Mouse Survival after 5- Fluorouracil treatment and the Role of Autophagic Clearance in Rapid Recovery

Abstract

Introduction: One of the most effective chemotherapeutic agents is 5-fluorouracil (5-FU). The aim of this study was to investigate its effects on bone marrow cell proliferation and autophagy in adult female C3H mice.Methods: C3H mice and bone marrow cells were exposed to 5-FU and its toxicity was evaluated mediating microscopic analysis, colonies formation, pH variations, apoptosis and autophagy.Results: After ablating bone marrow with 5-FU treatment, a rapid regeneration occurred during the subsequent 10 days. This was achieved by hematopoietic stem cells positive to autophagy/PI dye. Hence, the restoration of chemically depleted bone marrow was apparently initiated by cells normally resident in that tissue. We examined the recovery of colony formation by evaluating BFU-E, CFU-GM and CFU-GEMM. At 10 days post-administration of 5-FU, a full recovery of the formerly depopulated bone marrow was observed, with similar cell populations in treated and untreated mice. Bone marrow recovery is intrinsic to the hematopoietic progenitor cell compartment. Recovery was dependent on the autophagic cells that survived 5-FU ablation. Conclusion:A compartment of primitive stem cells exists in adult female C3H mice and suggest that these cells may have constituted the surviving population responsible for reconstituting the bone marrow after a single 5-FU treatment.