The Wound Response as a Key Element for an Understanding of Multistage Carcinogenesis in Skin

  • Friedrich Marks
  • Gerhard Fürstenberger
  • Michael Gschwendt
  • Michael Rogers
  • Bärbel Schurich
  • Bernd Kaina
  • Georg Bauer


The general appearance of skin carcinoma is that of a steadily growing wound. Thus, Haddow’s famous affirmation “the wound may be regarded as a tumor which heals itself”1 may be also read the other way around, i.e. that a tumor may be regarded as a wound which does not heal. A huge amount of literature dealing with the assumed relationship between wound repair and carcinogenesis has indeed been accumulated (see ref. 1, 6). Only very recently, however, the methods of cell biology, biochemistry and molecular biology have reached a level where they enable the investigator to proof this relationship in clear-cut experimental approaches aiming at an understanding of the molecular mechanisms involved in both wound repair and carcinogenesis. One of the most exciting results of these novel approaches is the discovery that the majority of proto-oncogenes code for components of cellular pathways which are required for the transduction of growth-stimulating signals, especially of those provided by the peptide growth factors2. While the physiological role of such growth factors is still not entirely understood, there is accumulating evidence indicating that at least some of them (such as EGF, TGFα, TGFß, PDGF) may be involved in tissue repair and regeneration rather than in the control of everyday tissue growth3.


Phorbol Ester Tumor Promotion Mouse Skin NMRI Mouse Skin Carcinogenesis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    A. Haddow, Molecular repair, wound healing and carcinogenesis: tumor production a possible overhealing? Adv. Cancer Res. 16:181 (1972).CrossRefPubMedGoogle Scholar
  2. 2.
    F. Marks, What’s new in oncogenes and growth factors? Pathology Res Pract. 182:831 (1988).CrossRefGoogle Scholar
  3. 3.
    M. B. Sporn and A. B. Roberts, Peptide growth factors and inflammation, tissue repair and cancer, J. Clin Invest. 78:329 (1986).CrossRefPubMedGoogle Scholar
  4. 4.
    H. Hennings and R. K. Boutwell, Studies on the mechanism of skin tumor promotion, Cancer Res. 30:312 (1970).PubMedGoogle Scholar
  5. 5.
    I. Clark-Lewis and A. W. Murray, Tumor promotion and the induction of epidermal ornithine decarboxylase activity in mechanically stimulated mouse skin, Cancer Res. 38:494 (1978).PubMedGoogle Scholar
  6. 6.
    T. S. Argyris, Regeneration and the mechanism of epidermal tumor promotion, CRC Crit. Rev. Toxicol. 14:211 (1986).CrossRefGoogle Scholar
  7. 7.
    G. Fürstenberger and F. Marks, Growth stimulation and tumor promotion in skin, J. Invest. Dermatol. 81:157s (1983).CrossRefPubMedGoogle Scholar
  8. 8.
    F. Marks and G. Fürstenberger, Multistage carcinogenesis: The mouse skin model, in: “Accomplishments in Oncology”, Vol. 2/1, H. zur Hausen and J. R. Schlehofer, eds., Lippincott, Philadelphia (1987).Google Scholar
  9. 9.
    F. Marks and G. Fürstenberger, From the normal cell to cancer: The multistep process of experimental skin carcinogenesis, in: “Concepts and Theories in Carcinogenesis”, A. P. Maskens, P. Ebbesen and A. Burny, eds., Excerpta Medica, Amsterdam (1987).Google Scholar
  10. 10.
    F. Marks and G. Fürstenberger, Multistage carcinogenesis in animal skin: The reductionist’s approach in cancer research, in: “Theories of Carcinogenesis”, O. H. Iversen, ed., Hemisphere, Washington D.C. (1988).Google Scholar
  11. 11.
    F. J. Burns, M. Vanderlaan, E. Snyder and R. E. Albert, Induction and progression kinetics of mouse skin papillomas, in: “Mechanisms of Tumor Promotion and Cocarcinogenesis”, T. J. Slaga, A. Sivak and R. K. Boutwell, eds., Raven Press, New York (1978).Google Scholar
  12. 12.
    E. E. Sisskin, T. Gray and J. C. Barrett, Correlation between sensitivity to tumor promotion and sustained epidermal hyperplasia of mice and rats treated with TPA, Carcinogenesis 3:403 (1982).CrossRefPubMedGoogle Scholar
  13. 13.
    R. K. Boutwell, Some biological aspects of skin carcinogenesis, Progr Exp Tumor Res. 4:207 (1964).PubMedGoogle Scholar
  14. 14.
    T. J. Slaga, S. M. Fischer, K. Nelson and G. L. Gleason, Studies on the mechanism of skin tumor promotion: Evidence for several stages of promotion, Proc Natl Acad Sci USA 77:3659 (1980).CrossRefPubMedGoogle Scholar
  15. 15.
    G. Fürstenberger, D. L. Berry, B. Sorg and F. Marks, Skin tumor promotion by phorbol esters is a two-stage process, Proc Natl Acad Sci. USA 78:7722 (1981).CrossRefPubMedGoogle Scholar
  16. 16.
    G. Fürstenberger, V. Kinzel, M. Schwarz and F. Marks, Partial inversion of the initiation-promotion sequence of multistage tumorigenesis in the skin of NMRI mice, Science 230:76 (1985).CrossRefPubMedGoogle Scholar
  17. 17.
    H. Hennings, R. Shores, M. L. Wenk, E. F. Spangler, R. Tarone and S. H. Yuspa, Malignant conversion of mouse skin tumors is increased by tumor initiators and unaffected by tumor promoters, Nature 304:67 (1983).CrossRefPubMedGoogle Scholar
  18. 18.
    A. L. Reddy, M. Caldwell and P. J. Fialkow, Studies of skin tumorigenesis in PGK mosaic mice: Many promoter-independent papillomas and carcinomas do not develop from pre-existing promoter-dependent papillomas, Int. J. Cancer 39:261 (1987).CrossRefPubMedGoogle Scholar
  19. 19.
    A. L. Reddy, M. Caldwell and P. J. Fialkow, Sequential studies of skin tumorigenesis in phosphoglycerate kinase mosaic mice: Effect of resumption of promotion on regressed papillomas, Cancer Res. 47:1947 (1987).PubMedGoogle Scholar
  20. 20.
    M. Quintanilla, K. Brown, M. Ramsden and A. Balmain, Carcinogen-specific mutation and amplification of Ha-ras during mouse skin carcinogenesis, Nature 322:78 (1986).CrossRefPubMedGoogle Scholar
  21. 21.
    A. Balmain and K. Brown, Oncogene activation in chemical carcinogenesis, Adv. Cancer Res. in press (1987).Google Scholar
  22. 22.
    F. Marks, S. Bertsch, G. Fürstenberger and H. Richter, Growth control in mouse epidermis: Facts and speculations, in: “Psoriasis: Cell Proliferation”, N. A. Wright and R. S. Camplejohn, eds., Churchill Livingstone, Edinburgh (1983).Google Scholar
  23. 23.
    F. Marks, G. Fürstenberger, M. Ganss, H. Richter and D. Seemann, Hyperplastic transformation: The response of mouse skin to injury, Brit J. Dermatol. 109, Suppl. 25:18 (1983).Google Scholar
  24. 24.
    G. S. Schultz, M. White and R. Mitchell, Epithelial wound healing enhanced by transforming growth factor-a and by Vaccinia growth factor, Science 235:350 (1987).CrossRefPubMedGoogle Scholar
  25. 25.
    A. B. Schreiber, M. E. Winkler and R. Derynck, Transforming growth factor-α: A more potent angiogenic mediator than epidermal growth factor, Science 232:1250 (1986).CrossRefPubMedGoogle Scholar
  26. 26.
    A. B. Roberts, M. B. Sporn, R. K. Assoian, J. M. Smith, N. S. Roche, L. M. Wakefield, U. I. Heine, L. A. Liotta, V. Falanger, J. H. Keteri and A. S. Fanci, Transforming growth factor type ß: Rapid induction of fibrosis and angiogenesis in vivo and stimulation of collagen formation in vitro, Proc. Natl. Acad. Sci. USA 83:4167 (1986).CrossRefGoogle Scholar
  27. 27.
    R. J. Coffey, R. Derynck, J. N. Wilcox, T. S. Bringman, A. S. Goustin, H. L. Moses and M. R. Pittelkow, Production and auto-induction of transforming growth factor-a in human keratinocytes, Nature 328:817 (1987).CrossRefPubMedGoogle Scholar
  28. 28.
    G. Fürstenberger and F. Marks, Prostaglandins, epidermal hyperplasia and skin tumor promotion, in: “Arachidonic Acid Metabolism and Tumor Promotion”, S. M. Fischer and T. J. Slaga, eds., Nijhoff, Boston (1985).Google Scholar
  29. 29.
    F. Marks and G. Fürstenberger, Tumor promotion in skin: Are active oxygen species involved? in: “Oxidative Stress”, H. Sies, ed., Academic Press, New York (1985).Google Scholar
  30. 30.
    W. Troll and R. Wiesner, The role of oxygen radicals as possible mechanism of tumor promotion, Ann. Rev. Pharmacol. Toxicol. 25:509 (1985).CrossRefGoogle Scholar
  31. 31.
    M. Castagna, Y. Takai, K. Kaibuchi, K. Sano, V. Kikkawa and Y. Nishizuka, Direct activation of calcium-activated, phospholipid-dependent protein-kinase by tumor-promoting phorbol esters, J. Biol Chem. 257:7847 (1982).PubMedGoogle Scholar
  32. 32.
    R. C. Smart, M. Huang and A. H. Conney, sn-1,2-Diacylglycerols mimic the effects of TPA in vivo by inducing biochemical changes associated with tumor promotion in mouse epidermis, Carcinogenesis 7:1865 (1986).CrossRefPubMedGoogle Scholar
  33. 33.
    H. Yamasaki, Aberrant control of intercellular communication and cell differentiation during carcinogenesis, in: “Concepts and Theories in Carcinogenesis”, A. P. Maskens, P. Ebbesen and A. Burny, eds., Excerpta Medica, Amsterdam (1987).Google Scholar
  34. 34.
    A. A. Abdel-Latif, Calcium-mobilizing receptors, polyphosphoinositides, and the generation of second messengers, Pharmacol. Rev. 38:228 (1986).Google Scholar
  35. 35.
    M. J. Berridge, Inositol lipids and cell proliferation, Biochim Biophys. Acta 907:33 (1987).PubMedGoogle Scholar
  36. 36.
    M. Gschwendt, W. Kittstein and F. Marks, Cyclosporin A inhibits phorbol ester-induced hyperplastic transformation and tumor promotion in mouse skin probably by suppression of Ca /calmodulin-dependent processes such as phosphorylation of elongation factor 2, Skin Pharmacol. in press (1988).Google Scholar
  37. 37.
    R. Sager, Genetic suppression of tumor formation, Adv. Cancer Res. 44:43 (1985).CrossRefPubMedGoogle Scholar
  38. 38.
    A. C. Knudson, Hereditary cancer, oncogenes and anti-oncogenes, Cancer Res. 45:1437 (1985).PubMedGoogle Scholar
  39. 39.
    J. A. McCutcheon, J. C. Bickenbach and J. C. Mackenzie, Effect on label-retaining cells of tumor prompters and differing levels of hyperplasia, J. Dental Res. 64:298 (1985).Google Scholar
  40. 40.
    A. R. Kinsella and M. Radman, Tumor promoter induces sister chromatid exchanges: Relevance to mechanisms of carcinogenesis, Proc. Natl. Acad. Sci. USA 75:6149 (1978).CrossRefPubMedGoogle Scholar
  41. 41.
    H. C. Birnboim, DNA strand breakage in human leukocytes exposed to a tumor promoter, phorbol myristate acetate, Science 211:1247 (1982).CrossRefGoogle Scholar
  42. 42.
    D. R. Dutton and G. T. Bowden, Indirect induction of clastogenic effect in epidermal cells by a tumor promoter, Carcinogensis 6:1279 (1985).CrossRefGoogle Scholar
  43. 43.
    J. A. Hartley, N. W. Gibson, L. A. Zwelling and S. H. Yuspa, The association of DNA strand breaks and terminal differentiation in mouse epidermal cells exposed to tumor promoters, Cancer Res. 45:4864 (1985).PubMedGoogle Scholar
  44. 44.
    J. M. Parry, E. M. Parry and J. C. Barrett, Tumor promoters induce mitotic aneuploidy in yeast, Nature 294:263 (1981).CrossRefPubMedGoogle Scholar
  45. 45.
    D. F. Callen and J. H. Ford, Chromosome abnormalities in chronic lymphocytic leukemia revealed by TPA as mitogen, Cancer Genet Cytogenet. 10:87 (1983).CrossRefPubMedGoogle Scholar
  46. 46.
    I. Emerit and P. A. Cerutti, Tumor promoter phorbol-12-myristate-13-acetate induces chromosomal damage via indirect action, Nature 293:144 (1981).CrossRefPubMedGoogle Scholar
  47. 47.
    R. J. Imbra and M. Karin, Phorbol ester induces the transcriptional stimulatory activity of the SV40 enhancer, Nature 323:555 (1986).CrossRefPubMedGoogle Scholar
  48. 48.
    P. B. Fisher, I. B. Weinstein, D. Eisenberg and H. S. Ginsberg, Interactions between adenovirus, a tumor promoter, and chemical carcinogens in transformation of rat embryo cell cultures, Proc. Natl. Acad. Sci. USA 75:2311 (1978).CrossRefPubMedGoogle Scholar
  49. 49.
    H. zur Hausen, F. J. O’Neill and U. K. Freese, Persisting oncogenic herpes-virus induced by the tumor promoter TPA, Nature 272:373 (1978).CrossRefPubMedGoogle Scholar
  50. 50.
    H. zur Hausen, G. W. Bornkamm, R. Schmidt and E. Hecker, Tumor initiators and promoters in the induction of Epstein-Barr virus, Proc. Natl. Acad. Sci. USA 76:782 (1979).CrossRefPubMedGoogle Scholar
  51. 51.
    A. K. Verma, D. Erickson and B. J. Dolnick, Increased mouse epidermal ornithine decarboxylase activity by the tumor promoter TPA involves increased amounts of both enzyme protein and messenger RNA, Biochem. J. 237:297 (1986).PubMedGoogle Scholar
  52. 52.
    S. K. Gilmour, A. K. Verma, Th. Madara and T. G. O’Brien, Regulation of ornithine decarboxylase gene expression in mouse epidermis and in epidermal tumors during two-stage tumorigenesis, Cancer Res. 47:1221 (1987).PubMedGoogle Scholar
  53. 53.
    S. Rose-John, G. Fürstenberger, P. Krieg, E. Besemfelder, G. Rincke and F. Marks, Differential effects of phorbol esters on c-fos and c-myc and ornithine decarboxylase gene expression in mouse skin in vivo, Carcinogenesis: in press (1988).Google Scholar
  54. 54.
    M. E. Greenberg and E. B. Ziff, Stimulation of 3T3 cells induces transcription of the c-fos protooncogene, Nature 311:433 (1984).CrossRefPubMedGoogle Scholar
  55. 55.
    R. Mueller, R. Bravo, J. Burckhardt and T. Curran, Induction of c-fos-gene and protein by growth factors precedes activation of c-myc, Nature 312:716 (1984).CrossRefGoogle Scholar
  56. 56.
    G. P. Dotto, M. Z. Gilman, M. Maruyama and R. A. Weinberg, c-myc and c-fos expression in differentiating mouse primary keratinocytes, Embo. J. 5:2853 (1986).PubMedGoogle Scholar
  57. 57.
    R. T. Petrusevska, G. Fürstenberger, F. Marks and N. E. Fusenig, Cytogenetic effects caused by phorbol ester tumor promoters in primary mouse keratinocyte cultures: Correlation with the convertogenic activity of TPA in multistage skin carcinogenesis, Carcinogenesis, in press (1988).Google Scholar
  58. 58.
    R. T. Petrusevska, N. Pohlmann and N. E. Fusenig, Induction of chromosomal abberations in primary mouse keratinocyte cultures by tumorpromoting phorbol esters and inhibition of cytogenetic effects by antipromoters, in: “Accomplishments in Oncology”, Vol. 2/1, H. zur Hausen and J. R. Schlehofer, eds., Lippincott, Philadelphia (1987).Google Scholar
  59. 59.
    E. Vogel and A. T. Natarajan, The relation between reaction kinetics and mutagenic actions of monofunctional alkylating agents in higher eukaryotic systems. II. Total and partial sex-chromosome loss in Drosophila, Mutation Res. 62:101 (1979).CrossRefPubMedGoogle Scholar
  60. 60.
    E. Vogel and A. T. Natarajan, The relation between reaction kinetics and mutagenic action of monofunctional alkylating agents in higher eukaryotic systems: Interspecies comparisons, in: “Chemical Mutagens”, Vol. 7, F. J. de Serres and A. Hollaender, eds., Plenum Press, New York (1982).Google Scholar
  61. 61.
    D. B. Couch, N. L. Forbes and A. W. Hsie, Comparative mutagenicity of alkyl sulfate and alkane sulfonate derivatives in Chinese hamster ovary cells, Mutation Res. 57:217 (1978).CrossRefPubMedGoogle Scholar
  62. 62.
    S. M. Morris, R. H. Heflich, D. T. Beranek and R. L. Kodell, Alkylation-induced sister-chromatid exchanges correlate with reduced cell survival, not mutations, Mutation Res. 105:163 (1982).CrossRefPubMedGoogle Scholar
  63. 63.
    A. T. Natarajan, J. W. I. M. Simons, E. W. Vogel and A. A. van Zeeland, Relationship between cell killing, chromosomal aberrations, sister-chromatid exchanges and point mutations induced by monofunctional alkylating agents in Chinese hamster cells. A correlation with different ethylation products in DNA, Mutation Res. 128:31 (1984).CrossRefPubMedGoogle Scholar
  64. 64.
    K. Frenkel and K. Chrzan, Hydrogen peroxide formation and DNA base modification by tumor promoter-activated polymorphonuclear leukocytes, Carcinogenesis 8:455 (1987).CrossRefPubMedGoogle Scholar
  65. 65.
    P. A. Cerutti, Pro-oxidant states and tumor promotion, Science 227:375 (1985).CrossRefPubMedGoogle Scholar
  66. 66.
    J. Emerit and P. A. Cerutti, Eicosanoids and chromosomal damage, in: “Icosanoids and Cancer”, H. Thaler-Dao, A. Crastes de Paulet and R. Paoletti, eds., Raven Press, New York (1984).Google Scholar
  67. 67.
    T. Ochi and P. Cerutti, Clastogenic action of hydroperoxy-5,8,11,13-icosatetraenoic acids on mouse embryo fibroblasts C3H/10T1/2, Proc. Natl. Acad. Sci. USA 84:990 (1987).CrossRefPubMedGoogle Scholar
  68. 68.
    G. Fürstenberger, M. Gschwendt, H. Hagedorn and F. Marks, Modulation of the conversion stage of multistep carcinogenesis in mouse skin by eicosanoids, in: “Prostaglandins in Cancer Research”, E. Garaci, R. Paoletti and M. G. Santoro, eds., Springer, Berlin-Heidelberg (1987).Google Scholar
  69. 69.
    G. Bauer, P. Höfler and M. Simon, Epstein-Barr-Virus induction by a serum factor: Purification of a high molecular weight protein that is responsible for induction, J. Biol. Chem. 257:11405 (1982).PubMedGoogle Scholar
  70. 70.
    G. Bauer, P. Höfler and M. Simon, Epstein-Barr-Virus induction by a serum factor: Characterization of the purified factor and the mechanism of its activation, J. Biol. Chem. 257:11411 (1982).PubMedGoogle Scholar
  71. 71.
    G. Bauer, Epstein-Barr-Virus inducing factor: A growth factor with tumor promoting activity, J. Cancer Res. Clin. Oncol. 109:A48 (1985).Google Scholar
  72. 72.
    M. Rogers, G. Fürstenberger, G. Bauer, P. Höfler and F. Marks, EIF (Epstein-Barr-Virus inducing factor), a peptide factor with TFGß-activity, is a convertogenic agent (“stage I tumor promoter”) in mouse skin in vivo. Proc. 3rd Int. Congress Hormones and Cancer, Raven Press, New York (1988) (in press).Google Scholar
  73. 73.
    V. Kinzel, H. Loehrke, K. Goerttler, G. Fürstenberger and F. Marks, Suppression of the first stage of TPA-effected tumor promotion in mouse skin by non-toxic inhibition of DNA synthesis, Proc. Natl. Acad. Sci. USA 81:5858 (1984).CrossRefPubMedGoogle Scholar
  74. 74.
    J. C. Gaal, K. R. Smith and C. K. Pearson, Cellular euthanasia mediated by a nuclear enzyme: a central role for nuclear ADP-ribosylation in cellular metabolism, Trends Bioch. Sci. 12:129 (1987).CrossRefGoogle Scholar
  75. 75.
    C. B. Croft and D. Tarin, Ultrastructural studies of wound healing in mouse skin. I. Epithelial behavior, J. Anat. 105:63 (1970).Google Scholar
  76. 76.
    J. J. Cohen and R. C. Duke, Glucocorticoid activation of a Ca2+− dependent endonuclease in lymphocyte nuclei leads to cell death, J. Immunol. 132:38 (1984).PubMedGoogle Scholar
  77. 77.
    E. Duvall and A. H. Wyllie, Death and the cell, Immunology Today 7:115 (1986).CrossRefGoogle Scholar
  78. 78.
    C. Richter, B. Frei and P. A. Cerutti, Mobilization of mitochondrial Ca2+ by hydroperoxyeicosatetraenoid acid, Biochim. Biophys. Res. Commun. 143:609 (1987).CrossRefGoogle Scholar
  79. 79.
    P. Csermely, R. Fodor and J. Somogyi, The tumor promoter TPA elecits redistribution of heavy metals in subcellular fractions of rabbit thymocytes as measured by plasma emission spectroscopy, Carcinogenesis 8:1663 (1987).CrossRefPubMedGoogle Scholar
  80. 80.
    T. Masui, L. M. Wakefield, J. F. Lechner, M. A. Laveck, M. B. Sporn and C. C. Harris, Type ß transforming growth factor is the primary differentiation-inducing serum factor for normal human bronchial cells, Proc. Natl. Acad. Sci. USA 83:2438 (1986).CrossRefPubMedGoogle Scholar
  81. 81.
    O. H. Iversen, ed., “Theories of Carcinogenesis”, Hemisphere, Washington (1988).Google Scholar
  82. 82.
    A. P. Maskens, P. Ebbesen and A. Burny, eds., “Concepts and Theories in Carcinogenesis”, Excerpta Medica, Amsterdam (1987).Google Scholar
  83. 83.
    J. J. Slaga, Can tumor promotion be effectively inhibited? in: “Models, Mechanisms and Etiology of Tumor Promotion”, M. Börszönyi, K. Lapis, N. E. Day and H. Yamasaki, eds., Int. Agency for Res. on Cancer, IARC, Lyon (1984).Google Scholar
  84. 84.
    T. J. Slaga, Multistage tumor promotion and specificity of inhibition, in: “Mechanisms of Tumor Promotion”, Vol II, T. J. Slaga, ed., CRC Press Boca Raton, Florida (1984).Google Scholar
  85. 85.
    M. Gschwendt, W. Kittstein and F. Marks, Cyclosporin A inhibits phorbol ester-induced cellular proliferation and tumor promotion as well as phosphorylation of a 100-kD protein in mouse epidermis, Carcinogenesis 8:203 (1987).CrossRefPubMedGoogle Scholar
  86. 86.
    M. Gschwendt, W. Kittstein and F. Marks, Didemnin B inhibits biological effects of tumor promoting phorbol esters on mouse skin, as well as phosphorylation of a 100 kD protein in mouse epidermis cytosol, Cancer Letters 34:187 (1987).CrossRefPubMedGoogle Scholar
  87. 87.
    M. Gschwendt, W. Kittstein and F. Marks, The weak immunosuppressant cyclosporine D as well as the immunologically inactive cyclosporine H are potent inhibitors in vivo of phorbol ester TPA-induced biological effects in mouse skin and of Ca2+/calmodulin-dependent EF-2 phosphorylation in vitro, Biochem. Biophys. Res. Commun. 150:545 (1988). press (1988).CrossRefPubMedGoogle Scholar
  88. 88.
    M. Gschwendt, G. Fürstenberger, W. Kittstein, E. Besemfelder, W. E. Hull, H. Hagedorn, H. J. Opferkuch and F. Marks, Generation of the arachidonic acid metabolite 8-HETE by extracts of mouse skin treated with phorbol ester in vivo; identification by 1H-n.m.r. and GC-MS spectroscopy, Carcinogenesis 7:449 (1986).CrossRefPubMedGoogle Scholar
  89. 89.
    S. M. Fischer, G. Fürstenberger, F. Marks and T. J. Slaga, Events associated with mouse skin tumor promotion with aspect to arachidonic acid metabolism: A comparison between SENCAR and NMRI mice, Cancer Res. 47:3174 (1987).PubMedGoogle Scholar
  90. 90.
    M. Gross, G. Fürstenberger and F. Marks, Isolation, characterization, and in vitro cultivation of keratinocyte subfractions from adult NMRI mouse epidermis: epidermal target cells for phorbol esters, Exp. Cell Res. 171:460 (1987).CrossRefPubMedGoogle Scholar
  91. 91.
    R. T. Dzarlieva-Petrusevska, N. E. Fusenig, Tumor promoter 12-0-tetra-decanoylphorbol-13-acetate (TPA)-induced chromosome aberrations in mouse keratinocyte cell lines: a possible genetic mechanism of tumor promotion, Carcinogenesis 6:1447 (1985).CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1988

Authors and Affiliations

  • Friedrich Marks
    • 1
  • Gerhard Fürstenberger
    • 1
  • Michael Gschwendt
    • 1
  • Michael Rogers
    • 1
  • Bärbel Schurich
    • 1
  • Bernd Kaina
    • 2
  • Georg Bauer
    • 3
  1. 1.Institute of BiochemistryGerman Cancer Research CenterHeidelbergGermany
  2. 2.Kernforschungszentrum (Nuclear Research Center)KarlsruheGermany
  3. 3.Institute of Medical Microbiology and HygieneUniversity of FreiburgFederal Republic of Germany

Personalised recommendations