Summary
The host cellular response to IP injection of mitomycin C was studied in C3H/HeN mice. As assessed by in vitro cytolysis assay using 125I-iododeoxyuridine-labelled tumour target cells, mitomycin C-induced peritoneal macrophages showed the maximum tumouricidal activity 4 days after the IP injection. The tumouricidal activity was dependent on the dose of mitomycin C injected and it was detectable against syngeneic, allogeneic and xenogeneic tumour target cells. In addition, these tumouricidal macrophages were found to be augmented in functions of both incorporation of 2-deoxy-D-glucose and phagocytosis of sheep red blood cells. Among the other anti-cancer drugs, which were used at a dose of three-fifths of LD50, only adriamycin (7.5 mg/kg) was capable of inducing activated macrophages as much as mitomycin C (3 mg/kg). Cyclophosphamide (225 mg/kg), methotrexate (60 mg/kg) and vincristin (1.5 mg/kg) were able to augment incorporation of 2-deoxy-D-glucose and phagocytosis of sheep red blood cells, but not tumouricidal actvity. Differential cytolysis assay was performed for two cell lines of P 388 tumour target cells, the mitomycin C-sensitive original cell line and the mitomycin C-resistant subline, demonstrating no significant difference in macro-phage-mediated tumour cell lysis between these cell lines. Based on these results, it was concluded that mitomycin C, when injected IP induced activated macrophages in the peritoneal cavity. A better understanding of the effect of anti-cancer drugs on macrophage tumouricidal activity may be useful in designing more effective local chemotherapy for malignant peritoneal effusions.
Similar content being viewed by others
References
Cohen SA, Salazar D, Eicher J (1983) Adriamycin-induced activation of NK activity may initially involve LAF production. Cancer Immunol Immunother 15:188
Giavazzi R, Bucana CD, Hart IR (1984) Correlation of tumour growth inhibitory activity of macrophages exposed to adriamycin and adriamycin sensitivity of the target tumour cells. J Natl Cancer Inst 73:447
Giordano M, Isturiz MA (1983) Enhancement of erythrophagocytosis by cyclophosphamide. Cell Immunol 81:187
Goto M, Mitsuoka A, Sugiyama M, Kitano M (1981) Enhancement of delayed hypersensitivity reaction with varieties of anticancer drugs. A common biological phenomenon. J Exp Med 154:204
Hancock EJ, Kilburn DG (1982) The effects of cyclophosphamide on in vitro cytotoxic responses to a syngeneic tumour. Cancer Immunol Immunother 14:54
Haskill JS (1981) Adriamycin-activated macrophages as tumour growth inhibitors. Cancer Res 41:3852
Kleinerman ES, Zwelling LA, Muchmore AV (1980) Enhancement of naturally occuring human spontaneous monocyte-mediated cytotoxicity by cis-diamine-dichloroplatinum (II). Cancer Res 40:3099
Kleinerman ES, Zwelling LA, Schwartz R, Muchmore AV (1982) Effect of L-phenylalanine mustard, adriamycin, actinomycin D and 4′-(9-acridinyl amino)-methanesulfon-manisidide on naturally occuring human spontaneous monocyte-mediated cytotoxicity. Cancer Res 42:1692
Martin F, Caignard A, Olsson O, Jeannin JF, Leclerc A (1982) Tumouricidal effect of macrophages exposed to adriamycin in vivo or in vitro. Cancer Res 42:3851
Mizushima Y, Sendo F, Miyake T, Kobayashi H (1981) Augmentation of specific cell-mediated immune responses to tumour cells in tumor-bearing rats pretreated with the antileukemia drug Busulfan. J Natl Cancer Inst 66:659
Ogura T, Namba M, Hirao F, Yamamura Y, Azuma I (1979) Association of macrophage activation with antitumour effect on rat syngeneic fibrosarcoma by Nocardia rubra cell wall skeleton. Cancer Res 39:4706
Ogura T, Shindo H, Namba M, Yamamura Y (1980) Tumouricidal activity of peritoneal exudate cells from rats treated with mitomycin-C. Gann 71:920
Ogura T, Shindo H, Shinzato O, Namba M, Masuno T, Inoue T, Kishimoto S, Yamamura Y (1982) In vitro tumour cell killing by peritoneal macrophages from mitomycin C-treated rats. Cancer Immunol Immunother 13:112
Salazar D, Cohen SA (1984) Multiple tumouricidal effector mechanisms induced by adriamycin. Cancer Res 44:2561
Santoni A, Richardi C, Sorci V, Herberman RB (1980) Effects of adriamycin on the activity of mouse natural killer cells. J Immunol 124:2329
Siddigi M, Iype PE (1975) Studies on the uptake of 2-deoxy-D-glucose in normal and malignant rat epithelial liver cells in culture. Int J Cancer 15:773
Stoychkov JN, Schultz RM, Chirigos MA, Pavlidis NA, Goldin A (1979) Effects of adriamycin and cyclophosphamide treatment on induction of macrophage cytotoxic function in mice. Cancer Res 39:3014
Vogel SN, Weedon LL, Oppenheim JJ, Rosenstreich DL (1981) Defective Fc-mediated phagocytosis in C3H/HeJ macrophages II Correction by c-AMP agonists. J Immunol 126:441
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Shindo, H., Ogura, T., Masuno, T. et al. Induction of activated macrophages by intraperitoneal injection of mitomylin C in mice. Cancer Immunol Immunother 20, 145–150 (1985). https://doi.org/10.1007/BF00205681
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00205681