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Renal cysts and associated renal tumours in male ddY mice injected with ferric nitrilotriacetate

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Abstract

In experiments using ferric nitrilotriacetate (Fe-NTA) as a renal carcinogen, multiple renal cysts are often observed in addition to renal tumours. In the present study, we used 3-week-old male ddY mice and examined the relation between renal cysts and cancer development. Four months after the start of Fe-NTA administration, we observed cysts in the renal cortex in all Fe-NTA-treated mice, but not in Fe-free NTA-treated mice. Three types of cysts were observed, but only those which originated from the renal proximal tubules showed multi-layered or papillary growth of cyst epithelial cells. Using histochemical staining, we found a cyst formation-tumour induction sequence, and the supposed cystic-papillary tumour induced by Fe-NTA was of proximal tubular cell origin. We also found that the minimum dose of Fe-NTA capable of inducing renal tumours in ddY mice was 10 mg of iron/kg/day, four times in 2 weeks.

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References

  1. Ahn Y, Chemeris G, Turusov V, Bannasch P (1994) Enzymic pattern of preneoplastic and neoplastic lesions induced in the kidney of CBA mice by 1,2-dimethylhydrazine. Toxicol Pathol 22:415–422

    Google Scholar 

  2. Awai M, Narasaki M, Yamanoi Y, Seno S (1979) Induction of diabetes in animals by parenteral administration of ferric nitrilotriacetate: a model of experimental hemochromatosis. Am J Pathol 95:663–674

    Google Scholar 

  3. Bannasch P, Zerban H (1990) Animal models and renal carcinogenesis. In: Eble J (ed) Tumors and tumor-like conditions of the kidney and ureters. Churchill Livingstone, New York, pp 4–21

    Google Scholar 

  4. Coppee I, Gabius HJ, Danguy A (1993) Histochemical analysis of carbohydrate moieties and sugar-specific acceptors in the kidneys of laboratory mouse and the golden spiny mouse (Acomys russatus). Histol Histopathol 8:673–683

    Google Scholar 

  5. Crabtree C (1941) The structure of Bowman's capsule as an index of age and sex variations in normal mice. Anat Rec 79:395–413

    Google Scholar 

  6. Dees JH, Reuber MD, Trump BF (1976) Adenocarcinoma of the kidney: I Ultrastructure of renal adenocarcinomas induced in rats by N-(4′-Fluoro-4-biphenylyl) acetamide. J Natl Cancer Inst 57:779–794

    Google Scholar 

  7. Dees JH, Heatfield BM, Reuber MD, Trump BF (1980) Adenocarcinoma of the kidney: III Histogenesis of renal adenocarcinoma induced in rats by ultrastructure of renal adenocarcinomas induced in rats by N-(4′-Fluoro-4-biphenylyl) acetamide. J Natl Cancer Inst 64:1537–1545

    Google Scholar 

  8. Dees JH, Heatfield BM, Trump BF (1980) Adenocarcinoma of the kidney: IV Electron microscopic study of the development of renal adenocarcinoma induced in rats by N-(4′-Fluoro-4-biphenylyl) acetamide. J Natl Cancer Inst 64:1547–1562

    Google Scholar 

  9. Deguchi J, Kawabata T, Kondo A, Okada S (1993) Transforming growth factor-α expression of renal proximal tubules in Wister rats treated with ferric and aluminum nitrilotriacetate. Jpn J Cancer Res 84:649–655

    Google Scholar 

  10. Dunnill MS, Millard PR, Oliver D (1977) Acquired cystic disease of the kidneys: a hazard of long-term intermittent maintenance haemodialysis. J Clin Pathol 30:868–877

    Google Scholar 

  11. Ebina Y, Okada S, Hamazaki S, Ogino F, Li JL, Midorikawa O (1986) Nephrotoxicity and renal cell carcinoma after use of iron- and aluminum-nitrilotriacetate complexes in rats. J Natl Cancer Inst 76:107–113

    Google Scholar 

  12. Hard GC (1985) Identification of a high-frequency model for renal carcinoma by the induction of renal tumors in the mouse with a single dose of streptozotocin. Cancer Res 45:703–708

    Google Scholar 

  13. Hard GC (1986) Experimental models for the sequential analysis of chemically-induced renal carcinogenesis. Toxicol Pathol 14:112–122

    Google Scholar 

  14. Holthöfer H (1983) Lectin binding sites in kidney, a comparative study of 14 animal species. J Histochem Cytochem 31:531–537

    Google Scholar 

  15. Ishikawa I, Horiguchi T, Shikura N (1989) Lectin peroxidase conjugate reactivity in acquired cystic disease of the kidney. Nephron 51:211–214

    Google Scholar 

  16. Kikuchi Y (1989) Lectin and immunohistochemical studies on acquired cystic kidney and associated renal cell carcinoma. Acta Pathol Jpn 39:373–380

    Google Scholar 

  17. Kikuchi Y, Aizawa S, Nikaido T (1987) Lectin histochemical and immunohistochemical studies on normal kidneys and renal cell carcinoma (in Japanese). Rinsho Hinyokika 41:951–955

    Google Scholar 

  18. Li JL, Okada S, Hamazaki S, Ebina Y, Midorikawa O (1987) Subacute nephrotoxicity and induction of renal cell carcinoma in mice treated with ferric nitrilotriacetate. Cancer Res 47:1867–1869

    Google Scholar 

  19. Lin JI, Saklayen M, Ehrenpresis M, Hillman NM (1992) Acquired cystic disease of kidney associated with renal cell carcinoma in chronic dialysis patients. Urology 39:190–193

    Google Scholar 

  20. Lojda Z, Gossrau R, Stoward PJ (1991) Appendix 31 Histochemical methods for proteases. In: Stoward PJ, Pearse AGE (eds) Histochemistry, theoretical and applied. Churchill Livingstone, Edinburgh pp 639

    Google Scholar 

  21. Miyao N, Kumamoto Y, Tsukamoto T (1991) Histopathological analysis of chemical carcinogenesis process by streptozotocin in the mouse kidney (in Japanese). Nippon Hinyouki Gakkaishi 82:1399–1407

    Google Scholar 

  22. Nogueria E, Klimek F, Weber E, Bannasch P (1989) Collecting duct origin of rat renal clear cell tumors. Virchows Arch m[B] 57:275–283

    Google Scholar 

  23. Nogueria E, Cardesa A, Mohr U (1993) Experimental models of kidney tumors. J Cancer Res Clin Oncol 119:190–198

    Google Scholar 

  24. Nyska A, Waner T, Pirak M, Gordon E, Bracha P, Klein B (1989) The renal carcinogenic effect of merpafol in the Fischer 344 rat. Isr J Med Sci 25:428–432

    Google Scholar 

  25. Ohmori T, Sekigawa S, Sunagawa M, Tatsumi Y, Ohshima M, Enoki N, Kitahori Y, Hiasa Y, Murata Y (1981) Confirmation of the development of multiple renal cell tumors in end-stage/long-term haemodialysis kidney revealed typical acquired cystic transformation. Acta Pathol Jpn 31:1097–1104

    Google Scholar 

  26. Okada S, Midorikawa O (1982) Induction of the rat renal adenocarcinoma by Fe-nitrilotriacetate (Fe-NTA) (in Japanese). Naika Houkan (Jpn Arch Int Med) 29:485–491

    Google Scholar 

  27. Okada S, Hamazaki S, Ebina Y, Li JL, Midorikawa O (1987) Nephrotoxicity and its prevention by vitamin E in ferric nitrilotriacetate-promoted lipid peroxidation. Biochim Biophys Acta 922:28–33

    Google Scholar 

  28. Okada S, Fukunaga Y, Hamazaki S, Yamada Y, Toyokuni S (1991) Sex differences in the localization and severity of ferric nitrilotriacetate-induced lipid peroxidation in the mouse kidney. Acta Pathol Jpn 41:221–226

    Google Scholar 

  29. Okada S, Minamiyama Y, Hamazaki S, Toyokuni S, Sotomatsu A (1993) Glutathione cycle dependency of ferric nitrilotriacetate-induced lipid peroxidation in mouse proximal renal tubules. Arch Biochem Biophys 301:138–142

    Google Scholar 

  30. Okada S, Hamazaki S, Akiyama T, Liu M (in press) Iron-induced carcinogenesis in experimental animals: a free radical mechanism of DNA damage and carcinogenesis. In: Cutler R, Packer L, Mori A (eds) Oxidative Stress and Aging. Birkhäuser, Basel

  31. Pompella A, Maellaro E, Casini AF, Comporti M (1987) Histochemical detection of lipid peroxidation in the liver of bromobenzene-poisoned mice. Am J Pathol 129:295–301

    Google Scholar 

  32. Rutenberg AM, Kim H, Fischbein JW, Hanker JS, Wasserkrug HL, Seligman AM (1968) Histochemical and ultrastructural demonstration of γ-glutamyl transpeptidase activity. J Histochem Cytochem 17:517–526

    Google Scholar 

  33. Shinohara Y, Frith C (1980) Morphologic characteristics of benign and malignant renal cell tumors in control and 2-acetylaminofluorene-treated BALB/c female mice. Am J Pathol 100:455–468

    Google Scholar 

  34. Spater HW, Poruchynsky MS, Quintana N, Inoue M, Novikoff AB (1982) Immunocytochemical localization of γ-glutamyl-transferase in rat kidney with protein A-horseradish peroxidase. Proc Natl Acad Sci USA 79:3547–3550

    Google Scholar 

  35. Toyokuni S, Okada S, Hamazaki S, Minamiyama Y, Yamada Y, Liang P, Fukunaga Y, Midorikawa O (1990) Combined histochemical and biochemical analysis of sex hormone dependence of ferric nitrilotriacetate-induced renal lipid peroxidation in ddY mice. Cancer Res 50:5574–5580

    Google Scholar 

  36. Turusov VS, Chemeris GY (1992) Renal cell tumors induced in CBA male mice by 1,2-dimethylhydrazine. Toxicol Pathol 20:570–575

    Google Scholar 

  37. Wachstein M (1955) Histochemical staining of the normally functioning and abnormal kidney. J Histochem Cytochem 3:246–270

    Google Scholar 

  38. Walker C, Everitt J, Freed JJ, Kundson AG, Whiteley LO (1991) Altered expression of Transforming Growth Factor-α in hereditary rat renal cell carcinoma. Cancer Res 51:2973–2978

    Google Scholar 

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Kondo, A., Deguchi, J. & Okada, S. Renal cysts and associated renal tumours in male ddY mice injected with ferric nitrilotriacetate. Vichows Archiv A Pathol Anat 427, 91–99 (1995). https://doi.org/10.1007/BF00203743

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