Different action of suicidal doses of tritiated thymidine and hydroxyurea on murine haemopoietic cells

ABSTRACT In order to gather information on the factors that cause the different action of suicidal doses of tritiated thymidine (3H‐TdR) and of hydroxyurea on murine stem cells, the incorporation of 3H‐TdR into DNA of bone marrow and spleen cells has been studied. Continuous death of labelled cells after suicidal 3H‐TdR is indicated by a more pronounced decline of total DNA‐bound radioactivity in bone marrow and spleen cells compared to that in control animals which had received tracer doses of 3H‐TdR. Extensive and rapid loss of DNA‐bound radioactivity occurred in 3H‐TdR labelled animals after hydroxyurea treatment indicating an instantaneous and highly effective killing of labelled cells. After double labelling of DNA with 3H‐TdR and 125iodo‐deoxyuridine (125I‐UdR), the decline of the ratio of DNA‐bound 125I to DNA‐bound 3H after suicidal 3H‐TdR indicates prolonged tritium reutilization. Following hydroxyurea, reutilization was completed within the first 12 hr after drug administration. These findings explain in part the slow recovery of different stem cell compartments after suicidal 3H‐TdR on the basis of protracted tritium reutilization as compared to the fast recovery which follows the rapid action of hydroxyurea.