Comparative effects of chlorozotocin and BCNU on hematopoietic precursor cells

Comparative studies to determine the suppressive effects of chlorozotocin (2-[3-(2-chloroethyl)-3-nitrosoureido]-D-glucopyranose) and BCNU (1,3-bis[2-chloroethyl]-1-nitrosourea) on mouse and human hematopoietic precursor cells: granulocyte-macrophage precursor cells (CFU-gm), late erythroid precursor cells (CFU-e), and early erythroid precursor cells (BFU-e) were performed after in vitro incubation of 1 h with drug concentrations based on clinical administration levels. The suppressive effect of chlorozotocin on CFU-gm, BFU-e, and CFU-e hematopoietic precursor cells in the mouse was less than that of BCNU with the most significant difference seen in CFU-e colony formation. For human hematopoietic progenitor cells, however, the suppressive effect of chlorozotocin was far less than that of BCNU. When the effects of 40 micrograms/ml of chlorozotocin and 20 micrograms/ml of BCNU on human marrow were compared, there were statistically significant differences found for CFU-gm colony formation, and BFU-e and CFU-e colony numbers were significantly different for the two drugs at all comparable concentrations tested. Our results confirm the clinical data, and establish that the effects of chlorozotocin on human hematopoietic precursor cells are minimal.