Toxicogenomic analysis of N-nitrosomorpholine induced changes in rat liver: Comparison of genomic and proteomic responses and anchoring to histopathological parameters

Toxicology and Applied Pharmacology

Volumn 241, Issue 2, 2009, Pages 230-245

  Oberemm, A ^a   Ahr, H J ^b   Bannasch, P ^c   Ellinger Ziegelbauer, H ^b   Gluckmann M ^e   Hellmann, J ^d   Ittrich, C ^c   Kopp Schneider, A ^c   Kramer, P J ^d   Krause, E ^f   Kroger M ^d   Kiss, E ^c   Richter Reichhelm, H B ^a   Scholz, G ^b   Seemann, K ^d   Weimer, M ^c   Gundert Remy, U ^a  

^a FEDERAL INSTITUTE FOR RISK ASSESSMENT   (Germany)

^b BAYER PHARMA AG   (Germany)

^c GERMAN CANCER RESEARCH CENTER DKFZ   (Germany)

^d MERCK KGAA   (Germany)

^e Applied Biosystems   (Germany)

^f LEIBNIZ INSTITUT FÜR MOLEKULARE PHARMAKOLOGIE   (Germany)

Author keywords

Genotoxic carcinogens; Mechanistic toxicology; Proteomics; Rat liver; Toxicogenomics; Transcriptomics

Indexed keywords

GLUTATHIONE TRANSFERASE; NITROSOMORPHOLINE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CHEMICAL CARCINOGENESIS; CONTROLLED STUDY; DOWN REGULATION; GENE EXPRESSION PROFILING; GENOMICS; HISTOPATHOLOGY; INTERMETHOD COMPARISON; LIVER CARCINOGENESIS; MALE; NONHUMAN; PRECANCER; PROTEIN EXPRESSION; PROTEOMICS; RAT; RISK ASSESSMENT; TOXICOGENETICS; TRANSCRIPTOMICS; TWO DIMENSIONAL GEL ELECTROPHORESIS; UPREGULATION;

ANIMALS; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION, NEOPLASTIC; GLUTATHIONE TRANSFERASE; HUMANS; LIVER; LIVER NEOPLASMS, EXPERIMENTAL; MALE; NITROSAMINES; PRECANCEROUS CONDITIONS; PROTEOMICS; RATS; RATS, WISTAR; TOXICOGENETICS; TUMOR MARKERS, BIOLOGICAL;

ANIMALIA; RATTUS; RATTUS NORVEGICUS;

EID: 70350218821     PISSN: 0041008X     EISSN: 10960333     Source Type: Journal    
DOI: 10.1016/j.taap.2009.08.020     Document Type: Article

References (79)

1. Anderson L., and Seilhamer J. A comparison of selected mRNA and protein abundances in human liver. Electrophoresis 18 (1997) 533-537
2. Arce A., Aicher L., Wahl D., Anderson N.L., Meheus L., Raymackers J., Cordier A., and Steiner S. Changes in the liver protein pattern of female Wistar rats treated with the hypoglycemic agent SDZ PGU 693. Life Sci. 63 (1998) 2243-2250
3. Ashida S., Nakagawa H., Katagiri T., Furihata M., Iiizumi M., Anazawa Y., Tsunoda T., Takata R., Kasahara K., Miki T., Fujioka T., Shuin T., and Nakamura Y. Molecular features of the transition from prostatic intraepithelial neoplasia (PIN) to prostate cancer: genome-wide gene-expression profiles of prostate cancers and PINs. Cancer Res. 64 (2004) 5963-5972
4. Bannasch P. The cytoplasm of hepatocytes during carcinogenesis. Rec. Res. Cancer Res. 19 (1968) 1-100
5. Beyer S., Walter Y., Hellmann J., Kramer P.J., Kopp-Schneider A., Kröger M., and Ittrich C. Comparison of software tools to improve the detection of carcinogen induced changes in the rat liver proteome by analyzing SELDI-TOF-MS spectra. J. Proteome Res. 5 (2006) 254-261
6. Carlson E.A., and Silkworth J.B. Toxicogenomics in human health risk assessment. Toxicol. Appl. Pharmacol. 236 (2009) 254-256
7. Corthals G.L., Wasinger V.C., Hochstrasser D.F., and Sanchez J.C. The dynamic range of protein expression: a challenge for proteomic research. Electrophoresis 21 (2000) 1104-1115
8. Corvi R., Ahr H.J., Albertini S., Blakey D.H., Clerici L., Coecke S., Douglas G.R., Gribaldo L., Groten J.P., Haase B., Hamernik K., Hartung T., Inoue T., Indans I., Maurici D., Orphanides G., Rembges D., Sansone S.A., Snape J.R., Toda E., Tong W.D., van Delft J.H., Weis B., and Schechtman L.M. Meeting report: validation of toxicogenomics-based test systems: ECVAM-ICCVAM/NICEATM considerations for regulatory use. Environ. Health Perspect. 114 (2006) 420-429
9. Cunningham M.L. A mouse is not a rat is not a human: species differences exist. Toxicol. Sci. 70 (2002) 157-158
10. de Gerlache J., Lans M., Preat V., Taper H., and Roberfroid M. Comparison of different models of rat liver carcinogenesis: conclusions from a systemic analysis. Toxicol. Pathol. 12 (1984) 374-382
11. de Leval L., Rickman D.S., Thielen C., de Reynies A., Huang Y.L., Delsol G., Lamant L., Leroy K., Briere J., Molina T., Berger F., Gisselbrecht C., Xerri L., and Gaulard P. The gene expression profile of nodal peripheral T-cell lymphoma demonstrates a molecular link between angioimmunoblastic T-cell lymphoma (AITL) and follicular helper T (T-FH) cells. Blood 109 (2007) 4952-4963
12. Donninger H., Bonome T., Radonovich M., Pise-Masison C.A., Brady J., Shih J.H., Barrett J.C., and Birrer M.J. Whole genome expression profiling of advance stage papillary serous ovarian cancer reveals activated pathways. Oncogene 23 (2004) 8065-8077
13. Eferl R., Ricci R., Kenner L., Zenz R., David J.P., Rath M., and Wagner E.F. Liver tumor development: c-Jun antagonizes the proapoptotic activity of p53. Cell 112 (2003) 181-192
14. Ellinger-Ziegelbauer H., Aubrecht J., Kleinjans J.C., and Ahr H.J. Application of toxicogenomics to study mechanisms of genotoxicity and carcinogenicity. Toxicol. Lett. 186 (2009) 36-44
15. Ellinger-Ziegelbauer H., Gmuender H., Bandenburg A., and Ahr H.J. Prediction of a carcinogenic potential of rat hepatocarcinogens using toxicogenomics analysis of short-term in vivo studies. Mutat. Res. 637 (2008) 23-39
16. Ellinger-Ziegelbauer H., Stuart B., Wahle B., Bomann W., and Ahr H.J. Comparison of the expression profiles induced by genotoxic and nongenotoxic carcinogens in rat liver. Mutat. Res. 575 (2005) 61-84
17. Ellinger-Ziegelbauer H., Stuart B., Wahle B., Bomann W., and Ahr H.J. Characteristic expression profiles induced by genotoxic carcinogens in rat liver. Toxicol. Sci. 77 (2004) 19-34
18. Evert M., Schneider-Stock R., and Dombrowski F. Apolipoprotein A-IV mRNA overexpression in early preneoplastic hepatic foci induced by low-number pancreatic islet transplants in streptozotocin-diabetic rats. Pathol. Res. Pract. 199 (2003) 373-379
19. Fella K., Glückmann M., Hellmann J., Karas M., Kramer P.J., and Kröger M. Use of two-dimensional gel electrophoresis in predictive toxicology: Identification of potential early protein biomarkers in chemically induced hepatocarcinogenesis. Proteomics 5 (2005) 1914-1927
20. Fielden M.R., Brennan R., and Gollub J. A gene expression biomarker provides early prediction and mechanistic assessment of hepatic tumor induction by nongenotoxic chemicals. Toxicol. Sci. 99 (2007) 90-100
21. Fielden M.R., Nie A., McMillian M., Elangbam C.S., Trela B.A., Yang Y., Dunn R.T., Dragan Y., Fransson-Stehen R., Bogdanffy M., Adams S.P., Foster W.R., Chen S.J., Rossi P., Kasper P., Jacobson-Kram D., Tatsuoka K.S., Wier P.J., Gollub J., Halbert D.N., Roter A., Young J.K., Sina J.F., Marlowe J., Martus H.J., Aubrecht J., Olaharski A.J., Roome N., Nioi P., Pardo I., Snyder R., Perry R., Lord P., Mattes W., and Car B.D. Interlaboratory evaluation of genomic signatures for predicting carcinogenicity in the rat. Toxicol. Sci. 103 (2008) 28-34
22. Fostel J.M., Burgoon L., Zwickl C., Lord P., Corton J.C., Bushel P.R., Cunningham M., Fan L., Edwards S.W., Hester S., Stevens J., Tong W., Waters M., Yang C., and Tennant R. Toward a checklist for exchange and interpretation of data from a toxicology study. Toxicol. Sci. 99 (2007) 26-34
23. Garner C.E., Matthews H.B., and Burka L.T. Phenolphthalein metabolite inhibits catechol-O-methyltransferase-mediated metabolism of catechol estrogens: a possible mechanism for carcinogenicity. Toxicol. Appl. Pharmacol. 162 (2000) 124-131
24. Gentleman R.C., Carey V.J., Bates D.M., Bolstad B., Dettling M., Dudoit S., Ellis B., Gautier L., Ge Y., Gentry J., Hornik K., Hothorn T., Huber W., Iacus S., Irizarry R., Leisch F., Li C., Maechler M., Rossini A.J., Sawitzki G., Smith C., Smyth G., Tierney L., Yang J.Y., and Zhang J. Bioconductor: open software development for computational biology and bioinformatics. Genome Biol 5 (2004) R80
25. Gerbracht U., Einig C., Oesterle D., Deml E., Schlatterer B., and Eigenbrodt E. Di(2-ethylhexyl)phthalate alters carbohydrate enzyme activities and foci incidence in rat liver. Carcinogenesis 11 (1990) 2111-2115
26. Glückmann M., Fella K., Waidelich D., Merkel D., Kruft V., Kramer P.J., Walter Y., Hellmann J., Karas M., and Kroger M. Prevalidation of potential protein biomarkers in toxicology using iTRAQ reagent technology. Proteomics 7 (2007) 1564-1574
27. Görg A., Obermaier C., Boguth G., Harder A., Scheibe B., and Wildgruber R. The current state of two-dimensional electrophoresis with immobilized pH gradients. Electrophoresis 21 (2000) 1037-1053
28. Görg A., Weiss W., and Dunn M.J. Current two-dimensional electrophoresis technology for proteomics. Proteomics 4 (2004) 3665-3685
29. Hacker H.J., Moore M.A., Mayer D., and Bannasch P. Correlative histochemistry of some enzymes of carbohydrate metabolism in preneoplastic and neoplastic lesions in the rat liver. Carcinogenesis 3 (1982) 1265-1272
30. Hamadeh H.K., Bushel P.R., Jayadev S., Martin K., DiSorbo O., Sieber S., Bennett L., Tennant R., Stoll R., Barrett J.C., Blanchard K., Paules R.S., and Afshari C.A. Gene expression analysis reveals chemical-specific profiles. Toxicol. Sci. 67 (2002) 219-231
31. Hamadeh H.K., Knight B.L., Haugen A.C., Sieber S., Amin R.P., Bushel P.R., Stoll R., Blanchard K., Jayadev S., Tennant R.W., Cunningham M.L., Afshari C.A., and Paules R.S. Methapyrilene toxicity: anchorage of pathologic observations to gene expression alterations. Toxicol. Pathol. 30 (2002) 470-482
32. Hegde P.S., White I.R., and Debouck C. Interplay of transcriptomics and proteomics. Drug Discov. Today 9 (2004) S53-S56
33. Hever A., Roth R.B., Hevezi P.A., Lee J., Willhite D., White E.C., Marin E.M., Herrera R., Acosta H.M., Acosta A.J., and Zlotnik A. Molecular characterization of human adenomyosis. Mol. Hum. Reprod. 12 (2006) 737-748
34. Holley S.L., Fryer A.A., Haycock J.W., Grubb S.E.W., Strange R.C., and Hoban P.R. Differential effects of glutathione S-transferase pi (GSTP1) haplotypes on cell proliferation and apoptosis. Carcinogenesis 28 (2007) 2268-2273
35. Huang Z.Z., Chen C.J., Zeng Z.H., Yang H.P., Oh J., Chen L.X., and Lu S.C. Mechanism and significance of increased glutathione level in human hepatocellular carcinoma and liver regeneration. FASEB J. 15 (2001) 19-21
36. Huber W., von Heydebreck A., Sultmann H., Poustka A., and Vingron M. Variance stabilization applied to microarray data calibration and to the quantification of differential expression. Bioinformatics 18 Suppl. 1 (2002) S96-S104
37. Iida M., Anna C.H., Hartis J., Bruno M., Wetmore B., Dubin J.R., Sieber S., Bennett L., Cunningham M.L., Paules R.S., Tomer K.B., Houle C.D., Merrick A.B., Sills R.C., and Devereux T.R. Changes in global gene and protein expression during early mouse liver carcinogenesis induced by non-genotoxic model carcinogens oxazepam and Wyeth-14,643. Carcinogenesis 24 (2003) 757-770
38. Iida M., Anna C.H., Holliday W.M., Collins J.B., Cunningham M.L., Sills R.C., and Devereux T.R. Unique patterns of gene expression changes in liver after treatment of mice for 2 weeks with different known carcinogens and non-carcinogens. Carcinogenesis 26 (2005) 689-699
39. Klimek F., and Bannasch P. Biochemical microanalysis of alpha-glucosidase activity in preneoplastic and neoplastic hepatic-lesions induced in rats by N-nitrosomorpholine. Virchows Archiv B-Cell Pathology Including Molec. Pathol. 57 (1989) 245-250
40. Klimek F., and Bannasch P. Isoenzyme shift from glucokinase to hexokinase is not an early but a late event in hepatocarcinogenesis. Carcinogenesis 14 (1993) 1857-1861
41. Korr H., Botzem B., Schmitz C., and Enzmann H. N-nitrosomorpholine induced alterations of unscheduled DNA synthesis, mitochondrial DNA synthesis and cell proliferation in different cell types of liver, kidney, and urogenital organs in the rat. Chem. Biol. Interact. 134 (2001) 217-233
42. Kramer J.A., Pettit S.D., Amin R.P., Bertram T.A., Car B., Cunningham M., Curtiss S.W., Davis J.W., Kind C., Lawton M., Naciff J.M., Oreffo V., Roman R.J., Sistare F.D., Stevens J., Thompson K., Vickers A.E., Wild S., and Afsharif C.A. Overview of the application of transcription profiling using selected nephrotoxicants for toxicology assessment. Environ. Health Perspect. 112 (2004) 460-464
43. Kuo C.C., Kuo C.W., Liang C.M., and Liang S.M. A transcriptomic and proteomic analysis of the effect of CpG-ODN on human THP-1 monocytic leukemia cells. Proteomics 5 (2005) 894-906
44. Lee I.N., Chen C.H., Sheu J.C., Lee H.S., Huang G.T., Yu C.Y., Lu F.J., and Chow L.P. Identification of human hepatocellular carcinoma-related biomarkers by two-dimensional difference gel electrophoresis and mass spectrometry. J. Proteome Res. 4 (2005) 2062-2069
45. Lijinsky W., Kovatch R.M., Riggs C.W., and Walters P.T. Dose-response study with N-nitrosomorpholine in drinking-water of F344 rats. Cancer Res. 48 (1988) 2089-2095
46. Lim S.O., Park S.J., Kim W., Park S.G., Kim H.J., Kim Y.I., Sohn T.S., Noh J.H., and Jung G. Proteome analysis of hepatocellular carcinoma. Biochem. Biophys. Res. Comm. 291 (2002) 1031-1037
47. Mayer D., Metzger C., Leonetti P., Beier K., Benner A., and Bannasch P. Differential expression of key enzymes of energy metabolism in preneoplastic and neoplastic rat liver lesions induced by N-nitrosomorpholine and dehydroepiandrosterone. Int. J. Cancer 79 (1998) 232-240
48. Melnick R.L., Thayer K.A., and Bucher J.R. Conflicting views on chemical carcinogenesis arising from the design and evaluation of rodent carcinogenicity studies. Environ. Health Perspect. 116 (2008) 130-135
49. Merrick B.A., and Bruno M.E. Genomic and proteomic profiling for biomarkers and signature profiles of toxicity. Curr. Opin. Mol. Ther. 6 (2004) 600-607
50. Michalik L., Desvergne B., and Wahli W. Peroxisome-proliferator-activated receptors and cancers: complex stories. Nat. Rev. Cancer 4 (2004) 61-70
51. Nie A.Y., McMillian M., Parker J.B., Leone A., Bryant S., Yieh L., Bittner A., Nelson J., Carmen A., Wan J., and Lord P.G. Predictive toxicogenomics approaches reveal underlying molecular mechanisms of nongenotoxic carcinogenicity. Mol. Carcinog. 45 (2006) 914-933
52. Nie L., Wu G., and Zhang W. Correlation of mRNA expression and protein abundance affected by multiple sequence features related to translational efficiency in Desulfovibrio vulgaris: a quantitative analysis. Genetics 174 (2006) 2229-2243
53. Nuwaysir E.F., Bittner M., Trent J., Barrett J.C., and Afshari C.A. Microarrays and toxicology: the advent of toxicogenomics. Mol. Carcinog. 24 (1999) 153-159
54. Oberemm A., Onyon L., and Gundert-Remy U. How can toxicogenomics inform risk assessment?. Toxicol. Appl. Pharmacol. 207 (2005) S592-S598
55. Oberemm A., Meckert C., Brandenburger L., Herzig A., Lindner Y., Kalenberg K., Krause E., Ittrich C., Kopp-Schneider A., Riecke K., Stahlmann R., Richter-Reichhelm H.B., and Gundert-Remy U. Differential signatures of protein expression in marmoset liver and thymus induced by single-dose TCDD treatment. Toxicology 206 (2005) 33-48
56. Oesterle D., Gerbracht U., Deml E., Schlatterer B., and Eigenbrodt E. Comparison of three rat liver foci bioassays incidence of preneoplastic foci initiated by diethylnitrosamine. Carcinogenesis 10 (1989) 1891-1895
57. Orphanides, G., 2003. Toxicogenomics: challenges and opportunities. Toxicol.Lett. 140-141, 145-148.
58. Plant N. Can systems toxicology identify common biomarkers of non-genotoxic carcinogenesis?. Toxicology 254 (2008) 164-169
59. Polgar N., Fogelgren B., Shipley J.M., and Csiszar K. Lysyl oxidase interacts with hormone placental lactogen and synergistically promotes breast epithelial cell proliferation and migration. J. Biol. Chem. 282 (2007) 3262-3272
60. R Development Core Team. A language and environment for statistical computing (2003), R Foundation for Statistical Computing. Computer Program, Vienna, Austria
61. Rabilloud T., Strub J.M., Luche S., van Dorsselaer A., and Lunardi J. A comparison between Sypro Ruby and ruthenium II tris (bathophenanthroline disulfonate) as fluorescent stains for protein detection in gels. Proteomics 1 (2001) 699-704
62. Seliger B., Dressler S.P., Wang E., Kellner R., Recktenwald C.V., Lottspeich F., Marincola F.M., Baumgärtner M., Atkins D., and Lichtenfels R. Combined analysis of transcriptome and proteome data as a tool for the identification of candidate biomarkers in renal cell carcinoma. Proteomics 9 (2009) 1567-1581
63. Uehara T., Hirode M., Ono A., Kiyosawa N., Omura K., Shimizu T., Mizukawa Y., Miyagishima T., Nagao T., and Urushidani T. A toxicogenomics approach for early assessment of potential non-genotoxic hepatocarcinogenicity of chemicals in rats. Toxicology 250 (2008) 15-26
64. Ulrich R.G., Rockett J.C., Gibson G.G., and Pettit S.D. Overview of an interlaboratory collaboration on evaluating the effects of model hepatotoxicants on hepatic gene expression. Environ. Health Perspect. 112 (2004) 423-427
65. Wang A.G., Yoon S.Y., Oh J.H., Jeon Y.J., Kim M., Kim J.M., Byun S.S., Yang J.O., Kim J.H., Kim D.G., Yeom Y.I., Yoo H.S., Kim Y.S., and Kim N.S. Identification of intrahepatic cholangiocarcinoma related genes by comparison with normal liver tissues using expressed sequence tags. Biochem..Biophys.Res. Comm. 345 (2006) 1022-1032
66. Ward J.M. Value of rodent carcinogenesis bioassays. Toxicol. Appl. Pharmacol. 226 (2008) 212
67. Waring J.F., Jolly R.A., Ciurlionis R., Lum P.Y., Praestgaard J.T., Morfitt D.C., Buratto B., Roberts C., Schadt E., and Ulrich R.G. Clustering of hepatotoxins based on mechanism of toxicity using gene expression profiles. Toxicol. Appl. Pharmacol. 175 (2001) 28-42
68. Waters M.D., and Fostel J.M. Toxicogenomics and systems toxicology: aims and prospects. Nature Rev.Genet. 5 (2004) 936-948
69. Weber E., and Bannasch P. Dose and time dependence of the cellular phenotype in rat hepatic preneoplasia and neoplasia induced by continuous oral exposure to N-nitrosomorpholine. Carcinogenesis 15 (1994) 1235-1242
70. Weber E., and Bannasch P. Dose and time-dependence of the cellular phenotype in rat hepatic preneoplasia and neoplasia induced in stop experiments by oral-exposure to N-nitrosomorpholine. Carcinogenesis 15 (1994) 1227-1234
71. Wei Y.H., Chan L.L., Wang D.Z., Zhang H.X., Wang J.S., and Dai J.Y. Proteomic analysis of hepatic protein profiles in rare minnow (Gobiocypris rarus) exposed to perfluorooctanoic acid. J. Proteome Res. 7 (2008) 1729-1739
72. Wei Y.H., Liu Y., Wang H.S., Tao Y., and Dai J.Y. Toxicogenomic analysis of the hepatic effects of perfluorooctanoic acid on rare minnows (Gobiocypris rarus). Toxicol. Appl. Pharmacol. 226 (2008) 285-297
73. Wetmore B.A., and Merrick B.A. Toxicoproteomics: proteomics applied to toxicology and pathology. Toxicol. Pathol. 32 (2004) 619-642
74. Wu M., Min C.Y., Wang X.B., Yu Z.Y., Kirsch K.H., Trackman P.C., and Sonenshein G.E. Repression of BCL2 by the tumor suppressor activity of the lysyl oxidase propeptide inhibits transformed phenotype of lung and pancreatic cancer cells. Cancer Res. 67 (2007) 6278-6285
75. Wu Z., and Irizarry R.A. Preprocessing of oligonucleotide array data. Nat. Biotechnol. 22 (2004) 656-658
76. Zerban H., Radig S., Kopp-Schneider A., and Bannasch P. Cell proliferation and cell death (apoptosis) in hepatic preneoplasia and neoplasia are closely related to phenotypic cellular diversity and instability. Carcinogenesis 15 (1994) 2467-2473
77. Zidek N., Hellmann J., Kramer P.J., and Hewitt P.G. Acute hepatotoxicity: a predictive model based on focused illumina microarrays. Toxicol. Sci. 99 (2007) 289-302
78. Anon 1978. Volume 17: Some N-nitroso Compounds. (17), 263. 1978. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. WHO/ IARC.
79. Anon 2007. Workshop on the Application of 'Omic Technologies in Toxicology and Ecotoxicology': Case Studies and Risk Assessment 6-7 December 2007, Malaga. 2008. Brussels, ECETOC AISBL. Workshop Report. 6-12-2007.