title: [Effect of cyclophosphamide on murine bone marrow hematopoietic cells and its possible mechanism].
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.
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Tian
authors.forename: Pei
authors.initials: P
authors.lastname: Yu
authors.forename: Wen-Xuan
authors.initials: WX
authors.lastname: Sun
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Li
authors.forename: Ke-Jing
authors.initials: KJ
authors.lastname: Tang
authors.forename: Zheng
authors.initials: Z
authors.lastname: Tian
authors.forename: Hai-Yan
authors.initials: HY
authors.lastname: Xing
authors.forename: Qing
authors.initials: Q
authors.lastname: Rao
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.forename: Jian-Xiang
authors.initials: JX
authors.lastname: Wang
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects*; D016922:Cellular Senescence / Q000187:drug effects*; D003520:Cyclophosphamide / Q000009:adverse effects*; D006410:Hematopoiesis / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D003520:Cyclophosphamide