Residual adriamycin (AdR)-induced hematopoietic damage: a consideration for subsequent radiotherapy.

The long-term effect of adriamycin (AdR) on the radiation response of hematopoietic marrow was studied at 16 weeks after treatment with a MTD (10 mg/kg) for the BDF1 mouse. The radiation response was monitored in both the "stem cell" (CFUs-8) and myeloid (CFU-gm, granulocyte, WBC) compartments, as well as the erythroid (BFUe, CFUe, HcT) compartments of the marrow for 14 days following a whole body dose (TBI) of 4.5 Gy X ray. At the time of irradiation, animal and spleen weight of AdR treated animals were reduced while HcT and WBC remained at control levels. At the same time the granulocyte and CFUs-8d compartments were depressed, while the BFUe compartment was expanded. The CFUe and CFU-gm compartments remained at control levels. For all marrow compartments, treatment with AdR 16 weeks prior to 4.5 Gy resulted in a radiation response deficit determined from the temporal recovery curves. The data suggest that manifestation of long-term AdR injury, at least through 16 weeks following treatment, is dependent on a subsequent stress of sufficient magnitude to enhance the proliferative activity associated with hematopoietic cell production and differentiation. A comparison is made between these observations and previously reported long-term drug-induced hematopoietic injury.

Enhancement of colony-stimulating activity (CSA) on murine CFU-gm by the H-4-II-E2 (H4) tumor cell line of the rat.

The effect of the H-4-II-E2 (H4) rat tumor cell line on murine granulocyte/macrophage colony-forming units (CFU-gm) was studied in vitro using a bilayer (agar/methylcellulose) culture system over the tumor cell feeder and 10% colony-stimulating activity (CSA). The H4 cells demonstrated an amplification of CSA from several sources and of CFU-gm growth of murine marrow, including the CSA present in L-cell-conditioned medium (L-CSA; 200% of control). The amplification did not result from CSA produced by the H4 cell line, nor was cell-to-cell contact necessary for enhanced CFU-gm growth. Amplification of L-CSA was not mediated by endogenous or exogenous prostaglandin E concentrations in the in vitro system. Furthermore, incubation of the non-adherent marrow cell population with H4 tumor cells for 24 h prior to assaying for CFU-gm resulted in more colonies, independent of the continued presence of H4 tumor cells. The data suggest that the H4 tumor cells produce a readily diffusable, soluble factor that may amplify the effect of L-CSA on CFU-gm by stimulating a more primitive progenitor cell that expands the CFU-gm population.