Cyclophosphamide modifies the induction kinetics but not cell types and cytotoxic mechanisms of antitumor cells elicited with OK-432 plus attenuated tumor cells.
The present study was designed to examine whether the antitumor cells induced by treatment with mitomycin-C-treated EL4 cells (EL4MMC) plus OK-432 plus cyclophosphamide differed from those induced by treatment with EL4MMC plus OK-432 in terms of their cell types and antitumor mechanisms. Antitumor activity of peritoneal exudate cells (PEC) from mice receiving either treatment was nonspecific, and inhibition of their target cell growth increased for up to 24 h. Macrophage toxin, silica and trypan blue abrogated the activity in vitro and in vivo, respectively. The activity of the PEC was inhibited with inhibitors of the arachidonic acid cascade, such as dexamethasone, 4-bromophenacyl bromide and nordihydroguaiaretic acid but not esculetin, ibuprofen, indomethacin and BW755C. NG-monomethyl-L-arginine, a specific competitive inhibitor of the L-arginine-dependent nitric oxide synthesis, also inhibited the activity. These results and morphological observations indicated that antitumor cells in the PEC from mice receiving either treatment were macrophages, and that their activity was closely related to the arachidonic acid cascade and to nitric oxide. Antitumor activity of the PEC spontaneously decayed in vitro and this decay was inhibited by the addition of OK-432 or lipopolysaccharide. On the other hand, cyclophosphamide sustained the appearance of antitumor cells in mice treated with EL4MMC plus OK-432. Therefore, cyclophosphamide treatment did not modify cell types and cytotoxic mechanisms of antitumor cells elicited with EL4MMC plus OK-432, but did modify the induction kinetics of such antitumor macrophages.
Ryoyama
K
K
Department of Experimental Therapeutics, Kanazawa University, Japan.
Ryoyama
C
C
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D003520:Cyclophosphamide / Q000494:pharmacology*; D005122:Exudates and Transudates / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D007700:Kinetics; D007939:Leukemia L1210 / Q000276:immunology / Q000473:pathology; D008070:Lipopolysaccharides; D008264:Macrophages / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016685:Mitomycin / Q000494:pharmacology; D009374:Neoplasms, Experimental / Q000276:immunology* / Q000473:pathology; D010529:Peritoneal Cavity / Q000166:cytology; D010844:Picibanil / Q000494:pharmacology*; D013154:Spleen / Q000187:drug effects / Q000502:physiology; D014118:Toxins, Biological / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects
D008070:Lipopolysaccharides; D014118:Toxins, Biological; D016718:Arachidonic Acid; D010844:Picibanil; D016685:Mitomycin; D003520:Cyclophosphamide