Time-dependent changes induced by azidothymidine in erythroid progenitor colonies in immunodeficient mice

Abstract

The effect of azidothymidine (AZT) on erythropoiesis in C57BL/6 mice made immunodeficient by infection with LP-BM5 murine leukemia virus (MuLV) was examined. Earlier work from our laboratory indicated that long-term treatment of LP-BM5 MuLV-infected mice with AZT induced peripheral anemia but increased the number of splenic and bone marrow erythroid burst-forming units (BFUe). In contrast, other workers have demonstrated that short-term intensive AZT treatment decreases bone marrow BFUe of normal mice. The purpose of the present study was to determine the effects of short-term oral AZT treatment in immune deficient animals. LP-BM5 MuLV-infected and normal mice were given 0, 1, and 2.5 mg/ml of AZT in their drinking water. Mice were killed after 2, 4, 8, 15, and 30 days of AZT treatment. The hematocrits of all AZT-treated mice decreased in a dose- and time-dependent fashion. AZT treatment decreased the absolute numbers of circulating reticulocytes in both normal and infected mice after 4 days of treatment. In contrast, the percentage of bone marrow early erythroblasts was increased in both normal and infected animals after 4 days of treatment. AZT at both doses decreased the number of BFUe per femur in both infected and normal mice after 2, 4, and 8 days. However, after 15 days the number of bone marrow BFUe increased. In spleen, the numbers of BFUe were increased only with high-dose AZT in both normal and infected mice at all time points, although the increases were more dramatic in infected mice. Our results indicate that the effect of AZT on bone marrow BFUe is time dependent, with inhibition being observed only at early time points. These results further demonstrate the complex effects of AZT on erythropoiesis in vivo.