SENSITIVITY OF HUMAN AND MURINE HEMATOPOIETIC PRECURSOR CELLS TO 2-[3-(2-CHLOROETHYL)-3-NITROSOUREIDO]-D-GLUCOPYRANOSE AND 1,3-BIS(2-CHLOROETHYL)-1-NITROSOUREA

  • 1 January 1978
    • journal article
    • research article
    • Vol. 38  (2) , 257-260
Abstract
The sensitivity of mouse and human bone marrow hematopoietic precursor cells [colony-forming units committed to granulocyte-macrophage differentiation (CFU-C)] was determined after in vitro incubation with chlorozotocin (2-[3-(2-chloroethyl)-3-nitrosoureido]-D-glucopyranose), or 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), with the use of drug concentrations achieved during clinical administration. Chlorozotocin, at a concentration of 1 .times. 10-4 M, did not increase mouse CFU-C below the control of 44 colonies/105 nucleated cells; 5 .times. 10-4 M produced a 70% reduction in CFU-C, and 1 .times. 10-3 M chlorozotocin eliminated all colony formation. BCNU at 1 .times. 10-4 M resulted in a 55% reduction in CFU-C, and at 5 .times. 10-4 M it eliminated all colony formation. For human marrow the threshold concentration for chlorozotocin toxicity was 1 .times. 10-4 M, which resulted in a 25% reduction in CFU-C as compared to the control of 32 colonies/105 nucleated cells. BCNU at 5 .times. 10-5 M decreased human CFU-C to 47% of control, and at 1 .times. 10-4 M it eliminated all colony formation. Twenty-four hours after in vitro exposure to 1 .times. 10-4 M chlorozotocin, there was no reduction in human bone marrow DNA synthesis in contrast to a 42% reduction with 1 .times. 10-4 M BCNU. The plasma concentration of drugs following a therapeutic dose in patients with measured and corresponded to the concentration range used in the in vitro studies of marrow toxicity.