Busulfan (NSC-750) is a cell cycle non-specific alkylating antineoplastic agent. Busulfan inducesapoptosis. In vitro
Busulfan inhibits the cobblestone area-forming cell frequency but fails to cause a significant increase in apoptosis in hematopoietic stem cell alike cells and progenitors. Busulfan inhibits the hematopoietic function of HSC alike cells and progenitors via an apoptosis-independent mechanism. Busulfan induces bone marrow hematopoietic cell senescence associated with an increased expression of p16Ink4a and p19Arf in a time-dependent manner. Busulfan, an alkylating agent that causes DNA damage by cross-linking DNAs and DNA and proteins, induces senescence in normal human diploid WI38 fibroblasts through the extracellular signal-regulated kinase (Erk) and p38 mitogen-activated protein kinase (p38 MAPK) cascade independent of the p53-DNA damage pathway. Busulfan induces a transient reduction in GSH but a continuous increase in ROS production. Busulfan-induced hypophosphorylation of Rb prevents apoptosis of spermatogonial stem cells by inhibiting PCNA expression in testicular cells.
In vivo
Busulfan-treated mice exhibit a marked increase in apoptosis and a decrease in testis weight. Busulfan is administered at the rate of 40 mg/kg body weight to induce a maximal number of apoptotic cells while minimizing the number of necrotic cells. Busulfan conditioning and irradiation results in comparable sensitivity of HSC detection as evaluated by limiting dilution analysis in NOD/SCID mice. Busulfan-transplanted mice has slow and incomplete lymphoid engraftment. Busulfan (20 mg/kg to 100 mg/kg) provides dose-dependent congenic lymphoid reconstitution in mice. Cell Data