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 bone-marrow progenitor cells has been shown to be a sensitive indicator of bone-marrow injury in laboratory rodents. The ability of a bone-marrow progenitor cell assay to detect myelotoxicity in a wild rodent model (cotton rat, Sigmodon hispidus) that inhabits many contaminated ecosystems in the southern United States was examined. Responsiveness of progenitor cells to recombinant murine granulocyte-macrophage colony-stimulating factor (GM-CSF) and cotton rat lung-conditioned medium (LCM) was determined to optimize culture conditions for cotton rats. Myelotoxicity was induced in cotton rats by treating animals with either cyclophosphamide (8 or 80 mg/kg) or dexamethasone (500 microg/kg) over a 5-d period. Administration of a high dose of cyclophosphamide caused nearly total suppression of colony formation of granulocyte-macrophage progenitor cells (CFU-GM). Marked histological changes in both the bone marrow and spleen were also observed in cotton rats treated with a high dose of cyclophosphamide. Although histological lesions were not apparent, the number of CFU-GM in the bone marrow of low-dose cyclophosphamide- and dexamethasone-treated cotton rats was significantly suppressed compared to controls. The number of CFU-GM was consistently higher using LCM than recombinant murine GM-CSF. This reproducible, quantitative, in vitro bone-marrow progenitor cell culture system was a sensitive indicator of myelotoxicity in wild cotton rats and should be useful for monitoring chronic exposures to low levels of environmental toxicants in wild rodent populations.
Kim
S
S
Department of Veterinary Pathobiology, College of Veterinary Medicine, Oklahoma State University, Stillwater, USA.
Stair
E L
EL
Lochmiller
R L
RL
Lish
J W
JW
Qualls
C W
CW
D000704:Analysis of Variance; D000818:Animals; D001855:Bone Marrow Diseases / Q000139:chemically induced* / Q000473:pathology*; D018929:Cell Culture Techniques / Q000379:methods; D002478:Cells, Cultured / Q000187:drug effects; D003114:Colony-Forming Units Assay / Q000379:methods* / Q000592:standards; D003520:Cyclophosphamide; D003907:Dexamethasone; D004195:Disease Models, Animal; D004781:Environmental Exposure / Q000032:analysis*; D004784:Environmental Monitoring / Q000379:methods* / Q000592:standards; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D008297:Male; D023461:Myeloid Progenitor Cells / Q000187:drug effects*; D051381:Rats; D011994:Recombinant Proteins; D012680:Sensitivity and Specificity; D016205:Sigmodontinae
D011994:Recombinant Proteins; D003907:Dexamethasone; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003520:Cyclophosphamide