In vivo protection of normal mouse hematopoiesis by a beta 2 blocking agent during S-phase chemotherapy

Butoxamine, a beta 2-adrenergic blocking agent, which temporarily blocks the G1-S transition of human bone marrow granulocyte precursors in vitro, was used in vivo together with 1-beta-D-arabinofuranosylcytosine (ara-C) in mice. Butoxamine alone depressed the granulocyte labeling index and granulocyte-monocyte colony-forming Cell (GM-CFC) suicide rate at a dose of 3 micrograms/g body weight. A maximum effect was produced 6 to 12 hr after injection. Butoxamine administered 8 hr before an injection of ara-C modified the proportion of GM-CFC in S phase as compared with the number found after ara-C alone. After a series of five ara-C injections, administered at intervals of 16 hr, 70% of the treated mice died within 2 weeks, whereas only 42% of mice pretreated with butoxamine 7 to 9 hr before each ara-C injection died. This difference was due to the more rapid return to normal of GM-CFC numbers and an increase in the proportion of GM-CFC and granulocyte precursors in S phase in the butoxamine-pretreated animals. These findings suggest that butoxamine may have a potential use in protecting hematopoiesis during intensive chemotherapy for cancer.