Effects of various therapeutic agents on leukocytes in vivo and in vitro: competition between the cytotoxic drugs and colony stimulating factors (CSF) in the action on the proliferation of myeloid stem cells (CFU-C).
The effect of a single or repeated intraperitoneal injection(s) of various therapeutic agents on peripheral leukocyte count in mice was studied. The results revealed a great deal of initial variation of leukocyte number in the animals and also variants in the capability of the animals to restore the decreased leukocyte level. On the other hand, a simple reproducible and highly sensitive method for the evaluation of the toxic effect of the chemicals on leukopoiesis has been provided by culturing mouse bone marrow cells in a semi-solid agar medium in the presence of purified colony stimulating factor (CSF). There was three groups of chemicals in regard to the effect on the proliferation of the myeloid cells (CFU-C) in culture: (1) Anti-cancer drugs such as mitomycin C and 5-fluorouracil were inhibitory to CFU-C at 10(-8) - 10(-7)M. (2) Many drugs such as erythromycin, cephalosporin etc. showed apparent toxicity in 10(-5) - 10(-4)M. (3) Drugs like penicillin, streptomycin, cysteine etc. showed no significant toxicity at concentrations higher than 10(-4)M. It was noted that the inhibition of CFU-C proliferation either by mitomycin C (an inhibitor of DNA synthesis) or by erythromycin(an inhibitor of protein synthesis) occurred in a manner competitive to the added CSF activity. The results suggest that CSF is capable of specifically protecting the myeloid stem cells from the toxic action of the chemicals.
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001854:Bone Marrow Cells; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D004917:Erythromycin / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D066298:In Vitro Techniques; D007962:Leukocytes / Q000187:drug effects*; D008297:Male; D051379:Mice; D008937:Mitomycins / Q000494:pharmacology
D000970:Antineoplastic Agents; D003115:Colony-Stimulating Factors; D008937:Mitomycins; D004917:Erythromycin