Abstract
We investigated the in vitro effects of ASTA-Z-7595, ASTA-Z-7557, ASTA-Z-7654, and 4-hydroperoxycyclophosphamide (4HC) on murine stromal fibroblastoid colony-forming units, committed hemopoietic progenitors (erythroid burst-forming units and granulocyte/macrophage colony-forming units), and pluripotent hemopoietic stem cells assayed by the spleen colony-forming unit (CFU-s) assay. In general, the drugs showed a time-and dose-dependent effect on colony-forming unit survival, and the relative toxicities were in the order in which the drugs are listed above. We found a relative sparing of day 12 CFU-s compared with day 7 CFU-s and committed hemopoietic and stromal progenitors, although colony size of day 12 CFU-s was reduced. Our results support two possible mechanisms for delayed or inadequate hemopoietic reconstitution in clinical studies using bone marrow purged with 4-hydroperoxycyclophosphamide or ASTA-Z-7557, i.e., damage to (a) transplantable stromal cells or (b) the hemopoietic stem cells.
| Original language | English |
|---|---|
| Pages (from-to) | 4001-5 |
| Number of pages | 5 |
| Journal | Cancer Research |
| Volume | 45 |
| Issue number | 9 |
| Publication status | Published - Sept 1985 |
Keywords
- Animals
- Bone Marrow
- Bone Marrow Transplantation
- Cell Survival
- Cyclophosphamide
- Dose-Response Relationship, Drug
- Hematopoietic Stem Cells
- In Vitro Techniques
- Male
- Mice
- Mice, Inbred Strains
- Spleen