Summary
Concanavalin A, endotoxin, poly I : C, and tumour necrosis serum (TNS) were compared for antitumour activity against Meth A sarcoma transplanted in syngeneic BALB/c mice and their capacity to induce tumour necrosis factor (TNF), heat-stable cytostatic factors, and heat-labile interferon in the blood of normal and Corynebacterium parvum-pretreated mice. All the agents induced hyperemia and inhibition of mitosis at 4 h, and by 24 h many tumours had a dark necrotic centre. Subsequent tumour growth was inhibited and in some of the treated mice tumours regressed completely. Poly A : U and normal mouse serum did not induce regression and their effects were less marked in all other respects, suggesting that these events may be linked. The necrotizing effects of concanavalin A and poly I : C are unlikely to be mediated by TNF, because neither agent could mimic endotoxin in eliciting RNase-resistant necrotizing and regressing activity in the serum of mice pretreated with C. parvum. Poly I : C did not induce strong cytostatic activity in the sera of C. parvum-treated mice, and for this and other reasons these factors are unlikely to be responsible for the observed effects. Concanavalin A, endotoxin, and poly I : C induced high levels of serum interferon but purified interferon had only weak antitumour activity in the Meth A system, suggesting that interferon may not be the mediator.
From these and other data it is concluded that there is no clear relationship between the capacity of the agents to induce tumour necrosis and their capacity to elicit TNF, cytostatic factors, and interferon.
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References
Alexander P, Evans R (1971) Endotoxin and double-stranded RNA render macrophages cytotoxic. Nature New Biol 232:76
Algire GE, Legallais FY (1951) Vascular reactions of normal and malignant tissues in vivo IV. The effect of peripheral hypotension on transplanted tumors. J Natl Cancer Inst 12:399
Bloksma N (1982) Anti-tumour activities of endotoxin in the mouse. A focus on the role of tumour necrosis factor. PhD thesis, State University of Utrecht, The Netherlands
Bloksma N, Hofhuis FMA, Schetters TP, Willers JMN (1980a) In vitro anti-tumour activity of tumour necrosis serum, role of natural antibodies and complement. INSERM 97:223
Bloksma N, Schetters TP, Figdor C, Van Dijk H, Willers JM (1980b) In vitro anti-tumour activity of tumour necrosis serum. Int J Immunopharm 2:95
Bloksma N, Hofhuis F, Benaissa-Trouw B, Willers J (1982a) Endotoxin-induced release of tumour necrosis factor and interferon in vivo is inhibited by prior adrenoceptor blockade. Cancer Immunol Immunother 14:41
Bloksma N, Hofhuis FM, Willers JMN (1982b) Effect of adrenoceptor blockade on hemorrhagic necrosis of Meth A sarcomata induced by endotoxin or tumor necrosis serum. Immunopharmacology 4:163
Carswell EA, Old LJ, Kassel RL, Green S, Fiore N, Williamson B (1975) An endotoxin-induced serum factor that causes necrosis of tumors. Proc Natl Acad Sci USA 72:3666
Gratia A, Linz R (1931) Le phénomène de Shwartzman dans le sarcome du Cobaye. CR Séance Soc Biol Ses Fil 108:427
Green S, Dobrjansky A, Chiasson MA, Carswell E, Schwartz MK, Old LJ (1977) Corynebacterium parvum as the priming agent in the production of tumor necrosis factor in the mouse. J Natl Cancer Inst 59:1519
Kull FC, Cuatrecases P (1981) Preliminary characterization of the tumor cell cytotoxin in tumor necrosis serum. J Immunol 126:1279
Kuper CF, Bloksma N, Hofhuis FM, Bruyntjes JP, Willers JM (1982) Influence of adrenoceptor blockade on endotoxin-induced histophathological changes in murine Meth A sarcoma. Int J Immunopharmacol 4:49
Oettgen HF, Carswell EA, Kassel RL, Fiore N, Williamson B, Hoffmann MK, Haranaka K, Old LJ (1980) Endotoxin-induced tumor necrosis factor. Recent Res Cancer Res 75:207
Riley FL, Morin ML, Lvovsky E, Stephens EE, Levy HB (1982) Polyriboinosinic-polyribocytidylic acid-poly-L-lysine complex (poly ICL) without carboxymethylcellulose (CMC): A new primate-effective interferon inducer. Proc Soc Exp Biol Med 169:183
Schultz RM, Papamatheakis JD, Chirigos MA (1977) Interferon: An inducer of macrophage activation by polyanions. Science 197:674
Shapiro CJ (1940) The effect of a toxic carbohydrate complex from S. enteritidis on transplantable rat tumors in tissue culture. Am J Hyg [B] 31:114
Siegel S (1959) The case of two independent samples. In: Harlow HF (ed) Nonparametric statistics for the behavioural sciences. McGraw-Hill/Kogakusha, Tokyo, p 95
Taylor CR, Chir B (1978) Immunoperoxidase techniques, practical and theoretical aspects. Arch Pathol Lab Med 102:113
Toh K, Yamamoto N, Suzuki T, Kikuchi K (1979) Effect of concanavalin A and lipopolysaccharide on the cytotoxicity of macrophages and neutrophils. J Reticuloendothel Soc 26:273
Van Dijk H, Rademaker PM, Willers JMN (1980a) Determination of alternative pathway of complement activity in mouse serum using rabbit erythrocytes. J Immunol Meth 36:29
Van Dijk H, Rademaker PM, Willers JMN (1980b) Estimation of classical pathway of mouse complement activity by use of sensitized rabbit erythrocytes. J Immunol Meth 39:257
Wagner RR (1961) Biological studies of interferon I. Suppression of cellular infection with Eastern equine encephalomyelitis virus. Virology 13:323
Youngner JS, Stinebring W (1965) Interferon appearance stimulated by endotoxin, bacteria or viruses in mice pre-treated with Escherichia coli endotoxin, or infected with Mycobacterium tuberculosis. Nature 208:456
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Bloksma, N., Kuper, C.F., Hofhuis, F.M.A. et al. Antitumour activity of endotoxin, concanavalin A and poly I: C and their ability to elicit tumour necrosis factor, cytostatic factors, and interferon in vivo. Cancer Immunol Immunother 16, 35–39 (1983). https://doi.org/10.1007/BF00199903
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DOI: https://doi.org/10.1007/BF00199903