Effect of cyclophosphamide on murine bone marrow hematopoietic cells and its possible mechanism.
- Author:
Jie TIAN
1
;
Pei YU
;
Wen-Xuan SUN
;
Xiao-Yan LI
;
Ke-Jing TANG
;
Zheng TIAN
;
Hai-Yan XING
;
Qing RAO
;
Min WANG
;
Jian-Xiang WANG
Author Information
1. State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
- Publication Type:Journal Article
- MeSH:
Animals;
Bone Marrow Cells;
cytology;
drug effects;
Cell Differentiation;
drug effects;
Cellular Senescence;
drug effects;
Cyclophosphamide;
adverse effects;
Hematopoiesis;
drug effects;
Mice;
Mice, Inbred C57BL
- From:
Journal of Experimental Hematology
2012;20(6):1316-1321
- CountryChina
- Language:Chinese
-
Abstract:
This study was purposed to investigate the effect of chemotherapeutic drug cyclophosphamide (CTX) on normal murine bone marrow hematopoietic cells, especially on the self-renewal, proliferation and differentiation of bone marrow hematopoietic cells, and possible mechanisms. The CTX-treated mouse model was established by CTX 200 mg/kg, ip. The exact time of complete recovery of hematopoiesis was determined by monitoring the recovery level of differential blood counts and the proportion of LKS(+) cells in bone marrow cells. The function of bone marrow hematopoietic cells such as self-renewal, proliferation and differentiation were assessed by non-competitive and competitive bone marrow transplantation. The potential effect of CTX on senescence of bone marrow hematopoietic cells was analyzed by detecting p16(Ink4a) mRNA relative expression and SA-β-galactosidase (gal) staining. The results showed that the CTX could induce long-term but latent damage to bone marrow hematopoietic cell function and lead to the decrease in competency of bone marrow hematopoietic cells to reconstitute while seemingly permitting a complete recovery. Furthermore, the serial-transplantation model showed that these mice received transplantation of bone marrow hematopoietic cells from CTX-treated mice exhibited a high expression of p16(Ink4a) mRNA and SA-β-gal staining. It is concluded that CTX-induced bone marrow cellular senescence may play an important role in CTX-induced long-term injury to bone marrow hematopoietic cells.
