Effect of beta adrenergic agonists and beta blocking agents on hemopoiesis in human bone marrow

The effect of propranolol (non specific blocking agent), acebutolol (beta 1 blocking agent), butoxamine (beta 2 blocking agent) and several beta adrenergic agonists was studied on 3H-thymidine (3H-TdR) incorporation and granulo-monocyte colony formation in agar by human bone marrow. Only butoxamine and propranolol decreased 3H-TdR incorporation by total normal bone marrow cells at concentrations above 10(-6) M for butoxamine and 10(-5) M for propranolol. Autoradiography showed that inhibition of 3H-TdR incorporation by butoxamine was slightly more pronounced on neutrophil precursors than on red cell precursors (neutrophil series LI..53 and erythroblasts .67 compared to control bone marrow cells at 10(-5) M concentration). The development of granulo-monocyte colonies in agar culture was delayed by preincubation with butoxamine at concentrations above 5 X 10(-6) M. Hydroxyurea suicide showed that this was due to a decrease in the number of CFU-C in S phase. beta 2 blocking agents are able to decrease the number of normal hematopoietic cells entering S phase. This effect is seen on both neutrophil and erythroblastic precursors and on granulo-monocyte progenitors. It could be used as a means of protecting bone marrow cells during cancer intensive chemotherapy.