Toxic effects of cyclophosphamide in differentiating chicken limb bud cell culture using rat liver 9,000 g supernatant or rat liver cells as an activation system: an in vitro short-term test for proteratogens.
Cells from 4-day chicken embryo limb buds plated as micromass cultures differentiate and form cartilage nodules after a 5- to 6-day growth period. The innate ability of these cells to biotransform compounds, such as cyclophosphamide (CP), into reactive metabolites is apparently inadequate. Protocols used rat liver S9 from Aroclor 1254-pretreated (PCB) rats or hepatocytes from control rats or polychlorinated biphenyls (PCB)-pretreated rats and were added to micromass cultures with CP causing concentration-related toxicity in the cell cultures. Coculturing chicken limb bud cells with PCB-hepatocytes was the most efficient method, yielding an IC50 of 2 micrograms CP per ml. Toxic CP metabolites accumulated in the medium of PCB-hepatocyte cultures and were quite stable. The toxicity of bioactivated CP was nearly identical for both proliferation and cartilage proteoglycan accumulation.
Wiger
R
R
Department of Toxicology, National Institute of Public Health, Oslo, Norway.
Trygg
B
B
Holme
J A
JA
D000818:Animals; D001711:Biotransformation; D002478:Cells, Cultured / Q000187:drug effects; D002642:Chick Embryo; D003520:Cyclophosphamide / Q000493:pharmacokinetics / Q000633:toxicity*; D005121:Extremities / Q000196:embryology*; D008099:Liver / Q000378:metabolism*; D008110:Liver Extracts; D008855:Microscopy, Electron, Scanning; D051381:Rats; D011919:Rats, Inbred Strains; D013723:Teratogens
D008110:Liver Extracts; D013723:Teratogens; D003520:Cyclophosphamide