Phenobarbital-mediated tumor promotion in transgenic mice with humanized CAR and PXR

Toxicological Sciences

Volumn 140, Issue 2, 2014, Pages 259-270

  Braeuning, Albert ^a   Gavrilov, Alina ^a   Brown, Susan ^b   Roland Wolf, C ^c   Henderson, Colin J ^c   Schwarz, Michael ^a  

^a UNIVERSITY OF TÜBINGEN   (Germany)

^b CXR Biosciences Ltd   (United Kingdom)

^c UNIVERSITY OF DUNDEE   (United Kingdom)

Author keywords

Constitutive androstane receptor; HCC; Liver tumor; Nongenotoxic carcinogen; Pregnane X receptor

Indexed keywords

BETA CATENIN; CARCINOGEN; CONSTITUTIVE ANDROSTANE RECEPTOR; DIETHYLNITROSAMINE; PHENOBARBITAL; PREGNANE X RECEPTOR; CELL RECEPTOR; DNA ADDUCT; PRIMER DNA; STEROID RECEPTOR;

ANIMAL TISSUE; ARTICLE; CANCER INCIDENCE; CANCER RISK; CARCINOGENESIS; CONTROLLED STUDY; DNA ADDUCT; GENOTYPE; HUMAN; HUMAN CELL; LIVER CANCER; LIVER WEIGHT; MALE; MOUSE; NONHUMAN; PROTEIN EXPRESSION; TRANSGENIC MOUSE; TUMOR PROMOTION; TUMOR VOLUME; ANIMAL; BODY WEIGHT; C57BL MOUSE; DRUG EFFECTS; GENETICS; LIVER; METABOLISM; NUCLEOTIDE SEQUENCE; ORGAN SIZE; POLYMERASE CHAIN REACTION;

ANIMALS; BASE SEQUENCE; BODY WEIGHT; CARCINOGENS; DNA ADDUCTS; DNA PRIMERS; HUMANS; LIVER; MICE; MICE, INBRED C57BL; MICE, TRANSGENIC; ORGAN SIZE; PHENOBARBITAL; POLYMERASE CHAIN REACTION; RECEPTORS, CYTOPLASMIC AND NUCLEAR; RECEPTORS, STEROID;

EID: 84984999069     PISSN: 10966080     EISSN: 10960929     Source Type: Journal    
DOI: 10.1093/toxsci/kfu099     Document Type: Article

References (35)

1. Aydinlik, H., Nguyen, T. D., Moennikes, O., Buchmann, A., and Schwarz, M. (2001). Selective pressure during tumor promotion by phenobarbital leads to clonal outgrowth of beta-catenin-mutated mouse liver tumors. Oncogene 20, 7812-7816.
2. Bachmanov, A. A., Reed, D. R., Beauchamp, G. K., and Tordoff, M. G. (2002). Food intake, water intake, and drinking spout side preference of 28 mouse strains. Behav. Genet. 32, 435-443.
3. Braeuning, A., Heubach, Y., Knorpp, T., Kowalik, M. A., Templin, M., Columbano, A., and Schwarz, M. (2011). Gender-specific interplay of signaling through beta-catenin and CAR in the regulation of xenobiotic-induced hepatocyte proliferation. Toxicol. Sci. 123, 113-122.
4. Braeuning, A., Sanna, R., Huelsken, J., and Schwarz, M. (2009). Inducibility of drug-metabolizing enzymes by xenobiotics in mice with liver-specific knockout of Ctnnb1. Drug Metab. Dispos. 37, 1138-1145.
5. Braeuning, A., Singh, Y., Rignall, B., Buchmann, A., Hammad, S., Othman, A., von Recklinghausen, I., Godoy, P., Hoehme, S., Drasdo, D. et al. (2010). Phenotype and growth behavior of residual beta-catenin-positive hepatocytes in livers of beta-catenin-deficient mice. Histochem. Cell Biol. 134, 469-481.
6. Bursch, W., Grasl-Kraupp, B., Wastl, U., Hufnagl, K., Chabicovsky, M., Taper, H., and Schulte-Hermann, R. (2004). Role of apoptosis for mouse liver growth regulation and tumor promotion: Comparative analysis of mice with high (C3H/He) and low (C57Bl/6J) cancer susceptibility. Toxicol. Lett. 149, 25-35.
7. Campbell, H. A., Pitot, H. C., Potter, V. R., and Laishes, B. A. (1982). Application of quantitative stereology to the evaluation of enzyme-altered foci in rat liver. Cancer Res. 42, 465-472.
8. Clemmesen, J., and Hjalgrim-Jensen, S. (1978). Is phenobarbital carcinogenic? A follow-up of 8078 epileptics. Ecotoxicol. Environ. Saf. 1, 457-470.
9. Diwan, B. A., Rice, J. M., Ohshima, M., and Ward, J. M. (1986). Interstrain differences in susceptibility to liver carcinogenesis initiated by Nnitrosodiethylamine and its promotion by phenobarbital in C57BL/6NCr, C3H/HeNCrMTV-and DBA/2NCr mice. Carcinogenesis 7, 215-220.
10. El-Masri, H. A., and Portier, C. J. (1998). Physiologically based pharmacokinetics model of primidone and its metabolites phenobarbital and phenylethylmalonamide in humans, rats, and mice. Drug Metab. Dispos. 26, 585-594.
11. Forrester, L.M., Henderson, C. J., Glancey, M. J., Back, D. J., Park, B. K., Ball, S. E., Kitteringham, N. R., McLaren, A. W., Miles, J. S., Skett, P. et al. (1992). Relative expression of cytochrome P450 isoenzymes in human liver and association with the metabolism of drugs and xenobiotics. Biochem. J. 281, 359-368.
12. Ganzenberg, K., Singh, Y., and Braeuning, A. (2013). The time point of beta-catenin knockout in hepatocytes determines their response to xenobiotic activation of the constitutive androstane receptor. Toxicology 308, 113-121.
13. Geter, D. R., Bhat, V. S., Gollapudi, B. B., Sura, R., and Hester, S. D. (2014). Dose-response modeling of early molecular and cellular key events in the CAR-mediated hepatocarcinogenesis pathway. Toxicol. Sci. 138, 425-445.
14. Hailfinger, S., Jaworski, M., Braeuning, A., Buchmann, A., and Schwarz, M. (2006). Zonal gene expression in murine liver: Lessons from tumors. Hepatology 43, 407-414.
15. Houghton, G. W., Richens, A., Toseland, P. A., Davidson, S., and Falconer, (1975). Brain concentrations of phenytoin, phenobarbitone and primidone in epileptic patients. Eur. J. Clin. Pharmacol. 9, 73-78.
16. Jones, H. B., Orton, T. C., and Lake, B. G. (2009). Effect of chronic phenobarbitone administration on liver tumour formation in the C57BL/10J mouse. Food Chem. Toxicol. 47, 1333-1340.
17. ALagenstein, I. (1983) Fieberkrämpfe Wandlung in der Bewertung. Dt. Ärzteblatt 80,.
18. Lamminpaa, A., Pukkala, E., Teppo, L., and Neuvonen, P. J. (2002). Cancer incidence among patients using antiepileptic drugs: A long-term follow-up of 28,000 patients. Eur. J. Clin. Pharmacol. 58, 137-141.
19. LeBaron, M. J., Geter, D. R., Rasoulpour, R. J., Gollapudi, B. B., Thomas, J., Murray, J., Kan, H. L., Wood, A. J., Elcombe, C., Vardy, A. et al. (2013). An integrated approach for prospectively investigating a mode-of-action for rodent liver effects. Toxicol. Appl. Pharmacol. 270, 164-173.
20. Lee, G. H. (2000). Paradoxical effects of phenobarbital on mouse hepatocarcinogenesis. Toxicol. Pathol. 28, 215-225.
21. Luisier, R., Lempiainen, H., Scherbichler, N., Braeuning, A., Geissler, M., Dubost, V., Mueller, A., Scheer, N., Chibout, S. D., and Hara, H. (2014). Phenobarbital induces cell cycle transcriptional responses in humanized CAR/PXR mouse liver. Toxicol. Sci. 139, 501-511.
22. Madan, A., Graham, R. A., Carroll, K. M., Mudra, D. R., Burton, L. A., Krueger, L. A., Downey, A. D., Czerwinski, M., Forster, J., Ribadeneira, M. D. et al. (2003). Effects of prototypical microsomal enzyme inducers on cytochrome P450 expression in cultured human hepatocytes. Drug Metab. Dispos. 31, 421-431.
23. Marx-Stoelting, P., Borowiak, M., Knorpp, T., Birchmeier, C., Buchmann, A., and Schwarz, M. (2009). Hepatocarcinogenesis in mice with a conditional knockout of the hepatocyte growth factor receptor c-Met. Int. J. Cancer 124, 1767-1772.
24. Meehan, R. R., Forrester, L. M., Stevenson, K., Hastie, N. D., Buchmann, A., Kunz, H. W., and Wolf, C. R. (1988). Regulation of phenobarbitalinducible cytochrome P-450s in rat and mouse liver following dexamethasone administration and hypophysectomy. Biochem. J. 254, 789-797.
25. Moennikes, O., Buchmann, A., Romualdi, A., Ott, T., Werringloer, J., Willecke, K., and Schwarz, M. (2000). Lack of phenobarbital-mediated promotion of hepatocarcinogenesis in connexin32-null mice. Cancer Res. 60, 5087-5091.
26. Olsen, J. H., Boice, J. D., Jr, Jensen, J. P., and Fraumeni, J. F., Jr (1989). Cancer among epileptic patients exposed to anticonvulsant drugs. J. Natl. Cancer Inst. 81, 803-808.
27. Olsen, J. H., Schulgen, G., Boice, J. D., Jr, Whysner, J., Travis, L. B., Williams, G. M., Johnson, F. B., and McGee, J. O. (1995). Antiepileptic treatment and risk for hepatobiliary cancer and malignant lymphoma. Cancer Res. 55, 294-297.
28. Pfaffl, M. W. (2001) A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res. 29, e45.
29. Rignall, B., Braeuning, A., Buchmann, A., and Schwarz, M. (2011). Tumor formation in liver of conditional beta-catenin-deficientmice exposed to a diethylnitrosamine/phenobarbital tumor promotion regimen. Carcinogenesis 32, 52-57.
30. Ross, J., Plummer, S. M., Rode, A., Scheer, N., Bower, C. C., Vogel, O., Henderson, C. J., Wolf, C. R., and Elcombe, C. R. (2010). Human constitutive androstane receptor (CAR) and pregnane X receptor (PXR) support the hypertrophic but not the hyperplastic response to the murine nongenotoxic hepatocarcinogens phenobarbital and chlordane in vivo. Toxicol. Sci. 116, 452-466.
31. Smith, G. C., Tew, D. G., and Wolf, C. R. (1994). Dissection of NADPHcytochrome P450 oxidoreductase into distinct functional domains. Proc. Natl. Acad. Sci. U.S.A. 91, 8710-8714.
32. Sotaniemi, E. A., Pelkonen, R. O., Ahokas, J., Pirttiaho, H. I., and Ahlqvist, J. (1978). Drug metabolism in epileptics: In vivo and in vitro correlations. Br. J. Clin. Pharmacol. 5, 71-76.
33. Wachstein, M., and Meisel, E. (1957). Histochemistry of hepatic phosphatases of a physiologic pH; with special reference to the demonstration of bile canaliculi. Am. J. Clin. Pathol. 27, 13-23.
34. Whysner, J., Ross, P. M., and Williams, G. M. (1996). Phenobarbital mechanistic data and risk assessment: Enzyme induction, enhanced cell proliferation, and tumor promotion. Pharmacol. Ther. 71, 153-191.
35. Yamamoto, Y., Moore, R., Goldsworthy, T. L., Negishi, M., and Maronpot, R. R. (2004). The orphan nuclear receptor constitutive active/androstane receptor is essential for liver tumor promotion by phenobarbital in mice. Cancer Res. 64, 7197-7200.