» Articles » PMID: 6498062

Cytotoxic Effect of Dose and Schedule on Normal Murine Hematopoietic Progenitor Cells Following the Administration of 4'-deoxydoxorubicin

Overview
Journal Br J Cancer
Specialty Oncology
Date 1984 Nov 1
PMID 6498062
Authors
Affiliations
Soon will be listed here.
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.

References
1.
Buick R, Messner H, Till J, McCulloch E . Cytotoxicity of adriamycin and daunorubicin for normal and leukemia progenitor cells of man. J Natl Cancer Inst. 1979; 62(2):249-55. View

2.
Bradley T, Metcalf D . The growth of mouse bone marrow cells in vitro. Aust J Exp Biol Med Sci. 1966; 44(3):287-99. DOI: 10.1038/icb.1966.28. View

3.
Till J, McCulloch E . A direct measurement of the radiation sensitivity of normal mouse bone marrow cells. Radiat Res. 1961; 14:213-22. View

4.
Bonfante V, Bonadonna G, Villani F, Di Fronzo G, Martini A, CASAZZA A . Preliminary phase I study of 4'-epi-adriamycin. Cancer Treat Rep. 1979; 63(5):915-8. View

5.
Giuliani F, Zirvi K, Kaplan N, 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; 27(1):5-13. DOI: 10.1002/ijc.2910270103. View