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The American Journal of Pathology logoLink to The American Journal of Pathology
. 1985 Sep;120(3):419–426.

Squamous and transitional elements in rat bladder carcinomas induced by N-butyl-N-4-hydroxybutyl-nitrosamine (BBN). A study of cytokeratin expression.

C J Herman, P D Vegt, F M Debruyne, G P Vooijs, F C Ramaekers
PMCID: PMC1887986  PMID: 2412446

Abstract

Three hundred rat bladders bearing tumors induced by N-butyl-N-4-(OH)butyl-nitrosamine (BBN) were examined by routine histologic study and immunohistochemical staining of intermediate filament types. Smaller lesions were similar to human urothelial dysplasia histologically and immunohistochemically. Progression of the lesions demonstrated large exophytic papillomas with extensive endophytic epithelial growth into abundant stroma. These lesions showed increasing predominance of squamous over transitional elements. Immunohistochemical findings confirmed these results and also demonstrated that morphologically indifferent cells, even in early lesions, express heavier cytokeratins characteristic of keratinizing squamous epithelium. These results demonstrate that BBN-induced bladder tumors show marked quantitative and qualitative differences from the most common, purely transitional, human bladder carcinomas. However, the development in BBN-treated rat bladders of two tumor types, squamous and transitional, from an altered urothelium may serve as an attractive model for further study of the molecular genetics of keratin expression.

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Selected References

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  1. Akagi G., Akagi A., Kimura M., Otsuka H. Comparison of bladder tumors induced in rats and mice with N-butyl-N-(4-hydroxybutyl)-nitrosoamine. Gan. 1973 Aug;64(4):331–336. [PubMed] [Google Scholar]
  2. Arai M., Kani T., Sugihara S., Matsumura K., Miyata Y., Shinohara Y., Ito N. Scanning and transmission electron microscopy of changes in the urinary bladder in rats treated with N-butyl-N-(4-hydroxybutyl)nitrosoamine. Gan. 1974 Dec;65(6):529–540. [PubMed] [Google Scholar]
  3. Cohen S. M., Friedell G. H. Carcinoma of the urinary bladder. Am J Pathol. 1979 Jun;95(3):849–852. [PMC free article] [PubMed] [Google Scholar]
  4. DRUCKREY H., PREUSSMANN R., IVANKOVIC S., SCHMIDT C. H., MENNEL H. D., STAHL K. W. SELEKTIVE ERZEUGUNG VON BLASENKREBS AN RATTEN DURCH DIBUTYL- UND N-BUTYL-N-BUTANOL(4)-NITROSAMIN. Z Krebsforsch. 1964 Nov 2;66:280–290. [PubMed] [Google Scholar]
  5. Druckrey H., Preussmann R., Ivankovic S., Schmähl D. Organotrope carcinogene Wirkungen bei 65 verschiedenen N-Nitroso-Verbindungen an BD-Ratten. Z Krebsforsch. 1967;69(2):103–201. [PubMed] [Google Scholar]
  6. Fukushima S., Hirose M., Tsuda H., Shirai T., Hirao K. Histological classification of urinary bladder cancers in rats induced by N-butyl-n-(4-hydroxybutyl)nitrosamine. Gan. 1976 Feb;67(1):81–90. [PubMed] [Google Scholar]
  7. Herman C. J., Moesker O., Kant A., Huysmans A., Vooijs G. P., Ramaekers F. C. Is renal cell (Grawitz) tumor a carcinosarcoma? Evidence from analysis of intermediate filament types. Virchows Arch B Cell Pathol Incl Mol Pathol. 1983;44(1):73–83. doi: 10.1007/BF02890161. [DOI] [PubMed] [Google Scholar]
  8. Ito N., Hiasa Y., Tamai A., Okajima E., Kitamura H. Histogenesis of urinary bladder tumors induced by N-butyl-N-(4-hydroxybutyl)nitrosamine in rats. Gan. 1969 Aug;60(4):401–410. [PubMed] [Google Scholar]
  9. Ito N., Matayoshi K., Arai M., Yoshioka Y., Kamamoto Y. Effect of various factors on induction of urinary bladder tumors in animals by N-butyl-n-(4-hydroxybutyl)nitrosoamine. Gan. 1973 Apr;64(2):151–159. [PubMed] [Google Scholar]
  10. King E. B., Vanderlaan M., Jensen R. H., Kromhout L. K., Hoffman J. W. Morphologic changes in rat urothelial cells during carcinogenesis: I. Histologic and cytologic changes. Cytometry. 1984 Sep;5(5):447–453. doi: 10.1002/cyto.990050503. [DOI] [PubMed] [Google Scholar]
  11. Knuze E., Schauer A. Morphology, classification and histogenesis of N-butyl-N-(4-hydroxybutyl)-nitrosamine-induced carcinomas in the urinary bladder of rats. Z Krebsforsch Klin Onkol Cancer Res Clin Oncol. 1977;88(3):273–289. doi: 10.1007/BF00305365. [DOI] [PubMed] [Google Scholar]
  12. Kunze E. Development of urinary bladder cancer in the rat. Curr Top Pathol. 1979;67:145–232. doi: 10.1007/978-3-642-67292-7_3. [DOI] [PubMed] [Google Scholar]
  13. Moll R., Franke W. W., Schiller D. L., Geiger B., Krepler R. The catalog of human cytokeratins: patterns of expression in normal epithelia, tumors and cultured cells. Cell. 1982 Nov;31(1):11–24. doi: 10.1016/0092-8674(82)90400-7. [DOI] [PubMed] [Google Scholar]
  14. Murphy W. M., Soloway M. S. Urothelial dysplasia. J Urol. 1982 May;127(5):849–854. doi: 10.1016/s0022-5347(17)54105-1. [DOI] [PubMed] [Google Scholar]
  15. Okada M., Hashimoto Y. Carcinogenic effect of N-nitrosoamines related to butyl(4-hydroxybutyl)nitrosoamine in ACI-N rats, with special reference to induction of urinary bladder tumors. Gan. 1974 Feb;65(1):13–19. [PubMed] [Google Scholar]
  16. Oud P. S., Henderik J. B., Beck H. L., Veldhuizen J. A., Vooijs G. P., Herman C. J., Ramaekers F. C. Flow cytometric analysis and sorting of human endometrial cells after immunocytochemical labeling for cytokeratin using a monoclonal antibody. Cytometry. 1985 Mar;6(2):159–164. doi: 10.1002/cyto.990060212. [DOI] [PubMed] [Google Scholar]
  17. Ramaekers F. C., Beck H., Vooijs G. P., Herman C. J. Flow-cytometric analysis of mixed cell populations using intermediate filament antibodies. Exp Cell Res. 1984 Jul;153(1):249–253. doi: 10.1016/0014-4827(84)90467-1. [DOI] [PubMed] [Google Scholar]
  18. Ramaekers F. C., Puts J. J., Kant A., Moesker O., Jap P. H., Vooijs G. P. Use of antibodies to intermediate filaments in the characterization of human tumors. Cold Spring Harb Symp Quant Biol. 1982;46(Pt 1):331–339. doi: 10.1101/sqb.1982.046.01.034. [DOI] [PubMed] [Google Scholar]
  19. Ramaekers F. C., Puts J. J., Moesker O., Kant A., Huysmans A., Haag D., Jap P. H., Herman C. J., Vooijs G. P. Antibodies to intermediate filament proteins in the immunohistochemical identification of human tumours: an overview. Histochem J. 1983 Jul;15(7):691–713. doi: 10.1007/BF01002988. [DOI] [PubMed] [Google Scholar]
  20. Ramaekers F., Huysmans A., Moesker O., Kant A., Jap P., Herman C., Vooijs P. Monoclonal antibody to keratin filaments, specific for glandular epithelia and their tumors. Use in surgical pathology. Lab Invest. 1983 Sep;49(3):353–361. [PubMed] [Google Scholar]
  21. Ramaekers F., Huysmans A., Moesker O., Schaart G., Herman C., Vooijs P. Cytokeratin expression during neoplastic progression of human transitional cell carcinomas as detected by a monoclonal and a polyclonal antibody. Lab Invest. 1985 Jan;52(1):31–38. [PubMed] [Google Scholar]
  22. Ramaekers F., Puts J., Moesker O., Kant A., Jap P., Vooijs P. Demonstration of keratin in human adenocarcinomas. Am J Pathol. 1983 May;111(2):213–223. [PMC free article] [PubMed] [Google Scholar]
  23. Summerhayes I. C., Chen L. B. Localization of a Mr 52,000 keratin in basal epithelial cells of the mouse bladder and expression throughout neoplastic progression. Cancer Res. 1982 Oct;42(10):4098–4109. [PubMed] [Google Scholar]
  24. Toyoshima K., Ito N., Hiasa Y., Kamamoto Y., Makiura S. Tissue culture of urinary bladder tumor induced in a rat by N-butyl-N-(-4-hydroxybutyl)nitrosamine: establishment of cell line, Nara Bladder Tumor II. J Natl Cancer Inst. 1971 Nov;47(5):979–985. [PubMed] [Google Scholar]

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