Activity of 4'-epi-doxorubicin on normal hematopoietic precursor cells in mice

The effects of 4'epi-doxorubicin (4'-epi-DX) on survival of in situ murine bone marrow hematopoietic precursor cells (HPC) were studied. The drug was given to (C57BL X C3H)F1 mice in increasing single doses, in repeated administration (three time in 5 days), or for a long period (twice a week for 10 weeks). Survival of colony-forming units (CFUs, spleen; CFUc, culture; and CFUe, erythroid) was assayed by in vivo and in vitro methods; dose survival curves were exponential. It appears that single doses of 4'epi-DX have a greater impact on murine HPC than single doses of the parent compound. Following repeated administrations, pluripotential stem cells recover better after the derivative than after its parent drug. During prolonged treatment, the bone marrow content of committed progenitors is depleted to a lesser extent in the animals treated with 4;-epi-DX than in those receiving DX. It is, however, possible that, following the same prolonged treatment, this difference is minimal. The conclusion, these experimental data seem to indicate that 4'-epi-DX has lower toxicity in murine HPC than DX and that this is evident mainly after repeated administrations for a short period of time.