Skip to main content
British Journal of Cancer logoLink to British Journal of Cancer
. 1984 Nov;50(5):647–656. doi: 10.1038/bjc.1984.231

Cytotoxic effect of dose and schedule on normal murine hematopoietic progenitor cells following the administration of 4'-deoxydoxorubicin.

I Pannacciulli, C Muzzulini, G Massa, G Bogliolo
PMCID: PMC1976966  PMID: 6498062

Abstract

In an experimental setting, 4'-deoxydoxorubicin (4'-deoxy-DX) shows minimal cardiotoxicity as well as the marked antitumoral activity shown by doxorubicin, its parent compound. In this experimental study, the haematologic toxicity of the new anthracycline was investigated by haematopoietic precursor cell (HPC) assays using in vivo (colony-forming units - spleen, CFUs) and in vitro (CFUc-culture) methods with (C57B1 X C3H)F1 mice. Dose-survival curves and time response of HPC in situ following 4'-deoxy-DX administration were determined. In the time-related experiments, the effects of a single dose, an intermittent treatment (Days 0, 2, and 5) and a prolonged biweekly administration were studied. All dose-survival curves were exponential, with statistically significant differences between the effects on the various cell classes. CFUc appeared more sensitive than CFUs. In time-related experiments, 4'-deoxy-DX toxicity for HPC seemed to be relatively mild. However, CFUc sensitivity was again high in comparison with other populations assayed. In long-term administration, the 4-deoxy-DX effects on the haematopoietic system were also rather slight.

Full text

PDF
647

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arcamone F., Penco S., Redaelli S., Hanessian S. Synthesis and antitumor activity of 4'-deoxydaunorubicin and 4'-deoxyadriamycin. J Med Chem. 1976 Dec;19(12):1424–1425. doi: 10.1021/jm00234a016. [DOI] [PubMed] [Google Scholar]
  2. Blackett N. M., Marsh J. C., Gordon M. Y., Okell S. F., Aguado M. Simultaneous assay by six methods of the effect on haemopoietic precursor cells of adriamycin, methyl CCNU, 60Co gamma-rays, vinblastine, and cytosine arabinoside. Exp Hematol. 1978 Jan;6(1):2–8. [PubMed] [Google Scholar]
  3. Bonfante V., Bonadonna G., Villani F., Di Fronzo G., Martini A., Casazza A. M. Preliminary phase I study of 4'-epi-adriamycin. Cancer Treat Rep. 1979 May;63(5):915–918. [PubMed] [Google Scholar]
  4. Bradley T. R., Metcalf D. The growth of mouse bone marrow cells in vitro. Aust J Exp Biol Med Sci. 1966 Jun;44(3):287–299. doi: 10.1038/icb.1966.28. [DOI] [PubMed] [Google Scholar]
  5. Buick R. N., Messner H. A., Till J. E., McCulloch E. A. Cytotoxicity of adriamycin and daunorubicin for normal and leukemia progenitor cells of man. J Natl Cancer Inst. 1979 Feb;62(2):249–255. [PubMed] [Google Scholar]
  6. Giuliani F. C., Kaplan N. O. New doxorubicin analogs active against doxorubicin-resistant colon tumor xenografts in the nude mouse. Cancer Res. 1980 Dec;40(12):4682–4687. [PubMed] [Google Scholar]
  7. Giuliani F. C., Zirvi K. A., Kaplan N. O., Goldin A. Chemotherapy of human colorectal tumor xenografts in athymic mice with clinically active drugs: 5-fluorouracil and 1-3-bis-(-2-chloroethyl)-1-nitrosourea (BCNU). Comparison with doxorubicin derivatives: 4'deoxydoxorubicin and 4'-O-methyldoxorubicin. Int J Cancer. 1981 Jan 15;27(1):5–13. doi: 10.1002/ijc.2910270103. [DOI] [PubMed] [Google Scholar]
  8. Huybrechts M., Symann M., Trouet A. Effects of daunorubicin and doxorubicin, free and associated with DNA, on hemopoietic stem cells. Cancer Res. 1979 Sep;39(9):3738–3743. [PubMed] [Google Scholar]
  9. Lajtha L. G. Haemopoietic stem cells. Br J Haematol. 1975 Apr;29(4):529–535. doi: 10.1111/j.1365-2141.1975.tb02739.x. [DOI] [PubMed] [Google Scholar]
  10. Marsh J. C. Comparison of the sensitivities of human, canine, and murine hematopoietic precursor cells to adriamycin and N-trifluoroacetyladriamycin-14-valerate. Cancer Res. 1979 Feb;39(2 Pt 1):360–364. [PubMed] [Google Scholar]
  11. Marsh J. C. The effects of cancer chemotherapeutic agents on normal hematopoietic precursor cells: a review. Cancer Res. 1976 Jun;36(6):1853–1882. [PubMed] [Google Scholar]
  12. Massa G., Bogliolo G., D'Amore F., Muzzulini C., Ghio R., Pannacciulli I. Hematopoietic precursor cells in mice treated with 4-demethoxydaunorubicin and doxorubicin. J Natl Cancer Inst. 1982 Jun;68(6):971–976. [PubMed] [Google Scholar]
  13. Muzzulini C., D'Amore F., Sobrero A., Massa G., Bogliolo G., Ghio R., Pannacciulli I. Valutazione della tossicità della doxorubicina sulle cellule staminali emopoietiche normali. Tumori. 1981 Aug;67(4):293–300. doi: 10.1177/030089168106700405. [DOI] [PubMed] [Google Scholar]
  14. Page P. L., Cook P. A., Greenberg H. M., Hartwell B. L., Robinson S. H. Cytotoxic reduction and regeneration of murine marrow stem cells. Exp Hematol. 1983 Mar;11(3):202–211. [PubMed] [Google Scholar]
  15. Pannacciulli I., Massa G., Bogliolo G., Ghio R., Sobrero A. Effects of high-dose methotrexate and leucovorin on murine hemopoietic stem cells. Cancer Res. 1982 Feb;42(2):530–534. [PubMed] [Google Scholar]
  16. Plumbridge T. W., Brown J. R. The interaction of adriamycin and adriamycin analogues with nucleic acids in the B and A conformations. Biochim Biophys Acta. 1979 Jun 20;563(1):181–192. doi: 10.1016/0005-2787(79)90019-4. [DOI] [PubMed] [Google Scholar]
  17. Razek A., Valeriote F., Vietti T. Survival of hematopoietic and leukemic colony-forming cells in vivo following the administration of daunorubicin or adriamycin. Cancer Res. 1972 Jul;32(7):1496–1500. [PubMed] [Google Scholar]
  18. Salmon S. E., Liu R. M., Casazza A. M. Evaluation of new anthracycline analogs with the human tumor stem cell assay. Cancer Chemother Pharmacol. 1981;6(2):103–109. doi: 10.1007/BF00262325. [DOI] [PubMed] [Google Scholar]
  19. Sobrero A., Muzzulini C., D'Amore F., Bogliolo G., Massa G., Ghio R., Pannacciulli I. Activity of 4'-epi-doxorubicin on normal hematopoietic precursor cells in mice. Cancer Treat Rep. 1982 Dec;66(12):2061–2070. [PubMed] [Google Scholar]
  20. TILL J. E., McCULLOCH E. A. A direct measurement of the radiation sensitivity of normal mouse bone marrow cells. Radiat Res. 1961 Feb;14:213–222. [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES