat hepatocyte primary cultures as a model for carbon tetrachloride hepatotoxicity: comparative studies in vivo and in vitro. Toxicol Appl Pharmacol. 1988 Feb;92(2):295–306. doi: 10.1016/0041-008x(88)90389-4. [DOI] [PubMed] [Google Scholar]
  127. Loretz L. J., Li A. P., Flye M. W., Wilson A. G. Optimization of cryopreservation procedures for rat and human hepatocytes. Xenobiotica. 1989 May;19(5):489–498. doi: 10.3109/00498258909042288. [DOI] [PubMed] [Google Scholar]
  128. Loyer P., Cariou S., Glaise D., Bilodeau M., Baffet G., Guguen-Guillouzo C. Growth factor dependence of progression through G1 and S phases of adult rat hepatocytes in vitro. Evidence of a mitogen restriction point in mid-late G1. J Biol Chem. 1996 May 10;271(19):11484–11492. doi: 10.1074/jbc.271.19.11484. [DOI] [PubMed] [Google Scholar]
  129. Mahéo K., Morel F., Langouët S., Kramer H., Le Ferrec E., Ketterer B., Guillouzo A. Inhibition of cytochromes P-450 and induction of glutathione S-transferases by sulforaphane in primary human and rat hepatocytes. Cancer Res. 1997 Sep 1;57(17):3649–3652. [PubMed] [Google Scholar]
  130. Mallédant Y., Siproudhis L., Tanguy M., Clerc C., Chesné C., Saint-Marc C., Guillouzo A. Effects of halothane on human and rat hepatocyte cultures. Anesthesiology. 1990 Mar;72(3):526–534. doi: 10.1097/00000542-199003000-00022. [DOI] [PubMed] [Google Scholar]
  131. Martelli A., Robbiano L., Ghia M., Giuliano L., Angelini G., Brambilla G. A study of the potential genotoxicity of cimetidine using human hepatocyte primary cultures: discrepancy from results obtained in rat hepatocytes. Cancer Lett. 1986 Jan;30(1):11–16. doi: 10.1016/0304-3835(86)90126-6. [DOI] [PubMed] [Google Scholar]
  132. Maslansky C. J., Williams G. M. Primary cultures and the levels of cytochrome P450 in hepatocytes from mouse, rat, hamster, and rabbit liver. In Vitro. 1982 Aug;18(8):683–693. doi: 10.1007/BF02796423. [DOI] [PubMed] [Google Scholar]
  133. McQueen C. A., Miller M. J., Williams G. M. Sex differences in the biotransformation of 2-acetylaminofluorene in cultured rat hepatocytes. Cell Biol Toxicol. 1986 Jun;2(2):271–281. doi: 10.1007/BF00122695. [DOI] [PubMed] [Google Scholar]
  134. Mendoza-Figueroa T., Hernandez A., De Lourdes Lopez M., Kuri-Harcuch W. Intracytoplasmic triglyceride accumulation produced by dexamethasone in adult rat hepatocytes cultivated on 3T3 cells. Toxicology. 1988 Nov 30;52(3):273–286. doi: 10.1016/0300-483x(88)90132-1. [DOI] [PubMed] [Google Scholar]
  135. Meredith M. J. Rat hepatocytes prepared without collagenase: prolonged retention of differentiated characteristics in culture. Cell Biol Toxicol. 1988 Dec;4(4):405–425. doi: 10.1007/BF00117769. [DOI] [PubMed] [Google Scholar]
  136. Mesnil M., Fraslin J. M., Piccoli C., Yamasaki H., Guguen-Guillouzo C. Cell contact but not junctional communication (dye coupling) with biliary epithelial cells is required for hepatocytes to maintain differentiated functions. Exp Cell Res. 1987 Dec;173(2):524–533. doi: 10.1016/0014-4827(87)90292-8. [DOI] [PubMed] [Google Scholar]
  137. Michalopoulos G., Pitot H. C. Primary culture of parenchymal liver cells on collagen membranes. Morphological and biochemical observations. Exp Cell Res. 1975 Aug;94(1):70–78. doi: 10.1016/0014-4827(75)90532-7. [DOI] [PubMed] [Google Scholar]
  138. Michalopoulos G., Russell F., Biles C. Primary cultures of hepatocytes on human fibroblasts. In Vitro. 1979 Oct;15(10):796–806. doi: 10.1007/BF02618306. [DOI] [PubMed] [Google Scholar]
  139. Mitaka T., Sattler C. A., Sattler G. L., Sargent L. M., Pitot H. C. Multiple cell cycles occur in rat hepatocytes cultured in the presence of nicotinamide and epidermal growth factor. Hepatology. 1991 Jan;13(1):21–30. [PubMed] [Google Scholar]
  140. Miyazaki M., Handa Y., Oda M., Yabe T., Miyano K., Sato J. Long-term survival of functional hepatocytes from adult rat in the presence of phenobarbital in primary culture. Exp Cell Res. 1985 Jul;159(1):176–190. doi: 10.1016/s0014-4827(85)80047-1. [DOI] [PubMed] [Google Scholar]
  141. Moffatt P., Marion M., Denizeau F. Cadmium-2-acetylaminofluorene interaction in isolated rat hepatocytes. Cell Biol Toxicol. 1992 Oct-Dec;8(4):277–290. doi: 10.1007/BF00156736. [DOI] [PubMed] [Google Scholar]
  142. Moore C. J., Gould M. N. Metabolism of benzo[a]pyrene by cultured human hepatocytes from multiple donors. Carcinogenesis. 1984 Dec;5(12):1577–1582. doi: 10.1093/carcin/5.12.1577. [DOI] [PubMed] [Google Scholar]
  143. Morel F., Beaune P. H., Ratanasavanh D., Flinois J. P., Yang C. S., Guengerich F. P., Guillouzo A. Expression of cytochrome P-450 enzymes in cultured human hepatocytes. Eur J Biochem. 1990 Jul 31;191(2):437–444. doi: 10.1111/j.1432-1033.1990.tb19140.x. [DOI] [PubMed] [Google Scholar]
  144. Morel F., Fardel O., Meyer D. J., Langouet S., Gilmore K. S., Meunier B., Tu C. P., Kensler T. W., Ketterer B., Guillouzo A. Preferential increase of glutathione S-transferase class alpha transcripts in cultured human hepatocytes by phenobarbital, 3-methylcholanthrene, and dithiolethiones. Cancer Res. 1993 Jan 15;53(2):231–234. [PubMed] [Google Scholar]
  145. Morel I., Lescoat G., Cillard J., Pasdeloup N., Brissot P., Cillard P. Kinetic evaluation of free malondialdehyde and enzyme leakage as indices of iron damage in rat hepatocyte cultures. Involvement of free radicals. Biochem Pharmacol. 1990 Jun 1;39(11):1647–1655. doi: 10.1016/0006-2952(90)90107-v. [DOI] [PubMed] [Google Scholar]
  146. Morel I., Sergent O., Cogrel P., Lescoat G., Pasdeloup N., Brissot P., Cillard P., Cillard J. EPR study of antioxidant activity of the iron chelators pyoverdin and hydroxypyrid-4-one in iron-loaded hepatocyte culture: comparison with that of desferrioxamine. Free Radic Biol Med. 1995 Feb;18(2):303–310. doi: 10.1016/0891-5849(94)e0144-8. [DOI] [PubMed] [Google Scholar]
  147. Morin O., Normand C. Long-term maintenance of hepatocyte functional activity in co-culture: requirements for sinusoidal endothelial cells and dexamethasone. J Cell Physiol. 1986 Oct;129(1):103–110. doi: 10.1002/jcp.1041290115. [DOI] [PubMed] [Google Scholar]
  148. Nakamura T., Teramoto H., Tomita Y., Ichihara A. L-proline is an essential amino acid for hepatocyte growth in culture. Biochem Biophys Res Commun. 1984 Aug 16;122(3):884–891. doi: 10.1016/0006-291x(84)91173-2. [DOI] [PubMed] [Google Scholar]
  149. Namiki M., Degawa M., Masuko T., Hashimoto Y. Changes in the quantity and activity of cytochrome P-450 isozymes in primary cultured rat hepatocytes. Jpn J Cancer Res. 1989 Feb;80(2):126–131. doi: 10.1111/j.1349-7006.1989.tb02279.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  150. Newman S., Guzelian P. S. Stimulation of de novo synthesis of cytochrome P-450 by phenobarbital in primary nonproliferating cultures of adult rat hepatocytes. Proc Natl Acad Sci U S A. 1982 May;79(9):2922–2926. doi: 10.1073/pnas.79.9.2922. [DOI] [PMC free article] [PubMed] [Google Scholar]
  151. Niemann C., Gauthier J. C., Richert L., Ivanov M. A., Melcion C., Cordier A. Rat adult hepatocytes in primary pure and mixed monolayer culture. Comparison of the maintenance of mixed function oxidase and conjugation pathways of drug metabolism. Biochem Pharmacol. 1991 Jul 5;42(2):373–379. doi: 10.1016/0006-2952(91)90725-k. [DOI] [PubMed] [Google Scholar]
  152. Oldham H. G., Standring P., Norman S. J., Blake T. J., Beattie I., Cox P. J., Chenery R. J. Metabolism of temelastine (SK&F 93944) in hepatocytes from rat, dog, cynomolgus monkey and man. Drug Metab Dispos. 1990 Mar-Apr;18(2):146–152. [PubMed] [Google Scholar]
  153. Padgham C. R., Paine A. J. Altered expression of cytochrome P-450 mRNAs, and potentially of other transcripts encoding key hepatic functions, are triggered during the isolation of rat hepatocytes. Biochem J. 1993 Feb 1;289(Pt 3):621–624. doi: 10.1042/bj2890621. [DOI] [PMC free article] [PubMed] [Google Scholar]
  154. Paine A. J., Hockin L. J. The maintenance of cytochrome P-450 in liver cell culture: recent studies on P-450 mediated mechanisms of toxicity. Toxicology. 1982;25(1):41–45. doi: 10.1016/0300-483x(82)90083-x. [DOI] [PubMed] [Google Scholar]
  155. Paine A. J., Maurer G., von Wartburg B. R. The application of hepatocyte culture to the identification of pathways of drug metabolism: studies with pindolol and fluperlapine. Biochem Pharmacol. 1984 Oct 1;33(19):3111–3114. doi: 10.1016/0006-2952(84)90620-8. [DOI] [PubMed] [Google Scholar]
  156. Paine A. J. The maintenance of cytochrome P-450 in rat hepatocyte culture: some applications of liver cell cultures to the study of drug metabolism, toxicity and the induction of the P-450 system. Chem Biol Interact. 1990;74(1-2):1–31. doi: 10.1016/0009-2797(90)90055-r. [DOI] [PubMed] [Google Scholar]
  157. Paul D., Höhne M., Pinkert C., Piasecki A., Ummelmann E., Brinster R. L. Immortalized differentiated hepatocyte lines derived from transgenic mice harboring SV40 T-antigen genes. Exp Cell Res. 1988 Apr;175(2):354–362. doi: 10.1016/0014-4827(88)90199-1. [DOI] [PubMed] [Google Scholar]
  158. Perrot N., Chesné C., De Waziers I., Conner J., Beaune P. H., Guillouzo A. 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. 1991 Aug 15;200(1):255–261. doi: 10.1111/j.1432-1033.1991.tb21074.x. [DOI] [PubMed] [Google Scholar]
  159. Pfeifer A. M., Cole K. E., Smoot D. T., Weston A., Groopman J. D., Shields P. G., Vignaud J. M., Juillerat M., Lipsky M. M., Trump B. F. Simian virus 40 large tumor antigen-immortalized normal human liver epithelial cells express hepatocyte characteristics and metabolize chemical carcinogens. Proc Natl Acad Sci U S A. 1993 Jun 1;90(11):5123–5127. doi: 10.1073/pnas.90.11.5123. [DOI] [PMC free article] [PubMed] [Google Scholar]
  160. Pichard L., Fabre I., Fabre G., Domergue J., Saint Aubert B., Mourad G., Maurel P. Cyclosporin A drug interactions. Screening for inducers and inhibitors of cytochrome P-450 (cyclosporin A oxidase) in primary cultures of human hepatocytes and in liver microsomes. Drug Metab Dispos. 1990 Sep-Oct;18(5):595–606. [PubMed] [Google Scholar]
  161. Pichard L., Fabre I., Fabre G., Domergue J., Saint Aubert B., Mourad G., Maurel P. Cyclosporin A drug interactions. Screening for inducers and inhibitors of cytochrome P-450 (cyclosporin A oxidase) in primary cultures of human hepatocytes and in liver microsomes. Drug Metab Dispos. 1990 Sep-Oct;18(5):595–606. [PubMed] [Google Scholar]
  162. Pohl L. R., Kenna J. G., Satoh H., Christ D., Martin J. L. Neoantigens associated with halothane hepatitis. Drug Metab Rev. 1989;20(2-4):203–217. doi: 10.3109/03602538909103537. [DOI] [PubMed] [Google Scholar]
  163. Poli G., Chiarpotto E., Albano E., Cottalasso D., Nanni G., Marinari U. M., Bassi A. M., Dianzani M. U. Carbon tetrachloride-induced inhibition of hepatocyte lipoprotein secretion: functional impairment of Golgi apparatus in the early phases of such injury. Life Sci. 1985 Feb 11;36(6):533–539. doi: 10.1016/0024-3205(85)90634-4. [DOI] [PubMed] [Google Scholar]
  164. Porter J. B., Gyparaki M., Burke L. C., Huehns E. R., Sarpong P., Saez V., Hider R. C. Iron mobilization from hepatocyte monolayer cultures by chelators: the importance of membrane permeability and the iron-binding constant. Blood. 1988 Nov;72(5):1497–1503. [PubMed] [Google Scholar]
  165. Poullain M. G., Fautrel A., Guyomard C., Chesne C., Grislain L., Guillouzo A. Viability and primary culture of rat hepatocytes after hypothermic preservation: the superiority of the Leibovitz medium over the University of Wisconsin solution for cold storage. Hepatology. 1992 Jan;15(1):97–106. doi: 10.1002/hep.1840150118. [DOI] [PubMed] [Google Scholar]
  166. Powis G., Santone K. S., Melder D. C., Thomas L., Moore D. J., Wilke T. J. Cryopreservation of rat and dog hepatocytes for studies of xenobiotic metabolism and activation. Drug Metab Dispos. 1987 Nov-Dec;15(6):826–832. [PubMed] [Google Scholar]
  167. Quistorff B., Grunnet N., Cornell N. W. Digitonin perfusion of rat liver. A new approach in the study of intra-acinar and intracellular compartmentation in the liver. Biochem J. 1985 Feb 15;226(1):289–297. doi: 10.1042/bj2260289. [DOI] [PMC free article] [PubMed] [Google Scholar]
  168. Rahmani R., Richard B., Fabre G., Cano J. P. Extrapolation of preclinical pharmacokinetic data to therapeutic drug use. Xenobiotica. 1988 Jan;18 (Suppl 1):71–88. [PubMed] [Google Scholar]
  169. Ratanasavanh D., Baffet G., Latinier M. F., Rissel M., Guillouzo A. Use of hepatocyte co-cultures in the assessment of drug toxicity from chronic exposure. Xenobiotica. 1988 Jun;18(6):765–771. doi: 10.3109/00498258809041715. [DOI] [PubMed] [Google Scholar]
  170. Ratanasavanh D., Berthou F., Dreano Y., Mondine P., Guillouzo A., Riche C. Methylcholanthrene but not phenobarbital enhances caffeine and theophylline metabolism in cultured adult human hepatocytes. Biochem Pharmacol. 1990 Jan 1;39(1):85–94. doi: 10.1016/0006-2952(90)90651-z. [DOI] [PubMed] [Google Scholar]
  171. Reddy J. K., Lalwai N. D. Carcinogenesis by hepatic peroxisome proliferators: evaluation of the risk of hypolipidemic drugs and industrial plasticizers to humans. Crit Rev Toxicol. 1983;12(1):1–58. doi: 10.3109/10408448309029317. [DOI] [PubMed] [Google Scholar]
  172. Rogiers V., Vandenberghe Y., Callaerts A., Verleye G., Cornet M., Mertens K., Sonck W., Vercruysse A. Phase I and phase II xenobiotic biotransformation in cultures and co-cultures of adult rat hepatocytes. Biochem Pharmacol. 1990 Oct 15;40(8):1701–1706. doi: 10.1016/0006-2952(90)90345-l. [DOI] [PubMed] [Google Scholar]
  173. Rojkind M., Gatmaitan Z., Mackensen S., Giambrone M. A., Ponce P., Reid L. M. Connective tissue biomatrix: its isolation and utilization for long-term cultures of normal rat hepatocytes. J Cell Biol. 1980 Oct;87(1):255–263. doi: 10.1083/jcb.87.1.255. [DOI] [PMC free article] [PubMed] [Google Scholar]
  174. Rubin K., Oldberg A., Hök M., Obrink B. Adhesion of rat hepatocytes to collagen. Exp Cell Res. 1978 Nov;117(1):165–177. doi: 10.1016/0014-4827(78)90439-1. [DOI] [PubMed] [Google Scholar]
  175. Ruch R. J., Klaunig J. E., Schultz N. E., Askari A. B., Lacher D. A., Pereira M. A., Goldblatt P. J. Mechanisms of chloroform and carbon tetrachloride toxicity in primary cultured mouse hepatocytes. Environ Health Perspect. 1986 Nov;69:301–305. doi: 10.1289/ehp.8669301. [DOI] [PMC free article] [PubMed] [Google Scholar]
  176. Saad B., Schawalder H., Maier P. Crude liver membrane fractions as substrate preserve liver-specific functions in long-term, serum-free rat hepatocyte cultures. In Vitro Cell Dev Biol. 1993 Jan;29A(1):32–40. doi: 10.1007/BF02634369. [DOI] [PubMed] [Google Scholar]
  177. Saad B., Scholl F. A., Thomas H., Schawalder H., Streit V., Waechter F., Maier P. Crude liver membrane fractions and extracellular matrix components as substrata regulate differentially the preservation and inducibility of cytochrome P-450 isoenzymes in cultured rat hepatocytes. Eur J Biochem. 1993 Apr 15;213(2):805–814. doi: 10.1111/j.1432-1033.1993.tb17823.x. [DOI] [PubMed] [Google Scholar]
  178. Sakaida I., Thomas A. P., Farber J. L. Increases in cytosolic calcium ion concentration can be dissociated from the killing of cultured hepatocytes by tert-butyl hydroperoxide. J Biol Chem. 1991 Jan 15;266(2):717–722. [PubMed] [Google Scholar]
  179. Sandker G. W., Slooff M. J., Groothuis G. M. Drug transport, viability and morphology of isolated rat hepatocytes preserved for 24 hours in University of Wisconsin solution. Biochem Pharmacol. 1992 Apr 1;43(7):1479–1485. doi: 10.1016/0006-2952(92)90205-w. [DOI] [PubMed] [Google Scholar]
  180. Sawada N., Tomomura A., Sattler C. A., Sattler G. L., Kleinman H. K., Pitot H. C. Extracellular matrix components influence DNA synthesis of rat hepatocytes in primary culture. Exp Cell Res. 1986 Dec;167(2):458–470. doi: 10.1016/0014-4827(86)90186-2. [DOI] [PubMed] [Google Scholar]
  181. Schanne F. A., Kane A. B., Young E. E., Farber J. L. Calcium dependence of toxic cell death: a final common pathway. Science. 1979 Nov 9;206(4419):700–702. doi: 10.1126/science.386513. [DOI] [PubMed] [Google Scholar]
  182. Schieble T. M., Costa A. K., Heffel D. F., Trudell J. R. Comparative toxicity of halothane, isoflurane, hypoxia, and phenobarbital induction in monolayer cultures of rat hepatocytes. Anesthesiology. 1988 Apr;68(4):485–494. doi: 10.1097/00000542-198804000-00003. [DOI] [PubMed] [Google Scholar]
  183. Schrode W., Mecke D., Gebhardt R. Induction of glutamine synthetase in periportal hepatocytes by cocultivation with a liver epithelial cell line. Eur J Cell Biol. 1990 Oct;53(1):35–41. [PubMed] [Google Scholar]
  184. Schuetz E. G., Li D., Omiecinski C. J., Muller-Eberhard U., Kleinman H. K., Elswick B., Guzelian P. S. Regulation of gene expression in adult rat hepatocytes cultured on a basement membrane matrix. J Cell Physiol. 1988 Mar;134(3):309–323. doi: 10.1002/jcp.1041340302. [DOI] [PubMed] [Google Scholar]
  185. Seglen P. O. Preparation of isolated rat liver cells. Methods Cell Biol. 1976;13:29–83. doi: 10.1016/s0091-679x(08)61797-5. [DOI] [PubMed] [Google Scholar]
  186. Seglen P. O. Protein-catabolic stage of isolated rat hepatocytes. Biochim Biophys Acta. 1977 Jan 24;496(1):182–191. doi: 10.1016/0304-4165(77)90126-x. [DOI] [PubMed] [Google Scholar]
  187. Sergent O., Morel I., Cogrel P., Chevanne M., Pasdeloup N., Brissot P., Lescoat G., Cillard P., Cillard J. Simultaneous measurements of conjugated dienes and free malondialdehyde, used as a micromethod for the evaluation of lipid peroxidation in rat hepatocyte cultures. Chem Phys Lipids. 1993 Jun;65(2):133–139. doi: 10.1016/0009-3084(93)90046-6. [DOI] [PubMed] [Google Scholar]
  188. Sharma B. K., Bacon B. R., Britton R. S., Park C. H., Magiera C. J., O'Neill R., Dalton N., Smanik P., Speroff T. Prevention of hepatocyte injury and lipid peroxidation by iron chelators and alpha-tocopherol in isolated iron-loaded rat hepatocytes. Hepatology. 1990 Jul;12(1):31–39. doi: 10.1002/hep.1840120107. [DOI] [PubMed] [Google Scholar]
  189. Sirica A. E., Pitot H. C. Drug metabolism and effects of carcinogens in cultured hepatic cells. Pharmacol Rev. 1979 Sep;31(3):205–228. [PubMed] [Google Scholar]
  190. Smith M. T., Thor H., Orrenius S. Toxic injury to isolated hepatocytes is not dependent on extracellular calcium. Science. 1981 Sep 11;213(4513):1257–1259. doi: 10.1126/science.7268433. [DOI] [PubMed] [Google Scholar]
  191. Smith P. F., Krack G., McKee R. L., Johnson D. G., Gandolfi A. J., Hruby V. J., Krumdieck C. L., Brendel K. Maintenance of adult rat liver slices in dynamic organ culture. In Vitro Cell Dev Biol. 1986 Dec;22(12):706–712. doi: 10.1007/BF02621087. [DOI] [PubMed] [Google Scholar]
  192. Somani P., Bandyopadhyay S., Klaunig J. E., Gross S. A. Amiodarone- and desethylamiodarone-induced myelinoid inclusion bodies and toxicity in cultured rat hepatocytes. Hepatology. 1990 Jan;11(1):81–92. doi: 10.1002/hep.1840110115. [DOI] [PubMed] [Google Scholar]
  193. Sorrentino D., Van Ness K., Ribeiro I., Miller C. M. Functional and morphological features of isolated hepatocytes preserved in University of Wisconsin solution. Hepatology. 1991 Aug;14(2):331–339. [PubMed] [Google Scholar]
  194. Spray D. C., Fujita M., Saez J. C., Choi H., Watanabe T., Hertzberg E., Rosenberg L. C., Reid L. M. Proteoglycans and glycosaminoglycans induce gap junction synthesis and function in primary liver cultures. J Cell Biol. 1987 Jul;105(1):541–551. doi: 10.1083/jcb.105.1.541. [DOI] [PMC free article] [PubMed] [Google Scholar]
  195. Stacey N. H., Kappus H. Comparison of methods of assessment of metal-induced lipid peroxidation in isolated rat hepatocytes. J Toxicol Environ Health. 1982 Feb;9(2):277–285. doi: 10.1080/15287398209530161. [DOI] [PubMed] [Google Scholar]
  196. Stacey N. H., Klaassen C. D. Comparison of the effects of metals on cellular injury and lipid peroxidation in isolated rat hepatocytes. J Toxicol Environ Health. 1981 Jan;7(1):139–147. doi: 10.1080/15287398109529965. [DOI] [PubMed] [Google Scholar]
  197. Stacey N. H., Klaassen C. D. Interaction of metal ions with cadmium-induced cellular toxicity. J Toxicol Environ Health. 1981 Jan;7(1):149–158. doi: 10.1080/15287398109529966. [DOI] [PubMed] [Google Scholar]
  198. Stacey N. H., Klaassen C. D. Lack of protection against chemically induced injury to isolated hepatocytes by omission of calcium from the incubation medium. J Toxicol Environ Health. 1982 Feb;9(2):267–276. doi: 10.1080/15287398209530160. [DOI] [PubMed] [Google Scholar]
  199. Stacey N. H., Ottenwälder H., Kappus H. CCl4-induced lipid peroxidation in isolated rat hepatocytes with different oxygen concentrations. Toxicol Appl Pharmacol. 1982 Mar 15;62(3):421–427. doi: 10.1016/0041-008x(82)90143-0. [DOI] [PubMed] [Google Scholar]
  200. Steward A. R., Dannan G. A., Guzelian P. S., Guengerich F. P. Changes in the concentration of seven forms of cytochrome P-450 in primary cultures of adult rat hepatocytes. Mol Pharmacol. 1985 Jan;27(1):125–132. [PubMed] [Google Scholar]
  201. Story D. L., Gee S. J., Tyson C. A., Gould D. H. Response of isolated hepatocytes to organic and inorganic cytotoxins. J Toxicol Environ Health. 1983 Apr-Jun;11(4-6):483–501. doi: 10.1080/15287398309530362. [DOI] [PubMed] [Google Scholar]
  202. Strom S. C., Jirtle R. L., Michalopoulos G. Genotoxic effects of 2-acetylaminofluorene on rat and human hepatocytes. Environ Health Perspect. 1983 Mar;49:165–170. doi: 10.1289/ehp.8349165. [DOI] [PMC free article] [PubMed] [Google Scholar]
  203. Strom S. C., Novicki D. L., Novotny A., Jirtle R. L., Michalopoulos G. Human hepatocyte-mediated mutagenesis and DNA repair activity. Carcinogenesis. 1983;4(6):683–686. doi: 10.1093/carcin/4.6.683. [DOI] [PubMed] [Google Scholar]
  204. Thibault N., Ballet F. Effect of bile acids on intracellular calcium in isolated rat hepatocyte couplets. Biochem Pharmacol. 1993 Jan 26;45(2):289–293. doi: 10.1016/0006-2952(93)90063-3. [DOI] [PubMed] [Google Scholar]
  205. Thibault N. Scanning laser cytometry: alterations induced by cholestatic agents in isolated rat hepatocyte couplets. Cell Biol Toxicol. 1994 Dec;10(5-6):323–328. doi: 10.1007/BF00755778. [DOI] [PubMed] [Google Scholar]
  206. Thomas J. A., Park E. M. Oxy radical-initiated protein S-thiolation and enzymic dethiolation. Basic Life Sci. 1988;49:365–368. doi: 10.1007/978-1-4684-5568-7_56. [DOI] [PubMed] [Google Scholar]
  207. Tolman K. G., Peterson P., Gray P., Hammar S. P. Hepatotoxicity of salicylates in monolayer cell cultures. Gastroenterology. 1978 Feb;74(2 Pt 1):205–208. [PubMed] [Google Scholar]
  208. Tomita Y., Yuasa C., Ni R., Ishimura K., Ichihara A. Long-term maintenance of functional rat hepatocytes in primary culture by additions of pyruvate and various hormones. Biochim Biophys Acta. 1995 Apr 13;1243(3):329–335. doi: 10.1016/0304-4165(94)00155-q. [DOI] [PubMed] [Google Scholar]
  209. Tong J. Z., De Lagausie P., Furlan V., Cresteil T., Bernard O., Alvarez F. Long-term culture of adult rat hepatocyte spheroids. Exp Cell Res. 1992 Jun;200(2):326–332. doi: 10.1016/0014-4827(92)90179-c. [DOI] [PubMed] [Google Scholar]
  210. Tyson C. A., Hawk-Prather K., Story D. L., Gould D. H. Correlations of in vitro and in vivo hepatotoxicity for five haloalkanes. Toxicol Appl Pharmacol. 1983 Sep 15;70(2):289–302. doi: 10.1016/0041-008x(83)90105-9. [DOI] [PubMed] [Google Scholar]
  211. Tyson C. A., Mitoma C., Kalivoda J. Evaluation of hepatocytes isolated by a nonperfusion technique in a prescreen for cytotoxicity. J Toxicol Environ Health. 1980 Jan;6(1):197–205. doi: 10.1080/15287398009529842. [DOI] [PubMed] [Google Scholar]
  212. Utesch D., Diener B., Molitor E., Oesch F., Platt K. L. Characterization of cryopreserved rat liver parenchymal cells by metabolism of diagnostic substrates and activities of related enzymes. Biochem Pharmacol. 1992 Jul 22;44(2):309–315. doi: 10.1016/0006-2952(92)90014-a. [DOI] [PubMed] [Google Scholar]
  213. Utesch D., Molitor E., Platt K. L., Oesch F. Differential stabilization of cytochrome P-450 isoenzymes in primary cultures of adult rat liver parenchymal cells. In Vitro Cell Dev Biol. 1991 Nov;27A(11):858–863. doi: 10.1007/BF02630988. [DOI] [PubMed] [Google Scholar]
  214. Vandenberghe Y., Glaise D., Meyer D. J., Guillouzo A., Ketterer B. Glutathione transferase isoenzymes in cultured rat hepatocytes. Biochem Pharmacol. 1988 Jun 15;37(12):2482–2485. doi: 10.1016/0006-2952(88)90378-4. [DOI] [PubMed] [Google Scholar]
  215. Vandenberghe Y., Morel F., Pemble S., Taylor J. B., Rogiers V., Ratanasavanh D., Vercruysse A., Ketterer B., Guillouzo A. Changes in expression of mRNA coding for glutathione S-transferase subunits 1-2 and 7 in cultured rat hepatocytes. Mol Pharmacol. 1990 Mar;37(3):372–376. [PubMed] [Google Scholar]
  216. Vandenberghe Y., Ratanasavanh D., Glaise D., Guillouzo A. Influence of medium composition and culture conditions on glutathione S-transferase activity in adult rat hepatocytes during culture. In Vitro Cell Dev Biol. 1988 Apr;24(4):281–288. doi: 10.1007/BF02628828. [DOI] [PubMed] [Google Scholar]
  217. Vickers A. E. Use of human organ slices to evaluate the biotransformation and drug-induced side-effects of pharmaceuticals. Cell Biol Toxicol. 1994 Dec;10(5-6):407–414. doi: 10.1007/BF00755790. [DOI] [PubMed] [Google Scholar]
  218. Vignais P. M., Vignais P. V. Fuscin, an inhibitor of mitochondrial SH-dependent transport-linked functions. Biochim Biophys Acta. 1973 Dec 14;325(3):357–374. doi: 10.1016/0005-2728(73)90197-7. [DOI] [PubMed] [Google Scholar]
  219. Villa P., Bégué J. M., Guillouzo A. Effects of erythromycin derivatives on cultured rat hepatocytes. Biochem Pharmacol. 1984 Dec 15;33(24):4098–4101. doi: 10.1016/0006-2952(84)90029-7. [DOI] [PubMed] [Google Scholar]
  220. Villa P., Bégué J. M., Guillouzo A. Erythromycin toxicity in primary cultures of rat hepatocytes. Xenobiotica. 1985 Aug-Sep;15(8-9):767–773. doi: 10.3109/00498258509047439. [DOI] [PubMed] [Google Scholar]
  221. Vukicevic S., Kleinman H. K., Luyten F. P., Roberts A. B., Roche N. S., Reddi A. H. Identification of multiple active growth factors in basement membrane Matrigel suggests caution in interpretation of cellular activity related to extracellular matrix components. Exp Cell Res. 1992 Sep;202(1):1–8. doi: 10.1016/0014-4827(92)90397-q. [DOI] [PubMed] [Google Scholar]
  222. Wang S. R., Renaud G., Infante J., Catala D., Infante R. Isolation of rat hepatocytes with EDTA and their metabolic functions in primary culture. In Vitro Cell Dev Biol. 1985 Sep;21(9):526–530. doi: 10.1007/BF02620846. [DOI] [PubMed] [Google Scholar]
  223. Watkins P. B., Wrighton S. A., Schuetz E. G., Maurel P., Guzelian P. S. Macrolide antibiotics inhibit the degradation of the glucocorticoid-responsive cytochrome P-450p in rat hepatocytes in vivo and in primary monolayer culture. J Biol Chem. 1986 May 15;261(14):6264–6271. [PubMed] [Google Scholar]
  224. Waxman D. J., Morrissey J. J., Naik S., Jauregui H. O. Phenobarbital induction of cytochromes P-450. High-level long-term responsiveness of primary rat hepatocyte cultures to drug induction, and glucocorticoid dependence of the phenobarbital response. Biochem J. 1990 Oct 1;271(1):113–119. doi: 10.1042/bj2710113. [DOI] [PMC free article] [PubMed] [Google Scholar]
  225. Wilton J. C., Williams D. E., Strain A. J., Parslow R. A., Chipman J. K., Coleman R. Purification of hepatocyte couplets by centrifugal elutriation. Hepatology. 1991 Jul;14(1):180–183. doi: 10.1002/hep.1840140129. [DOI] [PubMed] [Google Scholar]
  226. Wodey E., Fautrel A., Rissel M., Tanguy M., Guillouzo A., Malledant Y. Halothane-induced cytotoxicity to rat centrilobular hepatocytes in primary culture is not increased under low oxygen concentration. Anesthesiology. 1993 Dec;79(6):1296–1303. doi: 10.1097/00000542-199312000-00021. [DOI] [PubMed] [Google Scholar]
  227. Yap S. H., Rijntjes P. J., Moshage H. J., Croes H., Jap P. H. Amiodarone-induced lysosomal inclusions in primary cultures of human hepatocytes. Gastroenterology. 1987 Jan;92(1):272–273. doi: 10.1016/0016-5085(87)90896-1. [DOI] [PubMed] [Google Scholar]
  228. Yoshitomi S., Miyazaki K., Nakayama F. Demonstration and maintenance of mucus secretion in cultured human gallbladder epithelial cells. In Vitro Cell Dev Biol. 1987 Aug;23(8):559–566. doi: 10.1007/BF02620973. [DOI] [PubMed] [Google Scholar]
  229. de Leeuw A. M., McCarthy S. P., Geerts A., Knook D. L. Purified rat liver fat-storing cells in culture divide and contain collagen. Hepatology. 1984 May-Jun;4(3):392–403. doi: 10.1002/hep.1840040307. [DOI] [PubMed] [Google Scholar]
  230. van 't Klooster G. A., Woutersen-van Nijnanten F. M., Klein W. R., Blaauboer B. J., Noordhoek J., van Miert A. S. Effects of various medium formulations and attachment substrata on the performance of cultured ruminant hepatocytes in biotransformation studies. Xenobiotica. 1992 May;22(5):523–534. doi: 10.3109/00498259209053115. [DOI] [PubMed] [Google Scholar]

Articles from Environmental Health Perspectives are provided here courtesy of National Institute of Environmental Health Sciences

RESOURCES