EFFECTS OF DELTAMETHRIN ON THE GROWTH AND DIFFERENTIATION OF BONE-MARROW HEMATOPOIETIC STEM-CELLS

1. The effects of deltamethrin on mouse bone marrow and spleen progeni tor cell responsiveness to granulocyte and macrophage colony-stimulati ng factors (CSFs) were evaluated. 2. Deltamethrin (1-5 mg/kg) was admi nistered four times subcutaneously on alternate days for one week to m ale BALB/c mice, 5-8 weeks old (N = 6 mice/group), raised under pathog en-free conditions and maintained in conventional animal rooms for fou r weeks before use. Soft agar colony formation (CFU-C), marrow and spl een cell counts as well as body, spleen and thymus weights were determ ined. 3. Although treatment with the lowest dose (1 mg kg-1 48 h-1) pr oduced no significant effect on CFU-C, the administration of 3 and 5 m g kg-1 48 h-1 caused a more than two-fold increase in the formation of granulocyte and macrophage colonies in the marrow, but not in the spl een (control value = 100.5 +/- 12 for N = 6). Colony numbers returned to normal values within five days after the end of deltamethrin admini stration. 4. No changes were observed in the total (range: 1-3 x 10(8) per spleen) and differential marrow and spleen cell counts, nor was t here any alteration in spleen weight. However, treatment with the thre e doses resulted in a dramatic reduction in thymus weight. 5. These ef fects were not due to the liberation of endotoxin, because if endotoxi n had been present it would have been <0.060 ng/ml, a concentration th at would not have a biological effect. 6. In vitro addition of 0.10 to 10 muM deltamethrin to marrow cell cultures obtained from untreated m ice did not induce any response. 7. These data indicate that the CSF-d riven granulocyte and macrophage development provides a useful model f or the study of the effects of toxicants on myelopoiesis.