The sensitivities of human and murine hemopoietic cells exposed to cytotoxic drugs in an in vivo culture system.
An agar diffusion chamber technique has been used to measure the sensitivities of human and murine hemopoietic colony-forming cells to cytotoxic drugs. The cells were held in i.p. diffusion chambers and exposed to the cytotoxic drugs by i.v. injection of the host mice. This method allows some account to be taken of the continuous changes in activity during the metabolic degradation of the drug. To determine how far this system provides a valid measure of the sensitivity of the cells in hemopoietic tissue, the responses of mouse bone marrow exposed to the drugs in situ in the donor mouse were compared with those of mouse cells exposed in diffusion chambers. The dose-response curves for cyclophosphamide and 5-fluorouracil were exponential in all cases. Exponential survival curves were also seen when human and mouse colony-forming cells were exposed to vinblastine or methotrexate in diffusion chambers. The plateaus seen when mouse cells were exposed to these drugs in situ could, however, be regained by omitting agar from the chambers during the exposure period. The results indicate that there are differences between the sensitivities of human and mouse marrow cells to cytotoxic drugs and that any extrapolation from mouse to humans must be viewed with caution.
D000362:Agar; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D002478:Cells, Cultured; D003520:Cyclophosphamide / Q000633:toxicity; D004058:Diffusion; D004305:Dose-Response Relationship, Drug; D005472:Fluorouracil / Q000633:toxicity; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000633:toxicity; D051379:Mice; D014747:Vinblastine / Q000633:toxicity
D000970:Antineoplastic Agents; D014747:Vinblastine; D003520:Cyclophosphamide; D000362:Agar; D005472:Fluorouracil; D008727:Methotrexate