Abstract
Urinary bladder cancer is the tenth most common cancer worldwide with high morbidity and mortality. The majority of bladder cancers are urothelial carcinomas. More than half are papillomas or the papillary urothelial carcinomas (stages Ta and T1), which have a relatively good prognosis. Squamous cell carcinomas have a variable survival rate, while carcinomas in situ (Tis) can progress to muscle-invasive urothelial carcinomas (T2) with a poor prognosis. The most challenging feature of bladder cancer is its high recurrence rate, ranging from 50% to 90% of cases. The N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) model is an invaluable experimental tool for bladder cancer research, as BBN-induced bladder cancer in rodents resembles human bladder cancer in its morphological, biological, and molecular features. We present here a detailed protocol for the treatment of mice and the main expected results.
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References
Magers MJ, Lopez-Beltran A, Montironi R et al (2019) Staging of bladder cancer. Histopathology 74:112–134. https://doi.org/10.1111/his.13734
Siegel S, Noblett K, Mangel J et al (2018) Five-year followup results of a prospective, multicenter study of patients with overactive bladder treated with sacral neuromodulation. J Urol 199:229–236. https://doi.org/10.1016/j.juro.2017.07.010
Antoni S, Ferlay J, Soerjomataram I et al (2017) Bladder cancer incidence and mortality: a global overview and recent trends. Eur Urol 71:96–108. https://doi.org/10.1016/j.eururo.2016.06.010
Amin MB, Greene FL, Edge SB et al (2017) The eighth edition AJCC cancer staging manual: continuing to build a bridge from a population-based to a more “personalized” approach to cancer staging. CA Cancer J Clin 67:93–99. https://doi.org/10.3322/caac.21388
Kamat AM, Hahn NM, Efstathiou JA et al (2016) Bladder cancer. Lancet 388:2796–2810. https://doi.org/10.1016/S0140-6736(16)30512-8
Babjuk M, Burger M, Compérat EM et al (2019) European Association of Urology guidelines on non-muscle-invasive bladder cancer (TaT1 and carcinoma in situ) – 2019 update. Eur Urol 76:639–657. https://doi.org/10.1016/j.eururo.2019.08.016
Ritch CR, Velasquez MC, Kwon D et al (2020) Use and validation of the AUA/SUO risk grouping for nonmuscle invasive bladder cancer in a contemporary cohort. J Urol 203:505–510. https://doi.org/10.1097/Ju.0000000000000593
Tan TZ, Rouanne M, Tan KT et al (2019) Molecular subtypes of urothelial bladder cancer: results from a meta-cohort analysis of 2411 tumors. Eur Urol 75:423–432. https://doi.org/10.1016/j.eururo.2018.08.027
Witjes JA, Bruins HM, Cathomas R et al (2021) European Association of Urology guidelines on muscle-invasive and metastatic bladder cancer: summary of the 2020 guidelines. Eur Urol 79:82–104. https://doi.org/10.1016/j.eururo.2020.03.055
Matsuo T, Miyata Y, Asai A et al (2017) Green tea polyphenol induces changes in cancer-related factors in an animal model of bladder cancer. PLoS One 12:e0171091. https://doi.org/10.1371/journal.pone.0171091
Slocum SL, Kensler TW (2011) Nrf2: control of sensitivity to carcinogens. Arch Toxicol 85:273–284. https://doi.org/10.1007/s00204-011-0675-4
Fukushima S, Hirose M, Tsuda H et al (1976) Histological classification of urinary bladder cancers in rats induced by N-butyl-n-(4-hydroxybutyl)nitrosamine. Gan 67:81–90
Gofrit ON, Birman T, Dinaburg A et al (2006) Chemically induced bladder cancer-a sonographic and morphologic description. Urology 68:231–235. https://doi.org/10.1016/j.urology.2006.03.022
Ariel I, Ayesh S, Gofrit O et al (2004) Gene expression in the bladder carcinoma rat model. Mol Carcinog 41:69–76. https://doi.org/10.1002/mc.20046
Tsuda H, Miyata Y, Hagiwara A et al (1977) Damage and repair of DNA in urinary bladder epithelium of rats treated with N-butyl-N-(4-hydroxybutyl) nitrosamine. Gan 68:781–783
Fantini D, Glaser AP, Rimar KJ et al (2018) A carcinogen-induced mouse model recapitulates the molecular alterations of human muscle invasive bladder cancer. Oncogene 37:1911–1925. https://doi.org/10.1038/s41388-017-0099-6
Bertram JS, Craig AW (1972) Specific induction of bladder cancer in mice by butyl-(4-hydroxybutyl)-nitrosamine and the effects of hormonal modifications on the sex difference in response. Eur J Cancer 8:587–594
Airoldi L, Magagnotti C, Bonfanti M et al (1990) Alpha-oxidative metabolism of the bladder carcinogens N-nitrosobutyl(4-hydroxybutyl)amine and N-nitrosobutyl(3-carboxypropyl)amine within the rat isolated bladder. Carcinogenesis 11:1437–1440
Cohen SM (1998) Urinary bladder carcinogenesis. Toxicol Pathol 26:121–127. https://doi.org/10.1177/019262339802600114
Zupancic D, Korac-Prlic J, Kreft ME et al (2020) Vitamin a rich diet diminishes early urothelial carcinogenesis by altering retinoic acid signaling. Cancers (Basel) 12:1712. https://doi.org/10.3390/cancers12071712
Zupancic D, Kreft ME, Romih R (2014) Selective binding of lectins to normal and neoplastic urothelium in rat and mouse bladder carcinogenesis models. Protoplasma 251:49–59. https://doi.org/10.1007/s00709-013-0524-9
Zupančič D, Ovčak Z, Vidmar G (2011) Altered expression of UPIa, UPIb, UPII, and UPIIIa during urothelial carcinogenesis induced by N-butyl-N-(4-hydroxybutyl) nitrosamine in rats. Virchows Arch 458:603–613
Ohtani M, Kakizoe T, Nishio Y et al (1986) Sequential changes of mouse bladder epithelium during induction of invasive carcinomas by N-butyl-N-(4-hydroxybutyl)nitrosamine. Cancer Res 46:2001–2004
Acknowledgments
The authors gratefully acknowledge financial support from the P3-0108, J7-2594, J3 2521, MRIC UL IP-0510 Infrastructure Programme of the Slovenian Research and Innovation Agency ARIS. We thank Sabina Železnik, Nada Pavlica Dubarić, Sanja Čabraja, and Linda Štrus for their technical support.
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Zupančič, D., Romih, R. (2024). Urinary Bladder Cancer Induced by N-Butyl-N-(4-Hydroxybutyl)-Nitrosamine. In: Čemažar, M., Jesenko, T., Lampreht Tratar, U. (eds) Mouse Models of Cancer. Methods in Molecular Biology, vol 2773. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-3714-2_3
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DOI: https://doi.org/10.1007/978-1-0716-3714-2_3
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