The development and evaluation of in vitro systems from target organs for preliminary assessments of the potential for systemic toxic effects has been receiving increased attention. This review presents a synopsis of progress made in developing toxicity screens for three common target organs and identifies further work needed for more complete validation.
Acosta, D., Sorensen, E.M.B., Anuforo, D.C., Mitchell, D.B., Ramos, K., Santone, K.S. and Smith, M.A. (1985). An in vitro approach to the study of drugs and chemicals. In Vitro, Cell Dev. Biol. 21:495-504.
2.
Anwer, M.S., Kroker, R. and Hegner, D. (1978). Inhibition of hepatic uptake of bile acids by rifamycins. Naunyn-Schmiedeberg's Arch. Pharmacol. 302:19-24.
3.
Aune, T. and Berg, K. (1986). Use of freshly prepared rat hepatocytes to study toxicity of blooms of the blue-green algae Microcystis aeruginosa and Oscillatoria agardhii. J. Toxicol. Environ. Hlth. 19:325-336.
4.
Bach, P.H., Ketley, C.P., Ahmed, I. and Dixit, M. (1986). The mechanisms of target cell injury by nephrotoxins . Food Chem. Toxicol. 24:775-779.
5.
Begue, J.M., Bigot, J.F.L., Guillouzo, C.G., Kiechel, J.R. and Guillouzo, A. (1983). Cultured human adult hepatocytes; a new model for drug metabolism studies. Biochem. Pharmacol. 32:1643-1646.
6.
Bellemann, P. (1980). Primary monolayer culture of liver parenchymal cells and kidney cortical tubules as a useful new model for biochemical pharmacology and experimental toxicology. Arch. Toxicol. 44:63-84.
7.
Berg, K. and Aune, T. (1987). Freshly prepared rat hepatocytes used in screening the toxicity of blue-green algal blooms. J. Toxicol. Environ. Health20:187-197.
8.
Berger, M.L., Bhatt, H., Combes, B. and Estabrook, R.W. (1986). CCl4-induced toxicity in isolated hepatocytes: the importance of direct solvent injury. Hepatology6:36-45.
9.
Berger, M.L., Reynolds, R.C. and Combes, B. (1987). Carbon tetrachloride-induced morphologic alterations in isolated rat hepatocytes. Exp. Molec. Pathol. 46:245-257.
10.
Berr, F., Simon, F.R. and Reichen, J. (1984). Ethynylestradiol impairs bile salt uptake and Na-K pump function of rat hepatocytes. Am. J. Physiol. 247:G437-443.
11.
Bieri, F., Bentley, P., Waechter, F. and Staubli, W. (1984). Use of primary cultures of adult rat hepatocytes to investigate mechanisms of action of nafenopin, a hepatocarcinogenic peroxisome proliferator. Carcinogenesis5:1033-1039.
12.
Billings, R.E., Mcmahon, R.E., Ashmore, J. and Wagle, S.R. (1977). The metabolism of drugs in isolated rat hepatocytes. A comparison with in vivo drug metabolism and drug metabolism in subcellular liver fractions. Drug Metab. Disp. 5:518-525.
13.
Blaauboer, B.J., Van Holsteijn I., Van Graft, M. and Paine, A.J. (1985). The concentration of cytochrome P-450 in human hepatocyte culture. Biochem. Pharmacol. 34:2405- 2408.
14.
Boelsterli, U.A., Bouis, P. and Donatsch, P. (1987). Relative cytotoxicity of psychotropic drugs in cultured rat hepatocytes. Cell Biol. Toxicol. 3:231-250.
15.
Bondy, S.C. (1982). Neurotransmitter binding interactions as a screen for neurotoxicity. In: Mechanisms of Actions of Neurotoxic Substances. (Prasad, K.N. and Vemadakis, A., eds.), pp. 25-50, Raven Press, New York.
16.
Boobis, A.R., Tee, L.B.G., Hampden, C.E. and Davies, D.S. (1986). Freshly isolated hepatocytes as a model for studying the toxicity of paracetamol. Food Chem. Toxicol. 24:731-736.
17.
Bradbury, M.W.B. (1985). The blood-brain barrier in vitro. Neurochem. Int. 7:27-28.
18.
Brock, W. and Vore, M. (1984). The effect of pregnancy and treatment with 17B-estradiol on the transport of organic anions into isolated rat hepatocytes. Drug Metab. Dis. 12:712-716.
19.
Butterworth, B.E. (1987). Measurement of chemically induced DNA repair in hepatocytes in vivo and in vitro as an indicator of carcinogenic potential . In: The isolated hepatocyte: use in toxicology and xenobiotic biotransformation. (E.J. Rauckman and G.M. Padilla, eds.), pp. 241-264, Academic Press, New York.
20.
Byard, J.L. and Dougherty, K.K. (1985). Comparative metabolism and toxicity of chemical carcinogens in primary cultures of hepatocytes. In Vitro21:489-494.
21.
Clementi, F., Cabrini, D., Gotti, C., Fornasari, D. and Sher, E. (1987). A human neuroblastoma cell line for neurotoxicity testing in vitro: effects of heavy metals. In: Model Systems in Neurotoxicology. Alternative Approaches to Animal Testing. (Shakar, A. and Goldberg, A.M., eds.), pp. 137-149, Alan R. Liss, Inc., New York.
22.
Croci, T. and Williams, G.M. (1985). Activities of several Phase I and Phase II xenobiotic biotransformation enzymes in cultured hepatocytes from male and female rats . Biochem. Pharmacol. 34:3029-3035.
23.
Cunarro, J.A. and Weiner, M.W. (1978). Effects of ethacrynic acid and furosemide on respiration of isolated kidney tubules: the role of ion transport and the source of metabolic energy. J. Pharmacol. Exp. Therap. 206:198-206.
24.
Dewar, A.J. (1981). Neurotoxicity testing - with particular reference to biochemical methods. In: Testing for Toxicity. (Gorrod, J.W., ed.), pp. 199-217, Taylor & Francis, Ltd., London.
25.
Doolittle, D.J., Muller, G. AND Scribner, H.E. (1987). The in vivo-in vitro hepatocyte assay for assessing DNA repair and DNA replication: Studies in the CD-1 mouse. Food Chem. Toxicol. 25:399-405.
26.
Dougherty, K.K., Spilman, S.D., Green, C.E., Steward, A.R. and Byard, J.L. (1980). Primary cultures of adult mouse and rat hepatocytes for studying the metabolism of foreign chemicals. Biochem. Pharmacol. 29:2117-2124.
27.
Dujovne, C.A. and Salhab, A.S. (1980). Erythromycin estolate vs. erythromycin base, surface excess properties and surface scanning changes in isolated liver cell systems . Pharmacology20:285-291.
28.
Ekwall, B. (1980a). Preliminary studies on the validity of in vitro measurement of drug toxicity using HeLa cells II. Drug toxicity in the MIT-24 system compared with mouse and human lethal dosage of 52 drugs. Toxicol. Lett. 5:309-317.
29.
Ekwall, B. (1980b). Screening of toxic compounds in tissue culture . Toxicology17:127-142.
30.
Ekwall, B. (1980c). Toxicology to HeLa cells of 205 drugs as determined by the metabolic inhibition test supplemented by microscopy. Toxicology17:273-295.
31.
Ekwall, B. and Acosta, D. (1982). In vitro comparative toxicity of selected drugs and chemicals in HeLa cells, Chang liver cells, and rat hepatocytes. Drug Chem. Toxicol. 5:219-231.
32.
Ekwall, B. and Ekwall, K. (1988). Comments on the use of diverse cell systems in toxicity testing. ATLA15:193-201.
33.
Fisher, G.L. and Placke, M.E. (1987). In Vitro models of lung toxicity. Toxicology47:71-93.
34.
Fountain, S.B. and Teyler, T.J. (1987). Characterizing neurotoxicity using the in vitro hippocampal brain slice preparation: heavy metals. In: Model Systems in Neurotoxicology. Alternative Approaches to Animal Testing. (Shakar, A. and Goldberg, A.M., eds.), pp. 19-31, Alan R. Liss, Inc., New York.
35.
Frazier, J.M., Tyson, C.A., McCarthy, C., McCormick, J., Myers, D., Powis, G. and Ducat, L.Potential use of human tissues for toxicity studies and testing-a minireview . Toxicol. Appl. Pharmacol. (in press).
36.
Fry, J.R. and Bridges, J.W. (1976). The metabolism of xenobiotics in cell suspension and cell cultures. In: Prog. Drug Metab (J.W. Bridges and Chasseaud , eds), Vol. 2, pp. 71-117. John Wiley & Son, New York.
37.
Gardner, D.E., Crapo, J.D. and Massaro, E.J. (1988). Toxicology of the lung. Raven Press, New York.
38.
Gebhardt, R. (1986). Use of isolated and cultured hepatocytes in studies on bile formation. In: Isolated and cultured hepatocytes. (A. Gullouzo and C. Guguen-Gullouzo, eds.), pp. 353-376. John Libbey Eurotext Ltd., France.
39.
Glende, E.A., JR. and Lee, P.Y. (1985). Isopropanol and chlordecone potentiation of carbon tetrachloride liver injury: retention of potentiating action in hepatocyte suspensions prepared from rats given isopropanol or chlordecone . Exp. Molec. Pathol. 42:167-174.
40.
Goethals, F., Krack, G., Deboyser, D., Vossen, P. and Roberfroid, M. (1984). Critical biochemical function of isolated hepatocytes as sensitive indicators of chemical toxicity. Fundam. Appl. Toxicol. 4:441-450.
41.
Goldstein, R.S. and Hook, J.B. (1986). Biochemical mechanisms of cephaloridine nephrotoxicity . Dev. Toxicol. Environ. Sci. 14:41-50.
42.
Gottschall, D.W., Wiley, R.A. and Hanzlik, R.P. (1983). Toxicity of ortho-substituted bromobenzenes to isolated hepatocytes: comparison to in vivo results. Toxicol. Appl. Pharmacol, 69:55-65.
43.
Gotz, R., Schwarz, L.R. and Greim, H. (1980). Effects of pentachlorophenol and 2,4,6-trichlorophenol on the disposition of sulfobromophthalein and respiration of isolated liver cells. Arch. Toxicol.44:147-155.
44.
Grant, M.H., Burke, M.D., Hawksworth, G.M., Duthie, S.J., Engeset, J. and Petrie, J.C. (1987). Human adult hepatocytes in primary monolayer culture . Biochem. Pharmacol. 36:2311-2316.
45.
Grant, M.H., Melvin, M.A.L., Shaw, P., Melvin, W.T. and Burke, M.D. (1985). Studies on the maintenance of cytochromes P-450 and b5, monooxygenases and cytochrome reductases in primary cultures of rat hepatocytes. FEBS Lett. 190:99-103.
46.
Gray, T.J.B., Lake, B.G., Beamand, J.A., Foster, J.R. and Gangoli, S.D. (1983). Peroxisomal effects of phthalate esters in primary cultures of rat hepatocytes. Toxicology28:167-179.
47.
Gray, T.J.B. and Beamand, J.A. (1984). Effect of some phthalate esters and other testicular toxins on primary cultures of testicular cells. Chem. Toxicol . 22:123-132.
48.
Gray, T.J.B., Moss, E.J., Creasy, D.M. and Gangolli, S.D. (1985). Studies on the toxicity of some glycol esters and alkoxyacetic acids in primary testicular cell cultures. Toxicol. Appl. Pharmacol. 79:490-501.
49.
Green, C.E., Dabbs, J.E., Tyson, C.A. and Rauckman, E.The effect of oxygen tension and antioxidants on isolated rat renal proximal tubules. Submitted for publication.
50.
Green, C.E., Dabbs, J.E. and Tyson, C.A. (1984). Metabolism and cytotoxicity of acetaminophen in hepatocytes isolated from resistant and susceptible species. Toxicol. Appl. Pharmacol. 76:139-149.
51.
Green, C.E., Levalley, S.E. and Tyson, C.A. (1986). Comparison of amphetamine metabolism using isolated hepatocytes from five species including human. J. Pharmacol. Exp. Ther. 237:931-936.
52.
Grisham, J.W. (1979). Use of hepatic cell cultures to detect and evaluate the mechanisms of action of toxic chemicals. Int. Rev. Exp. Pathol. 20:123-210.
53.
Guillouzo, A., Begue, J.M., Campion, J.P., Gascoin, M.N. and Guguen-Guillouzo, C. (1985). Human hepatocyte cultures: a model of pharmacotoxicolagical studies. Xenobiotica15:635-641.
54.
Guillouzo, A., Beaune, P., Gascoin, M.N., Begue, J.M., Campion, J.P., Guengerich, F.P. and Guguen-Guillouzo, C. (1985). Maintenance of cytochrome p-450 in cultured adult human hepatocytes. Biochem. Pharmacol . 34:2991-2995.
55.
Guillouzo, A. (1986). Use of isolated and cultured hepatocytes for xenobiotic metabolism and cytotoxicity studies. In: Isolated and cultured hepatocytes. (A. Guillouzo and C. Guguen-Gillouzo, eds.), pp. 313-332. John Libbey Eurotext Ltd., France.
56.
Handler, J.S. (1986). The use of cultured kidney cells to study renal toxicology. In: Nephrotoxicity of Antibiotics and Immunosuppressants . (T. Tanabe, J.B. Hook, and H. Endou, eds.), pp. 189-197, Elsevier Science Publishers, New York.
57.
Hanigan, H.M. and Laishes, B.A. (1984). Toxicity of aflatoxin Bl in rat and mouse hepatocytes in vivo and in vitro. Toxicology30:185-193.
58.
Hanzlik, R.P., Gillesse, T.J. and Wiley, R.A. (1982). Toxicity and covalent binding of substituted bromobenzenes to isolated hepatocytes. Adv. Exp. Med. Biol. 136A:381-386.
59.
Harman, A.W. and Fischer, L.J. (1983). Hamster hepatocytes in culture as a model for acetaminophen toxicity: studies with inhibitors of drug metabolism. Toxicol. Appl. Pharmacol. 71:330-341.
60.
Harman, A.W. and McCamish, L.E. (1986). Age-related toxicity of paracetamol in mouse hepatocytes . Biochem. Pharmacol. 35:1731-1735.
61.
Holme, J.A. and Soderlund, E.J. (1984). Unscheduled DNA synthesis of rat hepatocytes in monolayer culture. Mutat. Res. 126:205-214.
62.
Holme, J.A. and Soderlund, E. (1986). Species differences in cytotoxic and genotoxic effects of phenacetin and paracetamol in primary monolayer cultures of hepatocytes . Mutat. Res. 164:167-175.
63.
Holme, J.A. (1985). Xenobiotic metabolism and toxicity in primary monolayer cultures of hepatocytes. NIPH Annals8:49-63.
64.
Holme, J.A., Trygg, B. and Soderlund, E. (1986). Species differences in the metabolism of 2-acetylaminofluorene by hepatocytes in primary monolayer culture. Canc. Res. 46:1627-1632.
65.
Hottendorf, G.H., Laska, D.A., Williams, P.D. and Ford, S.M. (1987). The role of desacetylation in the detoxification of cephatholin in renal cells in culture. J. Toxicol. Environ. Health22:101-111.
66.
Hurst, J.K. (1988). Oxygen activation by neutrophils. In: Oxygen Complexes and Oxygen Activation by Transition Metals. (A. E. Martell and D. T. Sawyer, eds), pp. 149-174, Plenum Press, New York.
67.
Inmon, J., Stead, A., Waters, M.D. and Lewtas, J. (1981). Development of a toxicity test system using primary rat liver cells. In Vitro17:1004-1010.
68.
Jatoe, S.D. and Gorrod, J.W. (1987). The in vitro/in vivo comparative metabolism of 4-aminobiphenyl using isolated hepatocytes. Arch. Toxicol . 60:65-68.
69.
Jernigan, J.D., Pounds, J.G. and Harbison, R.D. (1983). Potentiation of chlorinated hydrocarbon toxicity by 2,5-hexanedione in primary cultures of adult rat hepatocytes. Fund. Appl. Toxicol.3:22-26.
70.
Johnson, M.K. (1977). Improved assay of neurotoxic esterase for screening organophosphates for delayed neurotoxicity potential. Arch. Toxicol. 37:113-115.
71.
Klaassen, C.D. and Stacey; N.H. (1982). Use of isolated hepatocytes in toxicity assessment . In: Toxicology of the liver. (G. Plaa and W.R. Hewitt, eds.), pp. 147-179. Raven Press, New York.
72.
Klaassen, C.D. (1986). Principles of toxicology. In: Casarett and Doull's Toxicology. The Basic Science of Poisons. (Klaassen, C.D., Amdur, M.O. and Doull, J., eds.), 3rd Ed., p.16, Macmillan Publishing Co., New York.
73.
Knights, K.M., Cassidy, M.R. and Drew, R. (1986). Benoxaprofen induced toxicity in isolated rat hepatocytes. Toxicology40:327-339.
74.
Kontur, P.J., Hoffmann, P.C. and Heller, A. (1987). Neurotoxic effects of methamphetamine assessed in three-dimensional reaggregate tissue cultures. Dev. Brain Res. 31:7-14.
75.
Koster, H., Halsema, I., Scholtens, E., Knippers, M. and Mulder, G.J. (1981). Dose-dependent shifts in the sulfation and glucuronidation of phenolic compounds in the rat in vivo and in isolated hepatocytes. Biochem. Pharmacol. 30:2569-2575.
76.
Kukongviriyapan, V. and Stacey, N.H.Inhibition of taurocholate transport by cyclosporin A in cultured rat hepatocytes . J. Pharmacol. Exp. Ther. (in press).
77.
Lake, B.G., Gray, T.J.B., Lewis, D.F.V., Beamand, J.A., Hodder, K.D., Purchase, R. and Gangolli, S.D. (1987). Structure-activity relationships for induction of peroxisomal enzyme activities by phthalate monoesters in primary rat hepatocyte cultures. Toxicol. Indust. Health3:165-181.
78.
Long, R.M. and Moore, L. (1988). Biochemical evaluation of rat hepatocyte primary cultures as a model for carbon tetrachloride hepatotoxicity: Comparative studies in vivo and in vitro. Toxicol. Appl. Pharmacol. 92:295-306.
79.
Lotti, M. and Johnson, M.K. (1978). Neurotoxicity of organophosphorus pesticides: predictions can be based on in vitro studies with hen and human enzymes. Arch. Toxicol. 41:215-221.
80.
Lupo, S., Yodis, L.A., Mico, B.A. and Rush, G.F. (1987). In vivo and in vitro hepatotoxicity and metabolism of acetaminophen in Syrian hamsters. Toxicology44:229-239.
81.
Macdonald, J.R., Thayer, K.J. and White, C. (1987a). Inhibition of galactosamine cytotoxicity in an in vivo/ in vitro hepatocellular toxicity model. Toxicol. Appl. Pharmacol. 89:269-277.
82.
Macdonald, J.R., Thayer, K.J. and Smuckler, E.A. (1987b). Isolation and maintenance of monolayer hepatocytes from the livers of toxin-treated rats. Exp. Molec. Pathol . 46:64-77.
83.
McQueen, C.A. and Williams, G.M. (1982). Cytotoxicity of xenobiotics in adult rat hepatocytes in primary culture. Fundam. Appl. Toxicol. 2:139-144.
84.
McQueen, C.A., Kreiser, D.M. and Williams, G.M. (1983). The hepatocyte primary culture/ DNA repair assay using mouse or hamster hepatocytes. Environ. Mutag. 5:1-8.
85.
Mcqueen, C.A.In Vitro Models in Toxicology. Telford Press, Caldwell, NJ (in press).
86.
Michalopoulos, G.K., Strom, S.C. and Jirtle, R.L. (1986). Use of hepatocytes for studies of mutagenesis and carcinogenesis. In: Isolated and cultured hepatocytes. (A. Guillouzo and C. Guguen-Guillouzo, eds.), pp. 333-352. John Libbey Eurotext Ltd., France.
87.
Mirsalis, J.C., Tyson, C.K. and Butterworth, B.E. (1982). Detection of genotoxic carcinogens in the in vivo-in vitro hepatocyte DNA repair assay. Environ. Mutag. 4:553-562.
88.
Mitchell, A.M., Bridges, J.W. and Elcombe, C.R. (1984). Factors influencing peroxisome proliferation in cultured rat hepatocytes. Arch. Toxicol. 55:239-246.
89.
Moldeus, P. (1978). Paracetamol metabolism and toxicity in isolated hepatocytes from rat and mouse. Biochem. Pharmacol. 27:2859-2863.
90.
Norbury, K.C., Sandifer, S., Carthage, P., Sorensen, E.M.B. and Acosta, D. (1987). An interlaboratory study using postnatal rat hepatocytes to measure in vitro toxicity of known hepatotoxins. In Vitro Toxicol. 1:193-202.
91.
Oldham, H.G., Norman, S.J. and Chenery, R.J. (1985). Primary cultures of adult rat hepatocytes-a model for the toxicity of histamine H2-receptor antagonists. Toxicology36:215-229.
92.
Olsen, H. and Morland, J. (1981). Sulfonamide acetylation in isolated rat liver cells. Acta Pharmacol. Toxicol. 49:102-109.
93.
Ozturk, M., Lemonnier, F., Cresteil, D., Scotto, J. and Lemonnier, A. (1984). Methionine metabolism and ultrastructural changes with D-galactosamine in isolated rat hepatocytes. Chem.-Biol. Interac. 51:63-76.
94.
Paine, A.J. and Hockin, L.J. (1982). The maintenance of cytochrome P-450 in liver cell culture: recent studies on P-450 mediated mechanisms of toxicity. Toxicology25:41-45.
95.
Pessayre, D., Cobert, B., Descatoire, V., Degott, C., Babany, G., Funck-Brentano, C., Delaforge, M. and Larrey, D. (1982). Hepatotoxicity of trichloroethylene-carbon tetrachloride mixtures in rats: A possible consequence of potentiation by trichloroethylene of carbon tetrachloride-induced lipid peroxidation and liver lesions. Gastroenterology83:761-772.
96.
Phelps, J.S., Gandolfi, A.J., Brendel, K. and Dorr, R.T. (1987). Cisplatin nephrotoxicity: in vitro studies with precision-cut rabbit renal cortical slices. Toxicol. Appl. Pharmacol. 90:501-512.
97.
Phelps, J.S., Gandolfi, A.J. and Brendel, K. (1987). Cisplatinum toxicity in rabbit renal proximal tubule suspensions and precision-cut renal cortical slices. In: Approaches to Validation. Alternative Methods in Toxicology Series. Vol. V. (Goldberg, A.M. , ed.), pp. 411-420, Mary Ann Liebert, Inc., New York.
98.
Phillips, M.J., Oshio, C., Miyairi, M. and Smith, C.R. (1983). Intrahepatic cholestasis as a canalicular motility disorder. Lab. Invest. 48:205-211.
99.
Placke, M.E. and Fisher, G.L. (1987). Adult peripheral lung organ culture-a model for respiratory tract toxicology. Toxicol. Appl. Pharmacol. 90:284-298.
100.
Poli, G., Chiarpotto, E., Albano, E., Cottalasso, D., Nanni, G., Mari-Nari, U.M., Bassi, A.M. and Dianzani, M.U. (1984). Carbon tetrachloride induced inhibition of hepatocyte lipoprotein secretion: functional impairment of Golgi apparatus in the early phases of such injury. Life Sci. 36:533-539.
101.
Ratanasavanh, D., Beaune, P., Baffet, G., Rissel, M., Kremers, P., Guengerich, F.P. and Guillouzo, A. (1986). Immunocytochemical evidence for the maintenance of cytochrome P-450 isozymes, NADPH cytochrome c reductase and epoxide hydratase in pure and mixed primary cultures of adult human hepatocytes. Food Chem. Toxicol. 24:577-578.
102.
Reichen, J., Hoilien, C., Le, M. and Jones, R.H. (1987). Decreased uptake of taurocholate and ouabain by hepatocytes isolated from cirrhotic rat liver. Hepatology7:67-70.
103.
Reinhardt, C.A. and Pelli, D.A. (1986). Screening for hepatoxicity using freshly isolated and cryopreserved rat hepatocytes. Food Chem. Toxicol. 24:576.
104.
Rikans, L.E. and Hornbrook, K.R. (1986). Isolated hepatocytes as a model for aging effects on hepatoxicity: studies with ally alcohol. Toxicol. Appl. Pharmacol. 84:634-639.
105.
Ruch, R.J., Klaunig, J.E., Schultz, N.E., Askari, A.B., Lacher, D.A., Pereira, M.A. and Goldblatt, P.J. (1986). Mechanisms of chloroform and carbon tetrachloride toxicity in primary cultured mouse hepatocytes. Environ. Health Perspec. 69:301-305.
106.
Rudo, K., Meyers, W.C., Dauterman, W. and Langenbach, R. (1987). Comparison of human and rat hepatocyte metabolism and mutagenic activation of 2-acetylaminofluorene. Cancer Res. 47:5861-5867.
107.
Ruegg, C.E., Gandolfi, A.J., Nagle, R.B., Krumdieck, C.L. and Brendel, K. (1987a). Preparation of positional renal slices for study of cell-specific toxicity. J. Pharmacol. Meth. 17:111-123.
108.
Ruegg, C.E., Gandolfi, A.J., Nagle, R.B. and Brendel, K. (1987). Differential patterns of injury to the proximal tubule of renal cortical slices following in vitro exposure to mercuric chloride, potassium dichromate, or hypoxic conditions. Toxicol. Appl. Pharmacol. 90:261-273.
109.
Rylander, L.A., Phelps, J.S., Gandolfi, A.J. and Brendel, K. (1987). In vitro nephrotoxicity: response of isolated renal tubules to cadmium chloride and dichlorovinyl cysteine. In Vitro Toxicol. 1:111-127.
110.
Rylander, L.A., Gandolfi, A.J. and Brendel, K. (1985). Inhibition or organic acid J base transport in isolated rabbit renal tubules by nephrotoxins. In: In vitro Toxicology, Vol. 3, "Alternative Methods in Toxicology," (Goldberg, A.M., ed.), pp. 237-247, Mary Ann Liebert, Inc., New York.
111.
Schnellmann, R.G. and Mandel, L.J. (1986). Cellular toxicity of bromobenzene and bromobenzene metabolites to rabbit proximal tubules: the role and mechanism of 2-bromohydroquinone . J. Pharmacol. Exp. Therap. 237:456-461.
112.
Schwarz, L.R. and Greim, H. (1981). Frontiers in liver disease. In: Isolated hepatocytes: an analytical tool in hepatotoxicology. (P.D. Berk and T.C. Chalmers , eds.), pp. 61-79. Thieme-Stratton, New York.
113.
Schwarz, L.R., Schwenk, M., Pfaff, E. and Greim, H. (1977). Cholestatic steroid hormones inhibit taurocholate uptake into isolated rat hepatocytes. Biochem. Pharmacol. 26:2433-2437.
114.
Seale, T.W. and Rennert, O.M. (1982). Mechanisms of antibiotic-induced nephrotoxicity . Ann. Clin. Lab. Sci. 12:1-10.
115.
Shakar, A. and Goldberg, A.M., eds. (1987). Model Systems in Neurotoxicology. Alternative Approaches to Animal Testing. Alan R. Liss, Inc., New York.
116.
Sina, J.F., Bean, C.L., Bland, J.A., Macdonald, J.S., Noble, C., Robertson, R.T. and Bradley, M.O. (1986/87). An in vitro assay for cytotoxicity to proximal tubule suspensions from rabbit kidney. In Vitro Toxicol. 1:13-22.
117.
Sirica, A.E. and Pitot, H.C. (1980). Drug metabolism and effects of carcinogens in cultured hepatic cells. Pharmacol. Rev. 31:205-228.
118.
Smith, J.H. (1988). The use of renal cortical slices from the Fischer 344 rat as an in vitro model to evaluate nephrotoxicity. Toxicol. Appl. Pharmacol. 11:132-142.
119.
Smith, M.A., Acosta, D. and Bruckner, J.V. (1986). Development of a primary culture system of rat kidney cortical cells to evaluate the nephrotoxicity of xenobiotics. Food Chem. Toxic. 24:551-556.
120.
Smith, M.A., Acosta, D. and Bruckner, J.V. (1987). Cephaloridine toxicity in primary cultures of rat renal cortical epithelial cells. Toxic. In Vitro1:23-29.
121.
Smith, P.F., Fisher, R., McKee, R., Gandolfi, A.J., Krumideck, C.L. and Brendel, K.Precision cut liver slices: a new in vitro tool in toxicology. In: In vitro Models in Toxicology. (McQueen, C.A., ed.), Telford Press, Caldwell, NJ (in press).
122.
Smith, R.A., Orr, D.J. and McInnes, I.B. (1987). A refined primary culture system of adult mouse sensory neurons for neurotoxicity. In: Model Systems in Neurotoxicology. Alternative Approaches to Animal Testing. ( Shakar, A. and Goldberg, A.M., eds.), pp. 69-75, Alan R. Liss, Inc., New York.
123.
Sorensen, E.M.B. and Acosta, D. (1985). Relative toxicities of several nonsteroidal antiinflammatory compounds in primary cultures of rat hepatocytes. J. Toxicol. Environ. Health16:425-440.
124.
Spencer, P.S., Crain, S.M., Bornstein, M.B., Peterson, E.R. and Van DEWater, T. (1986). Chemical neurotoxicity: detection and analysis in organotypic cultures of sensory and motor systems. Food Chem. Toxicol. 24:539-544.
125.
Stacey, N.H. (1986). Effects of ethinyl estradiol on substrate uptake and efflux by isolated rat hepatocytes. Biochem. Pharmacol . 35:2495-2500.
126.
Stacey, N.H. (1987). Assessment of the toxicity of chemical mixtures with isolated rat hepatocytes: cadmium and chloroform. Fund. Appl. Toxicol. 9:616-622.
127.
Stacey, N.H. (in press). Toxicity of combinations of chlorinated aliphatic hydrocarbons in vitro and in vivo. Toxicol. In Vitro.
128.
Stacey, N.H. (submitted). Toxicity of mixtures of trichloroethylene, tetrachloroethylene and 1,1,1-trichloroethane: similarity of in vitro to in vivo responses.
129.
Stacey, N.H.Effects of chlorpromazine on taurocholate transport in isolated rat hepatocytes . Biochem. Pharmacol. (in press).
130.
Stacey, N.H. and Fanning, J.C. (1981). Ultrastructural changes in isolated rat hepatocytes after incubation with carbon tetrachloride. Toxicology22:69-77.
131.
Stacey, N.H. and Kotecka, B.Inhibition of taurocholate and ouabain transport in isolated rat hepatocytes by cyclosporin A. Gastroenterology (in press).
132.
Stacey, N.H., Muller, L. and Kefalas V. (1988). Toxicity of cadmium/chloroform combination in vivo. Med. Sci. Res. (in press).
133.
Stacey, N.H., Ottenwalder, H. and Kappus, H. (1982). CCl4-induced lipid peroxidation in isolated rat hepatocytes with different oxygen concentrations. Toxicol. Appl. Pharmacol. 62:421-427.
134.
Stacey, N.H. and Priestly, B.G. (1978a). Dose dependent toxicity of CCl4 in isolated rat hepatocytes and the effects of hepatoprotective treatments. Toxicol. Appl. Pharmacol. 45:29-39.
135.
Stacey, N.H. and Priestly, B.G. (1978b). Lipid peroxidation in isolated rat hepatocytes. Relationship to toxicity of CCl4, ADP/Fe3+ and diethylmaleate. Toxicol. Appl. Pharmacol. 45:41-48.
136.
Stacey, N.H., Priestly, B.G. and Hall, R.C. (1978). Toxicity of halogenated volatile anesthetics in isolated rat hepatocytes. Anesthesiology48:17-22.
137.
Steward, A.R., Dannan, G.A., Guzelian, P.S. and Guengerich, F.P. (1985). Changes in the concentration of seven forms of cytochrome P-450 in primary cultures of adult rat hepatocytes . Molec. Pharmacol. 27:125-132.
138.
Story, D.L., Gee, S.J. and Tyson, C.A. (1983). Response of isolated hepatocytes to organic and inorganic cytotoxins. J. Toxicol. Environ. Hlth. 11:483-501.
139.
Strom, S., Kilgerman, A.D. and Michalopoulos, G. (1981). Comparisons of the effects of chemical carcinogens in mixed cultures of rat hepatocytes and human fibroblasts . Carcinogenesis2:709-715.
140.
Strom, S.C., Jirtle, R.L. and Michalopoulos, G. (1983). Genotoxic effects of 2-acetylaminofluorene on rat and human hepatocytes. Environ. Health Perspec. 49: 165-170.
141.
Strom, S.C., Monteith, D.K., Manoharan, K. and Novotny, A. (1987). Genotoxicity studies with human hepatocytes. In: The isolated hepatocyte. Use in toxicology and xenobiotic biotransformations . (E.J. Rauckman and G.M. Padilla, eds.), pp. 265-280. Academic Press , New York.
142.
Suolinna, E.M. (1982). Isolation and culture of liver cells and their use in the biochemical research of xenobiotics. Med. Biol . 60:237-254.
143.
Tarao, K., Olinger, E.J., Ostrow, J.D. and Balistreri, W.F. (1982). Impaired bile acid efflux from hepatocytes isolated from the liver of rats with cholestasis. Am. J. Physiol. 243:G253-258.
144.
Tran-Thi, T.A., Phillips, J., Falk, H. and Decker, K. (1985). Toxicity of D-galactosamine for rat hepatocytes in monolayer culture. Exp. Mol. Pathol. 42:89-116.
145.
Tyson, C.A., Mitoma, C., and Kalivoda, J. (1980). Evaluation of hepatocytes isolated by a nonperfusion technique in a prescreen for cytotoxicity. J. Toxicol. Environm. Hlth. 6:197-205.
146.
Tyson, C.A., Hawk-Prather, C., Story, D.L. and Gould, D.H. (1983). Correlations of in vitro and in vivo hepatotoxicity for five haloalkanes. Toxicol. Appl. Pharmacol. 70:289-302.
147.
Tyson, C.A., Story, D.L. and Stephens, R.J. (1983). Ultrastructural changes in isolated rat hepatocytes exposed to different CC14 concentrations. Biochem. Biophys. Res. Commun. 114:511-517.
148.
Tyson, C.A. (1987). Correspondence of results from hepatocyte studies with in vivo response. Toxicol. Indus. Health3:459-477.
149.
Tyson, C.A., Gee, S.J., Hawk-Prather, K., Story, D.L. and Milman, H.A.Correlation between in vivo/in vitro toxicity with chlorinated aliphatics . Toxicol. In Vitro (in press).
150.
Van Dyke, R.W. and Scharschmidt, B.F. (1987). Effects of chlorpromazine on Na+-K+-ATPase pumping and solute transport in rat hepatocytes. Am. J. Physiol. 253:G613-621.
151.
Volpe, L.S., Biagioni, T.M. and Marquis, J.K. (1985). In vitro modulation of bovine caudate muscarinic receptor number by organophosphates and carbamates. Toxicol. Appl. Pharmacol. 78:226-234.
152.
Vonen, B. and Morland, J. (1984). Isolated rat hepatocytes in suspension: potential hepatotoxic effects of six different drugs. Arch. Toxicol . 56:33-37.
153.
Walker, R.M., McElligott, T.F., Massey, T.E. and Racz, W.J. (1983). Ultrastructural effects of acetaminophen in isolated mouse hepatocytes. Exp. Molec. Pathol. 39:163-175.
154.
Whetsell, W.O., JR. and Schwarz, R. (1984). Mechanisms of excitotoxins in organotypic cultures of rat central nervous system. Wenner-Gren Cent. Int. Symp. Ser.39:207-219.
155.
Williams, P.D., Laska, D.A., Tay, L.K. and Hottendorf, G.H. (1988). Comparative toxicities of cephalosporin antibiotics in a rabbit kidney cell line (LLC-RK1). Antimicrob. Agents Chemother. 32:314-318.
156.
Williams, G.M., Laspia, M.F. and Dunkel, V.C. (1982). Reliability of the hepatocyte primary culture/DNA repair test in testing of coded carcinogens and noncarcinogens. Mutat. Res. 97:359-370.
157.
Williams, G.M. (1985). Identification of genotoxic and epigenetic carcinogens in liver culture systems. Regul. Toxicol. Pharmacol. 5:132-144.
158.
Ziegler, K. and Frimmer, M. (1984). Cyclosporin A protects liver cells against phalloidin. Potent inhibition of the inward transport of cholate and phallotoxins. Biochim. Biophys. Acta. 805:174-180.
159.
Zimmerman, H.J., Kendler, J., Libber, S. and Lukacs, L. (1974). Hepatocyte suspensions as a model for demonstration of drug hepatotoxicity. Biochem. Pharmacol. 23:2187-2189.
160.
Zimmerman, H.J. and Abernathy, C.O. (1985). Employment of in vivo models for study of drug hepatotoxicity: applications of phenothiazines, related compounds, and erythromycins . In: Hepatology (Brunner, H. and Thaler, H., eds.), pp. 61-74. Raven Press, NY.
161.
Zimmerman, H.J., Jacob, L., Bassan, H., Gillespie, J., Lukacs, L. and Abernathy, C.O. (1986). Effects of H2-blocking agents on hepatocytes in vitro: correlation with potential for causing hepatic disease in patients (42373). Proc. Soc. Exp. Biol. Med. 182:511-14.
