EFFECTS OF DIFLUBENZURON AND CLANFENUR ON MOUSE BONE-MARROW CELLS

Diflubenzuron (DFB) and Clanfenur (CFN) belong to a group of compounds called Benzoylphenyl Ureas (BPUs). Several BPUs regulate cell growth in insects and/or inhibit growth of B-16 murine melanomas. In view of potential clinical use for these compounds, DFB and CFN were selected as examples of BPUs and tested for effects on hematopoiesis in C57Bl/6 mice housed in a conventional environment. DFB and CFN exhibit anti-t umor activity in mice, cause little or no morbidity and mortality and rather than causing bone marrow suppression, which is usual for anti-c ancer drugs, these agents stimulate hematopoiesis in vivo and in vitro . Stimulation in vivo was evidenced by increased (up to 112%) peripher al blood granulocytes 6 days after a single injection and enhanced gra nulopoiesis (similar to 25%) in bone marrow up to 18 days after treatm ent. That effects of DFB and CFN were on hematopoietic stem cells were indicated by 47% and 48%, respectively, increases in numbers of CFUs and 97% and 95%, respectively, increases in CFUgm. Further, bone marro w cells treated in vitro contained about twice the number of CFUs and CFUgm as control bone marrow cells. Almost all of the increase in numb er of spleen colonies, whether derived from donors treated in vivo or bone marrow cells treated in vitro, was accounted for by a correspondi ng increase in number of undifferentiated colonies. These data indicat e that DFB and CFN treatment enhance numbers of pluripotential stem ce lls both in vivo and in vitro. The mechanism of enhancement, direct or indirect, remains to be determined.