MEASUREMENT OF KINETIC STATUS OF BONE-MARROW PRECURSOR CELLS - 3 CAUTIONARY TALES

While using 3H-thymidine (TdR), tritiated uridine (3H-Ur), 125I-iodo-deoxyuridine and HU (hydroxyurea) in attempts to evaluate the kinetic status of bone marrow stem cells, it became clear that their use was not straightforward, and some of the pitfalls associated with their use are presented. Used in vitro in mice, high specific activity 3H-TdR gave false results, killing more CFU (spleen colony forming unit) than were in DNA synthesis, both in normal and regenerating CFU populations. In vitro, 3H-Ur was considerably more toxic to CFU than 3H-TdR. Large doses (up to 10 times those used in vitro) of 3H-Ur in vivo were not capable of killing CFU; an indication that in vitro conditions modified RNA precursor pool kinetics to an extent which rendered CFU highly susceptible to 3H-Ur. TdR and probably iodo-deoxyuridine were irreversibly incorporated into ERC (erythropoietin responsive cells) to the extent that the majority of the cells were killed. HU killed fewer ERC.