Use of transcriptomics in understanding mechanisms of drug-induced toxicity

Pharmacogenomics

Volumn 11, Issue 4, 2010, Pages 573-585

  Cui, Yuxia ^b   Paules, Richard S ^a  

^a NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES   (United States)

^b NONE

Author keywords

Adverse drug reaction; Hepatotoxicity; Idiosyncratic toxicity; Mechanism; Nephrotoxicity; Toxicogenomics

Indexed keywords

ANTIINFLAMMATORY AGENT; CARNITINE PALMITOYLTRANSFERASE I; CEFALORIDINE; CISPLATIN; CLOFIBRATE; CYCLOSPORIN; CYTOTOXIC AGENT; DIFLUNISAL; FLUFENAMIC ACID; GAMMA INTERFERON; GEMFIBROZIL; GENTAMICIN; INTERLEUKIN 8; METHAPYRILENE; METHOTREXATE; PARACETAMOL; PHENOBARBITAL; PIRINIXIC ACID; PUROMYCIN; TROVAFLOXACIN;

ADVERSE DRUG REACTION; AMINOACIDURIA; BLOOD CHEMISTRY; BLOOD SAMPLING; DNA MICROARRAY; DOWN REGULATION; FANCONI RENOTUBULAR SYNDROME; GENE EXPRESSION; GENE EXPRESSION PROFILING; GENETIC TOXICOLOGY; GENETIC TRANSCRIPTION; GENOME ANALYSIS; GLUCOSURIA; HISTOPATHOLOGY; HUMAN; KETONURIA; KIDNEY INJURY; LACTIC ACIDOSIS; LIVER INJURY; LIVER TOXICITY; NEPHROTOXICITY; NONHUMAN; OXIDATIVE STRESS; REVIEW; TRANSCRIPTOMICS; UPREGULATION;

ANIMALS; DRUG TOXICITY; DRUG-INDUCED LIVER INJURY; GENE EXPRESSION PROFILING; HUMANS; KIDNEY DISEASES; PHARMACEUTICAL PREPARATIONS; TOXICOGENETICS;

EID: 77950357495     PISSN: 14622416     EISSN: 17448042     Source Type: Journal    
DOI: 10.2217/pgs.10.37     Document Type: Review

References (99)

1. Edwards IR, Aronson JK: Adverse drug reactions: defnitions, diagnosis, and management. Lancet 356(9237), 1255-1259 (2000).
2. Lazarou J, Pomeranz BH, Corey PN: Incidence of adverse drug reactions in hospitalized patients-a meta-ana lysis of prospective studies. JAMA 279(15), 1200-1205 (1998).
3. Moore TJ, Cohen MR, Furberg CD: Serious adverse drug events reported to the Food and Drug Administration, 1998-2005. Arch. Intern. Med. 167(16), 1752-1759 (2007).
4. Gandhi TK, Weingart SN, Borus J et al.: Adverse drug events in ambulatory care. N. Engl. J. Med. 348(16), 1556-1564 (2003).
5. Pirmohamed M, James S, Meakin S et al.: Adverse drug reactions as cause of admission to hospital: prospective ana lysis of 18,820 patients. Br. Med. J. 329(7456), 15-19 (2004). (Pubitemid 38869995) (Pubitemid 38869995)
6. Harrill AH, Rusyn I: Systems biology and functional genomics approaches for the identifcation of cellular responses to drug toxicity. Expert Opin. Drug Metab. Toxicol. 4(11), 1379-1389 (2008).
7. Heijne WHM, Kienhuis AS, van Ommen B, Stierum RH, Groten JP: Systems toxicology: applications of toxicogenomics, transcriptomics, proteomics and metabolomics in toxicology. Expert Rev. Proteomics 2(5), 767-780 (2005).
8. Paules R: Phenotypic anchoring: linking cause and effect. Environ. Health Perspect. 111(6), A338-A339 (2003).
9. Nuwaysir EF, Bittner M, Trent J, Barrett JC, Afshari CA: Microarrays and toxicology: the advent of toxicogenomics. Mol. Carcinog. 24(3), 153-159 (1999).
10. Jelinsky SA, Samson LD: Global response of Saccharomyces cerevisiae to an alkylating agent. Proc. Natl. Acad. Sci. USA 96(4), 1486-1491 (1999).
11. Burczynski ME, McMillian M, Ciervo J et al.: Toxicogenomics-based discrimination of toxic mechanism in HEPG2 human hepatoma cells. Toxicol. Sci. 58(2), 399-415 (2000).
12. Bammert GF, Fostel JM: Genome-wide expression patterns in Saccharomyces cerevisiae: comparison of drug treatments and genetic alterations affecting biosynthesis of ergosterol. Antimicrob. Agents Chemother. 44(5), 1255-1265 (2000).
13. Wang YX, Rea T, Bian JH, Gray S, Sun Y: Identifcation of the genes responsive to etoposide-induced apoptosis: application of DNA chip technology. FEBS Lett. 445(2-3), 269-273 (1999).
14. Bulera SJ, Eddy SM, Ferguson E et al.: RNA expression in the early characterization of hepatotoxicants in wister rats by high-density DNA microarrays. Hepatology 33(5), 1239-1258 (2001).
15. Thomas RS, Rank DR, Penn SG et al.: Identifcation of toxicologically predictive gene sets using cDNA microarrays. Mol. Pharmacol. 60(6), 1189-1194 (2001).
16. Waring JF, Jolly RA, Ciurlionis R et al.: Clustering of hepatotoxins based on mechanism of toxicity using gene expression profles. Toxicol. Appl. Pharmacol. 175(1), 28-42 (2001).
17. Waring JF, Ciurlionis R, Jolly RA, Heindel M, Ulrich RG: Microarray ana lysis of hepatotoxins in vitro reveals a correlation between gene expression profles and mechanisms of toxicity. Toxicol. Lett. 120(1-3), 359-368 (2001).
18. Hamadeh HK, Bushel PR, Jayadev S et al.: Gene expression ana lysis reveals chemical-specifc profles. Toxicol. Sci. 67(2), 219-231 (2002).
19. Hamadeh HK, Bushel PR, Jayadev S et al.: Prediction of compound signature using high density gene expression profling. Toxicol. Sci. 67(2), 232-240 (2002).
20. Amacher DE, Beck R, Schomaker SJ, Kenny CV: Hepatic microsomal enzyme induction, b-oxidation, and cell proliferation following administration of clofbrate, gemfbrozil, or bezafbrate in the CD rat. Toxicol. Appl. Pharmacol. 142(1), 143-150 (1997).
21. Schoonjans K, Staels B, Auwerx J: Role of the peroxisome proliferator-activated receptor (PPAR) in mediating the effects of fbrates and fatty acids on gene expression. J. Lipid Res. 37(5), 907-925 (1996).
22. Hug G, McGraw CA, Bates SR, Landrigan EA: Reduction of serum carnitine concentrations during anticonvulsant therapy with phenobarbital, valproic acid, phenytoin, and carbamazepine in children. J. Pediatr. 119(5), 799-802 (1991).
23. Pannu N, Nadim MK: An overview of drug-induced acute kidney injury. Crit. Care Med. 36(4), S216-S223 (2008).
24. Taber SS, Mueller BA: Drug-associated renal dysfunction. Crit. Care Clin. 22(2), 357-374 (2006).
25. Huang Q, Dunn RT, Jayadev S et al.: Assessment of cisplatin-induced nephrotoxicity by microarray technology. Toxicol. Sci. 63(2), 196-207 (2001).
26. Fielden MR, Eynon BP, Natsoulis G, Jarnagin K, Banas D, Kolaja KL: A gene expression signature that predicts the future onset of drug-induced renal tubular toxicity. Toxicol. Pathol. 33(6), 675-683 (2005).
27. Thukral SK, Nordone PJ, Hu R et al.: Prediction of nephrotoxicant action and identifcation of candidate toxicity-related biomarkers. Toxicol. Pathol. 33(3), 343-355 (2005).
28. Suzuki H, Inoue T, Matsushita T et al.: In vitro gene expression ana lysis of nephrotoxic drugs in rat primary renal cortical tubular cells. J. Appl. Toxicol. 28(2), 237-248 (2008).
29. Xu EY, Perlina A, Vu H et al.: Integrated pathway ana lysis of rat urine metabolic profles and kidney transcriptomic profles to elucidate the systems toxicology of model nephrotoxicants. Chem. Res. Toxicol. 21(8), 1548-1561 (2008).
30. Thompson KL, Afshari CA, Amin RA et al.: Identifcation of platform-independent gene expression markers of cisplatin nephrotoxicity. Environ. Health Perspect. 112(4), 488-494 (2004).
31. Amin RA, Vickers AE, Sistare F et al.: Identifcation of putative gene-based markers of renal toxicity. Environ. Health Perspect. 112(4), 465-479 (2004).
32. Kramer JA, Pettit SD, Amin RP et al.: Overview of the application of transcription profling using selected nephrotoxicants for toxicology assessment. Environ. Health Perspect. 112(4), 460-464 (2004).
33. Singer D, Camargo SMR, Huggel K et al.: Orphan transporter SLC6A18 is renal neutral amino acid transporter B(0)AT3. J. Biol. Chem. 284(30), 19953-19960 (2009).
34. Ostapowicz G, Fontana RJ, Schiodt FV et al.: Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States. Ann. Intern. Med. 137(12), 947-954 (2002).
35. Blomme EAG, Yang Y, Waring JF: Use of toxicogenomics to understand mechanisms of drug-induced hepatotoxicity during drug discovery and development. Toxicol. Lett. 186(1), 22-31 (2009).
36. Jaeschke H, Bajt ML: Intracellular signaling mechanisms of acetaminophen-induced liver cell death. Toxicol. Sci. 89(1), 31-41 (2006).
37. Heinloth AN, Irwin RD, Boorman GA et al.: Gene expression profling of rat livers reveals indicators of potential adverse effects. Toxicol. Sci. 80(1), 193-202 (2004).
38. Powell CL, Kosyk O, Ross PK et al.: Phenotypic anchoring of acetaminophen-induced oxidative stress with gene expression profles in rat liver. Toxicol. Sci. 93(1), 213-222 (2006).
39. Zidek N, Hellmann J, Kramer PJ, Hewitt PG: Acute hepatotoxicity: a predictive model based on focused Illumina microarrays. Toxicol. Sci. 99(1), 289-302 (2007).
40. Reilly TP, Bourdi M, Brady JN et al.: Expression profling of acetaminophen liver toxicity in mice using microarray technology. Biochem. Biophys. Res. Commun. 282(1), 321-328 (2001).
41. Ruepp SU, Tonge RP, Shaw J, Wallis N, Pognan F: Genomics and proteomics ana lysis of acetaminophen toxicity in mouse liver. 135-150 (2002).
42. Beyer RP, Fry RC, Lasarev MR et al.: Multicenter study of acetaminophen hepatotoxicity reveals the importance of biological endpoints in genomic analyses. Toxicol. Sci. 99(1), 326-337 (2007).
43. Welch KD, Wen B, Goodlett DR et al.: Proteomic identifcation of potential susceptibility factors in drug-induced liver disease. Chem. Res. Toxicol. 18(6), 924-933 (2005).
44. Kienhuis AS, van de Poll MCG, Wortelboer H et al.: Parallelogram approach using rat-human in vitro and rat in vivo toxicogenomics predicts acetaminophen-induced hepatotoxicity in humans. Toxicol. Sci. 107(2), 544-552 (2009).
45. Harrill AH, Ross PK, Gatti DM, Threadgill DW, Rusyn I: Population-based discovery of toxicogenomics biomarkers for hepatotoxicity using a laboratory strain diversity panel. Toxicol. Sci. 110(1), 235-243 (2009).
46. Harrill AH, Watkins PB, Su S et al.: Mouse population-guided resequencing reveals that variants in CD44 contribute to acetaminophen-induced liver injury in humans. Genome Res. 19(9), 1507-1515 (2009).
47. Klaunig JE, Babich MA, Baetcke KP et al.: PPAR a agonist-induced rodent tumors: modes of action and human relevance. Crit. Rev. Toxicol. 33(6), 655-780 (2003).
48. Cariello NF, Romach EH, Colton HM et al.: Gene expression profling of the PPAR-a agonist ciprofbrate in the cynomolgus monkey liver. Toxicol. Sci. 88(1), 250-264 (2005).
49. Gonzalez FJ, Shah YA: PPAR a: mechanism of species differences and hepatocarcinogenesis of peroxisome proliferators. Toxicolog y 246(1), 2-8 (2008).
50. Burczynski ME, Dorner AJ: Transcriptional profling of peripheral blood cells in clinical pharmacogenomic studies. Pharmacogenomics 7(2), 187-202 (2006).
51. Liew CC, Ma J, Tang HC, Zheng R, Dempsey AA: The peripheral blood transcriptome dynamically refects system wide biology: a potential diagnostic tool. J. Lab. Clin. Med. 147(3), 126-132 (2006).
52. Mohr S, Liew CC: The peripheral-blood transcriptome: new insights into disease and risk assessment. Trends Mol. Med 13(10), 422-432 (2007).
53. Staratschek-Jox A, Classen S, Gaarz A, Debey-Pascher S, Schultze JL: Blood-based transcriptomics: leukemias and beyond. Expert Rev. Mol. Diagn. 9(3), 271-280 (2009).
54. Lobenhofer EK, Auman JT, Blackshear PE et al.: Gene expression response in target organ and whole blood varies as a function of target organ injury phenotype. Genome Biol. 9(6), R100 (2008).
55. Chao A, Wang TH, Lee YS et al.: Analysis of functional groups of differentially expressed genes in the peripheral blood of patients with cervical cancer undergoing concurrent chemoradiation treatment. Radiat. Res. 169(1), 76-86 (2008).
56. Sonis S, Haddad R, Posner M et al.: Gene expression changes in peripheral blood cells provide insight into the biological mechanisms associated with regimen-related toxicities in patients being treated for head and neck cancers. Oral Oncol. 43(3), 289-300 (2007).
57. Bushel PR, Heinloth AN, Li J et al.: Blood gene expression signatures predict exposure levels. Proc. Natl. Acad. Sci. USA 104(46), 18211-18216 (2007).
58. Fannin RD, Russo M, O'Connell TM et al.: Acetaminophen dosing of humans results in blood transcriptome and metabolome changes consistent with impaired oxidative phosphorylation. Hepatology 51(1), 227-236 (2010).
59. Chalasani N, Fontana RJ, Bonkovsky HL et al.: Causes, clinical features, and outcomes from a prospective study of drug-induced liver injury in the United States. Gastroenterology 135(6), 1924-1934 (2008).
60. Liguori MJ, Anderson MG, Bukofzer S et al.: Microarray ana lysis in human hepatocytes suggests a mechanism for hepatotoxicity induced by trovafoxacin. Hepatology 41(1), 177-186 (2005).
61. Waring JF, Liguori MJ, Luyendyk JP et al.: Microarray ana lysis of lipopolysaccharide potentiation of trovafoxacin-induced liver injury in rats suggests a role for proinfammatory chemokines and neutrophils. J. Pharmacol. Exp. Ther. 316(3), 1080-1087 (2006).
62. Shaw PJ, Ditewig AC, Waring JF et al.: Coexposure of mice to trovafoxacin and lipopolysaccharide, a model of idiosyncratic hepatotoxicity, results in a unique gene expression profle and interferon g-dependent liver injury. Toxicol. Sci. 107(1), 270-280 (2009).
63. Showe MK, Vachani A, Kossenkov AV et al.: Gene expression profles in peripheral blood mononuclear cells can distinguish patients with non-small cell lung cancer from patients with nonmalignant lung disease. Cancer Res. 69(24), 9202-9210 (2009).
64. Waters M, Stasiewicz S, Merrick BA et al.: CEBS-chemical effects in biological systems: a public data repository integrating study design and toxicity data with microarray and proteomics data. Nucleic Acids Res. 36, D892-D900 (2008).
65. Gallagher WM, Tweats D, Koenig J: Omic profling for drug safety assessment: current trends and public-private partnerships. Drug Discov. Today 14(7-8), 337-342 (2009).
66. Mattes WB: Public Consortium Efforts in Toxicogenomics. In: Essential Concepts in Toxicogenomics. Mendrick DL, William B (Eds). Humana Press, NJ, USA, 221-238 (2008).
67. Blomme EAG, Ciurlionis R, Marsh KC, Waring JF, Yang Y: Evaluation of the effects of serial phlebotomy on the transcriptome of major tissues and on the response to toxicants in rats. Toxicol. Lett. 176(2), 138-148 (2008).
68. Jiang Y, Gerhold DL, Holder DJ et al.: Diagnosis of drug-induced renal tubular toxicity using global gene expression profles. J. Transl. Med. 5, 47 (2007).
69. Leussink BT, Baelde HJ, Broekhuizen-van den Berg TM et al.: Renal epithelial gene expression profle and bismuth-induced resistance against cisplatin nephrotoxicity. Hum. Exp. Toxicol. 22(10), 535-540 (2003).
70. Oh JH, Park HJ, Lim JS et al.: Gene expression profling of early renal toxicity induced by gentamicin in mice. Mol. Cell. Toxicol. 2(3), 185-192 (2006).
71. Jennings P, Aydin S, Bennett J et al.: Inter-laboratory comparison of human renal proximal tubule (HK-2) transcriptome alterations due to cyclosporine A exposure and medium exhaustion. Toxicol. Vitro 23(3), 486-499 (2009).
72. Pallet N, Rabant M, Xu-Dubois YC et al.: Response of human renal tubular cells to cyclosporine and sirolimus: a toxicogenomic study. Toxicol. Appl. Pharmacol. 229(2), 184-196 (2008).
73. Rokushima M, Fujisawa K, Furukawa N et al.: Transcriptomic ana lysis of nephrotoxicity induced by cephaloridine, a representative cephalosporin antibiotic. Chem. Res. Toxicol. 21(6), 1186-1196 (2008).
74. Huang QH, Jin XD, Gaillard ET et al.: Gene expression profling reveals multiple toxicity endpoints induced by hepatotoxicants. Mutat. Res. 549(1-2), 147-168 (2004).
75. Minami K, Saito T, Narahara M et al.: Relationship between hepatic gene expression profles and hepatotoxicity in fve typical hepatotoxicant-administered rats. Toxicol. Sci. 87(1), 296-305 (2005).
76. Heinloth AN, Boorman GA, Foley JF, Flagler ND, Paules RS: Gene expression ana lysis offers unique advantages to histopathology in liver biopsy evaluations. Toxicol. Pathol. 35(2), 276-283 (2007).
77. Uehara T, Hirode M, Ono A et al.: A toxicogenomics approach for early assessment of potential non-genotoxic hepatocarcinogenicity of chemicals in rats. Toxicology 250(1), 15-26 (2008).
78. Kier LD, Neft R, Tang L et al.: Applications of microarrays with toxicologically relevant genes (TOX genes) for the evaluation of chemical toxicants in sprague dawley rats in vivo and human hepatocytes in vitro. Mutat. Res. 549(1-2), 101-113 (2004).
79. de Longueville F, Atienzar FA, Marcq L et al.: Use of a low-density microarray for studying gene expression patterns induced by hepatotoxicants on primary cultures of rat hepatocytes. Toxicol. Sci. 75(2), 378-392 (2003).
80. Noel S, Sharma S, Rath SK: Simultaneous application of t-test and fold change criteria to identify acetaminophen and carbon tetrachloride affected genes in mice liver. Environ. Toxicol. Pharmacol. 26(2), 150-161 (2008).
81. Suzuki H, Inoue T, Matsushita T et al.: In vitro gene expression ana lysis of hepatotoxic drugs in rat primary hepatocytes. J. Appl. Toxicol. 28(2), 227-236 (2008).
82. Reilly TP, Brady JN, Marchick MR et al.: A protective role for cyclooxygenase-2 in drug-induced liver injury in mice. 14(12), 1620-1628 (2001).
83. Liu J, Li CX, Waalkes MP et al.: The nitric oxide donor, v-pyrro/no, protects against acetaminophen-induced hepatotoxicity in mice. Hepatology 37(2), 324-333 (2003). (Pubitemid 36152531) (Pubitemid 36152531)
84. Shankar K, Vaidya VS, Corton JC et al.: Activation of PPAR-a in streptozotocin-induced diabetes is essential for resistance against acetaminophen toxicity. FASEB J. 17(10), 1748-1750 (2003).
85. Priyadarsiny P, Khattar SK, Malik R et al.: Differential gene expression ana lysis of a known hepatotoxin, N-acetyl-p-amino-phenol (APAP) as compared with its non-toxic analog, N-acetyl-m-amino-phenol (AMAP) in mouse liver. J. Toxicol. Sci. 33(2), 163-173 (2008).
86. Jeong YK, Kang JS, Kim JW et al.: Differences in gene expression profles refecting differences in drug sensitivity to acetaminophen in normal and transformed hepatic cell lines in vitro. Mol. Cell. Toxicol. 5(1), 32-43 (2009).
87. Harris AJ, Dial SL, Casciano DA: Comparison of basal gene expression profles and effects of hepatocarcinogens on gene expression in cultured primary human hepatocytes and HEPG2 cells. Mutat. Res. 549(1-2), 79-99 (2004).
88. Hamadeh HK, Knight BL, Haugen AC et al.: Methapyrilene toxicity: anchorage of pathologic observations to gene expression alterations. Toxicol. Pathol. 30(4), 470-482 (2002).
89. Waring JF, Ulrich RG, Flint N et al.: Interlaboratory evaluation of rat hepatic gene expression changes induced by methapyrilene. Environ. Health Perspect. 112(4), 439-448 (2004).
90. Ulrich RG, Rockett JC, Gibson GG, Pettit SD: Overview of an interlaboratory collaboration on evaluating the effects of model hepatotoxicants on hepatic gene expression. Environ. Health Perspect. 112(4), 423-427 (2004).
91. Craig A, Sidaway J, Holmes E et al.: Systems toxicology: integrated genomic, proteomic and metabonomic ana lysis of methapyrilene induced hepatotoxicity in the rat. J. Proteome Res. 5(7), 1586-1601 (2006).
92. Auman JT, Chou J, Gerrish K et al.: Identifcation of genes implicated in methapyrilene-induced hepatotoxicity by comparing differential gene expression in target and nontarget tissue. Environ. Health Perspect. 115(4), 572-578 (2007).
93. Beekman JM, Boess F, Hildebrand H, Kalkuhl A, Suter L: Gene expression ana lysis of the hepatotoxicant methapyrilene in primary rat hepatocytes: an interlaboratory study. Environ. Health Perspect. 114(1), 92-99 (2006).
94. Shaw PJ, Hopfensperger MJ, Ganey PE, Roth RA: Lipopolysaccharide and trovafoxacin coexposure in mice causes idiosyncrasy-like liver injury dependent on tumor necrosis factor-a. Toxicol. Sci. 100(1), 259-266 (2007).
95. Liguori MJ, Blomme EAG, Waring JF: Trovafoxacin-induced gene expression changes in liver-derived in vitro systems: Comparison of primary human hepatocytes to HEPG2 cells. Drug Metab. Dispos. 36(2), 223-233 (2008).
96. Jung J W, Kim SJ, Kim JS et al.: Gene expression ana lysis of methotrexate-induced hepatotoxicity between in vitro and in vivo. Mol. Cell. Toxicol. 1(4), 256-261 (2005).
97. Lee GJ, Kim YS, Jung JW et al.: Gene expression ana lysis of anticancer drug induced hepatotoxicity using cDNA microarray. Mol. Cell. Toxicol. 2(2), 141-149 (2006).
98. Ganter B, Tugendreich S, Pearson CI et al.: Development of a large-scale chemogenomics database to improve drug candidate selection and to understand mechanisms of chemical toxicity and action. J. Biotechnol. 119(3), 219-244 (2005).
99. Lee MH, Hong I, Kim M et al.: Gene expression profles of murine fatty liver induced by the administration of methotrexate. Toxicology 249(1), 75-84 (2008).