Evaluation of myelotoxicity in cotton rats (Sigmodon hispidus) exposed to environmental contaminants. I. In vitro bone-marrow progenitor culture

Bone marrow is extremely sensitive to toxicants, and in vitro culture of bo ne-marrow progenitor cells has been shown to be a sensitive indicator of bo ne-marrow injury in laboratory rodents. The ability of a bone-marrow progen itor cell assay to detect myelotoxicity in a wild rodent model ( cotton rat , Sigmodon hispidus) that inhabits many contaminated ecosystems in the sout hern United States was examined. Responsiveness of progenitor cells to reco mbinant murine granulocyte-macrophage colony-stimulating factor ( GM-CSF) a nd cotton rat lung-conditioned medium (LCM) was determined to optimize cult ure conditions for cotton rats. Myelotoxicity was induced in cotton rats by treating animals with either cyclophosphamide (8 or 80 mg/kg) or dexametha sone (500 mug/kg) over a 5-d period. Administration of a high dose of cyclo phosphamide caused nearly total suppression of colony formation of granuloc yte-macrophage progenitor cells ( CFU-GM). Marked histological changes in b oth the bone marrow and spleen were also observed in cotton rats treated wi th a high dose of cyclophosphamide. Although histological lesions were not apparent, the number of CFU-GM in the bone marrow of low-dose cyclophospham ide- and dexamethasone-treated cotton rats was significantly suppressed com pared to controls. The number of CFU-GM was consistently higher using LCM t han recombinant murine GM-CSF. This reproducible, quantitative, in vitro bo ne-marrow progenitor cell culture system was a sensitive indicator of myelo toxicity in wild cotton rats and should be useful for monitoring chronic ex posures to low levels of environmental toxicants in wild rodent populations .