Skip to main content
SpringerLink
Log in

Tumors in rat kidney generated by initiation withtrans-4-acetylaminostilbene and several promoting treatments

  • Original Papers
  • Experimental Oncology
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

trans-4-Acetylaminostilbene (AAS) is a complete carcinogen in rats and produces quite selectively tumors in Zymbal's glands. On the basis of DNA adduct formation, it has been proposed that this model arylamine initiates neoplastic transformation of cells in many tissues, particularly liver and kidney, which, in the classical sense are considered to be non-target tissues for this chemical. In the present study an initiating treatment with AAS was followed by unilateral nephrectomy and the application of two nephrotoxic substances, gentamycin or β-cyclodextrin which, among other activities, stimulate cell proliferation specifically in kidney. The initiating dose of AAS, given alone, gave rise to Zymbal's gland and mammary tumors in female Wistar rats within 88 weeks but not to liver or kidney tumors. When the initiation treatment was followed by unilateral nephrectomy, alone or in combination with gentamycin, or by β-cyclodextrin, four tumors in two out of ten animals, eight tumors in three/ten, and seven tumors in three/ten, respectively, were observed in the kidney. The administered dose of gentamycin was not sufficient to induce tumors on its own. The results support the view that the genotoxic effects of AAS produce promotable lesions in rat kidney. None of the animals that had been treated with AAS, with or without other treatments, developed tumors or the predominant types of preneoplastic lesions in the liver within 88 weeks; this supports the notion that liver, like kidney, is not a target for complete carcinogenesis for this chemical.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

AAS:

trans-4-acetylaminostilbene

References

  • Bannasch P, Zerban H (1990) Animal models and renal carcinogenesis. In: Elble JN (ed) Contemporary issues of surgical pathology. Churchill Livingstone, New York, pp 1–34

    Google Scholar 

  • Bannasch P, Schacht U, Storch E (1974) Morphogenese und Mikromorphologie epithelialer Nierentumoren bei Nitrosomorpholin-vergifteten Ratten (I. Induktion und Histologie der Tumoren). Z Krebsforsch 81:311–331

    Google Scholar 

  • Bannasch P, Krech R, Zerban H (1980) Morphogenese und Mikromorphologie epithelialer Nierentumoren bei Nitrosomorpholin-vergifteten Ratten (IV. Tubuläre Läsionen und basophile Tumoren). J. Cancer Res Clin Oncol 98:243–265

    PubMed  Google Scholar 

  • Bannasch P, Benner U, Enzmann H, Hacker H-J (1985) Tigroid cell foci and neoplastic nodules in the liver of rats treated with a single dose of aflatoxin B 1. Carcinogenesis 6:1641–1648

    PubMed  Google Scholar 

  • Baur H, Neumann H-G (1980) Correlation of nucleic acid binding by metabolites oftrans-4-aminostilbene derivatives with tissue specific acute toxicity and carcinogenicity in rats. Carcinogenesis 4:877–886

    Google Scholar 

  • Burstone MS (1962) Enzyme histochemistry and its application in the study of neoplasms. Academic Press, New York

    Google Scholar 

  • Cojocel C, Hook JB (1983) Aminoglycoside nephrotoxicity. Trends Pharmacol Sci 40: 174–179

    Google Scholar 

  • Dietrich DR, Swenberg JA (1991) Preneoplastic lesions in rodent kidney induced spontaneously or by non-genotoxic agents: predictive nature and comparison to lesions induced by genotoxic carcinogens. Mutat Res 248:239–260

    PubMed  Google Scholar 

  • Frank DW, Gray JE, Weaver RN (1976) Cyclodextrin nephrosis in the rat. Am J Pathol 83:367–374

    PubMed  Google Scholar 

  • Gilbert DN, Houghton DC, Bennet WM, PlampCE, Reger K, Poter GA (1979) Reversibility of gentamicin nephrotoxicity in rats: recovery during continuous drug administration. Proc Soc Exp Biol Med 160:99–103

    PubMed  Google Scholar 

  • Heine WD (1973) Das kompensatorische Nierenwachstum und seine Regulation. Habilitationsschrift Universität Würzburg

  • Hiasa Y, Ito N (1987) Experimental induction of renal tumours. CRC Crit Rev Toxicol 17:279–343

    Google Scholar 

  • Hiasa Y, Kitahori Y, Ohshima M (1981) Effects of β-cyclodextrin and lead acetate on the development of renal tubular cell tumors in rats treated with different doses ofN-ethyl-N-hydroxyethylnitrosamine. Proc Jpn Cancer Assoc 40:74

    Google Scholar 

  • Hiasa Y, Ohshima M, Kitahori Y, Konishi N, Fujita T, Yuasa T (1982) β-Cyclodextrin: promoting effect on the development of renal tubular cell tumors in rats treated withN-ethyl-N-hydroxyethylnitrosamine. JNCI 69:963–967

    PubMed  Google Scholar 

  • Hilpert D, Neumann H-G (1985) Accumulation and elimination of macromolecular lesions in susceptible and non-susceptible rat tissues after repeated administration oftrans-4-acetylaminostilbene. Chem Biol Interact 54:85–95

    PubMed  Google Scholar 

  • Hilpert D, Romen W, Neumann H-G (1983) The role of partial hepatectomy and of promotors in the formation of tumors in non-target tissues oftrans-4-acetylaminostilbene in rats. Carcinogenesis 1:1519–1525

    Google Scholar 

  • Hirose M, Imaida K, Ito H, Hayashi M, Ishihara Y, Ito N (1981 a) Effects of chloroform and dimethylnitrosamine on renal carcinogenesis in unilaterally nephrectomized rats fed formic acid-2-(4-(5-nitro-2-furyl)-2-thiazolyl)hydrazide. Carcinogenesis 2:703–708

    PubMed  Google Scholar 

  • Hirose M, Shirai T, Tsuda H, Kukushima S, Ogiso T, Ito N (1981 b) Effect of phenobarbital polychlorinated biphenyl and sodium saccharin on hepatic and renal carcinogenesis in unilaterally nephrectomized rats givenN-ethyl-N-hydroxyethylnitrosamine orally. Carcinogenesis 2:1299–1302

    PubMed  Google Scholar 

  • Houghthon DC, Hartnett M, Campbell-Boswell M, Porter G, Bennet W (1976) A light and electron microscopic analysis of gentamicin nephrotoxicity in rats. Am J Pathol 82:589–600

    PubMed  Google Scholar 

  • Ito N, Hiasa Y, Tamai A, Yoshida K (1969) Effect of unilateral nephrectomy on the development of kidney tumor in rats treated withN-nitrosodimethylamine. Gann 60:319–327

    PubMed  Google Scholar 

  • Ito N, Hiasa Y, Tamai A, Kamamoto Y, Makiura Y, Kondo Y (1970) The influence of unilateral nephrectomy on the development of renal tumor in rats treated with dimethylnitrosamine and basic lead acetate. Abstracts of papers from the 10th International Cancer Congress Houston, USA, p 12

  • Ito N, Sugihara S, Makiura S, Arai M, Hirao K, Denda A, Nishio O (1974) Effect ofN-(3,5-dichlorophenyl)succinimide on the histological pattern and incidence of kidney tumors in rats induced by dimethylnitrosamine. Gann 65:131–138

    PubMed  Google Scholar 

  • Kosek JC, Mazze RI, Cousins MJ (1974) Nephrotoxicity of gentamicin. Lab Invest 30:48–57

    PubMed  Google Scholar 

  • Kuchlbauer J, Romen W, Neumann H-G (1985) Syncarcinogenic effects on the initiation of rat liver tumors bytrans-4-acetylaminostilbene and 2-acetylaminofluorene. Carcinogenesis 6:1337–1342

    PubMed  Google Scholar 

  • Luft FC, Patel V, Yum MN, Patel B, Kleit SA (1975) Experimental aminoglycoside nephrotoxicity. J Lab Clin Med 86:213–220

    PubMed  Google Scholar 

  • Luft FC, Rankin LI, Sloan RS, Yum MN (1978) Recovery from aminoglycoside nephrotoxicity with continued drug administration. Antimicrob Agents Chemother 14:284–287

    PubMed  Google Scholar 

  • Metzler M, Neumann H-G (1971) Zur Bedeutung chemisch-biologischer Wechselwirkungen für die toxische und krebserzeugende Wirkung aromatischer Amine III. Synthese und Analytik einiger Stoffwechselprodukte vontrans-4-Dimethylaminostilben,cis-4-Dimethylaminostilben und 4-Dimethylaminobibenzyl. Tetrahedron 27:2225–2246

    Google Scholar 

  • Neumann H-G (1986) The role of DNA damage in chemical carcinogenesis of aromatic amines. J Cancer Res Clin Oncol 112:100–106

    PubMed  Google Scholar 

  • Neumann H-G, Ambs S, Hillesheim W (1992) The biochemical basis of hepatotoxicity. In: Kekant W, Neumann H-G (eds) Tissue specific toxicity: biochemical mechanisms. Academic Press, New York (pp 139–162

    Google Scholar 

  • Neumann-Redlin E (1969) Zur Proliferation der kompensatorisch regenerierenden Niere nach kontralateraler Nephrektomie. Dissertation Universität Würzburg

  • Porter GA, Laurent G, Maldague P, Tulkens P (1984) Gentamicin-induced stimulation of DNA synthesis in rat kidney-comparison between in vivo and in vitro models. Toxicol Lett 23:205–213

    PubMed  Google Scholar 

  • Rutenberg AH, Kim H, Fischbein JW, Hanker JS, Wasserkrug H, Seligmann AM (1969) Histochemical and ultrastructural demonstration of gamma-glutamyltranspeptidase activity. J Histochem Cytochem 17:517–526

    PubMed  Google Scholar 

  • Ruthsatz M, Neumann H-G (1988) Synergistic effects on the initiation of rat liver tumors bytrans-4-acetylaminostilbene and 2-acetylaminofluorene, studied at the level of DNA adduct formation. Carcinogenesis 9:265–269

    PubMed  Google Scholar 

  • Shinohara Y, Arai M, Hirao K (1976) Combination effect of citrinin and other chemicals on rat kidney tumorigenesis. Gann 67:147–156

    PubMed  Google Scholar 

  • Wachstein M, Meisel E (1957) Histochemistry of hepatic phosphatases at a physiologic pH with special reference to the demonstration of bile caniculi. Am J Clin Pathol 27:13–23

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Pharmacology and Toxicology, University of Würzburg, Versbacher Strasse 9, D-8700, Würzburg, Germany

    Andre Hoffmann & Hans-Günter Neumann

  2. Institute of Pathology, University of Würzburg, Versbacher Strasse 9, D-8700, Würzburg, Germany

    Werner Romen

Authors
  1. Andre Hoffmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Werner Romen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hans-Günter Neumann
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hoffmann, A., Romen, W. & Neumann, HG. Tumors in rat kidney generated by initiation withtrans-4-acetylaminostilbene and several promoting treatments. J Cancer Res Clin Oncol 119, 329–334 (1993). https://doi.org/10.1007/BF01208840

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01208840

Key words

Search

Navigation