Abstract
Concanavalin A (Con A) injected intraperitoneally at a dose of 50 mg per kg was not lethal for male BALB/c mice. Six hours after administration of 5 mg Con A/kg, the proportion of circulating granulocytes had increased from 23% to 74% of the white cell population; by 24 hr, the proportion of granulocytes had decreased to 56%. Administration of 5 mg Con A/kg 24 hr before 200 mg of 5-[3,3-bis(2chloroethyl)-triazeno]-imidazole-4-carboxamide per kg, or 100 mg of 5-fluorouracil per kg resulted in a significant enhancement of lethality. Simultaneous administration of 5 mg Con A/kg and 10 mg of daunomycin per kg also resulted in enhanced lethality. Administration of 5 mg Con A/kg 24 hr before 40 mg of 1,3-bis(2-chloroethyl)-1-nitrosourea per kg, 200 mg of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea per kg, 1000 mg of cytosine arabinoside per kg, 0.1 mg of mithramycin per kg, 2 mg of pactamycin per kg or 1 mg of vincristine per kg did not result in enhanced lethality. Lipid A prepared from Escherichia coli 0127:B8 Boivin lipopolysaccharide has been complexed to Con A. The lipid A-Con A complex (5mg/kg) was no more, or less effective in enhancing the lethality of 5-fluorouracil than 2.5 mg Con A/kg. The lipid A-Con A complex (40 mg/kg), given simultaneously with drug, enhanced lethality for mice given 0.1 mg mithramycin per kg or 1 mg vincristine per kg. In this regard, the lipid A-Con A complex had activity comparable to the complex formed between lipid A and bovine serum albumin. Conceivably, Con A can be used to enhance the susceptibility of neoplastic cells to phase-specific antitumor drugs, especially those acting on deoxyribonucleic acid synthesis.
This investigation was supported in part by Public Health Service grant CA-13715 from the National Cancer Institute.
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Reference
Anderson, J., Sjöberg, O., and Möller, G. (1972a). “Introduction of immunoglobulin and antibody synthesis in vitro by lipopolysaccharides.” Eur. J. ImmunoZ. 2, 349.
Anderson, J., Edelman, G. M., Möller, G., and Sjöberg, O. (1972b). “Activation of B lymphocytes by locally concentrated concanavalin A.” Eur. J. Immunol. 2, 233.
Eagan, H. S., Reeder, W. J., and Ekstedt, R. D. (1974). “Effect of concanavalin A in vivo in suppressing the antibody response in mice.” J. ImmunoZ. 112, 63.
Eaves, A. C., and Bruce, W. R. (1972). “Endotoxin-induced sensitivity of hematopoietic stem cells to chemotherapeutic agents.” Ser. Haemat. 5, 64.
Galanos, C., Luderitz, O., and Westphal, O. (1969). “A new method for the extraction of R lipopolysaccharides.” Eur. J. Biochem. 9, 245.
Galanos, C., Rietschel, E. Th., Luderitz, O., Westphal, O., Kim, Y. B., and Watson, D. W. (1972). “Biological activities of lipid A complexed with bovine serum albumin.” Eur. J. Biochem. 31, 230.
Gilman, A. G. (1970). “A protein binding assay for adenosine 3’,5’-cyclic monophosphate.” Proc. Nat. Acad. Sci. U.S.A. 67, 305.
Inbar, M., Ben-Bassat, H., and Sachs, L. (1972). “Inhibition of ascites tumor development by concanavalin A.” Internat. J. Cancer 9, 143.
Johnson, R. A. (1972). Assay of cyclic AMP. In “Methods in Cyclic Nucleotide Research” ( M. Chasin, ed.) Marcel Dekker, Inc. New York, p. 1.
MacGregor, R. R., Sheagren, J. N., and Wolff, S. M. (1969). “Endotoxin-induced modification of Plasmodium berghei infection in mice.” J. Immunol. 102, 131.
Marecki, N. M., and Bradley, S. G. (1973). “Enhanced toxicity for mice of combinations of bacterial endotoxin with antitumor drugs.” Antimicrob. Ag. Chemother. 3, 599.
Mayo, J. G., Laster, W. R., Jr., Andrews, C. M., and Schabel, F. M., Jr. (1972). “Success and failure in the treatment of solid tumors. III. ‘Cure’ of metastatic Lewis lung carcinoma with methyl-CCNU (NSC-95441) and surgery - chemotherapy.” Cancer Chemother. Rept. (1) 56, 183.
Peavy, D. L., Shands, J. W., Jr., Adler, W. H., and Smith, R. T. (1973). “Mitogenicity of bacterial endotoxins: characterization of the mitogenic principle.” J. Immunol. 111, 352.
Reinhold, R., and Fine, J. (1972). “A technique for quantitative measurement of endotoxin in human plasma.” Proc. Soc. Exp. BioZ. Med. 137, 334.
Rose, W. C. (1973). “Interaction of bacterial toxins in the toxicity of chemotherapeutic agents.” CRC Critical Rev. Toxicol. 3, 159.
Rose W. C., and Bradley, S. G. (1971). “Enhanced toxicity for mice of combinations of antibiotics with Escherichia coZi cells or Salmonella typhosa endotoxin.” Infect. Immun. 4, 550.
Stobo, J. D., Rosenthal, A. S., and Paul, W. E. (1972). “Functional heterogeneity of murine lymphoid cells. I. Responsiveness to and surface binding of concanavalin A and phytohemagglutinin.” J. Immunol. 108, 1.
Waravdekar, V. S., and Saslaw, L. D. (1959). “A sensitive colorimetric method for the estimation of 2-deoxy sugars with the use of the malonaldehyde-thiobarbituric acid reaction.” J. BioZ. Chem. 234, 1945.
Zubrod, C. G. (1974). “Present status of cancer chemotherapy.” Life Sciences 14, 809.
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© 1975 Plenum Press, New York
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Bradley, S.G., Marecki, N.M., Bond, J.S., Munson, A.E., John, D.T. (1975). Enhanced Cytotoxicity in Mice of Combinations of Concanavalin A and Selected Antitumor Drugs. In: Chowdhury, T.K., Weiss, A.K. (eds) Concanavalin A. Advances in Experimental Medicine and Biology, vol 55. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-0949-9_16
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