Sensitivity of human granulopoiesis in vitro to adriamycin before and after exposure in vivo.

The present studies were performed to determine whether the sensitivity of a normal human granulopoiesis to Adriamycin changes after repeated exposure to the drug in vivo. A single-layer agar culture for the in vitro growth of granulocytic colonies from committed stem cells was used as the assay system. The in vitro sensitivity of the human granulopoiesis to different doses of Adriamycin was determined from the reduction in colony incidence (a) following exposure of marrow cells to Adriamycin for 30 min before initiation of cultures and (b) in the presence of Adriamycin during the total culture period. Using both test systems, the sensitivity of granulopoiesis in vitro remained unchanged after patients had received six courses of chemotherapy incorporating Adriamycin. Sensitivity to Adriamycin appeared to increase by Day 4 after chemotherapy, probably as a result of the increased proliferative activity of granulopoietic precursor cells at this time. The data thus fail to provide evidence that a granulopoietic subpopulation with increased resistance to the cytotoxic effects of Adriamycin emerges after repeated in vivo exposure to the drug.