16
Views
3
CrossRef citations to date
0
Altmetric
Research Article

MODELING THE CHEMOPROTECTIVE FUNCTIONS OF GLUTATHIONE S-TRANSFERASES IN CULTURED CELL LINES BY HETEROLOGOUS EXPRESSION*

, , , , &
Pages 43-69 | Published online: 02 Aug 1999

REFERENCES

  • Weinstein I. B. The origins of human cancer: Molecular mechanisms of carcinogenesis and their implications for cancer prevention and treatment—Twenty-seventh G.H.A. Clowes memorial lecture. Cancer Res. 1988; 48: 4135–4143
  • Tlsty T. D., Briot A., Gualberto A., Hall I., Hess S., Hixon M., Kuppuswamy D., Romanov S., Sage M., White A. Genomic instability and cancer (Review). Mutat. Res. 1995; 337: 1–7
  • Loeb L. A. Mutator phenotype may be required for multistage carcinogenesis (Review). Cancer Res. 1991; 51: 3075–3079
  • Powis G., Alberts D. S. Inhibiting intracellular signalling as a strategy for cancer chemoprevention. Eur. J. Cancer 1994; 30a(8)1138–1144
  • Berenblum I. Cancer prevention as a realizable goal. Cancer 1981; 47: 2346–2348
  • Ames B. N., Magaw R., Gold L. S. Ranking possible carcinogenic hazards. Science 1987; 236: 271–280
  • Ames B. N., Profet M., Gold L. S. Nature's chemicals and synthetic chemicals: Comparative toxicology. Proc. Natl. Acad. Sci. USA 1990; 87: 7782–7786
  • Higginson J. Changing concepts in cancer prevention: Limitations and implications for future research in environmental carcinogenesis (Review). Cancer Res. 1988; 48: 1381–1389
  • Slaga T. J. Inhibition of the induction of cancer by antioxidants. Adv. Exp. Med. Biol. 1995; 369: 167–174
  • O'Brien P. J. Antioxidants and cancer: Molecular mechanisms. Adv. Exp. Med. Biol. 1994; 366: 215–239
  • Cerutti P., Ghosh R., Oya Y., Amstad P. The role of the cellular antioxidant defense in oxidant carcinogenesis (Review). Environ. Heatlh Perspect. 1994; 10: 123–129
  • Feig D. I., Reid T. M., Loeb L. A. Reactive oxygen species in tumorigenesis (Review). Cancer Res. 1994; 54: 1890s–1894s
  • Jakoby W. B. The Enzymatic Basis of Detoxification. Academic Press, New York 1980
  • Vickers P. J., Townsend A. J., Cowan K. H. Mechanisms of Resistance to Antineoplastic Drugs. CRC Press, Boca Raton, FL 1988; 2: 117–152
  • Wolf C. R. Metabolic factors in cancer susceptibility (Review). Cancer Surveys 1990; 9: 437–474
  • Meister A., Anderson M. Glutathione. Ann. Rev. Biochem. 1983; 52: 711–760
  • Meister A. Glutathione, ascorbate, and cellular protection. Cancer Res. 1994; 54: 1969s–1975s
  • Langouet 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; 55: 5574–5579
  • Helzlsouer K. J., Kensler T. W. Cancer chemoprotection by oltipraz: Experimental and clinical considerations (Review). Prevent. Med. 1993; 22: 783–795
  • Ketterer B. Protective role of glutathione and glutathione transferases in mutagenesis and carcinogenesis (Review). Mutat. Res. 1988; 202: 343–361
  • Paolini M., Mesirca R., Gialluca N., Bauer C., Biagi G. L., Cantelli F. G. On cancer chemoprevention: Complications and limitations of some proposed strategies. Carcinogenesis 1995; 16: 971–972
  • Wattenberg L. W. What are the critical attributes for cancer chemopreventive agents? (Review). Ann. NY Acad. Sci. 1995; 768: 73–81
  • Kelloff G. J., Boone C. W., Steele V. E., Fay J. R., Lubet R. A., Crowell J. A., Sigman C. C. Mechanistic considerations in chemopreventive drug development. J. Cell Biochem. 1994; 20: 1–24
  • Boone C. W., Wattenberg L. W. Current strategies of cancer chemoprevention: 13th Sapporo Cancer Seminar. Cancer Res. 1994; 54: 3315–3318
  • Kensler T., Styczynski P., Groopman J., Helzlsouer K., Curphey T., Maxuitenko Y., Roebuck B. D. Mechanisms of chemoprotection by oltipraz. J. Cell Biochem. 1992, Suppl.: 167–172
  • Egner P. A., Kensler T. W., Prestera T., Talalay P., Libby A. H., Joyner H. H., Curphey T. J. Regulation of phase 2 enzyme induction by oltipraz and other dithiolethiones. Carcinogenesis 1994; 15: 177–181
  • Clapper M. L., Everley L. C., Strobel L. A., Townsend A. J., Engstrom P. F. Coordinate induction of glutathione S-transferase alpha, mu, and pi expression in murine liver after a single administration of oltipraz. Molec. Pharmacol. 1994; 45: 469–474
  • Anderson L., Steele V. K., Kelloff G. J., Sharma S. Effects of oltipraz and related chemoprevention compounds on gene expression in rat liver (Review). J. Cell. Biochem. 1995; 22(Suppl.): 108–116
  • Stohs S. J., Lawson T. A., Anderson L., Bueding E. Effects of oltipraz, BHA, ADT and cabbage on glutathione metabolism, DNA damage and lipid peroxidation in old mice. Mech. Ageing Devel. 1986; 37: 137–145
  • Primiano T., Egner P. A., Sutter T. R., Kelloff G. J., Roebuck B. D., Kensler T. W. Intermittent dosing with oltipraz: Relationship between chemoprevention of aflatoxin-induced tumorigenesis and induction of glutathione S-transferases. Cancer Res. 1995; 55: 4319–4324
  • Williams G. M., Iatropoulos M. J. Inhibition of the hepatocarcinogenicity of aflatoxin B1 in rats by low levels of the phenolic antioxidants butylated hydroxyanisole and butylated hydroxytoluene. Cancer Lett. 1996; 104: 49–53
  • Kensler T. W., Egner P. A., Davidson N. E., Roebuck B. D., Pikul A., Groopman J. D. Modulation of aflatoxin metabolism, aflatoxin-N7-guanine formation, and hepatic tumorigenesis in rats fed ethoxyquin: Role of induction of glutathione S-transferases. Cancer Res. 1986; 46: 3924–3931
  • Sparnins V. L., Barany G., Wattenberg L. W. Effects of organosulfur compounds from garlic and onions on benzo[a]pyrene-induced neoplasia and glutathione S-transferase activity in the mouse. Carcinogenesis 1988; 9: 131–134
  • Monks T. J., Anders M. W., Dekant W., Stevens J. L., Lau S. S., van Bladeren P. J. Glutathione conjugate mediated toxicities. Toxicol. Appl. Pharmacol. 1990; 106: 1–19
  • Guengerich F. P. Metabolism and genotoxicity of dihaloalkanes (Review). Adv. Pharmacol. 1994; 27: 211–236
  • Simula T. P., Glancey M. J., Wolf C. R. Human glutathione S-transferase-expressing Salmonella typhimurium tester strains to study the activation/detoxification of mutagenic compounds: Studies with halogenated compounds, aromatic amines and aflatoxin B1. Carcinogenesis 1993; 14: 1371–1376
  • Nebert D., Petersen D., Fornace J. A. Cellular responses to oxidative stress: The [AH] gene battery as a paradigm. Environ. Health Perspect. 1990; 88: 13–25
  • Daniel V. Glutathione S-transferases: Gene structure and regulation of expression. Crit. Rev. Biochem. Molec. Biol. 1993; 28: 173–207
  • Buetler T. M., Gallagher E. P., Wang C., Stahl D. L., Hayes J. D., Eaton D. L. Induction of phase I and phase II drug-metabolizing enzyme mRNA, protein, and activity by BHA, ethoxyquin, and oltipraz. Toxicol. Appl. Pharmacol. 1995; 135: 45–57
  • Pinkus R., Weiner L. M., Daniel V. Role of oxidants and antioxidants in the induction of AP-1, NF-kappaB, and glutathione S-transferase gene expression. J. Biol. Chem. 1996; 271: 13422–13429
  • Pulford D. J., Hayes J. D. Characterization of the rat glutathione S-transferase Yc2 subunit gene, GSTA5: Identification of a putative antioxidant-responsive element in the 5′-flanking region of rat GSTA5 that may mediate chemoprotection against aflatoxin B1. Biochem. J. 1996; 318: 75–84
  • Liu S. X., Pickett C. B. The rat liver glutathione S-transferase Ya subunit gene: Characterization of the binding properties of a nuclear protein from HepG2 cells that has high affinity for the antioxidant response element. Biochemistry 1996; 35: 11517–11521
  • Mannervik B. Evolution of glutathione transferases and related enzymes for the protection of cells against electrophiles. Biochem. Soc. Trans. 1996; 24: 878–880
  • Mannervik B., Danielson U. H. Glutathione transferases—structure and catalytic activity (Review). Crit. Rev. Biochem. 1988; 23: 283–337
  • Hayes J. D., Pulford D. J. The glutathione S-transferase supergene family: Regulation of GST and the contribution of the isoenzymes to cancer chemoprotection and drug resistance. Crit. Rev. Biochem. Molec. Biol. 1995; 30: 445–600
  • Ketterer B., Meyer D. J., Taylor J. B., Pemble S., Coles B., Fraser G. GSTs and protection against oxidative stress. Glutatione S-Transferases and Drug Resistance, J. D. Hayes, C. B. Pickett, T. J. Mantle. Taylor and Francis, London 1990; 97–110
  • Commandeur J. N., Stijntjes G. J., Vermeulen N. P. Enzymes and transport systems involved in the formation and disposition of glutathione S-conjugates. Role in bioactivation and detoxication mechanisms of xenobiotics (Review). Pharmacol. Rev. 1995; 47: 271–330
  • Pickett C. Glutathione S-transferases: Gene structure, regulation, and biological function. Annu. Rev. Biochem. 1989; 58: 743–764
  • Moody D. E., Narloch B. A., Shull L. R., Hammock B. D. The effect of structurally divergent herbicides on mouse liver xenobiotic-metabolizing enzymes (P-450-dependent mono-oxygenases, epoxide hydrolases and glutathione S-transferases) and carnitine acetyltransferase. Toxicol. Lett. 1991; 59: 175–185
  • Townsend A. J., Cowan K. H. Glutathione S-transferases and drug resistance (Review). Cancer Bull. 1989; 41: 31–37
  • Morrow C. S., Cowan K. H. Glutathione S-transferases and drug resistance. Cancer Cells 1990; 2: 15–17
  • Black S. M., Wolf C. R. The role of glutathione-dependent enzymes in drug resistance (Review). Pharmacol. Therapeut. 1991; 51: 139–154
  • Puchalski R. B., Fahl W. E. Expression of recombinant glutathione S-transferase pi, Ya, or Yb1 confers resistance to alkylating agents. Proc. Natl. Acad. Sci. USA 1990; 87: 2443–2447
  • Manoharan T. H., Welch P. J., Gulick A. M., Puchalski R. B., Lathrop A. L., Fahl W. E. Expression of tandem glutathione S-transferase recombinant genes in COS cells for analysis of efficiency of protein expression and associated drug resistance. Molec. Pharmacol. 1991; 39: 461–467
  • Miyazaki M., Kohno K., Saburi Y., Matsuo K., Ono M., Kuwano M., Tsuchida S., Sato K., Sakai M., Muramatsu M. Drug resistance to cis-diamminedichloroplatinum(II) in Chinese hamster ovary cell lines transfected with glutathione S-transferase Pi gene. Biochem. Biophys. Res. Commun. 1990; 166: 1358–1364
  • Nakagawa K., Saijo N., Tsuchida S., Sakai M., Tsunokawa Y., Yokota J., Muramatsu M., Sato K., Terada M., Tew K. D. Glutathione-S-transferase pi as a determinant of drug resistance in transfectant cell lines. J. Biol. Chem. 1990; 265: 4296–4301
  • Townsend A. J., Goldsmith M. E., Pickett C. B., Cowan K. H. Isolation, characterization, and expression in Escherichia coli of two murine mu class glutathione S-transferase cDNAs homologous to the rat subunits 3 (Yb1) and 4 (Yb2). J. Biol. Chem. 1989; 264: 21582–21590
  • Leyland-Jones B., Townsend A. J., Tu C. P., Cowan K. H., Goldsmith M. E. Antineoplastic drug sensitivity of human MCF-7 breast cancer cells stably transfected with a human alpha class glutathione S-transferase gene. Cancer Res. 1991; 51: 587–594
  • Moscow J. A., Townsend A. J., Cowan K. H. Elevation of pi class glutathione S-transferase activity in human breast cancer cells by transfection of the GSTπ gene and its effect on sensitivity to toxins. Molec. Pharmacol. 1989; 36: 22–28
  • Leier I., Jedlitschky G., Buchholz U., Cole S., Deeley R. G., Keppler D. The MRP gene encodes an ATP-dependent export pump for leukotriene C4 and structurally related conjugates. J. Biol. Chem. 1994; 269: 27807–27810
  • Müller M., Meijer C., Zaman G., Borst P., Scheper R. J., Mulder N. H., De Vries E., Jansen P. Overexpression of the gene encoding the multidrug resistance-associated protein results in increased ATP-dependent glutathione S-conjugate transport. Proc. Natl. Acad. Sci. USA 1994; 91: 13033–13037
  • Keppler D., Leier I., Jedlitschky G. Transport of glutathione conjugates and glucuronides by the multidrug resistance proteins MRP1 and MRP2 (Review). Biol. Chem. 1997; 378: 787–791
  • Paul S., Breuninger L. M., Tew K. D., Shen H. X., Kruh G. D. ATP-dependent uptake of natural product cytotoxic drugs by membrane vesicles establishes MRP as a broad specificity transporter. Proc. Natl. Acad. Sci. USA 1996; 93: 6929–6934
  • Grant C. E., Valdimarsson G., Hipfner D. R., Almquist K. C., Cole S., Deeley R. G. Overexpression of multidrug resistance-associated protein (MRP) increases resistance to natural product drugs. Cancer Res. 1994; 54: 357–361
  • Shen H. X., Paul S., Breuninger L. M., Ciaccio P. J., Laing N. M., Helt M., Tew K. D., Kruh G. D. Cellular and in vitro transport of glutathione conjugates by MRP. Biochemistry 1996; 35: 5719–5725
  • Müller M., De V. E., Jansen P. Role of multidrug resistance protein (MRP) in glutathione S-conjugate transport in mammalian cells. J. Hepatol. 1996; 1: 100–108
  • Pulaski L., Jedlitschky G., Leier I., Buchholz U., Keppler D. Identification of the multidrug-resistance protein (MRP) as the glutathione-S-conjugate export pump of erythrocytes. Eur. J. Biochem. 1996; 241: 644–648
  • Morrow C. S., Diah S., Smitherman P. K., Schneider E., Townsend A. J. Multidrug resistance protein and glutathione S-transferase P1-1 act in synergy to confer protection from 4-nitroquinoline 1-oxide toxicity. Carcinogenesis 1998; 19: 109–115
  • Fields W. R., Li Y., Townsend A. J. Protection by transfected glutathione S-transferase isozymes against carcinogen-induced alkylation of cellular macromolecules in human MCF-7 cells. Carcinogenesis 1994; 15: 1155–1160
  • Morrow C. S., Smitherman P. K., Diah S. K., Schneider E., Townsend A. J. Coordinated action of glutathione S-transferases (GST) and multidrug resistance protein (MRP) in antineoplastic drug detoxification: Mechanism of GSTA1-1- and MRP-associated resistance to chlorambucil in MCF-7 breast carcinoma cells. J. Biol. Chem. 1998; 273: 20114–20120
  • Simula A. P., Crichton M. B., Black S. M., Pemble S., Bligh H. F., Beggs J. D., Wolf C. R. Heterologous expression of drug-metabolizing enzymes in cellular and whole animal models (Review). Toxicology 1993; 82: 3–20
  • Langenbach R., Smith P. B., Crespi C. Recombinant DNA approaches for the development of metabolic systems used in in vitro toxicology (Review). Mutat. Res. 1992; 277: 251–275
  • Townsend A. J., Tu C. P., Cowan K. H. Expression of human mu or alpha class glutathione S-transferases in stably transfected human MCF-7 breast cancer cells: Effect on cellular sensitivity to cytotoxic agents. Molec. Pharmacol. 1992; 41: 230–236
  • Morrow C. S., Chiu J., Cowan K. H. Posttranscriptional control of glutathione S-transferase pi gene expression in human breast cancer cells. J. Biol. Chem. 1992; 267: 10544–10550
  • Bunting K. D., Townsend A. J. De novo expression of transfected human class 1 aldehyde dehydrogenase (ALDH) causes resistance to oxazaphosphorine anti-cancer alkylating agents in hamster V79 cell lines. J. Biol. Chem. 1996; 271: 11884–11890
  • Moscow J. A., Fairchild C. R., Madden M. J., Ransom D. T., Wieand H. S., O'Brien E. E., Poplack D. G., Cossman J., Myers C. E., Cowan K. H. Expression of anionic glutathione-S-transferase and P-glycoprotein genes in human tissues and tumors. Cancer Res. 1989; 49: 1422–1428
  • Rhoads D. M., Zarlengo R. P., Tu C. P. The basic glutathione S-transferases from human livers are products of separate genes. Biochem. Biophys. Res. Commun. 1987; 145: 474–481
  • DeJong J. L., Chang C.-M., Whang-Peng J., Knutsen T., Tu C.-P. D. The human liver glutathione S-transferase gene superfamily: Expression and chromosome mapping of an Hb subunit cDNA. Nucl. Acids Res. 1988; 16: 8541–8554
  • Buetler T. M., Eaton D. L. Complementary DNA cloning, messenger RNA expression, and induction of alpha-class glutathione S-transferases in mouse tissues. Cancer Res. 1992; 52: 314–318
  • Townsend A. J., Goldsmith M. E., Pickett C. B., Cowan K. H. Isolation, characterization, and expression in Escherichia coli of two murine mu class glutathione S-transferase cDNAs homologous to the rat subunits 3 (Yb1) and 4 (Yb2). J. Biol. Chem. 1989; 264: 21582–21590
  • Dogra S., Doehmer J., Glatt H., Molders H., Siegert P., Freidberg T., Seidel A., Oesch F. Stable expression of rat cytochrome P-4501A1 cDNA in V79 chinese hamster cells and their use in mutagenicity testing. Mol. Pharm. 1990; 37: 608–613
  • Doehmer J., Dogra S., Friedberg T., Monier S., Adesnik M., Glatt H., Oesch F. Stable expression of rat cytochrome P-450IIB1 cDNA in Chinese hamster cells (V79) and metabolic activation of aflatoxin B1. Proc. Natl. Acad. Sci. USA 1988; 85: 5769–5773
  • Schneider E., Horton J. K., Yang C. H., Nakagawa M., Cowan K. H. Multidrug resistance-associated protein gene overexpression and reduced drug sensitivity of topoisomerase II in a human breast carcinoma MCF7 cell line selected for etoposide resistance. Cancer Res. 1994; 54: 152–158
  • Fields W. R., Morrow C. S., Townsend A. J. Overexpression of stably transfected human glutathione S-transferase (GST) P1-1 protects against DNA damage by benzo[a]pyrene diol epoxide (BPDE) in human T47D cells. Molec. Pharmacol. 1998; 54: 298–304
  • Townsend A. J., Fields W. R., Haynes R. L., Karper A. J., Li Y., Doehmer J., Morrow C. S. Chemoprotective functions of glutathione S-transferases in cell lines induced to express specific isozymes by stable transfection. Chem. Biol. Interact. 1998; 111–112: 389–407
  • Sims P. The metabolic activation of chemical carcinogens (Review). Br. Med. Bull. 1980; 36: 11–18
  • Shimada T., Martin M. V., Pruess S. D., Marnett L. J., Guengerich F. P. Roles of individual human cytochrome P-450 enzymes in the bioactivation of benzo(a)pyrene, 7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene, and other dihydrodiol derivatives of polycyclic aromatic hydrocarbons. Cancer Res. 1989; 49: 6304–6312
  • Wei S. J., Chang R. L., Hennig E., Cui X. X., Merkler K. A., Wong C. Q., Yagi H., Jerina D. M., Conney A. H. Mutagenic selectivity at the HPRT locus in V-79 cells: Comparison of mutations caused by bay-region benzo[a]pyrene 7,8-diol-9,10-epoxide enantiomers with high and low carcinogenic activity. Carcinogenesis 1994; 15: 1729–1736
  • Wei S. J., Chang R. L., Bhachech N., Cui X. X., Merkler K. A., Wong C. Q., Hennig E., Yagi H., Jerina D. M., Conney A. H. Dose-dependent differences in the profile of mutations induced by (+)-7R,8S-di-hydroxy-9S,10R-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene in the coding region of the hypoxanthine (guanine) phosphoribosyltransferase gene in Chinese hamster V-79 cells. Cancer Res. 1993; 53: 3294–3301
  • Robertson I. G., Guthenberg C., Mannervik B., Jernstrom B. Differences in stereoselectivity and catalytic efficiency of three human glutathione transferases in the conjugation of glutathione with 7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-oxy-7,8,9,10-tetrahydrobenzo(a)pyrene. Cancer Res. 1986; 46: 2220–2224
  • Vickers P., Dufresne M., Cowen K. Relation between cytochrome P4501A1 expression and estrogen receptor content of human breast cancer cells. Mol. Endocrinol. 1989; 3: 157–164
  • Glatt H., Gemperlein I., Turchi G., Heinritz H., Doehmer J., Oesch F. Search for cell culture systems with diverse xenobiotic-metabolizing activities and their use in toxicological studies (Review). Molec. Toxicol. 1987; 1: 313–334
  • McLean M., Dutton M. F. Cellular interactions and metabolism of aflatoxin: An update. Pharmacol. Ther. 1995; 65: 163–192
  • Eaton D. L., Gallagher E. P. Mechanisms of aflatoxin carcinogenesis (Review). Annu. Rev. Pharmacol. Toxicol. 1994; 34: 135–172
  • Buetler T. M., Slone D., Eaton D. L. Comparison of the aflatoxin B1-8,9-epoxide conjugating activities of two bacterially expressed alpha class glutathione S-transferase isozymes from mouse and rat. Biochem. Biophys. Res. Commun. 1992; 188: 597–603
  • Hayes J. D., Judah D. J., McLellan L. I., Kerr L. A., Peacock S. D., Neal G. E. Ethoxyquin-induced resistance to aflatoxin B1 in the rat is associated with the expression of a novel Alpha-class glutathione S-transferase subunit, Yc2, which possesses high catalytic activity for aflatoxin B1-8,9-epoxide. Biochem. J. 1991; 279: 385–398
  • Johnson W. W., Harris T. M., Guengerich F. P. Kinetics and mechanism of hydrolysis of aflatoxin B1 exo-8,9-epoxide and rearrangement of the dihydrodiol. J. Am. Chem. Soc. 1996; 118: 8213–8220
  • Merlos M., Sanchez R. M., Camarasa J., Adzet T. Flavonoids as inhibitors of rat liver cytosolic glutathione S-transferase. Experientia 1991; 47: 616–619
  • Ahmad H., Singh S. V., Awasthi Y. C. Inhibition of bovine lens glutathione S-transferases by hematin, bilirubin, and bromosulfophthalein. Lens Eye Toxic Res. 1991; 8: 431–440
  • Datta K., Kulkarni A. P. Inhibition of mammalian hepatic glutathione S-transferases by acetylenic fatty acids. Toxicol. Lett. 1994; 73: 157–165
  • Hayes J. D., Chalmers J. Bile acid inhibition of basic and neutral glutathione S-transferases in rat liver. Biochem. J. 1983; 215: 581–588
  • Bogaards J., Venekamp J. C., Van B. P. Stereoselective conjugation of prostaglandin A2 and prostaglandin J2 with glutathione, catalyzed by the human glutathione S-transferases A1-1, A2-2, M1a-1a, and P1-1. Chem. Res. Toxicol. 1997; 10: 310–317
  • Listowsky I., Abramovitz M., Homma H., Niitsu Y. Intracellular binding and transport of hormones and xenobiotics by glutathione-S-transferases (Review). Drug Metab. Rev. 1988; 19: 305–318
  • Redegeld F., Hofman G. A., Van de Loo P. G. F., Koster A. S., Noordhoek J. Nephrotoxicity of the glutathione conjugate of menadione (2-methyl-1,4-naphthoquinone) in the isolated perfused rat kidney. Role of metabolism by gamma-glutamyltranspeptidase and probenecid-sensitive transport. J. Pharmacol. Exp. Ther. 1991; 256: 665–669
  • Horvath J. J., Witmer C. M., Witz G. Nephrotoxicity of the 1:1 acrolein–glutathione adduct in the rat. Toxicol. Appl. Pharmacol. 1992; 117: 200–207
  • Ramu K., Perry C. S., Ahmed T., Pakenham G., Kehrer J. P. Studies on the basis for the toxicity of acrolein mercapturates. Toxicol. Appl. Pharmacol. 1996; 140: 487–498

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.