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-tumor activity in mice, cause little or no morbidity and mortality and rather than causing bone marrow suppression, which is usual for anti-cancer drugs, these agents stimulate hematopoiesis in vivo and in vitro. Stimulation in vivo was evidenced by increased (up to 112%) peripheral blood granulocytes 6 days after a single injection and enhanced granulopoiesis (approximately 25%) in bone marrow up to 18 days after treatment. 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 marrow cells treated in vitro contained about twice the number of CFUs and CFUgm as control bone marrow cells. Almost all of the increase in number of spleen colonies, whether derived from donors treated in vivo or bone marrow cells treated in vitro, was accounted for by a corresponding increase in number of undifferentiated colonies. These data indicate that DFB and CFN treatment enhance numbers of pluripotential stem cells both in vivo and in vitro. The mechanism of enhancement, direct or indirect, remains to be determined.