Abstract
Carcinogenesis is a multistage, multimechanism process, involving the irreversible alteration of an initiated cell, followed by its clonal proliferation, from which the acquisition of the invasive and metastatic phenotypes are generated (Trosko and Chang, 2001). Chemically induced and spontaneous liver tumors share some metabolic alterations. We have developed an experimental mice model, by administrating p-dimethylaminoazobenzene (DAB) in the diet, to study the onset of hepatocarcino-genesis, that includes a primary activating liver stage, provoking biochemical alterations that lead to the true initiation step (Gerez et al., 1997; Vazquez et al., 1999). Tamoxifen (TMX) has proven to be an effective palliative treatment for advanced breast cancer with low reported incidence of side effects (Forbes, 1997). It has been observed, that TMX is a carcinogen capable of both initiating and promoting liver carcinogenesis in female rats (Dragan et al., 1996). Recently, we have demonstrated that TMX produced changes in hepatic enzyme activities which may be relevant to the metabolism and disposition of this and/or other drugs. We have found that long-term treatment with TMX enhances hepatocarcinogenesis induced by DAB (Caballero et al., 2001).
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Abraham N.G., Lavrovsky Y., Schwartzman M., Stoltz R., Levere R., Gerritsen M., Shibahara S., and Kappas A., 1995. Transfection of the human heme oxygenase gene into rabbit coronary microvessel endothelial cells: protective effect against heme and hemoglobin toxicity. Proc Natl Acad Sci USA 92:6798.
Abraham N.G., Drummed J.D., Lutton A., and Kappas A., 1996. The biological significance and physiological role of heme oxygenase. Cell Physiol Biochem 6:129.
Alam J., Camhi S., and Choi A.M., 1995. Identification of a second region upstream of the mouse heme oxygenase-1 gene that functions as a basal level and inducer-dependent transcription enhancer. J Biol Chem 210:11977.
Caballero F., Gerez E., Oliveri L., Falcoff N., Batlle A., and Vazquez E., 2001. On the promoting action of tamoxifen in a model of hepatocarcinogenesis induced by p-dimethylaminoazobenzene in CF1 mice. Int J Biochem Cell Biol 33:681.
Cerutti P., Ghosh R., Oya Y., and Amstad P., 1994. The role of the cellular antioxidant defense in oxidant carcinogenesis. Env Health Persped 102:123.
Clark J., Foresti R., Green C., and Motterlini R., 2000. Dynamics of haem oxygenase-1 expression and bilirubin production in cellular protection against oxidative stress. Biochem J 348:615.
Doi K., Akaike T., Fujii S., Tanaka S., Ikebe N., Beppu T., Shibahara S., Ogawa M., and Maeda H., 1999. Induction of haem oxygenase-1 nitric oxide and ischaemia in experimental solid tumours and implications for tumour growth. Br J Cancer 80:1945.
Dragan Y. and Pitot H., 1992. The role of the stages of initiation and promotion in phenotypic diversity during hepatocarcinogenesis in the rat. Carcinogenesis 13:739.
Dragan Y., Fahey S., Nuwaysir E., Sattler C., Babcock K., Vaughan J., McCague R., and Pitot H., 1996. The effect of tamoxifen and two of its non-isomerizable fixed-ring analogues on multistage rat hepatocarcinogenesis. Carcinogenesis 17:585.
Elbirt K. and Bonkovsky H., 1999. Heme oxygenase: recent advances in understanding its regulation and role. Proc Assoc Am Physicians 111:438.
Forbes J. 1997. Scientific review of tamoxifen. Semin Oncol 24.S1–5.
Galbraith R., 1999. Heme oxygenase: who needs it?. Proc Soc Exp Biol Med 222:299.
Gerez E., Vazquez E., Caballero F., Polo C., and Batlle A., 1997. Altered heme pathway regulation and drug metabolizing enzyme system in a mouse model of hepatocarcinogenesis. Effect of veronal. Gen Pharmac 29:569.
Gerez E., Caballero F., Vazquez E., Polo C., and Batlle A., 1998. Hepatic enzymatic metabolism alteration and oxidative stress during the onset of carcinogenesis: protective role of alpha tocopherol. Eur J Cancer Prevention 7:69.
Greaves P., Goonetilleke R., Nunn G., Topham J., and Orton T., 1993. Two-year carcinogenicity study of tamoxifen in Alderley Park Wistar-derived rats. Cancer Res 53:3919.
Halliwell B. and Aruoma O., 1993. In: DNA and free Radicals (Ed. Ellis Horwood) Chichester, England.
Harris C., 1991. Chemical and physical carcinogenesis: advances and perspectives for the 1990s. Cancer Res 51:5023.
Hirsimäki P., Hirsimäki Y., Nieminen L., and Payne B., 1993. Tamoxifen induces hepatocellular carcinoma in rat liver: a one year study with two carcinogens. Arch Toxicol 67:49.
Klaunig J., Xu Y., Isenberg J., Bachowski S., Kolaja K., Jiang J., Stevenson D., and Walborg E., 1998. Environ Health Perspect 106:289.
Loeb K. and Loeb L., 2001. Significance of multiple mutations in cancer. Carcinogenesis 21:379.
Maines M.D., 1997. The heme oxygenase system: a regulator of second messenger gases. Annu Rev Pharmacol Toxicol 37:517.
Maines M.D., 1999. In: Heme Oxygenase: Clinical Applications and Functions. (Ed. Maines MD.) Boca Ratón, Fl, CRC Press, pp. 109.
Maines M.D. and Kappas A., 1974. Cobalt induction of hepatic heme oxygenase, with evidence that cytochrome P-450 is not essential for this enzyme activity. Proc. Natl Acad. Sci. U.S.A. 71:4293.
Maines M.D., Traskhel G.M., and Kutty R.K., 1986. Characterization of two constitutive forms of micro-somal heme oxygenase ony one molecular species of the enzyme is inducible. J. Biol. Chem 261:411–419.
McCord J.M., 1998. Iron, free radicals, and oxidative injury. Semin Hematol 35:5.
McCoubrey W.K., Huang T., and Maines M.D., 1997. Isolation and characterization of a cDNA from the rat brain that encodes hemoprotein heme oxygenase-3. Eur J Biochem 247:725.
Nishie A., Ono M., Shono T., Fukushi J., Otsubo M., Onoue H., Ito Y., Inamura T., Ikezaki K., Fukui M., Iwaki T., and Kuwano M., 1999. Macrophage infiltration and heme oxygenase-1 expression cor-relate with angiogenesis in human gliomas. Clin Cancer Res 5:1107.
Nuwaysir E.F., Daggett D.A., Jordan V.C., and Pitot H.C., 1996. Phase II enzyme expression in rat liver in response to the antiestrogen tamoxifen. Cancer Res. 56:3704.
Pathak D.N. and Badell W.Y., 1994. DNA adducts formation by tamoxifen with rat and human liver micro-somal activating systems. Carcinogenesis 15:529.
Pitot H., 1991. Endogenous carcinogenesis: the role of tumor promotion. Proc Soc Exp Biol Med 198:661.
Pitot H., 1993. The molecular biology of carcinogenesis. Cancer 72:962.
Pitot H. and Dragan Y., 1991. Facts and theories concerning the mechanisms of carcinogenesis. FASEB J 5:2280.
Poss K. and Tonegawa S., 1997. Heme oxygenase 1 is required for mammalian iron reutilization. Proc Natl Acad Sci USA 94:10919.
Stocker R., Yamamoto Y., Ms Donagh AF., Glazer AN., and Ames BN., 1987. Bilirubin is an antioxidant of possible physiological importance. Science 235:1043–1046.
Tomaro M.L. and Batlle A., 2001. Bilirubin: its role in cytoprotection against oxidative stress. Int. J. Biochem. Cell Biol. 33:1.
Tsuji M., Yanagawa T., Iwasa S., Tabuchi K., Onizawa K., Bannai S., Toyooka H., and Yoshida H., 1999. Heme oxygenase-1 expression in oral squamous cell carcinoma as involved in lymph node metastasis. Cancer Lett 138:53.
Trosko J. and Chang C., 2001. Mechanism of up-regulated gap junctional intercellular communication during chemoprevention and chemotherapy of cancer. Mutat Res 480-481:219.
Vazquez E., Gerez E., Caballero F., Polo C., and Batlle A., 1999. Drug metabolizing enzyme system and heme pathway in hepatocarcinogenesis. Cancer Biochem Biophys 17:25.
Wagner K., Hua Y., De Courten-Myers G., Broderick J., Nishimura R., Lu S., and Dwyer B., 2000. Tin-mesoporphyrin, a potent heme oxygenase inhibitor, for treatment of intracerebral hemorrhage: in vivo and in vitro studies. Cell Mol Biol 46:597.
White I.N.H., Davies A., Smith L.L., Dawson S., and De Matteis F., 1993. Induction of CYP2B1 and 3A1 and associated monooxygenase activities by tamoxifen and certain analogues in the liver of female rats and mice. Biochem Pharmacol 45:21.
Wogan G., 1997. Review of the toxicology of tamoxifen. Seminars in Oncology 24:S1–87.
Yachie A., Niida Y., Wada T., Igarashi N., Kaneda H., Toma T., Ohta K., Kasahara Y., and Koizumi S., 1999. Oxidative stress causes enhanced endothelial cell injury in human heme oxygenase-1 deficiency. J Clin Invest 103:129.
Yan Y., Higashi K., Yamamura K., Fukamachi Y., Abe T., Gotoh S., Sugiura T., Hirano T., Higashi T., and Ichiba M., 1998. Different responses other than the formation of DNA-adducts between the livers of carcinogen-resistant rats (DRH) and carcinogen-sensitive rats (Donryu) to 3′-methyl-4-dimethylaminoazobenzene administration. Jpn J Cancer Res 89:806.
Yuspa S. and Shields P., 1997. In: Cancer: Principles & Practice of Oncology (Ed. V. DeVita, S. Hellman, S. Rosenberg) Lippincott-Raven Publishers, Philadelphia, pp. 185.
Zbaida S., 1995. The mechanism of microsomal azoreduction: predictions based on electronic aspects of structure-activity relationships. Drug Metab Rev 27:497.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2002 Springer Science+Business Media New York
About this chapter
Cite this chapter
Vázquez, E. et al. (2002). On the Promoting Action of Tamoxifen in the P-Dimethylaminoazobenzene Induced Hepatocarcinogenesis CF1 Mice Model and the Cytoprotective Role of Heme Oxygenase. In: Abraham, N.G. (eds) Heme Oxygenase in Biology and Medicine. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-0741-3_42
Download citation
DOI: https://doi.org/10.1007/978-1-4615-0741-3_42
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4613-5219-8
Online ISBN: 978-1-4615-0741-3
eBook Packages: Springer Book Archive