The Granuloma Pouch Assay

  • Peter Maier


Chemicals to which man is potentially exposed or that are already distributed in the environment are tested for their mutagenic activity in simple, inexpensive screening tests utilizing prokaryotic and/or eukaryotic cells. These phase I or tier I tests should have a low potential to produce false negative results. This is often achieved by the acceptance of a certain number of false positive results. Therefore chemicals that show positive, contradictory, or inconclusive results in this battery of tier I tests and are still of importance should be further tested in phase II (tier II) tests to provide a broader basis on which risk assessment can be made.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    S. Aho, P. Lethinen, and E. Kulonen, Penetration of macrophage ribonucleases into fibroblasts and the effects on nucleic acid and collagen metabolism,Acta Pathol. Microbiol Immunol Scand. C 90 147–154 (1982).Google Scholar
  2. 2.
    P. C. Bragt and I. L. Bonta,In vivo metabolism of [1-14C] arachidonic acid during different phases of granuloma development in the rat,Biochem. Pharmacol.28: 1581– 1586 (1979).CrossRefGoogle Scholar
  3. 3.
    G. Bronzetti, E. Zeiger, and H. V. Mailing, Genetic toxicity of procarbazine in bacteria and yeast,Mutat. Res. 68, 51–58 (1979).CrossRefGoogle Scholar
  4. 4.
    A. Dalhoff, G. Frank, and G. Luckhaus, The granuloma pouch—anin vivo model for pharmacokinetic and chemotherapeutical investigations. I. Biochemical and histological characterization,Infection 10, 354–360 (1982).CrossRefGoogle Scholar
  5. 5.
    A. Dalhoff, G. Frank, and G. Luckhaus, The granuloma pouch—anin vivo model for pharmacokinetic and chemotherapeutical investigations, II. Microbiological characterization,Infection 11, 41 –46 (1983).CrossRefGoogle Scholar
  6. 6.
    R. F. Diegelmann, I. K. Cohen, and A. M. Kaplan, Effect of macrophages on fibroblast DNA synthesis and proliferation,Proc. Soc. Exp. Biol. Med. 169, 445–451 (1982).CrossRefGoogle Scholar
  7. 7.
    U. H. Ehling, Specific-locus mutations in mice, in:Chemical Mutagens, Principles and Methods for Their Detection (F. J. de Serres and A. Hollaender, eds.), Vol. 5, pp. 233– 256, Springer Science+Business Media New York (1978).Google Scholar
  8. 8.
    T. E. Eling, J. A. Boyd, G. A. Reed, R. P. Mason, and K. Sivarajah, Xenobiotic metabolism by prostaglandin endoperoxide synthetase,Drug Metab. Rev.14 (5), 1023– 1053 (1983).CrossRefGoogle Scholar
  9. 9.
    B. G. Flückiger, Wachstum and chemisch induzierte maligne Transformation von Zellen eines subcutanen Granuloms der Ratte unter dem Einfluss von Stimulatoren der Zellproliferation, Dissertation ETH Nr. 7292 Swiss Federal Institute of Technology, Zurich, Switzerland (1983).Google Scholar
  10. 10.
    K. Frei, P. Maier and G. Zbinden, Aldrin epoxidase activity in freshly isolated cells from extrahepatic rat tissues, (submitted) (1984)Google Scholar
  11. 11.
    B. Helpap and H. Cremer, Autoradiographische Untersuchungen am Granulationsgewebe mit radioaktiv markiertem und unmarkiertem Thymidin,Virchows Arch. Abt. B Zellpathol. 10, 145–151 (1972).Google Scholar
  12. 12.
    C. Holzer, P. Maier and G. Zbinden, Mesenchymal rat cells stimulate growth of their transformed counterpart in vivo and in vitro, Experientia, (in press) (1984)Google Scholar
  13. 13.
    M. A. Kastenbaum and K. O. Bowman, Tables for determining the statistical significance of mutation frequencies,Mutat. Res. 9, 527–549 (1970).CrossRefGoogle Scholar
  14. 14.
    B. Lang, P. Maier and G. Zbinden, Metabolic activation of aldrin in extrahepatic cells, Experientia, (in press) (1984).Google Scholar
  15. 15.
    IP. Lee and G. Zbinden, Differential DNA damage induced by chemical mutagens in cells growing in a modified Selye’s granuloma pouch,Exp. Cell Biol. 47, 92–106 (1979).Google Scholar
  16. 16.
    S. J. Leibovich and R. Ross, A macrophage dependent factor that stimulates the proliferation of fibroblastsin vivo, Am. J. Pathol.84, 501–513, (1976).Google Scholar
  17. 17.
    P. Maier, The granuloma pouch assay for mutagenmicity testing,Arch. Toxicol. 46, 151–157, (1980).CrossRefGoogle Scholar
  18. 18.
    P. Maier, P. Manser, and G. Zbinden, Granuloma pouch assay. I. Induction of ouabain resistance by MNNGin vivo, Mutat. Res.57, 159–165 (1978).CrossRefGoogle Scholar
  19. 19.
    P. Maier, P. Manser, and G. Zbinden, II. Induction of 6–thioguanine resistance by MNNG and benzo[a]pyrenein vivo, Mutat. Res.77, 165–173 (1980).CrossRefGoogle Scholar
  20. 20.
    P. Maier and G. Zbinden, Specific locus mutations induced in somatic cells of rats by orally and parenterally administered procarbazine,Science 109, 299–301 (1980).CrossRefGoogle Scholar
  21. 21.
    P. Maier, B. Weibel, and G. Zbinden, The mutagenic activity of BrdUin vivo, Environ. Mutagene.5, 695–703 (1983).CrossRefGoogle Scholar
  22. 22.
    P. Maier, K. Frei, B. Weibel, and G. Zbinden, Granuloma pouch assay IV. Induction of sister chromatid exchangesin vivo, Mutat. Res.97, 349–357 (1982).CrossRefGoogle Scholar
  23. 23.
    P. Maier, B. Lang, H. P. Schawalder, and G. Zbinden, Influence of physiological pO2 in vitro on growth, enzymic activity and mutation frequency in freshly isolated mesenchymal rat cells, (submitted).Google Scholar
  24. 24.
    P. Maier, H. P. Schawalder, and G. Zbinden, The mutagenic activity of heptocarcin– ogens in an extrahepatic tissuein vivo in rats, (submitted).Google Scholar
  25. 25.
    B. E. Matter and J. Grauwiler, Micronuclei in mouse bone-marrow cells. A simplein vivo model for the evaluation of drug induced chromosomal aberrations.Mutat. Res. 23, 239–249 (1974).CrossRefGoogle Scholar
  26. 26.
    S. Murato and I. Morita, Prostaglandin-synthesizing systems in rat liver: Changes with aging and various stimuli, in:Advances in Prostaglandin and Thromboxane Research (B. Samuelsson, P. W. Ramwell and R. Paoletti, eds.), Vol. 8, pp. 1495–1506, Raven Press, New York (1980).Google Scholar
  27. 27.
    J. V. Neel, a consideration of two biochemical approachest approaches to monitoring human populations for a change in germ cell mutation rates, in:Genetic damages in Man Caused by Environmental Agents (K. Berg, ed.), pp. 29–62, Academic Press, New York (1979).Google Scholar
  28. 28.
    R. Parkin, H. B. Waynforth, and P. N. Magee, The activity of some nitroso compounds in the mouse dominant lethal assay,Mutat. Res. 21, 155–161 (1973).CrossRefGoogle Scholar
  29. 29.
    J. M. Parry, E. M. Parry, and J. C. Barrett, Tumor promoters induce mitotic aneuploidy in yeast,Nature 294, 263–265 (1981).CrossRefGoogle Scholar
  30. 30.
    A. R. Peterson, D. F. Krahn, H. Peterson, C. Heidelberger, B. K. Bhuyan, and L. H. Li, The influence of serum components on the growth and mutation of Chinese hamster cells in medium containing 8-azaguanine,Mutat. Res. 36, 345–356 (1976).CrossRefGoogle Scholar
  31. 31.
    M. Radman, P. Jeggo, and R. Wagner, Chromosomal rearrangement and carcinogenesis,Mutat, Res.98, 249–264 (1982).CrossRefGoogle Scholar
  32. 32.
    H. Selye, Use of granuloma pouch technique in the study of antiphlogistic corticoids,Proc. Soc. Exp. Biol. Med. 82, 328–333 (1952).CrossRefGoogle Scholar
  33. 33.
    T. Tsutsui, T. H. Maizumi, J. A. McLachlan, and J. C. Barrett, Aneuploidy induction and cell transformation by diethylstilbestrol: A possible chromosomal mechanism in carcinogenesis,Cancer Res.43(8), 3814–3821 (1983).Google Scholar
  34. 34.
    H. Vainio and E. Hietanen, Role of extrahepatic metabolism, in:Concepts in Drug Metabolism (P. Jenner and B. Testa, eds.), Part A, pp. 251–284, Marcel Dekker, New York (1963).Google Scholar
  35. 35.
    T. Wolff, IE. Demi, and H. Wanders, Aldrin epoxidation a highly sensitive indicator specific foR cytochrome P-450 dependent monooxygenase activities,Drug Metab. Disp. 7, 301–305 (1979).Google Scholar
  36. 36.
    G. Zbinden and C. Schlatter, New approaches to mutagenicity and carcinogenicity testingin vivo in mammalian systems, in:Chemical Toxicology of Food (C. L. Galli, R. Oaoletti, and G. Vettorazzi, eds.), pp. 153–166, Elsevier, Amsterdam (1978).Google Scholar
  37. 37.
    G. Zbinden, P. Maier, and S. Alder, Granuloma pouch assay, III. Enhancement of the carcinogenic effect of MNNG,Arch. Toxicol. 45, 227–232 (1980).CrossRefGoogle Scholar
  38. 38.
    G. Zbinden and P. Maier, Single dose carcinogenicity of procarbazine in rats,Cancer Lett.21, 155–161 (1983).CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1984

Authors and Affiliations

  • Peter Maier
    • 1
  1. 1.Institute of ToxicologySwiss Federal Institute of Technology and University of ZurichSchwerzenbachSwitzerland

Personalised recommendations