In two studies, haematopoietic late effects of prolonged bleomycin treatment were evaluated in mice given serial injections of 21 mg bleomycin/m2 weekly for 31 and 44 weeks, respectively. Femoral bone marrow cellularity measured at 43, 45, and 49 weeks after discontinuation of the drug in the first and after 20 weeks in the second study was found to be significantly (P<0.05) lower in the treated mice than in the controls. CFU-S, BFU-E, and CFU-C contents were also reduced in the treated bone marrow, but with the exception of CFU-S in the second study, differences from control values were not significant. Additional long-term bone marrow cultures performed in the second study revealed no marked changes in the marrow proliferative activity and the self-renewal of stem cells to explain the reduced marrow cellularity and stem cell content. These last findings might, therefore, be due to a decrease in femoral size with less marrow content in the treated mice, since measurements of the tibial weights in both groups showed that the bones in the treated animals were significantly (P<0.05) lighter than those in the controls.
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Blodgett FM, Burgin L, Iezzoni D, Gribetz D, Talbot NB (1956) Effects of prolonged cortisone therapy on the statural growth, skeletal maturation and metabolic status of children, N Engl J Med 254: 636
Boggs SS, Sartiaho GP, Mezza A de (1974) Minimal bone marrow damage in mice given Bleomycin. Cancer Res 34: 1938
Bogliolo GV, Massa GG, Sobrero AF, Lanfranco EO, Pannacciulli JM (1979) Sensitivity of spleen-colony-forming units to chronic Bleomycin. Br J Cancer 40: 489
Bornstein RS, Hungerford DA, Haller G, Engstrom PF, Yarbro JW (1971) Cytogenetic effects of Bleomycin therapy in man. Cancer Res 31: 2004
Botnick LE, Hannon EC, Hellman S (1978) Multisystem stem cell failure after apparent recovery from alkylating agents. Cancer Res 38: 1942
Bradley TR, Metcalf D (1966) The growth of mouse bone marrow cells in vitro. Aust J Exp Biol Med Sci 44: 287
Briganti G, Galloni L, Levi G, Spletta V, Mauro F (1975) Effects of Bleomycin on mouse bone marrow stem cells. J Natl Cancer Inst 55: 53
Byrne PV, Heit W, Kubanek B (1978) Stimulation of in vitro granulocyte macrophage colony formation by mouse heart conditioned medium. Br J Haematol 40: 197
Crooke ST, Bradner WT (1976) Bleomycin, a review. J Med 7: 333
Dexter TM, Testa NG (1976) Differentiation and proliferation of hemo poietic cells in culture. Methods Cell Biol 14: 387
Freireich EJ, Gehan EA, Rall DP, Schmidt LH, Skipper HE (1969) Quantitative comparison of toxicity of anticancer agents in mouse, rat, hamster, dog, monkey and man. Cancer Chemother Rep 50: 219
Gallicchio VS, Murphy J Jr (1979) Erythropoiesis in vitro. II. Cytochemical enumeration of erythroid stem cells (CFU-E and BFU-E) from normal mouse and human hematopoietic tissues. Exp Hematol 7: 219
Goldsmith MA, Slavik M, Carter SK (1975) Quantitative prediction of drug toxicity in humans from toxicology in small and large animals. Cancer Res 35: 1354
Iscove NN (1972) Technique for culture of human CFU-C: In: Van Bekkum DW, Dicke KA (eds) In vitro culture of hemopoietic cells. Radiobiological Institute, Rijswijk (The Netherlands). p 459
Iscove NN, Sieber F (1975) Erythroid progenitors in mouse bone marrow detected by macroscopic colony formation in culture. Exp Hematol 3: 32
Mauch P, Greenberger JS, Botnick L, Hannon E, Hellman S (1980) Evidence for structured variation in self renewal capacity within long-term bone marrow cultures. Proc Natl Acad Sci USA 7: 2927
Murphy MJ Jr, Sullivan ME (1978) Culture of erythroid stem cells from murine and human marrow and blood. In: Murphy MJ Jr (ed) In vitro aspects of erythropoiesis. Springer, New York, p 262
Nowrousian MR, Schaefer UW, Öhl S, Boecker WR, Schmidt CG (1980) Long-term treatment with Bleomycin: proliferative activity of murine bone marrow and self renewal of stem cells. Exp Hematol [Suppl 7] 8: 172
Pinkel D (1971) Five-year follow-up of “total therapy” of childhood lymphocytic leukemia. JAMA 216: 643
Till JE, McCulloch EA (1961) A direct measurement of the radiation sensitivity of normal mouse bone marrow cells. Radiat Res 14: 213
Trainor KJ, Ram SS, Morley AA (1979) Residual marrow injury following cytotoxic drugs. Leuk Res 3: 205
Twentyman PR, Bleehen NM (1973) The sensitivity to Bleomycin of spleen colony forming units in the mouse. Br J Cancer 28: 66
Wiktor-Jedrzejczak W, Aftab A, Szczlik C (1981) Conditions of adherent cell growth from murine bone marrow in liquid cultures, and partial characterization of function. Exp Hematol 9: 835
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Nowrousian, M.R., Schmidt, C.G. Haematopoietic late effects of prolonged bleomycin treatment in mice. Cancer Chemother. Pharmacol. 9, 6–9 (1982). https://doi.org/10.1007/BF00296752
- Stem Cell
- Bone Marrow
- Cancer Research
- Proliferative Activity