4′-O-Tetrahydropyranyl adriamycin (THP-ADM)-induced modifications of murine peritoneal macrophages

  • A. Bravo-Cuellar
  • G. Mathé
  • S. Orbach-Arbouys
Clinical Use of Immunomodulating Agents


4′-O-tetrahydropyranyl adriamycin (THP-ADM) is a newly synthetized anthracyclin reported to be an efficient oncostatic drug in animals and in humans and which is less cardiotoxic than adriamycin (ADM). Since part of the efficiency of anthracyclins may be due to their immunoregulatory activity, we investigated to what extent THP-ADM had such properties and we observed that THP-ADM stimulates free oxygen radical secretion by murine peritoneal macrophages. They could thus help the control of infections cancer patients have a tendency to develop. Peritoneal macrophages of THP-ADM-treated mice have anin vitro cytostatic activity towards P815 tumor cells higher than normal cells and when stimulated with LPS they secrete more IL-1, an important effector of the immune response.

Key words

Anthracyclins THP-ADM Macrophages Chemoluminescence IL-1 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Mathé G: Immune status and cancer chemotherapy efficacy.Cancer Immun Immunother 2, 81 (1977).Google Scholar
  2. 2.
    Pouillart P, Palangié T, Huguenin P, Morin P, Gauthier H, Baron A, Mathé G., Lededente A, Botto G: Cancers épidermoïdes bronchiques inopérables. Etude de la signification pronostique de l’état immunitaire et résultats d’un essai d’immunorestauration par le BC.Nouv Presse med 7, 265 (1978).PubMedGoogle Scholar
  3. 3.
    Bravo-Cuellar A, Scott Algara D, Metzger G, Orbach-Arbouys S: Enhanced activity of mouse peritoneal cells after aclacinomycin administration.Cancer Res 47, 3477 (1987).Google Scholar
  4. 4.
    Salazar D, Cohen S A: Multiple tumoricidal effector mechanism induced by adriamycin.Cancer Res 44, 2561 (1984).PubMedGoogle Scholar
  5. 5.
    Orbach-Arbouys S, Bravo-Cuellar A, Andrade-Mena C E: Mechanisms of the enhancement of the immune response by aclacinomycin, in Mathé G, Umezawa H (eds):Progress in Cancer Chemo-immunotherapy, pp. 19–25. Tokyo, JARA (1984).Google Scholar
  6. 6.
    Martin F, Caignard A, Olsson O, Jeannin J F, Leclerc A: Tumoricidal effect of macrophages exposed to adriamycinin vivo orin vitro.Cancer Res 42, 3851 (1982).PubMedGoogle Scholar
  7. 7.
    Doroshow J H: Anthracycline antibiotic-stimulated Superoxide, hydrogen peroxide and hydroxyl radical production by NADH dehydrogenase.Cancer Res 43, 4543 (1983).PubMedGoogle Scholar
  8. 8.
    Doroshow J H: Effect of anthracycline antibiotics on oxygen radical formation in rat heart.Cancer Res 43, 460 (1983).PubMedGoogle Scholar
  9. 9.
    Dantchev D, Slioussartchouk V, Paintrand M, Hayat M, Bourut C, Mathé G: Electron microscoplc studies of the heart and light microscoplc studies of the skin after treatment of golden hamsters with adriamycin, detorubicin, AD-32, and aclacinomycin.Cancer Treat Rep 63, 875 (1979).PubMedGoogle Scholar
  10. 10.
    Tsuruo T, Iida H, Tsukagoshi S, Sakurai Y: 4′-O-tetrahydropyranyladiramycin as a potential new antitumor agent.Cancer Res 42, 1462 (1982).PubMedGoogle Scholar
  11. 11.
    Dantchev D, Paintrand M, Hyata M, Bourut C, Mathé G: Low heart and skin toxicity of a tetrahydropyranyl derivative of adriamycin (THP-ADM) as observed by electron and light microscopy.J Antibiot 32, 1085 (1979).PubMedGoogle Scholar
  12. 12.
    Mathé G, Umezawa H, Oka S, Misset J L, Brienza S, de Vassal F, Musset M, Ribaud P, Tapiero H: An oriented phase II trial of THP-adriamycin in breast carcinoma.Biomed Pharmacother 40, 376 (1986).PubMedGoogle Scholar
  13. 13.
    Florentin I, Hayat M, Kiger N, Mathé G: Comparative analysis of the immunopharmacological properties of three new nitrosourea analogues: RPCNU, RFCNU and Chlorozotocin.Int J Immunopharmac 5, 201 (1983).CrossRefGoogle Scholar
  14. 14.
    Pucetti P, Santoni A, Ricardi C, Holden H T, Heberman R B: Activation of mouse macrophages by pyran copolymer and role in augmentation of natural killer activity.Int J Cancer 24, 819 (1979).CrossRefGoogle Scholar
  15. 15.
    Sasada M, Johnston R B Jr: Macrophage microbicidal activity. Correlation between phagocytosis-associated oxidative metabolism and the killing ofCandida by macrophages.J exp Med 152, 85 (1980).PubMedCrossRefGoogle Scholar
  16. 16.
    Allen R C, Loose L D: Phagocytic activation of a luminol-dependent chemiluminescence in rabbit alveolar and peritoneal macrophages.Biochem biophys Res Commun 69, 245 (1976).PubMedCrossRefGoogle Scholar
  17. 17.
    Bravo-Cuellar A, Homo-Delarche F, Cabannes J, Orbach-Arbouys S: Enhanced activity of murine peritoneal cells after aclacinomycin injection: characteristics of the enhanced respiratory burst.Cancer Res 48, 3440 (1988).PubMedGoogle Scholar
  18. 18.
    Cheung K, Archibald A C, Robinson M F: The origin of chemiluminescence produced by neutrophils stimulated by zymosan.J Immun 130, 2324 (1983).PubMedGoogle Scholar
  19. 19.
    Dinarelo C A: Biology of interleukin-1.FASEB J 2, 108 (1988).Google Scholar
  20. 20.
    Ehrke M J, Maccubbin D, Ryoyama K, Cohen S A, Mihich E: Correlation between adriamycin-induced augmentation of interleukin-2 production and cellmediated cytotoxicity in mice.Cancer Res 46, 54 (1986).PubMedGoogle Scholar

Copyright information

© Humana Press Inc. 1989

Authors and Affiliations

  • A. Bravo-Cuellar
    • 1
  • G. Mathé
    • 1
  • S. Orbach-Arbouys
    • 1
  1. 1.Hôpital Paul-BrousseInstitut du Cancer et d’Immunogénétique (Univ. Paris-Sud, CNRS UA 04-1163, Assoc. Cl.-Bernard & ARC)VillejuifFrance

Personalised recommendations