Protein targets of xenobiotic reactive intermediates

Annual Review of Pharmacology and Toxicology

Volumn 37, Issue , 1997, Pages 91-117

  Pumford, Neil R ^a   Halmes, N Christine ^a  

^a UNIVERSITY OF ARKANSAS FOR MEDICAL SCIENCES   (United States)

Author keywords

acetaminophen; halothane; protein adducts; protein conjugates; trichloroethylene

Indexed keywords

ALCOHOL; AMODIAQUINE; BUTYLCRESOL; CLOFIBRIC ACID; CYANOGINOSIN; DICLOFENAC; DIFLUNISAL; ENFLURANE; HALOTHANE; IBUPROFEN; IMIPRAMINE; ISOFLURANE; METHAPYRILENE; PARACETAMOL; SKATOLE; SULINDAC; TETRACHLOROETHYLENE; TIENILIC ACID; TOLUENE DIISOCYANATE; TRICHLOROETHYLENE; VALPROIC ACID; XENOBIOTIC AGENT; ZOMEPIRAC;

AUTOIMMUNITY; COVALENT BOND; HUMAN; HYPERSENSITIVITY; NONHUMAN; PRIORITY JOURNAL; PROTEIN BINDING; REVIEW; SIDE EFFECT;

EID: 0030927213     PISSN: 03621642     EISSN: None     Source Type: Book Series    
DOI: None     Document Type: Review

References (168)

1. Miller EC, Miller JA. 1947. The presence and significance of bound aminoazo dyes in the livers of rats fed p-dimethylaminoazobenzene. Cancer Res. 7:468-80
2. Hinson JA, Roberts DW. 1992. Role of covalent and noncovalent interactions in cell toxicity: effects on proteins. Annu. Rev. Pharmacol. Toxicol. 32:471-510
3. Chang LW, Hsia SM, Chan PC, Hsieh LL. 1994. Macromolecular adducts: biomarkers for toxicity and carcinogenesis. Annu. Rev. Pharmacol. Toxicol. 34:41-67
4. Nelson SD, Pearson PG. 1990. Covalent and noncovalent interactions in acute lethal cell injury caused by chemicals. Annu. Rev. Pharmacol. Toxicol. 30:169-95
5. Brodie BB, Reid WD, Cho AK, Sipes G, Krishna G, et al. 1971. Possible mechanism of liver necrosis caused by aromatic organic compounds. Proc. Natl. Acad. Sci. USA 68:160-64
6. Boelsterli UA. 1993. Specific targets of covalent drug-protein interactions in hepatocytes and their toxicological significance in drug-induced liver injury. Drug Metab. Rev. 25:395-451
7. Beaune P, Pessayre D, Dansette P, Mansuy D, Manns M. 1994. Autoantibodies against cytochromes P450: role in human diseases. Adv. Pharmacol. 30:199-245
8. Hinson JA. 1980. Biochemical toxicology of acetaminophen. Rev. Biochem. Toxicol. 2:103-29
9. Mitchell JR, Jollow DJ, Potter WZ, Davis DC, Gillette JR, et al. 1973. Acetaminophen-induced hepatic necrosis. I. Role of drug metabolism. J. Pharmacol. Exp. Ther. 187:185-94
10. Potter WZ, Davis DC, Mitchell JR, Jollow DJ, Gillette JR, et al. 1973. Acetaminophen-induced hepatic necrosis. III. Cytochrome P-450-mediated covalent binding in vitro. J. Pharmacol. Exp. Ther. 187:203-10
11. Jollow DJ, Mitchell JR, Potter WZ, Davis DC, Gillette JR, et al. 1973. Acetaminophen-induced hepatic necrosis. II. Role of covalent binding in vivo. J. Pharmacol. Exp. Ther. 187:195-202
12. Mitchell JR, Jollow DJ, Potter WZ, Gillette JR, Brodie BB. 1973. Acetaminophen-induced hepatic necrosis. IV. Protective role of glutathione. J. Pharmacol. Exp. Ther. 187:211-17
13. Raucy JL, Lasker JM, Lieber CS, Black M. 1989. Acetaminophen activation by human liver cytochromes P450IIE1 and P450IA2. Arch. Biochem. Biophys. 271:270-83
14. Patten CJ, Thomas PE, Guy RL, Lee M, Gonzalez FJ, et al. 1993. Cytochrome P450 enzymes involved in acetaminophen activation by rat and human liver microsomes and their kinetics. Chem. Res. Toxicol. 6:511-18
15. Thummel KE, Lee CA, Kunze KL, Nelson SD, Slattery JT. 1993. Oxidation of acetaminophen to N-acetyl-p-benzoquinoneimine by human CYP3A4. Biochem. Pharmacol. 45:1563-69
16. Lee SST, Buters JTM, Pineau T, Fernandez-Salguero P, Gonzalez FJ. 1996. Role of CYP2E1 in the hepatotoxicity of acetaminophen. J. Biol. Chem. 271:12063-67
17. Dahlin DC, Miwa GT, Lu AYH, Nelson SD. 1984. N-Acetyl-p-benzoquinone imine: A cytochrome P-450-mediated oxidation product of acetaminophen. Proc. Natl. Acad. Sci. USA 81:1327-31
18. Hinson JA, Monks TJ, Hong M, Highet RJ, Pohl LR. 1982. 3-(glutathion-S-yl)acetaminophen: a biliary metabolite of acetaminophen. Drug Metab. Dispos. 10:47-50
19. Bartolone JB, Sparks K, Cohen SD, Khairallah EA. 1987. Immunochemical detection of acetaminophen-bound liver proteins. Biochem. Pharmacol 36:1193-96
20. Pumford NR, Hinson JA, Benson RW, Roberts DW. 1990. Immunoblot analysis of protein containing 3-(cystein-S-yl)acetaminophen adducts in serum and subcellular liver fractions from acetaminophen-treated mice. Toxicol. Appl. Pharmacol. 104:521-32
21. Vermeulen NPE, Bessems JGM, Van de Straat R. 1992. Molecular aspects of paracetamol-induced hepatotoxicity and its mechanism-based prevention. Drug Metab. Rev. 24:367-407
22. 2+ in the nucleus during acetaminophen-induced liver injury. Toxicol. Appl. Pharmacol. 106:346-51
23. 2+)-endonuclease, DNA repair, and glutathione depletion inhibitors on DNA fragmentation and cell death. Toxicol. Appl. Pharmacol 112:32-40
24. Laskin DL, Pendino KJ. 1995. Macrophages and inflammatory mediators in tissue injury. Annu. Rev. Pharmacol. Toxicol. 35:655-77
25. Hinson JA, Pumford NR, Nelson SD. 1994. The role of metabolic activation in drug toxicity. Drug Metab. Rev. 26:395-412
26. Gillette JR. 1974. Commentary. A perspective on the role of chemically reactive metabolites of foreign compounds in toxicity. I. Correlation of changes in covalent binding of reactive metabolites with changes in the incidence and severity of toxicity. Biochem. Pharmacol. 23:2785-94
27. Roberts DW, Pumford NR, Potter DW, Benson RW, Hinson JA. 1987. A sensitive immunochemical assay for acetaminophen-protcin adducts. J. Pharmacol. Exp. Ther. 241:527-33
28. Pumford NR, Roberts DW, Benson RW, Hinson JA. 1990. Immunochemical quantitation of 3-(cystein-S-yl)acetaminophen protein adducts in subcellular liver fractions following a hepatotoxic dose of acetaminophen. Biochem. Pharmacol. 40:573-79
29. Bulera SJ, Birge RB, Cohen SD, Khairallah EA. 1995. Identification of the mouse liver 44-kDa acetaminophen-binding protein as a subunit of glutamine synthetase. Toxicol. Appl. Pharmacol. 134:313-20
30. Hong M, Cohen SD, Khairallah EA. 1994. Translocation of the major cytosolic acetaminophen (APAP) protein adducts into the nucleus. Toxicologist 14:427
31. Pumford NR, Martin BM, Hinson JA. 1992. A metabolite of acetaminophen covalently binds to the 56 kDa selenium binding protein. Biochem. Biophys. Res. Commun. 182:1348-55
32. Bartolone JB, Birge RB, Bulera SJ, Bruno MK, Nishanian EV, et al. 1992. Purification, antibody production, and partial amino acid sequence of the 58-kDa acetaminophen-binding liver proteins. Toxicol. Appl. Pharmacol. 113:19-29
33. Halmes NC, Hinson JA, Martin BM, Pumford NR. 1996. Glutamate dehydrogenase covalently binds to a reactive metabolite of acetaminophen. Chem. Res. Toxicol. 9:541-46
34. Landin JS, Cohen SD. Khairallah EA. 1996. Identification of a 54-kDa mitochondrial acetaminophen-binding protein as aldehyde dehydrogenase. Toxicol. Appl. Pharmacol. 141:299-307
35. Pumford NR, Halmes NC, Martin BM, Cook RJ, Wagner C, Hinson JA. 1997. Covalent binding to N-10-formyl tetrahydrofolate dehydrogenase in mice. J. Pharmacol. Exp. Ther. 280: In press
36. Gupta S, Rogers LK, Smith CV. 1995. Inhibition of carbamyl phosphate synthetase I (CPS I) by hepatotoxic doses of acetaminophen (AP) in mice. Fundam. Appl. Toxicol. 15:153
37. Lanfear J, Fleming J, Walker M, Harrison P. 1993. Different patterns of regulation of the genes encoding the closely related 56 kDa selenium- and acetaminophen-binding proteins in normal tissues and during carcinogenesis. Carcinogenesis 14:335-40
38. Bulera SJ, Birge RB, Cohen SD, Khairallah EA. 1995. Identification of the mouse liver 44-kDa acetaminophen-binding protein as a subunit of glutamine synthetase. Toxicol. Appl. Pharmacol. 134:313-20
39. Birge RB, Bulera SJ, Bartolone JB, Ginsberg GL, Cohen SD, et al. 1991. The arylation of microsomal membrane proteins by acetaminophen is associated with the release of a 44 kDa acetaminophen-binding mouse liver protein complex into the cytosol. Toxicol. Appl. Pharmacol. 109:443-54
40. Walker RM, Racz WJ, McElligott TF. 1980. Acetaminophen-induced hepatotoxicity in mice. Lab. Invest. 42:181-89
41. Burcham PC, Harman AW. 1990. Mitochondrial dysfunction in paracetamol hepatotoxicity: in vitro studies in isolated mouse hepatocytes. Toxicol. Lett. 50:37-48
42. Ramsay RR, Rashed MS, Nelson SD. 1989. In vitro effects of acetaminophen metabolites and analogs on the respiration of mouse liver mitochondria. Arch. Biochem. Biophys. 273:449-57
43. Meyers LL, Beierschmitt WP, Khairallah EA, Cohen SD. 1988. Acetaminophen-induced inhibition of hepatic mitochondrial respiration in mice. Toxicol. Appl. Pharmacol. 93:378-87
44. Donnelly PJ, WalkerRM, Racz WJ. 1994. Inhibition of mitochondrial respiration in vivo is an early event in acetaminophen-induced hepatotoxicity. Arch. Toxicol. 68:110-18
45. +-ATPase ion pump during acetaminophen-induced hepatotoxicity in rat. Biochem. Biophys. Res. Commun. 149:203-7
46. Roberts SA, Jollow DJ. 1979. Acetaminophen structure-toxicity relationships: Why is 3HAA not hepatotoxic? Pharmacologist 21:259
47. Nelson EB. 1980. The pharmacology and toxicology of meta-substituted acetanilide: I. Acute toxicity of 3HAA in mice. Res. Commun. Chem. Pathol. Pharmacol. 28:447-56
48. Roberts SA, Jollow DJ. 1980. Acetaminophen structure-toxicity studies: In vivo covalent binding of a non-hepatotoxic analog, 3-hydroxyacetanilide. Fed. Proc. 38:426
49. Roberts SA, Price VF, Jollow DJ. 1990. Acetaminophen structure-toxicity studies: in vivo covalent binding of a nonhepatotoxic analog, 3-hydroxyacetanilide. Toxicol. Appl. Pharmacol. 105:195-208
50. Tirmenstein MA, Nelson SD. 1989. Subcellular binding and effects on calcium homeostasis produced by acetaminophen and a nonhepatotoxic regioisomer, 3′-hydroxyacetanilide, in mouse liver. J. Biol. Chem. 264:9814-19
51. Tirmenstein MA, Nelson SD. 1991. Hepatotoxicity after 3′-hydroxyacetanilide administration to buthionine sulfoximine pretreated mice. Chem. Res. Toxicol. 4:214-17
52. Hamilton M, Kissinger PT. 1986. The metabolism of 2- and 3-hydroxyacetanilide. Drug Metab. Dispos. 14:5-12
53. Rashed MS, Nelson SD. 1989. Use of thermospray liquid chromatography-mass spectrometry for characterization of reactive metabolites of 3′-hydroxyacetanilide, a non-hepatotoxic regioisomer of acetaminophen. J. Chromatog. 474:209-22
54. Rashed MS, Myers TG, Nelson SD. 1990. Hepatic protein arylation, glutathione depletion, and metabolite profiles of acetaminophen and a non-hepatotoxic regioisomer, 3′-hydroxyacetanilide, in the mouse. Drug Metab. Dispos. 18:765-70
55. Myers TG, Dietz EC, Anderson NL, Khairallah EA, Cohen SD, et al. 1995. A comparative study of mouse liver proteins arylated by reactive metabolites of acetaminophen and its nonhepatotoxic regioisomer, 3′-hydroxyacetanilide. Chem. Res. Toxicol. 8:403-13
56. Matthews AM, Roberts DW, Hinson JA, Pumford NR. 1996. Acetaminophen-induced hepatotoxicity: Analysis of total covalent binding versus specific binding to cysteine. Drug Metab. Dispos. 24:1192-96
57. Matthews AM, Hinson JA, Roberts DW, Pumford NR. 1996. Immunochemical analysis of covalent binding of acetaminophen and the regioisomer 3-hydroxyacetanilide to protein. Tox. Letters 90:77-82
58. Halmes NC, Samokyszyn VM, Hinton TW, Pumford NR, Hinson JA. 1996. Comparison of the effects of acetaminophen and 3-hydroxyacetanilide on covalent binding and cytochrome p450 2E1 activity in vivo and in vitro. Submitted
59. Anderson NL, Copple DC, Bendele RA, Probst GS, Richardson FC. 1992. Covalent protein modifications and gene expression changes in rodent liver following administration of methapyrilene: A study using two-dimensional electrophoresis. Fundam. Appl. Toxicol. 18:570-80
60. Reed M, Thompson DC. 1996. Immunochemical visualization of rat liver proteins adducted by butylated hydroxytoluene (BHT). Fundam. Appl. Toxicol. 30:280
61. Clarke JB, Maggs JL, Kitteringham NR, Park BK. 1990. Immunogenicity of amodiaquine in the rat. Int. Arch. Allergy Appl. Immunol. 91:335-42
62. Clarke JB, Neftel K, Kitteringham NR, Park BK. 1991. Detection of antidrug IgG antibodies in patients with adverse drug reactions to amodiaquine. Int. Arch. Allergy Appl. Immunol. 95:369-75
63. Harrison AC, Kitteringham NR, Clarke JB, Park BK. 1992. The mechanism of bioactivation and antigen formation of amodiaquine in the rat. Biochem. Pharmacol. 43:1421-30
64. Dekant W, Vamvakas S, Anders MW. 1989. Bioactivation of nephrotoxic haloalkenes by glutathione conjugation: formation of toxic and mutagenic intermediates by cysteine conjugate beta-lyase. Drug Metab. Rev. 20:43-83
65. Monks TJ, Anders MW, Dekant W, Stevens JL, Lau SS, et al. 1990. Glutathione conjugate mediated toxicities. Toxicol. Appl. Pharmacol. 106:1-19
66. Boogaard PJ, Commandeur JN, Mulder GJ, Vermeulen NP, Nagelkerke JF. 1989. Toxicity of the cysteine-S-conjugates and mercapturic acids of four structurally related difluoroethylenes in isolated proximal tubular cells from rat kidney. Up-take of the conjugates and activation to toxic metabolites. Biochem. Pharmacol. 38:3731-41
67. Hayden PJ, Ichimura T, McCann DJ, Pohl LR, Stevens JL. 1991. Detection of cysteine conjugate metabolite adduct formation with specific mitochondrial proteins using antibodies raised against halothane metabolite adducts. J. Biol. Chem. 266:18415-18
68. Harris JW, Dekant W, Anders MW. 1992. In vivo detection and characterization of protein adducts resulting from bioactivation of haloethene cysteine S-conjugates by 19F NMR: chlorotrifluoroethene and tetrafluoroethene. Chem. Res. Toxicol. 5:34-41
69. Satoh H, Fukuda Y, Anderson DK, Ferrans VJ, Gillette JR, et al. 1985. Immunological studies on the mechanism of halothane-induced hepatotoxicity: immunohistochemical evidence of trifluoroacetylated hepatocytes. J. Pharmacol. Exp. Ther. 233:857-62
70. Bruschi SA, West KA, Crabb JW, Gupta RS, Stevens JL. 1993. Mitochondrial HSP60 (P1 protein) and a HSP70-like protein (mortalin) are major targets for modification during S-(1,1,2,2-tetrafluoroethyl)-L-cysteine-induced nephrotoxicity. J. Biol. Chem. 268:23157-61
71. Monks TJ, Jones TW, Hill BA, Lau SS. 1991. Nephrotoxicity of 2-bromo-(cystein-S-yl) hydroquinone and 2-bromo-(N-acetyl-L-cystein-S-yl) hydroquinone thioethers. Toxicol. Appl. Pharmacol. 111:279-98
72. Kleiner HE, Pumford NR, Monks TJ, Lau SS. 1996. Covalent and oxidative protein modification by nephrotoxic quinonethioethers in vivo. Fundam. Appl. Toxicol. 30:331
73. 1966. Summary of the National Halothane Study. JAMA 197:121-34
74. Vergani D, Tsantoulas D, Eddleston AL, Davis M, Williams R. 1978. Sensitisation to halothane-altered liver components in severe hepatic necrosis after halothane anaesthesia. Lancet 2:801-3
75. Vergani D, Mieli VG, Alberti A, Neuberger J, Eddleston AL, et al. 1980. Antibodies to the surface of halothane-altered rabbit hepatocytes in patients with severe halothane-associated hepatitis. N. Engl. J. Med. 303:66-71
76. Kenna JG, Neuberger J, Williams R. 1987. Identification by immunoblotting of three halothane-induced liver microsomal polypeptide antigens recognized by antibodies in sera from patients with halothane-associated hepatitis. J. Pharmacol. Exp. Ther. 242:733-40
77. Kenna JG, Satoh H, Christ DD, Pohl LR. 1988. Metabolic basis for a drug hypersensitivity: antibodies in sera from patients with halothane hepatitis recognize liver neoantigens that contain the trifluoroacetyl group derived from halothane. J. Pharmacol. Exp. Ther. 245:1103-9
78. Kenna JG, Neuberger J, Williams R. 1988. Evidence for expression in human liver of halothane-induced neoantigens recognized by antibodies in sera from patients with halothane hepatitis. Hepatology 8:1635-41
79. Martin JL, Kenna JG, Martin BM, Thomassen D, Reed GF, et al. 1993. Halothane hepatitis patients have serum antibodies that react with protein disulfide isomerase. Hepatology 18:858-63
80. Martin JL, Pumford NR, LaRosa AC, Martin BM, Gonzaga HM, et al 1991. A metabolite of halothane covalently binds to an endoplasmic reticulum protein that is highly homologous to phosphatidylinositol-specific phospholipase C-alpha but has no activity. Biochem. Biophys. Res. Commun. 178:679-85
81. Bourdi M, Demady D, Martin JL, Jabbour SK, Martin BM, et al. 1995. cDNA cloning and baculovirus expression of the human liver endoplasmic reticulum P58: Characterization as a protein disulfide isomerase isoform, but not as a protease or a carnitine acyltransferase. Arch. Biochem. Biophys. 323:397-403
82. Satoh H, Martin BM, Schulick AH, Christ DD, Kenna JG, et al. 1989. Human antiendoplasmic reticulum antibodies in sera of patients with halothane-induced hepatitis are directed against a trifluoroacetylated carboxylesterase. Proc. Natl. Acad. Sci. USA 86:322-26
83. Butler LE, Thomassen D, Martin JL, Martin BM, Kenna JG, et al. 1992. The calcium-binding protein calreticulin is covalently modified in rat liver by a reactive metabolite of the inhalation anesthetic halothane. Chem. Res. Toxicol. 5:406-10
84. Pumford NR, Martin BM, Thomassen D, Burris JA, Kenna JG, et al. 1993. Serum antibodies from halothane hepatitis patients react with the rat endoplasmic reticulum protein Erp72. Chem. Res. Toxicol. 6:609-15
85. Davila JC, Pumford NR, Martin BM, Thomassen D, Martin JL, et al. 1991. A trifluoroacetylated 82 kDa stress protein appears to be a neoantigen associated with halothane hepatitis. Toxicologist 11:268
86. Thomassen D, Martin BM, Martin JL, Pumford NR, Pohl LR. 1990. Characterization of a halothane induced trifluoroacetylated 100 kDa neoantigen that is related to a glucose-regulated protein. FASEB J. 4:A599
87. Amouzadeh HR, Bourdi M, Martin JL, Martin BM, Pohl LR. 1996. UDP-glucose:glycoprotein glucosyltranserase associates with endoplasmic reticulum chaperons and its activity is decreased in vivo. Chem. Res. Toxicol. In press
88. Eliasson E, Kenna JG. 1996. Cytochrome P450 2E1 is a cell surface autoantigen in halothane hepatitis. Mol. Pharmacol. 50:573-82
89. Bourdi M, Chen W, Peter RM, Martin JL, Buters JTM, et al. 1996. Human P4502E1 is a major autoantigen associated with halothane hepatitis and the epitopes are conformational. Chem. Res. Toxicol. 9:1159-66
90. Brown AP, Hastings KL, Gandolfi AJ, Liebler DC, Brendel K. 1992. Formation and identification of protein adducts to cytosolic proteins in guinea pig liver slices exposed to halothane. Toxicology 73:281-95
91. Kenna JG, Martin JL, Satoh H, Pohl LR. 1990. Factors affecting the expression of trifluoroacetylated liver microsomal protein neoantigens in rats treated with halothane. Drug Metab. Dispos. 18:788-93
92. Satoh H, Gillette JR, Davies HW, Schulick RD. Pohl LR. 1985. Immunochemical evidence of trifluoroacetylated cytochrome P-450 in the liver of halothane-treated rats. Mol. Pharmacol. 28:468-74
93. Smith GC, Kenna JG, Harrison DJ, Tew D, Wolf CR. 1993. Autoantibodies to hepatic microsomal carboxylesterase in halothane hepatitis. Lancet 342:963-64
94. Pohl LR, Thomassen D, Pumford NR, Butler LE, Satoh H. et al. 1990. Hapten carrier conjugates associated with halothane hepatitis. Adv. Exp. Med. Biol. 283:111-20
95. Dorner AJ, Wasley LC, Raney P, Haugejorden S, Green M, et al. 1990. The stress response in Chinese hamster ovary cells: Regulation of ERp72 and protein disulfide isomerase expression and secretion. J. Biol. Chem. 265:22029-34
96. Mazzarella RA, Srinivasan M, Haugejorden SM, Green M. 1990. ERp72, an abundant luminal endoplasmic reticulum protein, contains three copies of the active site sequences of protein disulfide isomerase. J. Biol. Chem. 265:1094-101
97. Urade R, Takenaka Y, Kito M. 1993. Protein degradation by ERp72 from rat and mouse liver endoplasmic reticulum. J. Biol. Chem. 268:22004-9
98. Mazzarella RA, Green M. 1987. ERp99, an abundant, conserved glycoprotein of the endoplasmic reticulum, is homologous to the 90-kDa heat shock protein (hsp90) and the 94-kDa glucose regulated protein (GRP94). J. Biol. Chem. 262:8875-83
99. Amouzadeh HR, Pohl LR. 1995. Processing of endoplasmic reticulum luminal antigens associated with halothane hepatitis in rat hepatocytes. Hepatology 22:936-43
100. Harris JW, Pohl LR, Martin JL, Anders MW. 1991. Tissue acylation by the chlorofluorocarbon substitute 2,2-dichloro-1,1,1-trifluoroethane. Proc. Natl. Acad. Sci. USA 88:1407-10
101. Harris JW, Jones JP, Martin JL, LaRosa AC, Olson MJ, et al. 1992. Pentahaloethane-based chlorofluorocarbon substitutes and halothane: correlation of in vivo hepatic protein trifluoroacetylation and urinary trifluoroacetic acid excretion with calculated enthalpies of activation. Chem. Res. Toxicol. 5:720-25
102. Brown AP, Gandolfi AJ. 1994. Glutathione-S-transferase is a target for covalent modification by a halothane reactive intermediate in the guinea pig liver. Toxicology 89:35-4-7
103. Pohl LR, Pumford NR, Martin JL. 1996. Mechanisms, chemical structures, and drug metabolism. Eur. J. Haematol. 57:98-104 (Suppl.)
104. Kitteringham NR, Kenna JG, Park BK. 1995. Detection of autoantibodies directed against human hepatic endoplasmic reticulum in sera from patients with halothane-associated hepatitis. Br. J. Clin. Pharmacol. 40:379-86
105. Christ DD, Kenna JG, Kammerer W, Satoh H, Pohl LR. 1988. Enflurane metabolism produces covalently bound liver adducts recognized by antibodies from patients with halothane hepatitis. Anesthesiology 69:833-88
106. Christ DD, Satoh H, Kenna JG, Pohl LR. 1988. Potential metabolic basis for enflurane hepatitis and the apparent cross-sensitization between enflurane and halothane. Drug Metab. Dispos. 16:135-40
107. Clarke JB, Thomas C, Chen M, Hastings KL, Gandolfi AJ. 1995. Halogenated anesthetics form liver adducts and antigens that cross-react with halothane-induced antibodies. Int. Arch. Allergy Immunol. 108:24-32
108. Pariente EA, Pessayre D, Bernuau J, Degott C, Benhamou JP. 1983. Dihydralazine hepatitis: report of a case and review of the literature. Digestion 27:47-52
109. 2) in tienilic acid-induced hepatitis. Clin. Exp. Immunol. 55:561-70
110. Bourdi M, Larrey D, Nataf J, Bernuau J, Pessayre D, et al. 1990. Anti-liver endoplasmic reticulum autoantibodies are directed against human cytochrome P-450IA2. A specific marker of dihydralazine-induced hepatitis. J. Clin. Invest 85:1967-73
111. Beaune P, Bourdi M, Belloc C, Gautier JC, Guengerich FP, et al. 1993. Immunotoxicology and expression of human cytochrome P450 in microorganisms. Toxicology 82:53-60
112. Bourdi M, Tinel M, Beaune PH, Pessayre D. 1994. Interactions of dihydralazine with cytochromes P4501A: a possible explanation for the appearance of anti-cytochrome P4501A2 autoantibodies. Mol. Pharmacol. 45:1287-95
113. Beaune P, Dansette PM, Mansuy D, Kiffel L, Finck M, et al. 1987. Human anti-endoplasmic reticulum autoantibodies appearing in a drug-induced hepatitis are directed against a human liver cytochrome P-450 that hydroxylates the drug. Prac. Natl. Acad. Sci. USA 84:551-5
114. Dansette PM, Amar C, Smith C, Pons C, Mansuy D. 1990. Oxidative activation of the thiophene ring by hepatic enzymes. Hydroxylation and formation of electrophilic metabolites during metabolism of tienilic acid and its isomer by rat liver microsomes. Biochem. Pharmacol. 39:911-18
115. Pons C, Dansette PM, Amar C, Jaouen M, Wolf CR, et al. 1991. Detection of human hepatitis anti-liver kidney microsomes (LKM2) autoantibodies on rat liver sections is predominantly due to reactivity with rat liver P-450 IIC11. J. Pharmacol. Exp. Ther. 259:1328-34
116. Lecoeur S, Bonierbale E, Challine D, Gautier JC, Valadon P, et al. 1994. Specificity of in vitro covalent binding of tienilic acid metabolites to human liver microsomes in relationship to the type of hepatotoxicity: comparison with two directly hepatotoxic drugs. Chem. Res. Toxicol. 7:434-42
117. Donohue TM Jr, Tuma DJ, Sorrell MF. 1983. Acetaldehyde adducts with proteins: binding of [14C]acetaldehyde to serum albumin. Arch. Biochem. Biophys. 220:239-46
118. Donohue TM Jr, Tuma DJ, Sorrell MF. 1983. Binding of metabolically derived acetaldehyde to hepatic proteins in vitro. Lab. Invest. 49:226-29
119. Barry RE, Williams AJ, McGivan JD. 1987. The detection of acetaldehyde/liver plasma membrane protein adduct formed in vivo by alcohol feeding. Liver 7:364-68
120. Worrall S, De Jersey J, Shanley BC, Wilce PA. 1990. Detection of acetaldehyde-modified proteins in the livers of ethanolfed rats. Biochem. Soc. Trans. 18:678-79
121. Lin RC, Smith RS, Lumeng L. 1988. Detection of a protein-acetaldehyde adduct in the liver of rats fed alcohol chronically. J. Clin. Invest. 81:615-19
122. Zhu Y, Fillenwarth MJ, Crabb D. Lumeng L, Lin RC. 1996. Identification of the 37-kd rat liver protein that forms an acetaldehyde adduct in vivo as delta 4-3-ketosteroid 5 beta-reductase. Hepatology 23:115-22
123. Behrens UJ, Hoerner M, Lasker JM, Lieber CS. 1988. Formation of acetaldehyde adducts with ethanol-inducible P450IIE1 in vivo. Biochem, Biophys. Res. Commun. 154:584-90
124. Israel Y, Hurwitz E, Niemela O, Arnon R. 1986. Monoclonal and polyclonal antibodies against acetaldehyde-containing epitopes in acetaldehyde-protein adducts. Proc. Natl. Acad. Sci. USA 83:7923-7
125. Worrall S, De Jersey J, Shanley BC, Wilce PA. 1989. Ethanol induces the production of antibodies to acetaldehyde-modified epitopes in rats. Alcoh. Alcoh. 24:217-23
126. Lin RC, Lumeng L, Shahidi S, Kelly T, Pound DC. 1990. Protein-acetaldehyde adducts in serum of alcoholic patients. Alcoh. Clin. Exp. Res. 14:438-43
127. Niemela O. 1993. Acetaldehyde adducts of proteins: diagnostic and pathogenic implications in diseases caused by excessive alcohol consumption. Scand. J. Clin. Lab. Invest. Suppl. 213:45-54
128. Hoerner M, Behrens UJ, Worner T, Lieber CS. 1986. Humoral immune response to acetaldehyde adducts in alcoholic patients. Res. Commun. Chem. Pathol. Pharmacol. 54:3-12
129. Niemela O, Klajner F, Orrego H, Vidins E, Blendis L, et al. 1987. Antibodies against acetaldehyde-modified protein epitopes in human alcoholics. Hepatology 7:1210-14
130. Hoerner M, Behrens UJ, Worner TM, Blacksberg I, Braly LF, et al. 1988. The role of alcoholism and liver disease in the appearance of serum antibodies against acetaldehyde adducts. Hepatology 8:569-74
131. Worrall S, De Jersey J, Shanley BC, Wilce PA. 1990. Antibodies against acetaldehyde-modified epitopes: presence in alcoholic, non-alcoholic liver disease and control subjects. Alcoh. Alcoh. 25:509-17
132. Niemela O, Parkkila S, Yla-Herttuala S, Villanueva J, Ruebner B, et al. 1995. Sequential acetaldehyde production, lipid peroxidation, and fibrogenesis in micropig model of alcohol-induced liver disease. Hepatology 22:1208-14
133. Tuma DJ, Thiele GM, Xu D, Klassen LW, Sorrell MF. 1996. Acetaldehyde and malondialdehyde react together to generate distinct protein adducts in the liver during long-term ethanol administration. Hepatology 23:872-80
134. Bruckner JV, Davis BD, Blancato JN. 1989. Metabolism, toxicity, and carcino-genicity of trichloroethylene. Crit. Rev. Toxicol. 20:31-50
135. Davidson IW, Beliles RP. 1991. Consideration of the target organ toxicity of trichloroethylene in terms of metabolite toxicity and pharmacokinetics. Drug Metab. Rev. 23:493-599
136. Lockey JE, Kelly CR, Cannon GW, Colby TV, Aldrich V, et al. 1987. Progressive systemic sclerosis associated with exposure to trichloroethylene. J. Occup. Med. 29:493-96
137. Kilburn KH, Warshaw RH. 1992. Prevalence of symptoms of systemic lupus erythematosus (SLE) and of fluorescent antinuclear antibodies associated with chronic exposure to trichloroethylene and other chemicals in well water. Environ. Res. 57:1-9
138. +/+ mice. Toxicol. Appl. Pharmacol. 134:155-60
139. Guengerich FP, Kim DH, Iwasaki M. 1991. Role of human cytochrome P-450 IIE1 in the oxidation of many low molecular weight cancer suspects. Chem. Res. Toxicol. 4:168-79
140. Buben JA, O'Flaherty EJ. 1985. Delineation of the role of metabolism in the hepatotoxicity of trichloroethylene and perchloroethylene: a dose-effect study. Toxicol. Appl. Pharmacol. 78:105-22
141. Allemand H, Pessayre D, Descatoire V, Degott C, Feldmann G, et al. 1978. Metabolic activation of trichloroethylene into a chemically reactive metabolite toxic to the liver. J. Pharmacol. Exp. Ther. 204:714-23
142. Miller RE, Guengerich FP. 1982. Oxidation of trichloroethylene by liver microsomal cytochrome P-450: evidence for chlorine migration in a transition state not involving trichloroethylene oxide. Biochemistry 21:1090-91
143. Miller RE, Guengerich FP. 1983. Metabolism of trichloroethylene in isolated hepatocytes, microsomes, and reconstituted enzyme systems containing cytochrome P-450. Cancer Res. 43:1145-52
144. Uehleke H, Poplawski-Tabarelli S. 1977. Irreversible binding of 14C-labelled trichloroethylene to mice liver constituents in vivo and in vitro. Arch. Toxicol. 37:289-94
145. Bolt HM, Filser JG. 1977. Irreversible binding of chlorinated ethylenes to macromolecules. Environ. Health Perspect. 21:107-12
146. Stevens DK, Eyre RJ, Bull RJ. 1992. Adduction of hemoglobin and albumin in vivo by metabolites of trichloroethylene, trichloroacetate, and dichloroacetate in rats and mice. Fundam. Appl. Toxicol. 19:336-42
147. Halmes NC, McMillan DC, Oatis JE Jr, Pumford NR. 1996. Immunochemical detection of protein adducts in mice treated with trichloroethylene. Chem. Res. Toxicol. 9:451-56
148. Halmes NC, Perkins EJ, McMillan DC, Pumford NR. 1996. Detection of trichloroethylene-protein adducts in rat liver and plasma. Submitted for publication
149. Halmes NC, Samokyszyn VM, Pumford NR 1996. Covalent binding and inhibition of cytochrome P450 2E1 by trichloroethylene. Xenobiotica. In press
150. Zimmerman HJ. 1990. Update of hepatotoxicity due to classes of drugs in common clinical use: non-steroidal drugs, antiinflammatory drugs, antibiotics, antihypertensives, and cardiac and psychotropic agents. Semin. Liver Dis. 10:322-38
151. Banks AT, Zimmerman HJ, Ishak KG, Harter JG. 1995. Diclofenac-associated hepatotoxicity: analysis of 180 cases reported to the Food and Drug Administration as adverse reactions. Hepatology 22:820-27
152. Salama A, Gottsche B, Muellereckhardt C. 1991. Autoantibodies and drug-dependent or metabolite-dependent antibodies in patients with diclofenacinduced immune haemolysis. Br. J. Haematol. 77:546-49
153. Sallie RW, McKenzie T, Reed WD, Quinlan MF, Shilkin KB. 1991. Diclofenac hepatitis. Austr. N. Z. J. Med. 21:251-55
154. Scully LJ, Clarke D, Barr RJ. 1993. Diclofenac induced hepatitis 3 cases with features of autoimmune chronic active hepatitis. Dig. Dis. Sci. 38:744-51
155. Pumford NR, Myers TG, Davila JC, Highet RJ, Pohl LR. 1993. Immunochemical detection of liver protein adducts of the nonsteroidal antiinflammatory drug diclofenac. Chem. Res. Toxicol. 6:147-50
156. Hargus SJ, Amouzedeh HR, Pumford NR, Myers TG, McCoy SC, et al. 1994. Metabolic activation and immunochemical localization of liver protein adducts of the nonsteroidal anti-inflammatory drug diclofenac. Chem. Res. Toxicol. 7:575-82
157. Hargus SJ, Martin BM, George JW, Pohl LR. 1995. Covalent modification of rat liver dipeptidyl peptidase. IV. (CD26) by the nonsteroidal anti-inflammatory drug diclofenac. Chem. Res. Toxicol. 8:993-96
158. Kretz-Rommel A, Boelsterli UA. 1994. Selective protein adducts to membrane proteins in cultured rat hepatocytes exposed to diclofenac: Radiochemical and immunochemical analysis. Mol. Pharmacol. 45:237-44
159. Gil ML, Ramirez MC, Terencio MC, Castell JV. 1995. Immunochemical detection of protein adducts in cultured human hepatocytes exposed to diclofenac. Biochim. Biophys. Acta. 1272:140-46
160. Bailey MJ, Dickinson RG. 1996. Covalent binding and immunochemical comparison of protein adduct formation of four carboxylate drugs in rat liver and plasma. Chem. Res. Toxicol. 9:659-66
161. Wade LT, Kenna JG, Bora R, Reece DH, Siefert M, et al. 1995. Covalent modification of mouse hepatic proteins by non-steroidal anti-inflammatory drugs. ISSX Proc. 8:213
162. Jennett RB, Sorrell MF, Saffari-Fard A, Ockner JL, Tuma DJ. 1989. Preferential covalent binding of acetaldehyde to the alpha-chain of purified rat liver tubulin. Hepatology 9:57-62
163. Masubuchi Y, Igarashi S, Horie T, Suzuki T, Narimatsu S. 1995. Inactivation of a cytochrome P450 isozyme in the CYP2D subfamily by imipramine in rats: In relation to covalent binding of its metabolite to liver microsomal protein. ISSX Proc. 8:215
164. Gardner I, Bergin P, Stening P, Kenna JG, Caldwell J. 1996. Immunochemical detection of covalently modified protein adducts in livers of rats treated with methyleugenol. Chem. Res. Toxicol. 9:713-21
165. Kaster JK, Yost GS. 1996. Targets of a 3-methylindole reactive intermediate are characterized by a selective antibody. Fund. Appl. Toxicol. 30:283
166. Runnegar M, Berndt N, Kong S, Lee EYC, Zhang L. 1995. In vivo and in vitro binding of microcystin to protein phosphatases 1 and 2A. Biochem. Biophys. Res. Commun. 216:162-69
167. Birner G, Richling C, Henschler D, Anders MW, Dekant W. 1994. Metabolism of tetrachloroethene in rats: identification of N epsilon-(dichloroacetyl)-L-lysine and N epsilon-(trichloroacetyl)-L-lysine as protein adducts. Chem. Res. Toxicol. 7:724-32
168. Jin R, Day BW, Karol MH. 1993. Toluene diisocyanate protein adducts in