Assessment of Drug Sensitivity of Human Leukaemic Myeloblasts. II: The Toxic Effect

Summary.-The compound 125IUdR can be incorporated in a stable form into the DNA of cells. The isotope is released if labelled cells or their progeny die. Conse-quently the rate of 1251 excretion from mice can be used to follow the fate of labelled cells in vivo. Using these principles we show: (1) Sufficient label can be incorporated in vitro into both fresh and cryopreserved human leukaemic myeloblasts, in non-toxic concentrations, to allow their survival in mice to be estimated by whole-body counting; (2) The release of isotope from labelled cells is sufficiently slow to offer reasonable expectation that this technique can be used for assessing the sensitivity of myelo-blasts to cytotoxic agents in vivo (an application described in the second paper in this series, Sonis, Falcao and MacLennon, 1977); (3) The rate of 1251 excretion from mice injected with myeloblasts from different donors varies. This probably reflects different rates of spontaneous death of injected myeloblasts; (4) Active rejection of myeloblasts starts within 48 h of their injection into mice;(5) Indirect evidence that phagocytic cells may be active agents in myeloblas