Abstract
The effects of mitomycin C (MMC) on the generation of cell-mediated cytotoxicity in primary stimulation culture of human peripheral blood mononuclear cells (PBM) with the B lymphoblastoid Raji cell line were assessed. The cell-mediated cytotoxicity induced in culture was significantly augmented when MMC was added to cultures on day −1 to day 3 for 24 h at concentrations of 2.5×10−2 μg/ml and 2.5×10−3 μg/ml. To identify the cell populations affected by MMC, PBM were separated by adherence to plastic after treatment with MMC for 24 h (day −1). The two populations were recombined with untreated separated cells and stimulated with antigen. The ability to develop an augmented cell-mediated cytotoxicity was associated with the adherent cell fraction of MMC-treated PBM. Therefore, the ability of MMC-treated adherent cells to produce interleukin 1 (IL 1) was examined. Significantly higher levels of IL 1 were produced by treated cells as compared to untreated adherent cells. The results appear to indicate that the selective effects of MMC on the adherent cell fraction, especially the modification of IL 1 production, may be involved in the mechanisms of MMC-induced augmented cell-mediated cytotoxicity.
Keywords: Cancer Research, Cell Population, Mononuclear Cell, Peripheral Blood Mononuclear Cell, Adherent Cell
References
- 1.Arinaga S, Akiyoshi T, Tsuji H. Augmentation of the cell-mediated cytotoxic response induced in mixed cell culture by adriamycin. Jpn J Cancer Res. 1985;76:414. [PubMed] [Google Scholar]
- 2.Arinaga S, Akiyoshi T, Tsuji H. Augmentation of the generation of cell-mediated cytotoxicity after a single dose of adriamycin in cancer patients. Cancer Res. 1986;46:4213. [PubMed] [Google Scholar]
- 3.Cohen SA, Salazar D, Wicher J. Adriamycin-induced activation of NK activity may initially involve LAF production. Cancer Immunol Immunother. 1983;15:188. doi: 10.1007/BF00199163. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Ehrke MJ, Tomazic V, Ryoyama K, Cohen SA, Mihich E. Adriamycin induced immunomodulation: Dependence upon time of administration. Int J Immunopharmacol. 1983;5:43. doi: 10.1016/0192-0561(83)90070-x. [DOI] [PubMed] [Google Scholar]
- 5.Ehrke MJ, Maccubbin D, Ryoyama K, Cohen SA, Mihich E. Correlation between adriamycin-induced augmentation of interleukin 2 production and of cell-mediated cytotoxicity in mice. Cancer Res. 1986;46:54. [PubMed] [Google Scholar]
- 6.Ogura T, Shindo H, Shinzato O, Namba M, Masuno T, Inoue T, Kishimoto S, Yamamura Y. In vitro tumour cell killing by peritoneal macrophages from mitomycin C-treated rats. Cancer Immunol Immunother. 1982;13:112. doi: 10.1007/BF00205310. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Orsini F, Pavelic Z, Mihich E. Increased primary cell-mediated immunity in culture subsequent to adriamycin or daunorubicin treatment of spleen donor mice. Cancer Res. 1977;37:1719. [PubMed] [Google Scholar]
- 8.Potter MR, Moore M. In vitro augmentation of human natural cytotoxicity. Clin Exp Immunol. 1981;44:332. [PMC free article] [PubMed] [Google Scholar]
- 9.Shindo H, Ogura T, Masuno T, Hayashi S, Kishimoto S. Induction of activated macrophages by intraperitoneal injection of mitomycin C in mice. Cancer Immunol Immunother. 1985;20:145. doi: 10.1007/BF00205681. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Tomazic V, Ehrke MJ, Mihich E. Modulation of the cytotoxic response against allogeneic tumor cells in culture by adriamycin. Cancer Res. 1980;40:2748. [PubMed] [Google Scholar]
- 11.Tomazic V, Ehrke MJ, Mihich E. Augmentation of the development of immune response of mice against allogeneic tumor cells after adriamycin treatment. Cancer Res. 1981;41:3370. [PubMed] [Google Scholar]