Experimental models of kidney tumors

  • Enrique Nogueira
  • Antonio Cardesa
  • Ulrich Mohr
Guest Editorial


We here present in outline some outstanding results on the animal models of renal tumors submitted to the highest attention, which include two kinds of epithelial neoplams: those developed from the epithelium lining each the renal tubules (renal cell tumors) and pelvis; the mesenchymal tumor of rat; and tumors with embryonal appearance: the nephroplastoma as well as the variant of it known as the estrogen-induced tumor in the hamster. The review deals with methods for tumor induction and the pathobiology of tumors, the latter mainly focussed on the indendification of the precise types of renal cells committed in tumor origin. The existence of closely related counterparts of these animal tumors in man is also emphasized, by representing a situation of great potentiality, already exploited, to improve understanding of both the nature and development of renal tumors in man.

Key words

Renal tumors Animal models Cytotropism of nephrocarcinogens Histogenesis Cells of origin 



renal cell tumors


renal pelvis epithelium tumors


renal mesenchymal tumor


estrogen-induced renal tumors of the hamster


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Alexander RW, Moscovici C, Vogt PK (1979) Avian oncovirus Mill Hill no. 2: pathogenicity in chickens. JNCI 62:359–266Google Scholar
  2. Bach PH, Bridges JW (1984) The role of metabolic activation of analgesics and non-steroidal anti-inflammatory drugs in the development of renal papillary necrosis and upper urothelial carcinoma. Prostaglandins Leukotrienes Med 15:251–274Google Scholar
  3. Bannasch P, Zerban H (1986) Renal cell adenoma and carcinoma, rat. In: Jones TC, Mohr U, Hunt RD (eds) Monographs on pathology of laboratory animals; urinary system. Springer, Berlin Heidelberg New York, pp 112–139Google Scholar
  4. Bannasch P, Zerban H (1990) Animal models and renal carcinogenesis. In: Eble JN (ed) Tumors and tumor-like conditions of the kidney and ureters. Churchill Livingstone, New York, pp 1–34Google Scholar
  5. Bannasch P, Krech P, Zerban H (1978a) Morphogenese und Mikromorphologie epithelialer Nierentumoren bei Nitrosomorpholin-vergifteten Ratten: II. Tubuläre Glykogenose und die Genese von klar- oder acidophilzelligen Tumoren Z Krebsforsch 92:63–86Google Scholar
  6. Bannasch P, Krech R, Zerban H (1978b) Morphogenese und Mikromorphologie epithelialer Nierentumoren bei Nitrosomorpholin-vergifteten Ratten: III. Oncocytentubuli und Oncocytome. Z Krebsforsch 92:87–104Google Scholar
  7. Bannasch P, Krech R, Zerban H (1980) Morphogenese und Mikromorphologie epithelialer Nierentumoren bei Nitrosomorpholin-vergifteten Ratten: IV. Tubulären Läsionen und basophile Tumoren. J Cancer Res Clin Oncol 98:243–265Google Scholar
  8. Bannasch P, Nogueira E, Zerban H (1989) Cytology and cytogenesis of experimental kidney tumors. Verh Dtsch Ges Pathol 73:301–313Google Scholar
  9. Beard JW (1963) Avian virus growths and their etiologic agents. Adv Cancer Res 7:1–127Google Scholar
  10. Beard JW, Chabot JF, Beard D, Heine U, Houts GE (1976) Renal neoplastic response to leukosis virus strains BAI A (avian myeloblastosis virus) and MC29. Cancer Res 36:339–353Google Scholar
  11. Berdjis CC (1963) Kidney tumors and irradiation pathogenesis of kidney tumors in irradiated rats. Oncologia 16:312–324Google Scholar
  12. Bolande RP, Brough AJ, Izant RJ (1967) Congenital mesoblastic nephroma of infancy; a report of 8 cases and their relationship to Wilms' tumor. Pediatrics 40:272–278Google Scholar
  13. Bourgoin JJ, Cueff J, Bailly C, Dargent M (1972) Incidence of nephroblastomas in immunosuppressed Sprague-Dawley rats treated with DMBA. Bull Cancer 29:429–434Google Scholar
  14. Campbell JG (1969) Tumors of the fowl. Heinemann Medical, LondonGoogle Scholar
  15. Cardesa A, Merchan J, Bullón-Ramírez A (1978) Morphological and biological comparison of tumors prenatally induced in Wistar rats by ethylnitrosourea with their counterpart in man. In: Severi L (ed) Tumors of early life in man and animals. 6th Quadrenial Int Conf Cancer, Perugia, pp 1071–1085Google Scholar
  16. Cardesa A, Pour P, Rustia M, Althoff J, Mohr U (1973) The syncarcinogenic effect of methylcholanthrene and dimethylnitrosamine in Swiss mice. Z Krebsforsch 79:98–107Google Scholar
  17. Cardesa A, Ribalta T (1986) Nephroblastoma, kidney, rat. In: Jones TC, Mohr U, Hunt RD (eds) Monographs on pathology of laboratory animals; urinary system. Springer, Berlin Heidelberg New York, pp 71–80Google Scholar
  18. Cardesa A, Ribalta T, von Schilling B, Palacín A, Mohr U (1989) Experimental model of tumors associated with neurofibromatosis. Cancer 63:1737–1749Google Scholar
  19. Carr JG (1956) Renal adenocarcinoma induced by fowl leukaemia virus. Br J Cancer 10:379–383Google Scholar
  20. Carr JG (1960) Kidney carcinomas of the fowl induced by the MH2 reticuloendothelioma virus. Br J Cancer 14:77–82Google Scholar
  21. Chouroulinkov I, Riviére MR (1959) Tumeurs rénales à virus de la poule: I. Etude morphologique. Bull Cancer 46:722–736Google Scholar
  22. Claude A (1958) Adénocarcinome rénal endémique chez une souche pure de souris. Son effect sur la croissance. Rev Fr Étud Clin Biol 3:261–262Google Scholar
  23. Claude A (1967) An active cell factor inhibiting body growth in mice: its origin and mode of action. In: Teir H (ed) Symposium on the control of cellular growth in the adult organism. Academic Press, New York, pp 302–309Google Scholar
  24. Clayson DB, Cooper EH (1970) Cancer of the urinary tract. Adv Cancer Res 13:271–381Google Scholar
  25. Cohen SM, Erturk E, Esch AM von, Crovetti AJ, Bryan GT (1975) Carcinogenicity of 5-nitrofurans and related compounds with aminoheterocyclic substituents. JNCI 54:841–850Google Scholar
  26. Dees JH, Heatfield BM, Reuber MD, Trump BF (1980) Adenocarcinoma of the kidney: III. Histogenesis of renal adenocarcinomas induced in rats byN-(4′-fluoro-4-biphenylyl)acetamide. JNCI 64:1537–1545Google Scholar
  27. Dontenwill W, Eder M (1959) Histogenese und biologische Verhaltensweise hormonell ausgelöster Geschwülste. Beitr Pathol Anat Allg Pathol 120:270–301Google Scholar
  28. Druckrey H, Preussmann R, Ivankovic S (1969) N-Nitroso compounds in organotropic and transplacental carcinogenesis. Ann NY Acad Sci 163:676–696Google Scholar
  29. Eker R (1954) Familial renal adenomas in Wistar rats. A preliminary report. Acta Path Microbiol Scand 34:554–562Google Scholar
  30. Eker R, Mossige J (1961) A dominant gene for renal adenomas and adenocarcinomas in the rat. Nature 189:858–859Google Scholar
  31. Ertürk E, Price JM, Morris JE, Cohen S, Leith RS, Esch AM von, Crovetii AJ (1967) The production of carcinoma of the urinary bladder in rats by feedingN-(4-(5-nitro-2-furyl)-2-thiazolyl)formamide. Cancer Res 27:1998–2002Google Scholar
  32. Fox RR, Diwan BA, Meier H (1975) Transplacental induction of primary renal tumors in rabbits treated with 1-ethyl-1-nitrosourea. JNCI 54:1439–1448Google Scholar
  33. Gagné F, Poulin M, Lacour M, Guérin M (1954) Cancérisation du bassinet parbenzopyrène provoquée après hydronephrose chez le rat et la souris. Bull Cancer 41:270–279Google Scholar
  34. Goldfarb S, Pugh TD (1990) Morphology and anatomic localization of renal microneoplasms and proximal tubule dysplasias induced by four different estrogens in the hamster. Cancer Res 50:113–119Google Scholar
  35. González A, Oberley TD, Li JJ (1989) Morphologic and immunochemical studies of estrogen-induced Syrian hamster renal tumors: probable cell of origin. Cancer Res 49:1020–1028Google Scholar
  36. González-Crussi F (1984) Experimental Wilms' tumor animal models. In: González-Crussi F (ed) Wilms' tumor (nephroblastoma) and related renal neoplasms of childhood. CRC, Boca Raton, pp 21–28Google Scholar
  37. Graf T, Stéhelin D (1982) Avian leukemia viruses. Oncogenes and genome structure. Biochim Biophys Acta 651:245–271Google Scholar
  38. Guérin M, Chouroulinkov I, Riviére MR (1969) Experimental kidney tumors. In: Rouiller C, Muller AF (eds) The kidney, morphology, biochemistry, physiology, vol. 2. Academic Press, New YorkGoogle Scholar
  39. Hacker HJ, Bannasch P, Liehr JG (1988) Histochemical analysis of the development of estradiol-induced kidney tumors in male Syrian hamsters. Cancer Res 48:971–976Google Scholar
  40. Hacker HJ, Vollmer G, Chiquet-Ehrismann R, Bannasch P, Liehr JG (1991) Changes in the cellular phenotype and extracellular matrix during progression of estrogen-induced mesenchymal kidney tumors in Syrian hamsters. Virchows Arch Cell Pathol 60:213–223Google Scholar
  41. Haenichen T, Stavrou D (1979) Animal models of human disease; nephroblastoma. Comp Pathol Bull 11:2–4Google Scholar
  42. Hamilton JM (1975) Renal carcinogenesis. Adv Cancer Res 22:1–56Google Scholar
  43. Hard GC (1984a) Comparative oncology: I. Nephroblastoma in laboratory animals. In: Pochedly C, Baum E (eds) Wilms' tumor. Clinical and biological manifestations. Elsevier, Amsterdam, pp 147–167Google Scholar
  44. Hard GC (1984b), Comparative oncology: II. Nephroblastoma in domesticated and wild animals. In: Pochedly C, Baum E (eds) Wilms' tumor. Clinical and biological manifestations. Elsevier, Amsterdam. pp 169–189Google Scholar
  45. Hard GC (1986) Renal carcinogenesis, rat. In: Jones TC, Mohr U, Hunt RD (eds) Monographs on pathology of laboratory animals; urinary system. Springer, Berlin Heidelberg New York, pp 45–49Google Scholar
  46. Hard GC (1990) Tumors of the kidney, renal pelvis and ureter. IARC Sci Publ 99:301–344Google Scholar
  47. Hard GC, Butler WH (1970) Cellular analysis of renal neoplasia. Light microscope study of the development of interstitial lesions in the rat kidney by a single, carcinogenic dose of dimethylnitrosamine. Cancer Res 30:2806–2815Google Scholar
  48. Hard GC, Butler WH (1971) Morphogenesis of epithelial neoplasms induced in the rat kidney by dimethylnitrosamine. Cancer Res 31:1496–1505Google Scholar
  49. Hard GC, Fox RR (1983) Histological characterization of renal tumors (nephroblastomas) induced transplacentally in IIIVO/J and WH/J rabbits byN-ethylnitrosourea. Am J Pathol 113:8–18Google Scholar
  50. Hiasa Y, Ito N (1987) Experimental induction of renal tumors. CRC Crit Rev Toxicol 17:279–343Google Scholar
  51. Hiasa Y, Oshima M, Iwata C, Tanikake T (1979) Histopathological studies on renal tubular cell tumors in rats treated withN-ethyl-N-hydroxyethylnitrosamine. Gann 70:817–820Google Scholar
  52. Hiasa Y, Oshima M, Kitahori Y, Fujita T, Yuasa T, Miyashiro A (1983) Basic lead acetate: promoting effect on the development of renal tubular cell tumors in rats treated withN-ethyl-N-hydroxyethylnitrosamine. JNCI 70:761–765Google Scholar
  53. Horning ES, Whittick JW (1954) The histogenesis of stilbestron-induced renal tumors in the male golden hamster. Br J Cancer 8:451–457Google Scholar
  54. Horton L, Fox C, Corrin B, Sönksen PH (1977) Streptozotocin-induced renal tumors in rats. Br J Cancer 36:692–699Google Scholar
  55. Ishiguro H, Beard D, Sommer JR, Heine U, De Thé G, Beard JW (1962) Multiplicity of cell response to the BAI strain A (myeloblastosis) avian tumor virus: I. Nephroblastoma (Wilms' tumor): gross and microscopic pathology. JNCI 29:1–39Google Scholar
  56. Ito N, Fukushima S (1986) Carcinogenesis, urinary tract, rat. In: Jones TC, Mohr U, Hunt RD (eds) Monographs on pathology of laboratory animals; urinary system. Springer, Berlin Heidelberg New York, pp 317–322Google Scholar
  57. Ito N, Makiura S, Yokota Y, Kamamoto Y, Hiasa Y, Sugihara S (1971) Effect of unilateral ureter ligation on development of tumors in the urinary system of rats treated withN-butyl-N-(4-hydroxybutyl)nitrosamine. Gann 62:359–365Google Scholar
  58. Jasmin G, Riopelle JL (1970) Nephroblastomas induced in ovariectomized rats by dimethylbenzanthracene. Cancer Res 30:321–326Google Scholar
  59. Johansson SL (1981) Carcinogenicity of analgesics: long-term treatment of Sprague-Dawley rats with phenacetin, phenazone, caffeine and paracetamol (acetamidophen) Int J Cancer 27:521–529Google Scholar
  60. Kirkman H, Bacon RL (1950) Malignant renal tumors in male hamsters (Cricetus auratus) treated with estrogen. Cancer Res 10:122–124Google Scholar
  61. Kirkman H, Robbins M (1959) Estrogen-induced tumors of the kidney. V. Histology and histogenesis in the Syrian hamster. NCI Monogr 1:93–139Google Scholar
  62. Laqueur GL, Spatz M (1968) Toxicology of cycasin. Cancer Res 28:2262–2267Google Scholar
  63. Leaver DD, Swann PF, Magee PN (1969) The induction of tumors in the rat by a single dose ofN-nitrosomethylurea. Br J Cancer 23:177–187Google Scholar
  64. Li JJ, Li SA, Klicka JK, Parsons JA, Lam LKT (1983) Relative Carcinogenic activity of various synthetic and natural estrogens in the Syrian hamster kidney. Cancer Res 43:5200–5204Google Scholar
  65. Lipsky MM, Trump BF (1988) Chemically induced renal epithelial neoplasia in experimental animals. Rev Exp Pathol 30:357–383Google Scholar
  66. Llombart-Bosch A, Peydró A (1975) Morphological, histochemical and ultrastructural observations of diethylstilbestrol-induced kidney tumors in the Syrian hamster. Eur J Cancer 11:403–412Google Scholar
  67. Llombart-Bosch A, Peydró-Olaya A (1986) Estrogen-induced malignant tumor, kidney, Syrian hamster. In: Jones TC, Mohr U, Hunt RD (eds) Monographs on pathology of laboratory animals; urinary system. Springer, Berlin Heidelberg New York, pp 141–152Google Scholar
  68. Lucké B (1952) Kidney carcinoma in the leopard frog: a virus tumor. Ann N Y Acad Sci 54:1093–1109Google Scholar
  69. McLean AEM, Magee PN (1970) Increased renal carcinogenesis by dimethylnitrosamine in protein deficient rats. Br J Exp Pathol 51:587–590Google Scholar
  70. Mohr U, Haas H (1975) Die chemische Carcinogenese im Harntrakt der Laboratoriumstiere. In: Altmann HW et al. (eds) Handbuch der allgemeinen Pathologie. Springer, Berlin Heidelberg New York, pp 839–939Google Scholar
  71. Mohr U, Hilfrich J (1974) Tumor incidencec in the rat kidney with different dosages of DEN (diethylnitrosamine): frequency, latency and morphology of the tumors. Recent Results Cancer Res 44:130–137Google Scholar
  72. Mole RH (1964) Cancer production by chronic exposure to penetrating gamma irradiation. NCI Monogr 14:271–290Google Scholar
  73. Nicoll JW, Swann PF, Pegg AE (1975) Effect of dimethylnitrosamine on persistence of methylated guanines in rat liver and kidney DNA. Nature 254:261–262Google Scholar
  74. Nogueira E (1987) Rat renal carcinogenesis after chronic simultaneous exposure to lead acetate and N-nitrosodiethylamine. Virchows Arch Cell Pathol 53:365–374Google Scholar
  75. Nogueira E, Bannasch P (1987) Oncocytic transformation of the rat renal collecting duct epithelium by various carcinogens. J Cancer Res Clin Oncol 113:19Google Scholar
  76. Nogueira E, Bannasch P (1988) Cellular origin of rat renal oncocytoma. Lab Invest 59:337–343Google Scholar
  77. Nogueira E, Klimek F, Weber E, Bannasch P (1989) Collecting duct origin of rat renal clear cell tumors. Virchows Arch Cell Pathol 57:275–283Google Scholar
  78. Nogueira E, Alonson A, Komitowski D, Lörke H, Martínez A, Llombart-Bosch A (1991) Cellular and molecular mechanisms involved in development of spontaneous renal adenocarcinoma of BALB/c/Cd mice. Oncología (Madrid) 14:363Google Scholar
  79. Nogueira E, Stumpf H, Rütter G, Llombart-Bosch A, Bannasch P (1992) Cellular and molecular mechanisms of renal carcinogenesis induced by avian erythroblastosis virus. Lab Invest 66:152–165Google Scholar
  80. Oberley TD, González A, Lauchner LJ, Oberley LW, Li JJ (1991) Characterization of early kidney lesions in estrogen-induced tumors in the Syrian hamster. Cancer Res 51:1922–1929Google Scholar
  81. Okazaki W, Purchase HG, Crittenden LB (1982) Pathogenicity of avian leukosis viruses. Avian Dis 26:553–559Google Scholar
  82. Ortmann M, Vierbuchen M, Koller G, Fischer R (1988) Renal oncocytoma: I. Cytochromec oxidase in normal and neoplastic renal tissue as detected by immunohistochemistry — a valuable aid to distinguish oncocytomas from renal cell carcinomas. Virchows Arch Cell Pathol 56:175–184Google Scholar
  83. Rafferty KA (1972) Lucké tumor-associated viruses. IARC Sci Publ 2: 171–182Google Scholar
  84. Reznik G, Mohr U (1976) Induction of renal pelvic tumors in Sprague-Dawley rats by di-isopropanolnitrosamine. Cancer Lett 2:87–92Google Scholar
  85. Rosen VJ, Castanera TJ, Kimeldorf DJ, Jones DC (1962) Pancreatic islet-cell tumors and renal tumors in male rat following neutron exposure. Lab Invest 11:204–210Google Scholar
  86. Sanotskii VA, Erleksova EV (1964) Morphological changes in rats at long intervals after administration of Po210. Fed Proc 23: [Trans Suppl] 785–788Google Scholar
  87. Sass B (1986) Adenoma, adenocarcinoma, kidney, mouse. In: Jones TC, Mohr U, Hunt RD (eds) Monographs on pathology of laboratory animals; urinary system. Springer, Berlin Heidelberg New York, pp 87–101Google Scholar
  88. Singer B (1979)N-Nitroso alkylating agents: formation and persistence of alkyl derivates in mammalian nucleic acids as contributing factors in carcinogenesis. JNCI 62:1329–1339Google Scholar
  89. Sole M, Cardesa A, Domingo J, Mohr U (1992) The carcinogenic effect of 2,2-dioxopropylnitrosamine on the renal pelvic epithelium of Sprague-Dawley rats, after chronic subcutaneous injections. J Cancer Res Clin Oncol118:222–227Google Scholar
  90. Soudah B, Green U, Schneider P, Althoff J (1981) Neoplastic lesions in the urinary tract of Wistar rats after treatment withN-methyl-N-nitrosourea (MNU) and artificial sweeteners. Exp Pathol 20:197–202Google Scholar
  91. Squire RA, Goodman DG, Valerio MG, Fredrickson TN, Strandberg JD, Levitt MH, Lingeman CH, Harshbarger JC, Dawe CJ (1978) Tumors. In: Benirschke K, Garner FM, Jones TC (eds) Pathology of laboratory animals, vol 2. Springer, Berlin Heidelberg New York, pp 1052–1283Google Scholar
  92. Stanton MF, Otsuka H (1963) Morphology of the oncogenic response of hamsters to polyoma virus infection. JNCI 31:365–407Google Scholar
  93. Stavrou D, Hänichen T, Wriedt-Lubbe I (1975) Oncogene Wirkung von Äthylnitroso Harnstoff beim Kaninchen während der pränatalen Periode. Z Krebsforsch 84:207–215Google Scholar
  94. Stevenson JL, Haam E von (1962) Induction of kidney tumors in mice by the use of 20-methylcholanthrene-impregnated strings. Cancer Res 22:1177–1179Google Scholar
  95. Stewart SE (1963) Polyoma virus carcinogenesis. Acta Unio Int Contra Cancrum 19:255–262Google Scholar
  96. Storkel S, Pannen B, Thoenes W, Steart PV, Wagner S, Drenckhahn D (1988a) Intercalated cells as a probable source for the development of renal oncocytoma. Virchows Arch Cell Pathol 56:185–189Google Scholar
  97. Storkel S, Steart PV, Drenckhahn D, Thoenes W (1988b) The human chromophobe cell renal carcinoma-its probable relation to intercalated cells of the collecting duct. Virchows Arch Cell Pathol 56:237–277Google Scholar
  98. Sunter JP, Senior PV (1983) Induction of renal tumors in rats by the administration of 1,2-dimethylhydrazine. J Pathol 140:69–76Google Scholar
  99. Swann PF, Magee PN (1969) Induction of rat kidney tumors by ethyl methanesulphonate and nervous tissue tumors by methyl methanesulphonate and ethyl methanesulphonate. Nature 223:947–949Google Scholar
  100. Tanner DC, Lipsky MM (1984) Effect of lead acetate onN-(4′-fluoro-4-biphenyl)acetamide induced renal carcinogenesis. Carcinogenesis 5:1109–113Google Scholar
  101. Terracini B, Campobasso (1979) Tumors of the kidney, renal pelvis and ureter. IARC Sci Publ 23:289–299Google Scholar
  102. Terracini B, Magee PN (1964) Renal tumors in rats following injection of dimethylnitrosamine at birth. Nature 202:502–503Google Scholar
  103. Thoenes W, Störkel S, Rumpelt HJ (1986) Histopathology and classification of renal cell tumors (adenomas, oncocytomas, and carcinomas). The basic cytological and histopathological elements and their use for diagnostics. Pathol Res Pract 181:125–143Google Scholar
  104. Thoenes W, Störkel S, Rumpelt HJ, Moll R, Baum HP, Werner S (1988) Chromophobe cell renal carcinoma and its variants—a report on 32 cases. J Pathol 155:277–287Google Scholar
  105. Turusov VS, Alexandrov VA, Timoshenko IV (1980) Nephroblastoma and renal mesenchymal tumor induced in rats byN-nitrosoethyl-andN-nitrosomethylurea. Neoplasma 27:229–235Google Scholar
  106. Watts SL, Smith RE (1980) Pathology of chickens infected with avian nephroblastoma virus MAV-2(N). Infect Immun 27:501–512Google Scholar
  107. Weiler O, Delain E, Lacour F (1971) Studies on a viral nephroblastic nephroblastoma of the chicken: an electron microscope comparison of the sequence of development of the virions in different organs. Eur J Cancer 7:491–494Google Scholar
  108. Zerban H, Nogueira E, Riedasch G, Bannasch P (1987) Renal oncocytoma: origin from the collecting duct. Virchows Arch Cell Pathol 52:375–387Google Scholar

Copyright information

© Springer-Verlag 1993

Authors and Affiliations

  • Enrique Nogueira
    • 1
  • Antonio Cardesa
    • 2
  • Ulrich Mohr
    • 3
  1. 1.Department of Pathology, Medical SchoolUniversity of ValenciaSpain
  2. 2.Department of Pathology, Medical SchoolUniversity of BarcelonaSpain
  3. 3.Institute of Experimental PathologyMedizinische HochschuleHannoverFederal Republic of Germany

Personalised recommendations