LEUKOPENIA AND ALTERED HEMATOPOIETIC ACTIVITY IN MICE EXPOSED TO THE ABUSED INHALANT, ISOBUTYL NITRITE

Isobutyl nitrite is representative of a group of inhalants abused prim arily by male homosexuals; abuse of this drug may be a risk factor for AIDS or Kaposi's sarcoma. Using a 14-day exposure regimen, we previou sly reported that inhaled isobutly nitrite was immunotoxic to mice, se verely compromising T-dependent antibody responses and cytokine T cell and macrophage tumoricidal activity. In addition, exposure to the inh alant dramatically reduced spleen cellularity. A single 45-minute inha lation exposure produced anemia in mice. In the present study, we exam ined the effects of subchronic exposure to the drug on peripheral bloo d cellularity and hematopoietic activity. Mice were exposed to 900 ppm isobutyl nitrite in an inhalation chamber for 45 minutes/day for 14 d ays. One day after the final exposure, the number of peripheral blood leukocytes was reduced by 32%; however, the number of erythrocytes was increased by 7%. This was accompanied by an apparent shift from myelo poiesis to erythropoiesis. The numbers of bone marrow and spleen burst -forming units-erythroid (BFU-E) were increased about two-fold, while the numbers of colony-forming units-granulocyte/macrophage (CFU-GM) we re decreased by about half. Bone marrow stromal cells also had reducti ons in the production of myeloid colony-stimulating activity after sub chronic exposure to the inhalant. In addition, the numbers of hematopo ietic stem cells, colony-forming units-spleen. Peripheral blood erythr ocyte and leukocyte counts returned to normal levels by 7 days after t he final exposure, as did the number of BFU-E. The number of CFU-GM re mained depressed, however, even after 7 days of recovery. These data s uggest that repeated exposures nonspecifically depleted cells and that erythropoiesis was stimulated, apparently at the expense of myelopoie sis.