Summary
Disturbances in the functional properties of tumor mitochondria have been studied during the course of induction of haemorrhage brought about by endotoxin in the murine Crocker sarcoma (S 180). Extensive impairment of function was already present in mitochondria isolated from control tumors, as shown by low respiratory control ratios. The existing mitochondrial damage intensified promptly in response to injection of endotoxin long before the onset of haemorrhage at 4 h. The nature of the additional damage took two forms, depending on the duration of exposure to endotoxin; first, at 30 min, a true uncoupling of oxidative phosphorylation was seen, largely reversible in vitro by pre-treatment of the isolated organelles with bovine serum albumin (BSA). Second, at 1 h and later, oxygen utilisation in the presence of succinate, ADP and inorganic phosphate (P i) was depressed. The pre-addition of BSA consistently lowered respiration rates with succinate andP i in all preparations. The extent of endogenous inhibition of the adenine nucleotide translocase appeared unaltered by endotoxin in vivo.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Aisenberg, A.C.: The glycolysis and respiration of tumors, pp. 102–107. New York, London: Academic Press 1961
Bjørnstad, P.: Phospholipase activity in rat liver mitochondria studied by the use of endogenous substrates. J. Lipid Res.7, 612–620 (1966)
Borst, P., Loos, J.A., Christ, E.J., Slater, E.C.: Uncoupling activity of long-chain fatty acids. Biochim. Biophys. Acta62, 509–518 (1962)
Dey, P.K., Feldberg, W., Wendlandt, S.: Lipid A and prostaglandin. J. Physiol. (Lond.)239, 102P (1974)
Egdahl, R.H.: The differential response of the adrenal cortex and medulla to bacterial endotoxin. J. Clin. Invest.38, 1120–1125 (1959)
Engel, H.: Chemotherapeutische Versuche mit Adrenalin und ähnlich constituierten Stoffen bei tumor-kranken Thieren. Z. Exp. Pathol.11, 9–39 (1912)
Fogg, L.C.: Effect of certain bacterial products upon the growth of mouse tumour. Public Hlth. Reps., U.S. Public Hlth. Service, Washington51, 56–64 (1936)
Habermann, E.: Hemmung der oxydativen Phosphorylierung durch tierische Gifte. Naturwissenschaften18, 429–430 (1954)
Heiffer, M.H., Mundy, R.L., Grimm, L.J.E.: Effect of bacterial lipopolysaccharides on plasma catecholamine levels. Fed. Proc.17, 68 (1958)
Hirsch, R.L., McKay, D.G., Travers, R.I., Skraly, R.K.: Hyperlipidaemia, fatty liver, and bromsulphophthalein in rabbits injected intravenously with bacterial endotoxins. J. Lipid Res.5, 563–568 (1964)
Hutner, S.H., Zahl, P.A.: Action of bacterial toxins on tumors. IV. Distribution of tumor-haemorrhage agents among bacterial species. Proc. Soc. Exp. Biol. Med. N. Y.52, 364–368 (1943)
Jones, G.R.N.: Cancer: Restriction of chemical energy by fatty acids as the common pathway whereby various anti-tumor procedures selectively damage malignant cells in situ. Med. Hypoth.2, 50–54 (1976)
Jones, G.R.N.: The basic biochemical lesion in shock. Biochem. Soc. Trans.5, 213–214 (1977)
Jones, G.R.N., Krämer, R.: Translocase inhibition in endotoxic shock: a late step in the sequence of lethal events. Biochem. Pharmacol.27, 2931–2937 (1978)
Jones, G.R.N., Winter, H., Merkel, R.: Alterations in the adenine nucleotide pattern as a sensitive means of assessing injury in a solid tumor. Hoppe-Seyler Z. Physiol. Chem.359, 1102–1103 (1978)
Kirtland, S.J., Baum, H.: Prostaglandin E1 may act as a “calcium ionophore”. Nature N. Biol.236, 47–49 (1972)
Malmström, K., Carafoli, E.: Effects of prostaglandins on the interaction of Ca2+ with mitochondria. Arch. Biochem. Biophys.171, 418–423 (1975)
Pande, S.V., Blanchaer, M.C.: Reversible inhibition of mitochondrial adenosine diphosphate phosphorylation by long chain acyl coenzyme A esters. J. Biol. Chem.246, 402–411 (1971)
Petrushka, E., Quastel, J.H., Scholefield, P.G.: Role of structure in mitochondrial metabolism. Canad. Cancer Conf.2, 106–115 (1957)
Petrushka, E., Quastel, J.H., Scholefield, P.G.: Role of phospholipids in mitochondrial respiration. Canad. J. Biochem. Physiol.37, 975–987 (1959)
Pfaff, E.: Unspezifische Permeabilität und spezifischer Austausch der Adeninnucleotide als Beispiel mitochondrialer Compartmentierung. Inaugural Dissertation der Philipps-Universität, Marburg (Lahn), pp. 37–43 (1965)
Pradhan, S.N., Achinstein, B., Shear, M.J.: Independence of drug-induced damage in sarcoma 37 and carotid blood pressure in mice. Arch. Exp. Path. Pharmak.230, 228–235 (1957)
Pressman, B.C., Lardy, H.A.: Effect of surface active agents on the latent ATPase of mitochondria. Biochim. Biophys. Acta21, 458–466 (1956)
Rasmussen, H.: Cell communication, calcium ion, and cyclic adenosine monophosphate. Science170, 404–412 (1970)
Reicher, K.: Experimentelle Beiträge zur Therapie maligner Tumoren. Deutsch. Med. Wochenschr.36, 1356–1359 (1910)
Rossi, C.R., Rossi, C.S., Sartorelli, L., Siliprandi, D., Siliprandi, N.: Protective action of phosphorylcholine on mitochondrial oxidative phosphorylation. Arch. Biochem. Biophys.99, 214–221 (1962)
Seligman, A.M., Shear, M.J., Leiter, J., Sweet, B.: Chemical alteration of polysaccharide from Serratia marcescens. I. Tumor-necrotizing polysaccharide tagged with radioactive iodine. J. Natl. Cancer Inst.9, 13–18 (1948)
Shapiro, C.J.: The effect of a toxic carbohydrate complex from S. enteritides on transplantable rat tumors in tissue culture. Am. J. Hyg.31 (B), 114–126 (1940)
Shear, M.J., Andervont, H.B.: Chemical treatment of tumors. III. Separation of haemorrhage-producing fraction of B. coli. filtrate. Proc. Soc. Exp. Biol. Med. N.Y.34, 323–325 (1936)
Shear, M.J., Perrault, A.: Chemical treatment of tumors. IX. Reactions of mice with primary subcutaneous tumors to injection of a haemorrhage-producing bacterial polysaccharide. J. Natl. Cancer Inst.4, 461–476 (1944)
Sutherland, E.W., Rall, T.W.: Fractionation and characterization of a cyclic adenine ribonucleotide formed by tissue particles. J. Biol. Chem.232, 1077–1091 (1958)
Szarkowska, L., Klingenberg, M.: On the role of ubiquinone in mitochondria. Spectrophotometric and chemical measurements of its redox reactions. Biochem. Z.338, 674–697 (1963)
Thorne, R.F.W., Bygrave, F.L.: Interaction of calcium with mitochondria isolated from Ehrlich ascites tumor cells. Biochem. Biophys. Res. Comm.50, 294–299 (1973)
Thorne, R.F.W., Bygrave, F.L.: The role of mitochondria in modifying the cellular ionic environment. Calcium-induced respiratory activities in mitochondria isolated from various tumor cells. Biochem. J.144, 551–558 (1974)
Weinbach, E.C., Garbus, J.: The rapid restoration of respiratory control to uncoupled mitochondria. J. Biol. Chem.241, 3708–3713 (1966)
Witter, R.F., Cottone, M.A.: The effect of lysolecithin and related compounds on the swelling of isolated mitochondria. Biochim. Biophys. Acta22, 372–377 (1956)
Witter, R.F., Morrison, A., Shephardson, G.R.: Effect of lysolecithin on oxidative phosphorylation. Biochim. Biophys. Acta26, 120–129 (1957)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Jones, G.R.N. Early mitochondrial damage in the induction of haemorrhagic necrosis in the Crocker sarcoma (S 180) by endotoxin. J Cancer Res Clin Oncol 93, 245–254 (1979). https://doi.org/10.1007/BF00964580
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00964580