Autologous Bone Marrow Transplantation - Blog Science Connections

Pharmacological Manipulation and Purging 183
Table 3. Effect of Tubercidin on Viability of HeLa Cells in G 1 and S Phase
-•• j w«»€> ••• unu w m a w
Colony-forming Ability
(% control ± SD) a
Condition G-i phase S phase
Without drug 100.0 ± 9.0 100.0 ± 11.1
Tubercidin (1 /uM) 55.7 ± 5.1 49.7 ± 4.8
Vincristine (0.05 uM) b 64.8 ± 7.7 21.5 ± 6.3
Nofe: HeLa/S3 cells were synchronized by mitotic detachment (19), plated in 60-mm
culture flasks, and subjected to 1-hr drug exposures during (4 hr after detachment)
and S (15 hr after detachment) phases. Colonies were scored after 14 days of
incubation at 37° C. The absolute plating efficiencies of untreated G, and S-phase
cultures (100 cells/plate) were 50.3 ± 4.5 and 50.3 ± 5.6, respectively.
" Percentage of control values plus or minus standard deviation (mean ± SD; n =
20).
b
Data, from Cass et al. (8), illustrate the effects of an agent whose activity is
specific to cell cycle.
1 I 1 1 1 1—*—I 1 1 1 1 1—*—I 1 r
pM TUBERCIDIN |T|
Figure 3. Effects of various concentrations of tubercidin alone (open circles) and with a
fixed concentration (3 uM) of an inhibitor of nucleoside transport fsolid circles; on the
survival of CFU-GM, BFU-E, and CFU-GEMM colonies (mean ± SE; n = 5) (A, NBMPR; B,
dipyridamole; C, dilazep).
stem cells. Pretreatment of bone marrow cells with dipyridamole (Fig 3B)
spared about 50% of CFU-GM and CFU-GEMM colonies from toxicity during
1 -hour exposures to 10-/jtM tubercidin, and pretreatment with dilazep (Fig 3C)
spared about 40% of CFU-GM and 70% of mixed colonies.
To be successful, pharmacological purging techniques should simultaneously
preserve hematopoietic stem cells and achieve a 5- to 6-log kill of
neoplastic cells. We have demonstrated that human hematopoietic stem cells
are sensitive to specific, tight-binding inhibitors of nucleoside transport and can
thus be protected against tubercidin and probably against other nucleosides