Use of traditional end points and gene dysregulation to understand mechanisms of toxicity: Toxicogenomics in mechanistic toxicology

Methods in Molecular Biology

Volumn 460, Issue , 2008, Pages 23-44

  Buck, Wayne R ^a   Waring, Jeffrey F ^a   Blomme, Eric A ^a  

^a ABBOTT LABORATORIES   (United States)

Author keywords

Gene expression; Mechanism of toxicity; Microarray; Phenotype

Indexed keywords

EID: 84934444321     PISSN: 10643745     EISSN: None     Source Type: Book Series    
DOI: 10.1007/978-1-60327-48-9_2     Document Type: Article

References (68)

1. Barefoot, J. C., Gronbaek, M., Feaganes, J. R., McPherson, R. S., Williams, R. B., and Siegler, I. C. (2002) Alcoholic beverage preference, diet, and health habits in the UNC Alumni Heart Study. Am. J. Clin. Nutr. 76, 466-472.
2. Bono, H., and Okazaki, Y. (2002) Functional transcriptomes: comparative analysis of biological pathways and processes in eukaryotes to infer genetic networks among transcripts. Curr. Opin. Struct. Biol. 12, 355-361.
3. Larrey, D., Tinel, M., and Pessayre, D. (1983) Formation of inactive cytochrome P-450 Fe(II)-metabolite complexes with several erythromycin derivatives but not with josamycin and midecamycin in rats. Biochem. Pharmacol. 32, 1487-1493.
4. Amacher, D. E., Schomaker, S. J., Boldt, S. E., and Mirsky, M. (2006) The relationship among microsomal enzyme induction, liver weight, and histological change in cynomolgus monkey toxicology studies. Food Chem. Toxicol. 44, 528-537.
5. Lai, D. Y. (2004) Rodent carcinogenicity of peroxisome proliferators and issues on human relevance. J. Environ. Sci. Health C Environ. Carcinog. Ecotoxicol. Rev. 22, 37-55.
6. Waring, J. F., Gum, R., Morfitt, D., Jolly, R. A., Ciurlionis, R., Heindel, M., et al. (2002) Identifying toxic mechanisms using DNA microarrays: evidence that an experimental inhibitor of cell adhesion molecule expression signals through the aryl hydrocarbon nuclear receptor. Toxicology 181-182, 537-550.
7. Wolfgang, G. H., Robertson, D. G., Welty, D. F., and Metz, A. L. (1995) Hepatic and adrenal toxicity of a novel lipid regulator in beagle dogs. Fundam. Appl. Toxicol. 26, 272-281.
8. Grasso, P., and Hinton, R. H. (1991) Evidence for and possible mechanisms of non-genotoxic carcinogenesis in rodent liver. Mutat. Res. 248, 271-290.
9. Hamadeh, H. K., Bushel, P. R., Jayadev, S., Martin, K., DiSorbo, O., Sieber, S., et al. (2002) Gene expression analysis reveals chemical-specific profiles. Toxicol. Sci. 67, 219-231.
10. Kemper, B. (1998) Regulation of cytochrome P450 gene transcription by phenobarbital. Prog. Nucleic Acid Res. Mol. Biol. 61, 23-64.
11. Voss, K. A., Liu, J., Anderson, S. P., Dunn, C., Miller, J. D., Owen, J. R., et al. (2006) Toxic effects of fumonisin in mouse liver are independent of the peroxisome proliferator-activated receptor alpha. Toxicol. Sci. 89, 108-119.
12. Fielden, M. R., Brennan, R., and Gollub, J. (2007) A gene expression biomarker provides early prediction and mechanistic assessment of hepatic tumor induction by non-genotoxic chemicals. Toxicol. Sci. 99, 90-100.
13. Nie, A. Y., McMillian, M., Parker, J. B., Leone, A., Bryant, S., Yieh, L., et al. (2006) Predictive toxicogenomics approaches reveal underlying molecular mechanisms of nongenotoxic carcinogenicity. Mol. Carcinog. 45, 914-933.
14. Wallace, K. B., Hausner, E., Herman, E., Holt, G. D., MacGregor, J. T., Metz, A. L., et al. (2004) Serum troponins as biomarkers of drug-induced cardiac toxicity. Toxicol. Pathol. 32, 106-121.
15. Singal, P. K., and Iliskovic, N. (1998) Doxorubicin-induced cardiomyopathy. N. Engl. J. Med. 339, 900-905.
16. Kalivendi, S. V., Konorev, E. A., Cunningham, S., Vanamala, S. K., Kaji, E. H., Joseph, J., and Kalyanaraman, B. (2005) Doxorubicin activates nuclear factor of activated T-lymphocytes and Fas ligand transcription: role of mitochondrial reactive oxygen species and calcium. Biochem. J. 389, 527-539.
17. Minotti, G., Menna, P., Salvatorelli, E., Cairo, G., and Gianni, L. (2004) Anthracyclines: molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity. Pharmacol. Rev. 56, 185-229.
18. Robert, J. (2007) Preclinical assessment of anthracycline cardiotoxicity in laboratory animals: Predictiveness and pitfalls. Cell. Biol. Toxicol. 23, 27-37.
19. Chaiswing, L., Cole, M. P., St Clair, D. K., Ittarat, W., Szweda, L. I., and Oberley, T. D. (2004) Oxidative damage precedes nitrative damage in adriamycin-induced cardiac mitochondrial injury. Toxicol. Pathol. 32, 536-547.
20. Jang, Y. M., Kendaiah, S., Drew, B., Phillips, T., Selman, C., Julian, D., and Leeuwenburgh, C. (2004) Doxorubicin treatment in vivo activates caspase-12 mediated cardiac apoptosis in both male and female rats. FEBS Lett. 577, 483-490.
21. Gu, Y. G., Weitzberg, M., Clark, R. F., Xu, X., Li, Q., Lubbers, N. L., et al. (2007) N-{3-[2-(4-alkoxyphenoxy)thiazol-5-yl]-1-methylprop-2-ynyl}carboxy derivatives as acetyl-coA carboxylase inhibitors-improvement of cardiovascular and neurological liabilities via structural modifications. J. Med. Chem. 50, 1078-1082.
22. Ganter, B., Tugendreich, S., Pearson, C. I., Ayanoglu, E., Baumhueter, S., Bostian, K. A., et al. (2005) Development of a large-scale chemogenomics database to improve drug candidate selection and to understand mechanisms of chemical toxicity and action. J. Biotechnol. 119, 219-244.
23. Diel, P., Smolnikar, K., Schulz, T., Laudenbach-Leschowski, U., Michna, H., and Vollmer, G. (2001) Phytoestrogens and carcinogenesis-differential effects of genistein in experimental models of normal and malignant rat endometrium. Hum. Reprod. 16, 997-1006.
24. Kuiper, G. G., Enmark, E., Pelto-Huikko, M., Nilsson, S., and Gustafsson, J. A. (1996) Cloning of a novel receptor expressed in rat prostate and ovary. Proc. Natl. Acad. Sci. U. S. A. 93, 5925-5930.
25. Okada, A., Ohta, Y., Buchanan, D. L., Sato, T., Inoue, S., Hiroi, H., et al. (2002) Changes in ontogenetic expression of estrogen receptor alpha and not of estrogen receptor beta in the female rat reproductive tract. J. Mol. Endocrinol. 28, 87-97.
26. Matthews, J., and Gustafsson, J. A. (2003) Estrogen signaling: a subtle balance between ER alpha and ER beta. Mol. Interv. 3, 281-292.
27. Moriarty, K., Kim, K. H., and Bender, J. R. (2006) Minireview: estrogen receptormediated rapid signaling. Endocrinology 147, 5557-5563.
28. Hall, J. M., and McDonnell, D. P. (2005) Coregulators in nuclear estrogen receptor action: from concept to therapeutic targeting. Mol. Interv. 5, 343-357.
29. Filardo, E. J., and Thomas, P. (2005) GPR30: a seven-transmembrane- spanning estrogen receptor that triggers EGF release. Trends Endocrinol. Metab. 16, 362-367.
30. Bjornstrom, L., and Sjoberg, M. (2005) Mechanisms of estrogen receptor signaling: convergence of genomic and nongenomic actions on target genes. Mol. Endocrinol. 19, 833-842.
31. Levin, E. R. (2005) Integration of the extranuclear and nuclear actions of estrogen. Mol. Endocrinol. 19, 1951-1959.
32. Houston, K. D., Copland, J. A., Broaddus, R. R., Gottardis, M. M., Fischer, S. M., and Walker, C. L. (2003) Inhibition of proliferation and estrogen receptor signaling by peroxisome proliferator-activated receptor gamma ligands in uterine leiomyoma. Cancer Res. 63, 1221-1227.
33. Rhen, T., Grissom, S., Afshari, C., and Cidlowski, J. A. (2003) Dexamethasone blocks the rapid biological effects of 17beta-estradiol in the rat uterus without antagonizing its global genomic actions. FASEB J. 17, 1849-1870.
34. Kazi, A. A., Jones, J. M., and Koos, R. D. (2005) Chromatin immunoprecipitation analysis of gene expression in the rat uterus in vivo: estrogen-induced recruitment of both estrogen receptor alpha and hypoxia-inducible factor 1 to the vascular endothelial growth factor promoter. Mol. Endocrinol. 19, 2006-2019.
35. Li, X. H., and Ong, D. E. (2003) Cellular retinoic acid-binding protein II gene expression is directly induced by estrogen, but not retinoic acid, in rat uterus. J. Biol. Chem. 278, 35819-35825.
36. Wu, X., Pang, S. T., Sahlin, L., Blanck, A., Norstedt, G., and Flores-Morales, A. (2003) Gene expression profiling of the effects of castration and estrogen treatment in the rat uterus. Biol. Reprod. 69, 1308-1317.
37. Moggs, J. G., Tinwell, H., Spurway, T., Chang, H. S., Pate, I., Lim, F. L., et al. (2004) Phenotypic anchoring of gene expression changes during estrogen-induced uterine growth. Environ. Health Perspect. 112, 1589-1606.
38. Naciff, J. M., Overmann, G. J., Torontali, S. M., Carr, G. J., Khambatta, Z. S., Tiesman, J. P., et al. (2007) Uterine temporal response to acute exposure to 17{alpha}-ethinyl estradiol in the immature rat. Toxicol. Sci. 97, 467-490.
39. Heryanto, B., Lipson, K. E., and Rogers, P. A. (2003) Effect of angiogenesis inhibitors on oestrogen-mediated endometrial endothelial cell proliferation in the ovariectomized mouse. Reproduction 125, 337-346.
40. Naciff, J. M., Overmann, G. J., Torontali, S. M., Carr, G. J., Tiesman, J. P., Richardson, B. D., and Daston, G. P. (2003) Gene expression profile induced by 17 alpha-ethynyl estradiol in the prepubertal female reproductive system of the rat. Toxicol. Sci. 72, 314-330.
41. Naciff, J. M., Overmann, G. J., Torontali, S. M., Carr, G. J., Tiesman, J. P., and Daston, G. P. (2004) Impact of the phytoestrogen content of laboratory animal feed on the gene expression profile of the reproductive system in the immature female rat. Environ. Health Perspect. 112, 1519-1526.
42. Helvering, L. M., Adrian, M. D., Geiser, A. G., Estrem, S. T., Wei, T., Huang, S., et al. U. (2005) Differential effects of estrogen and raloxifene on messenger RNA and matrix metalloproteinase 2 activity in the rat uterus. Biol. Reprod. 72, 830-841.
43. Creasy, D. M. (1997) Evaluation of testicular toxicity in safety evaluation studies: the appropriate use of spermatogenic staging. Toxicol. Pathol. 25, 119-131.
44. Stewart, J., and Turner, K. J. (2005) Inhibin B as a potential biomarker of testicular toxicity. Cancer Biomarkers 1, 75-91.
45. Murugesan, P., Balaganesh, M., Balasubramanian, K., and Arunakaran, J. (2007) Effects of polychlorinated biphenyl (Aroclor 1254) on steroidogenesis and antioxidant system in cultured adult rat Leydig cells. J. Endocrinol. 192, 325-338.
46. Adachi, T., Koh, K. B., Tainaka, H., Matsuno, Y., Ono, Y., Sakurai, K., Fet al. (2004) Toxicogenomic difference between diethylstilbestrol and 17beta-estradiol in mouse testicular gene expression by neonatal exposure. Mol. Reprod. Dev. 67, 19-25.
47. Adachi, T., Ono, Y., Koh, K. B., Takashima, K., Tainaka, H., Matsuno, Y., et al. (2004) Long-term alteration of gene expression without morphological change in testis after neonatal exposure to genistein in mice: toxicogenomic analysis using cDNA microarray. Food Chem. Toxicol. 42, 445-452.
48. Moustafa, G. G., Ibrahim, Z. S., Hashimoto, Y., Alkelch, A. M., Sakamoto, K. Q., Ishizuka, M., and Fujita, S. (2007) Testicular toxicity of profenofos in matured male rats. Arch Toxicol. 81, 875-881.
49. Richburg, J. H., Johnson, K. J., Schoenfeld, H. A., Meistrich, M. L., and Dix, D. J. (2002) Defining the cellular and molecular mechanisms of toxicant action in the testis. Toxicol. Lett. 135, 167-183.
50. Shultz, V. D., Phillips, S., Sar, M., Foster, P. M., and Gaido, K. W. (2001) Altered gene profiles in fetal rat testes after in utero exposure to di(n-butyl) phthalate. Toxicol. Sci. 64, 233-242.
51. Tully, D. B., Bao, W., Goetz, A. K., Blystone, C. R., Ren, H., Schmid, J. E., et al. (2006) Gene expression profiling in liver and testis of rats to characterize the toxicity of triazole fungicides. Toxicol. Appl. Pharmacol. 215, 260-273.
52. Rockett, J. C., Christopher Luft, J., Brian Garges, J., Krawetz, S. A., Hughes, M. R., Hee Kirn, K., et al. (2001) Development of a 950-gene DNA array for examining gene expression patterns in mouse testis. Genome Biol. 2, 1-10.
53. Ryu, J. Y., Lee, B. M., Kacew, S., and Kim, H. S. (2007) Identification of differentially expressed genes in the testis of Sprague-Dawley rats treated with di(n-butyl) phthalate. Toxicology 234, 103-112.
54. Page, B. D., and Lacroix, G. M. (1995) The occurrence of phthalate ester and di-2-ethylhexyl adipate plasticizers in Canadian packaging and food sampled in 1985-1989: a survey. Food Addit. Contam. 12, 129-151.
55. Saillenfait, A. M., Payan, J. P., Fabry, J. P., Beydon, D., Langonne, I., Gallissot, F., and Sabate, J. P. (1998) Assessment of the developmental toxicity, metabolism, and placental transfer of di-n-butyl phthalate administered to pregnant rats. Toxicol. Sci. 45, 212-224.
56. Mylchreest, E., Cattley, R. C., and Foster, P. M. (1998) Male reproductive tract malformations in rats following gestational and lactational exposure to Di(n-butyl) phthalate: an antiandrogenic mechanism? Toxicol. Sci. 43, 47-60.
57. Thompson, C. J., Ross, S. M., and Gaido, K. W. (2004) Di(n-butyl) phthalate impairs cholesterol transport and steroidogenesis in the fetal rat testis through a rapid and reversible mechanism. Endocrinology 145, 1227-1237.
58. Fukushima, T., Yamamoto, T., Kikkawa, R., Hamada, Y., Komiyama, M., Mori, C., and Horii, I. (2005) Effects of male reproductive toxicants on gene expression in rat testes. J. Toxicol. Sci. 30, 195-206.
59. Pelletier, G., Li, S., Luu-The, V., Tremblay, Y., Belanger, A., and Labrie, F. (2001) Immunoelectron microscopic localization of three key steroidogenic enzymes (cytochrome P450(scc), 3 beta-hydroxysteroid dehydrogenase and cytochrome P450(c17)) in rat adrenal cortex and gonads. J. Endocrinol. 171, 373-383.
60. Dalla Valle, L., Vianello, S., Belvedere, P., and Colombo, L. (2002) Rat cytochrome P450c17 gene transcription is initiated at different start sites in extraglandular and glandular tissues. J. Steroid Biochem. Mol. Biol. 82, 377-384.
61. Kaplowitz, N. (2005) Idiosyncratic drug hepatotoxicity. Nat. Rev. Drug Discov. 4, 489-499.
62. Liguori, M. J., and Waring, J. F. (2006) Investigations toward enhanced understanding of hepatic idiosyncratic drug reactions. Expert Opin. Drug Metab. Toxicol. 2, 835-846.
63. Uetrecht, J. (2007) Idiosyncratic drug reactions: current understanding. Annu. Rev. Pharmacol. Toxicol. 47, 513-539.
64. Waring, J. F., and Anderson, M. G. (2005) Idiosyncratic toxicity: mechanistic insights gained from analysis of prior compounds. Curr. Opin. Drug Discov. Dev. 8, 59-65.
65. Fielden, M. R., and Halbert, D. N. (2007) Iconix Biosciences, Inc. Pharmacogenomics 8, 401-405.
66. Leone, A. M., Kao, L. M., McMillian, M. K., Nie, A. Y., Parker, J. B., Kelley, M. F., et al. (2007) Evaluation of felbamate and other antiepileptic drug toxicity potential based on hepatic protein covalent binding and gene expression. Chem. Res. Toxicol. 20, 600-608.
67. Dieckhaus, C. M., Thompson, C. D., Roller, S. G., and Macdonald, T. L. (2002) Mechanisms of idiosyncratic drug reactions: the case of felbamate. Chem. Biol. Interact. 142, 99-117.
68. Naito, Y., Kuroda, M., Uchiyama, K., Mizushima, K., Akagiri, S., Takagi, T., et al. (2006) Inflammatory response of esophageal epithelium in combined-type esophagitis in rats: a transcriptome analysis. Int. J. Mol. Med. 18, 821-828.