Changes of the proliferation kinetics of human bone marrow in vivo through hydroxyurea

A 10-hour oral continuous infusion with hydroxyurea (HU) at a non-toxic concentration was performed in 20 malignoma patients with undisturbed bone marrow. Bone marrow taken before, during and after HU-administration was examined for 3H-TdR incorporation by means of autoradiography and liquid scintimetry, for cell phase distribution by means of flow cytophotometry, morphologically and by means of CFUc. 3H-TdR incorporation into bone marrow cells dropped to 16% of the initial value under HU and rose to 156% 10 h after HU-effect terminated. Cytophotometry did not furnish any proof of a decrease of S-phase cells or increase of cells in G1-to-S-transition during HU. S-cells rise to 129% of the initial value 10 h after having fallen below minimum inhibition concentration. Under HU, there is an equal number of cells in S which incorporate much less 3H-thymidine; after HU more S-cells incorporate more 3H-thymidine than before HU. During HU action, DNA synthesis activity is reduced to 17% and reaches the initial value with 105% afterwards. In human bone marrow, hydroxyurea in non-toxic concentration causes a temporary DNA synthesis inhibition in terms of activity reduction and partial arrest in S. A stop-and-go of the cell cycle effected by HU does not occur; the effect is rather a slow-down of DNA synthesis. (orig./MG)