Archives of Dermatological Research

, Volume 272, Issue 1–2, pp 37–47 | Cite as

DMBA-induced tumors and their prevention by aromatic retinoid (Ro 10-9359)

  • G. Mahrle
  • H. Berger
Original Contributions


Both auricles of 21 domestic rabbits were painted with dimethylbenz-anthracene (DMBA). Eleven animals of this group were additionally fed aromatic retinoid (AR) by an esophageal tube. Two control animals were not treated at all.

Eight or 9 weeks after the beginning of the study six of the seven remaining animals, which had only been painted with DMBA, developed a total of 25 keratoacanthoma-like tumors (KA). On the other hand, none of the seven animals left, which were painted with DMBA and fed AR showed any tumor by this time.

The systemic effect of AR was studied in biopsies from the snout and the back. The epidermis of the snout showed ‘mucous mataplasia’ by histochemical and electron-microscopic criteria, whereas the epidermis of the back was not significantly altered. The production of intra- and extracellular lamellated material indicated an additional effect of AR on epidermal lipid metabolism. The effect of AR in the prevention of DMBA-induced tumors was characterized by ‘mucoid cytolysis’ and karyolysis.

Key words

Tumor prevention Retinoid Skin 


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  1. 1.
    Lotan R (1980) Effects of vitamin A and its analogs (retinoids) on normal and neoplastic cells. Biochim Biophys Acta 605:33–91Google Scholar
  2. 2.
    Orfanos CE (1980) Oral retinoids — present status. Br J Dermatol 103:473–481Google Scholar
  3. 3.
    Elias PM, Williams ML (1981) Retinoids, cancer, and the skin. Arch Dermatol 117:160–180Google Scholar
  4. 4.
    Mahrle G, Berger H (1981) Antitumoreffekt der Retinoide. Z Hautkr (in press)Google Scholar
  5. 5.
    Braun-Falco O, Christophers E (1969) Psoriasiforme Epidermisreaktion der Meerschweinchenhaut durch örtliche Vitamin A-Säure-Applikation. Arch Klin Exp Dermatol 234:70–86Google Scholar
  6. 6.
    Tsambaos D, Mahrle G, Orfanos CE (1980) Epidermal changes induced by oral excess of aromatic retinoid in guinea pigs. Arch Dermatol Res 267:141–152Google Scholar
  7. 7.
    Levij IS, Polliack A (1968) Potentiating effect of vitamin A on 9–10 dimethyl 1–2 benzanthrancene carcinogenesis in the hamster cheek pouch. Cancer 22:300–306Google Scholar
  8. 8.
    Smith DM, Rogers AE, Herndon BJ, Newberne PM (1975) Vitamin A (retinyl acetate) and benzo(a)pyrene-induced respiratory tract carcinogenesis in hamsters fed a commercial diet. Cancer Res 35:11–16Google Scholar
  9. 9.
    Epstein JH (1977) Chemicals and photocarcinogenesis. Aust J Dermatol 18:57–61Google Scholar
  10. 10.
    Forbes PD, Urbach F, Davies RE (1979) Enhancement of experimental photocarcinogenesis by topical retinoic acid. Cancer Lett 7:85–90Google Scholar
  11. 11.
    Prutkin L (1975) Mucous metaplasia and gap junctions in the vitamin A acid-treated skin tumor, keratoacanthoma. Cancer Res 35:364–369Google Scholar
  12. 12.
    Mahrle G, Meyer-Hamme S, Ippen H (1981) Systemic treatment of keratinizing disorders of the skin and the mucous membrane with an aromatic retinoid (Ro 10-9359). Comparative study on 113 patients. Arch Dermatol (in press)Google Scholar
  13. 13.
    Mayer H, Bollag W, Hänni R, Rüegg R (1978) Retinoids a new class of compounds with prophylactic and therapeutic activities in oncology and dermatology. Experientia 34:1105–1246Google Scholar
  14. 14.
    Schultz-Ehrenburg U, Orfanos CE (1981) Light and electron microscopic changes of human epidermis under oral retinoid treatment. In: Orfanos CE, Braun-Falco O, Farber EM, Grupper Ch, Polano MK, Schuppli R (eds) Retinoids. Advances in basic research and therapy. Springer, Berlin Heidelberg New York, pp 5–11Google Scholar
  15. 15.
    Harms V, Olmos L, Hunziker N, Laugier P (1976) Das experimentelle Keratoakanthom am Kaninchenohr (KA). Arch Dermatol Res 257:131–142Google Scholar
  16. 16.
    Levinson SS, Wolf G (1972) The effect of vitamin A acid on glycoprotein synthesis in skin tumors (keratoacanthomas). Cancer Res 32:2248–2252Google Scholar
  17. 17.
    Baer RL, Kopf AW (1962) Keratoacanthoma. In: Baer RL, Kopf AW (eds) The year book of dermatology. Year Book Medical Publishers Chicago, pp 7–41Google Scholar
  18. 18.
    Matter A, Bollag W (1977) A fine structural study on the therapeutic effect of an an aromatic retioid on chemically induced skin papillomas of the mouse. Eur J Cancer 13:831–838Google Scholar
  19. 19.
    Yuspa SH, Hennings H, Saffiotti U (1976) Cutaneous chemical carcinogenesis: Past, present, and future. J Invest Dermatol 67:199–208Google Scholar
  20. 20.
    Iversen OH (1974) Dynamic aspects of epidermal skin carcinogenesis. In: Flarer F, Servi F, Cotton DWK, (eds) Dermatology. Proceedings of the XIV International Congress, Padua-Venice, May 22–27, 1972. Excerpta Medica, Amsterdam, pp 552–554Google Scholar
  21. 21.
    Mahrle GO, Wilkinson DI, Farber EM (1981) Effect of retinoids on keratinocytes in vitro. In: Orfanos CE, Braun-Falco O, Farber EM, Grupper Ch, Polano MK, Schuppli R (eds) Retinoids. Advances in basic research and therapy. Springer, Berlin Heidelberg New York, pp 145–152Google Scholar
  22. 22.
    Mahrle GO, Gray B (1981) The effect of vitamin A acid on homeostasis and differentiation of epidermal cells cultured on collagen. Dermatologia (submitted)Google Scholar

Copyright information

© Springer-Verlag 1982

Authors and Affiliations

  • G. Mahrle
    • 1
  • H. Berger
    • 1
  1. 1.Dept. of DermatologyUniversity of GöttingenGöttingenGermany

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