Berger J
Folia Haematol Int Mag Klin Morphol Blutforsch. 1982;109(2):255-63.
Rat erythropoiesis was experimentally depressed by repeated doses of cyclophosphamide (CY) or by restriction of food consumption and the diagnostic value of quantitative haematology examinations of rat marrow erythroid morphology was evaluated. A slight depression of rat erythropoiesis (following a dose of 5 mg/kg/day) as well as a higher one (15 mg/kg/day) and the following recovery were determined by a quantitation of marrow erythroid morphology and by peripheral reticulocyte counts, yet a lower validity of peripheral erythrocyte and marrow relative erythroid cell counts was obtained; erythrocyte counts did not change even after a high depletion of marrow erythroid cells. The restriction of food consumption led to a similar depression of rat marrow erythropoiesis as that observed after CY administration. Our data may suggest that the quantitation of marrow erythroid morphology and peripheral reticulocyte counts are desirable in haematological examinations in preclinical safety evaluations performed on rats provided a new drug administered in repeated doses can be cytotoxic.
通过重复给予环磷酰胺(CY)或限制食物摄入,实验性地抑制大鼠红细胞生成,并评估大鼠骨髓红细胞形态定量血液学检查的诊断价值。通过骨髓红细胞形态定量和外周网织红细胞计数,确定了大鼠红细胞生成的轻度抑制(剂量为5mg/kg/天)、更高程度的抑制(15mg/kg/天)以及随后的恢复情况,但外周红细胞计数和骨髓相对红细胞计数的有效性较低;即使在骨髓红细胞大量减少后,红细胞计数也没有变化。食物摄入限制导致大鼠骨髓红细胞生成受到与CY给药后类似的抑制。我们的数据可能表明,在对大鼠进行的临床前安全性评估的血液学检查中,如果重复给药的新药具有细胞毒性,那么骨髓红细胞形态定量和外周网织红细胞计数是可取的。