Genomic profiling uncovers a molecular pattern for toxicological characterization of mutagens and promutagens in vitro

Toxicological Sciences

Volumn 122, Issue 1, 2011, Pages 185-197

  Boehme, Kathleen ^a   Dietz, Yasmin ^a   Hewitt, Philip ^a   Mueller, Stefan O ^a,b  

^a Merck Serono GmbH   (Germany)

^b KARLSRUHE INSTITUTE OF TECHNOLOGY   (Germany)

Author keywords

Genotoxicity; Global gene expression profiling; HepG2; Illumina; Mutagens; Promutagens

Indexed keywords

7,12 DIMETHYLBENZ[A]ANTHRACENE; AFLATOXIN B1; CYCLOPHOSPHAMIDE; DACTINOMYCIN; DIETHYLNITROSAMINE; ETOPOSIDE; MESYLIC ACID METHYL ESTER; METFORMIN; MUTAGENIC AGENT; PROMUTAGEN; PROTEIN P53; STAT1 PROTEIN; THEOPHYLLINE; TRANSCRIPTION FACTOR SP1;

ARTICLE; CELL DIFFERENTIATION; CELL STRESS; CONTROLLED STUDY; DNA DAMAGE; GENE EXPRESSION PROFILING; GENOTOXICITY; HUMAN; HUMAN CELL; LIVER HOMOGENATE; METABOLIC ACTIVATION; TOXICITY TESTING; TRANSCRIPTION REGULATION; TRANSCRIPTOMICS;

RATTUS;

EID: 79960986144     PISSN: 10966080     EISSN: 10960929     Source Type: Journal    
DOI: 10.1093/toxsci/kfr090     Document Type: Article

References (75)

1. Alaminos, M., Davalos, V., Ropero, S., Setien, F., Paz, M. F., Herranz, M., Fraga, M. F., Mora, J., Cheung, N. K., Gerald, W. L., et al. (2005). EMP3, a myelin-related gene located in the critical 19q13.3 region, is epigenetically silenced and exhibits features of a candidate tumor suppressor in glioma and neuroblastoma. Cancer Res. 65, 2565-2571.
2. Alfano, D., Franco, P., Vocca, I., Gambi, N., Pisa, V., Mancini, A., Caputi, M., Carriero, M. V., Iaccarino, I., and Stoppelli, M. P. (2005). The urokinase plasminogen activator and its receptor: role in cell growth and apoptosis. Thromb. Haemost. 93, 205-211.
3. Andersen, J. B., and Hassel, B. A. (2006). The interferon regulated ubiquitinlike protein, ISG15, in tumorigenesis: friend or foe? Cytokine Growth Factor Rev. 17, 411-421.
4. Bartek, J., and Lukas, J. (2001). Mammalian G1- and S-phase checkpoints in response to DNA damage. Curr. Opin. Cell Biol. 13, 738-747.
5. Benjamini, J., and Hochberg, Y. (1995). Controlling the false dicovery rate: a practical and powerful approach to multiple testing. J.R. Statist. Soc. 57, 289-300.
6. Boehme, K., Dietz, Y., Hewitt, P., and Mueller, S. O. (2010). Activation of P53 in HepG2 cells as surrogate to detect mutagens and promutagens in vitro. Toxicol. Lett. 198, 272-281.
7. Boehme, K., Simon, S., and Mueller, S. O. (2009). Gene expression profiling in Ishikawa cells: a fingerprint for estrogen active compounds. Toxicol. Appl. Pharmacol. 236, 85-96.
8. Brandon, E. F.,Raap,C.D.,Meijerman, I.,Beijnen, J.H., and Schellens, J.H. (2003). An update on in vitro test methods in human hepatic drug biotransformation research: pros and cons. Toxicol. Appl. Pharmacol. 189, 233-246.
9. Brantley-Finley, C., Lyle, C. S., Du, L., Goodwin, M. E., Hall, T., Szwedo, D., Kaushal, G. P., and Chambers, T. C. (2003). The JNK, ERK and p53 pathways play distinct roles in apoptosis mediated by the antitumor agents vinblastine, doxorubicin, and etoposide. Biochem. Pharmacol. 66, 459-469.
10. Bretschneider, E., Uzonyi, B., Weber, A. A., Fischer, J. W., Pape, R., Lotzer, K., and Schror, K. (2007). Human vascular smooth muscle cells express functionally active endothelial cell protein C receptor. Circ. Res. 100, 255-262.
11. Calmon, M. F., Rodrigues, R. V., Kaneto, C. M., Moura, R. P., Silva, S. D., Mota, L. D., Pinheiro, D. G., Torres, C., de Carvalho, A. F., et al. (2009). Epigenetic silencing of CRABP2 and MX1 in head and neck tumors. Neoplasia 11, 1329-1339.
12. Carrier, F., Georgel, P. T., Pourquier, P., Blake, M., Kontny, H. U., Antinore, M. J., Gariboldi, M., Myers, T. G., Weinstein, J. N., Pommier, Y., et al. (1999). Gadd45, a p53-responsive stress protein, modifies DNA accessibility on damaged chromatin. Mol. Cell. Biol. 19, 1673-1685.
13. Castell, J. V., Jover, R., Martinez-Jimenez, C. P., and Gomez-Lechon, M. J. (2006). Hepatocyte cell lines: their use, scope and limitations in drug metabolism studies. Expert Opin. Drug Metab. Toxicol. 2, 183-212.
14. Chu, S., and Ferro, T. J. (2005). Sp1: regulation of gene expression by phosphorylation. Gene 348, 1-11.
15. Chua, Y. L., Ito, Y., Pole, J. C., Newman, S., Chin, S. F., Stein, R. C., Ellis, I. O., Caldas, C., O'Hare, M. J., Murrell, A., et al. (2009). The NRG1 gene is frequently silenced by methylation in breast cancers and is a strong candidate for the 8p tumour suppressor gene. Oncogene 28, 4041-4052.
16. Cromme, F. V., Airey, J., Heemels, M. T., Ploegh, H. L., Keating, P. J., Stern, P. L., Meijer, C. J., and Walboomers, J. M. (1994). Loss of transporter protein, encoded by the TAP-1 gene, is highly correlated with loss of HLA expression in cervical carcinomas. J. Exp. Med. 179, 335-340.
17. Ding, K. K., Shang, Z. F., Hao, C., Xu, Q. Z., Shen, J. J., Yang, C. J., Xie, Y. H., Qiao, C., Wang, Y., Xu, L. L., et al. (2009). Induced expression of the IER5 gene by gamma-ray irradiation and its involvement in cell cycle checkpoint control and survival. Radiat. Environ. Biophys. 48, 205-213.
18. Dudley, A. C., Thomas, D., Best, J., and Jenkins, A. (2004). The STATs in cell stress-type responses. Cell Commun. Signal. 2, 8.
19. Edwards, S. W., and Preston, R. J. (2008). Systems biology and mode of action based risk assessment. Toxicol. Sci. 106, 312-318.
20. Ellinger-Ziegelbauer, H., Fostel, J. M., Aruga, C., Bauer, D., Boitier, E., Deng, S., Dickinson, D., Le Fevre, A. C., Fornace, A. J., Jr., et al. (2009). Characterization and interlaboratory comparison of a gene expression signature for differentiating genotoxic mechanisms. Toxicol. Sci. 110, 341-352.
21. Ellinger-Ziegelbauer, H., Gmuender, H., Bandenburg, A., and Ahr, H. J. (2008). Prediction of a carcinogenic potential of rat hepatocarcinogens using toxicogenomics analysis of short-term in vivo studies. Mutat. Res. 637, 23-39.
22. Ellinger-Ziegelbauer, H., Stuart, B., Wahle, B., Bomann, W., and Ahr, H. J. (2004). Characteristic expression profiles induced by genotoxic carcinogens in rat liver. Toxicol. Sci. 77, 19-34.
23. Ellinger-Ziegelbauer, H., Stuart, B., Wahle, B., Bomann, W., and Ahr, H. J. (2005). Comparison of the expression profiles induced by genotoxic and nongenotoxic carcinogens in rat liver. Mutat. Res. 575, 61-84.
24. EMA (2008). ICH Topic S2 (R1) Guidance on Genotoxicity Testing and Data Interpretation for Pharmaceuticals Intended for Human Use. Stand: März 2008. Available at: http://www.emea.europa.eu/pdfs/human/ich/12664208en.pdf. Accessed June 12, 2010.
25. Hengstler, J. G., Foth, H., Kahl, R., Kramer, P. J., Lilienblum, W., Schulz, T., and Schweinfurth, H. (2006). The REACH concept and its impact on toxicological sciences. Toxicology 220, 232-239.
26. ICH (2010). ICH S2A, S2B and Draft S2 (R1) Guidelines for Genotoxicity Testing of Pharmaceuticals. Stand: 13/09/2010. Available at: http://www.ich.org/cache/compo/502-272-1.html#S2. Accessed: July 12, 2010.
27. Iida, M., Anna, C. H., Holliday, W. M., Collins, J. B., Cunningham, M. L., Sills, R. C., and Devereux, T. R. (2005). Unique patterns of gene expression changes in liver after treatment of mice for 2 weeks with different known carcinogens and non-carcinogens. Carcinogenesis 26, 689-699.
28. Illumina, Inc. (2006). Human-6 v2 and HumanRef-8 v2 Expression BeadChips. Stand: 23.12.2006. http://www.switchtoi.com/pdf/GXHuman6-8v2Datasheet.pdf. Accessed July 12, 2010.
29. Ishiguro, K., and Xavier, R. (2004). Homer-3 regulates activation of serum response element in T cells via its EVH1 domain. Blood 103, 2248-2256.
30. Jeon, Y. J., Yoo, H. M., and Chung, C. H. (2010). ISG15 and immune diseases. Biochim. Biophys. Acta. 1802, 485-496.
31. Jorgensen, E. D., Dozmorov, I., Frank, M. B., Centola, M., and Albino, A. P. (2004). Global gene expression analysis of human bronchial epithelial cells treated with tobacco condensates. Cell Cycle 3, 1154-1168.
32. Kang, J. S., Wanibuchi, H., Morimura, K., Gonzalez, F. J., and Fukushima, S. (2007). Role of CYP2E1 in diethylnitrosamine-induced hepatocarcinogenesis in vivo. Cancer Res. 67, 11141-11146.
33. Kirkland, D., Aardema, M., Henderson, L., and Muller, L. (2005). Evaluation of the ability of a battery of three in vitro genotoxicity tests to discriminate rodent carcinogens and non-carcinogens I. Sensitivity, specificity and relative predictivity. Mutat. Res. 584, 1-256.
34. Kirkland, D., Aardema, M., Muller, L., and Makoto, H. (2006). Evaluation of the ability of a battery of three in vitro genotoxicity tests to discriminate rodent carcinogens and non-carcinogens II. Further analysis of mammalian cell results, relative predictivity and tumour profiles. Mutat. Res. 608, 29-42.
35. Krones-Herzig, A., Mittal, S., Yule, K., Liang, H., English, C., Urcis, R., Soni, T., Adamson, E. D., and Mercola, D. (2005). Early growth response 1 acts as a tumor suppressor in vivo and in vitro via regulation of p53. Cancer Res. 65, 5133-5143.
36. Kubbutat, M. H., and Vousden, K. H. (1998). Keeping an old friend under control: regulation of p53 stability. Mol. Med. Today. 4, 250-256.
37. Kyo, S., Takakura, M., Fujiwara, T., and Inoue, M. (2008). Understanding and exploiting hTERT promoter regulation for diagnosis and treatment of human cancers. Cancer Sci. 99, 1528-1538.
38. Lents, N. H., Wheeler, L. W., Baldassare, J. J., and Dynlacht, B. D. (2008). Identification and characterization of a novel Mdm2 splice variant acutely induced by the chemotherapeutic agents adriamycin and actinomycin D. Cell Cycle 7, 1580-1586.
39. Leslie, E. M., Ito, K., Upadhyaya, P., Hecht, S. S., Deeley, R. G., and Cole, S. P. (2001). Transport of the beta -O-glucuronide conjugate of the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) by the multidrug resistance protein 1 (MRP1). Requirement for glutathione or a non-sulfur-containing analog. J. Biol. Chem. 276, 27846-27854.
40. Li, Y., Tennekoon, G. I., Birnbaum, M., Marchionni, M. A., and Rutkowski, J. L. (2001). Neuregulin signaling through a PI3K/Akt/Bad pathway in Schwann cell survival. Mol. Cell. Neurosci. 17, 761-767.
41. Li, Z., Srivastava, S., Yang, X., Mittal, S., Norton, P., Resau, J., Haab, B., and Chan, C. (2007). A hierarchical approach employing metabolic and gene expression profiles to identify the pathways that confer cytotoxicity in HepG2 cells. BMC Syst. Biol. 1, 21.
42. Ljungman, M., O'Hagan, H. M., and Paulsen, M. T. (2001). Induction of ser15 and lys382 modifications of p53 by blockage of transcription elongation. Oncogene 20, 5964-5971.
43. Ljungman, M., Zhang, F., Chen, F., Rainbow, A. J., and McKay, B. C. (1999). Inhibition of RNA polymerase II as a trigger for the p53 response. Oncogene 18, 583-592.
44. Majer, B. J., Mersch-Sundermann, V., Darroudi, F., Laky, B., de Wit, K., and Knasmuller, S. (2004). Genotoxic effects of dietary and lifestyle related carcinogens in human derived hepatoma (HepG2, Hep3B) cells. Mutat. Res. 551, 153-166.
45. Martelli, A., Robbiano, L., Gazzaniga, G. M., and Brambilla, G. (1988). Comparative study of DNA damage and repair induced by ten N-nitroso compounds in primary cultures of human and rat hepatocytes. Cancer Res. 48, 4144-4152.
46. Melaragno, M. G., Cavet, M. E., Yan, C., Tai, L. K., Jin, Z. G., Haendeler, J., and Berk, B. C. (2004). Gas6 inhibits apoptosis in vascular smooth muscle: role of Axl kinase and Akt. J. Mol. Cell. Cardiol. 37, 881-887.
47. Nakamura, S. I., Oda, Y., Shimada, T., Oki, I., and Sugimoto, K. (1987). SOSinducing activity of chemical carcinogens and mutagens in Salmonella typhimurium TA1535/pSK1002: examination with 151 chemicals. Mutat. Res. 192, 239-246.
48. Nakayama, K., Kawano, Y., Kawakami, Y., Moriwaki, N., Sekijima, M., Otsuka, M., Yakabe, Y., Miyaura, H., Saito, K., Sumida, K., et al. (2006). Differences in gene expression profiles in the liver between carcinogenic and non-carcinogenic isomers of compounds given to rats in a 28-day repeatdose toxicity study. Toxicol. Appl. Pharmacol. 217, 299-307.
49. Olofsson, B. A., Kelly, C. M., Kim, J., Hornsby, S. M., and Azizkhan Clifford, J. (2007). Phosphorylation of Sp1 in response to DNA damage by ataxia telangiectasia-mutated kinase. Mol. Cancer Res. 5, 1319-1330.
50. Pfuhler, S., Albertini, S., Fautz, R., Herbold, B., Madle, S., Utesch, D., and Poth, A. (2007). Genetic toxicity assessment: employing the best science for human safety evaluation part IV: recommendation of a working group of the Gesellschaft fuer Umwelt-Mutationsforschung (GUM) for a simple and straightforward approach to genotoxicity testing. Toxicol. Sci. 97, 237-240.
51. Quinones, A., Dobberstein, K. U., and Rainov, N. G. (2003). The egr-1 gene is induced by DNA-damaging agents and non-genotoxic drugs in both normal and neoplastic human cells. Life Sci. 72, 2975-2992.
52. Reich, N. C. (2007). STAT dynamics. Cytokine Growth Factor Rev. 18, 511-518.
53. Rostkowska, K., Zwierz, K., Rozanski, A., Moniuszko-Jakoniuk, J., and Roszczenko, A. (1998). Formation and Metabolism of N-Nitrosamines. Pol. J. Environ. Stud. 7, 321-325.
54. Seo, Y. R., and Jung, H. J. (2004). The potential roles of p53 tumor suppressor in nucleotide excision repair (NER) and base excision repair (BER). Exp. Mol. Med. 36, 505-509.
55. Simmon, V. F. (1979). In vitro mutagenicity assays of chemical carcinogens and related compounds with Salmonella typhimurium. J. Natl. Cancer Inst. 62, 893-899.
56. Streffer, C. (2004). Low Dose Exposures in the Environment-Dose-Effect Relations and Risk Evaluation. Springer-Verlag, Berlin, Germany.
57. Takizawa, C. G., and Morgan, D. O. (2000). Control of mitosis by changes in the subcellular location of cyclin-B1-Cdk1 and Cdc25C. Curr. Opin. Cell Biol. 12, 658-665.
58. Tapias, A., Ciudad, C. J., Roninson, I. B., and Noe, V. (2008). Regulation of Sp1 by cell cycle related proteins. Cell Cycle 7, 2856-2867.
59. Townsend, P. A., Cragg, M. S., Davidson, S. M., McCormick, J., Barry, S., Lawrence, K. M., Knight, R. A., Hubank, M., Chen, P. L., Latchman, D. S., et al. (2005). STAT-1 facilitates the ATM activated checkpoint pathway following DNA damage. J. Cell Sci. 118, 1629-1639.
60. Tsugawa, K., Jones, M. K., Akahoshi, T., Moon, W. S., Maehara, Y., Hashizume, M., Sarfeh, I. J., and Tarnawski, A. S. (2003). Abnormal PTEN expression in portal hypertensive gastric mucosa: A key to impaired PI 3-kinase/Akt activation and delayed injury healing? FASEB J. 17, 2316-2318.
61. Vairapandi, M., Balliet, A. G., Hoffman, B., and Liebermann, D. A. (2002). GADD45b and GADD45g are cdc2/cyclinB1 kinase inhibitors with a role in S and G2/M cell cycle checkpoints induced by genotoxic stress. J. Cell. Physiol. 192, 327-338.
62. Van Aelst, L., and D'Souza-Schorey, C. (1997). Rho GTPases and signaling networks. Genes Dev. 11, 2295-2322.
63. Vinken, M., Doktorova, T., Ellinger-Ziegelbauer, H., Ahr, H. J., Lock, E., Carmichael, P., Roggen, E., van Delft, J., Kleinjans, J., Castell, J., et al. (2008). The carcinoGENOMICS project: critical selection of model compounds for the development of omics-based in vitro carcinogenicity screening assays. Mutat. Res. 659, 202-210.
64. Vousden, K. H., and Lane, D. P. (2007). p53 in health and disease. Nat. Rev. Mol. Cell Biol. 8, 275-283.
65. Wang, H. T., Kong, J. P., Ding, F., Wang, X. Q., Wang, M. R., Liu, L. X., Wu, M., and Liu, Z. H. (2003). Analysis of gene expression profile induced by EMP-1 in esophageal cancer cells using cDNA Microarray. World J. Gastroenterol. 9, 392-398.
66. Wang, S., Tian, C., Xiao, T., Xing, G., He, F., Zhang, L., and Chen, H. (2010). Differential regulation of Apak by various DNA damage signals. Mol. Cell. Biochem. 333, 181-187.
67. Westerink, W. M., and Schoonen, W. G. (2007). Phase II enzyme levels in HepG2 cells and cryopreserved primary human hepatocytes and their induction in HepG2 cells. Toxicol. In Vitro 21, 1592-1602.
68. Westphal, G. A., Bunger, J., Schulz, T. G., Muller, M. M., and Hallier, E. (2000). Mutagenicity of N-nitrosodiethylamine in the Ames test with S. typhimurium TA1535 is due to volatile metabolites and is not dependent on cytochrome P4502E1 induction. Arch. Toxicol. 74, 638-641.
69. Wiench, K., Frei, E., Schroth, P., and Wiessler, M. (1992). 1-C-glucuronidation of N-nitrosodiethylamine and N-nitrosomethyl-n-pentylamine in vivo and in primary hepatocytes from rats pretreated with inducers. Carcinogenesis 13, 867-872.
70. Xu, Q. Y., Gao, Y., Liu, Y., Yang, W. Z., and Xu, X. Y. (2008). Identification of differential gene expression profiles of radioresistant lung cancer cell line established by fractionated ionizing radiation in vitro. Chin. Med. J. (Engl.) 121, 1830-1837.
71. Yamazaki, H., Inui, Y., Yun, C. H., Guengerich, F. P., and Shimada, T. (1992). Cytochrome P450 2E1 and 2A6 enzymes as major catalysts for metabolic activation of N-nitrosodialkylamines and tobacco-related nitrosamines in human liver microsomes. Carcinogenesis 13, 1789-1794.
72. Yoshimoto, T., Morishima, N., Mizoguchi, I., Shimizu, M., Nagai, H., Oniki, S., Oka, M., Nishigori, C., and Mizuguchi, J. (2008). Antiproliferative activity of IL-27 on melanoma. J. Immunol. 180, 6527-6535.
73. Yoshitomi, S., Ikemoto, K., Takahashi, J., Miki, H., Namba, M., and Asahi, S. (2001). Establishment of the transformants expressing human cytochrome P450 subtypes in HepG2, and their applications on drug metabolism and toxicology. Toxicol. In Vitro 15, 245-256.
74. Zhang, F., Lin, M., Abidi, P., Thiel, G., and Liu, J. (2003). Specific interaction of Egr1 and c/EBPbeta leads to the transcriptional activation of the human low density lipoprotein receptor gene. J. Biol. Chem. 278, 44246-44254.
75. Zidek, N., Hellmann, J., Kramer, P. J., and Hewitt, P. G. (2007). Acute hepatotoxicity: A predictive model based on focused illumina microarrays. Toxicol Sci 99, 289-302.