Comparative effects of methotrexate, two nonclassic folic acid antagonists, and cytarabine on hematopoietic precursor cells.
The effects of three antifolates, methotrexate (MTX), triazinate (TZT), and a trimethoxyquinazoline derivative (TMQ), and of cytarabine (ara-C) on leukocyte-committed colony-forming cells from three species were compared using an assay allowing in vivo metabolism in an agar diffusion chamber. Dose-survival curves approximated plateaus, and the level of the plateau was variable among species. Canine marrow colony-forming cells were less sensitive to MTX (about 90% survival) than those from mice or man (25%-40% survival). Human marrow colony-forming cells were less sensitive (70% survival) to TZT than those from mice or dogs (25% survival). No interspecies differences were found for TMQ or ara-C. Mouse marrow in situ was less sensitive to iv MTX than mouse marrow in the chamber. No such difference was found for iv TMQ or ara-C. This comparison could not be made for ip TZT.
D000818:Animals; D002470:Cell Survival; D003114:Colony-Forming Units Assay; D003561:Cytarabine / Q000494:pharmacology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005493:Folic Acid Antagonists / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D008727:Methotrexate / Q000494:pharmacology*; D051379:Mice; D011799:Quinazolines / Q000494:pharmacology*; D013045:Species Specificity; D014227:Triazines / Q000494:pharmacology; D016597:Trimetrexate
D005493:Folic Acid Antagonists; D011799:Quinazolines; D014227:Triazines; D003561:Cytarabine; C012071:triazinate; D016597:Trimetrexate; D008727:Methotrexate