Summary
This research was undertaken in order to determine if known biochemical processes involving the conversion of fluoroacetate are reflected morphologically at the electron microscopic level. No changes were observed in the hepatocytes after 2.5 mg/kg of fluoroacetate and sacrifice at 3 hours, but with 5 mg/kg of the drug there was an increase in the amount of agranular endoplasmic reticulum, an aberrant shape of mitochondria, and a disappearance of visible glycogen. One hour after 10, 15, 20, or 30 mg/kg of fluoroacetate the results showed a tremendous increase in the amount of agranular endoplasmic reticulum, an aberration in mitochondrial structure, and a disappearance of the intramitochondrial granules and glycogen. The possible relationship of these changes to fluoroacetate poisoning is discussed.
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References
Bruni, C., Porter, K. R.: The fine structure of the parenchymal cell of the normal rat liver. I. General observations. Amer. J. Path. 46, 691–756 (1965).
Buffa, P., Peters, R. A.: Formation of citrate “in vivo” induced by fluoroacetate poisoning. Nature (Lond.) 163, 914 (1949).
—: The “in vivo” formation of citrate induced by fluoroacetate and its significance. J. Physiol. (Lond.) 110, 488–500 (1950).
Busch, H., Potter, V.: Multiple effects of fluoroacetate on pyruvate metabolism “in vitro”. Proc. Soc. exp. Biol. (N.Y.) 80, 701–704 (1952).
Dubois, K., Cochran, K., Doull, J.: Inhibition of citric acid synthesis “in vivo” by x-irradiation. Proc. Soc. exp. Biol. (N.Y.) 76, 422–427 (1951).
Ernster, L.: Control of cell metabolism at the mitochondrial level. Fed. Proc. 24, 1222–1235 (1965).
Fawcett, D. W.: Observations on the cytology and electron microscopy of hepatic cells. J. nat. Cancer Inst. 15, 1475–1504 (1955).
Gal, E., Drewes, P., Taylor, N.: Metabolism of fluoroacetic acid-2-C14 in the intact rat. Arch. Biochem. 93, 1–14 (1961).
—, Peters, R. A., Wakelin, R. W.: Some effects of synthetic fluorocompounds on the metabolism of acetate and citrate. Biochem. J. 64, 161–168 (1956).
—, Smith, R. E.: Conditions affecting inhibition of tricarboxylic acid cycle by fluoroacetate in rat liver mitochondria. Proc. Soc. exp. Biol. (N.Y.) 103, 401–404 (1960).
Greenwalt, J., Rossi, C., Lehninger, A.: Effect of active accumulation of calcium and phosphorus ions on the structure of rat liver mitochondria. J. Cell Biol. 23, 21–38 (1964).
Hruban, Z., Swift, H., Slesers, A.: Effect of triparanol and diethanolamine on the fine structure of hepatocytes and pancreatic acinar cells. Lab. Invest. 14, 1652–1672 (1965).
Ito, S.: Structural changes in the mitochondria and microvilli of the gastric parietal cell during digestive activity. 2nd Ann. Meet. Amer. Soc. Cell. Biol. 78 (1962).
Lahiri, S., Quastel, J. H.: Fluoroacetate and the metabolism of ammonia in brain. Biochem. J. 89, 157–163 (1963).
Liebecq, C., Peters, R. A.: The toxicity of fluoroacetate and the tricarboxylic acid cycle. Biochem. biophys. Acta (Amst.) 3, 215 (1949).
Morselli, R., Garattini, S., Marcucci, F., Mussini, E., Rewersky, W., Valzelli, L., Peters, R.: The effect of injections of fluoroacetate into the brains of rats. Biochem. Pharmacol. 17, 195–202 (1968).
Ord, M., Stocken, L. A.: Sex differences in effect of radiation and fluoroacetate poisoning on liver metabolism. Proc. Soc. exp. Biol. (N.Y.) 83, 695–697 (1953).
Orrenuis, S., Ericsson, J.: Enzyme-membrane relationship in phénobarbital induction of synthesis of drug-metabolizing enzyme system on proliferation of endoplasmic membranes. J. Cell Biol. 28, 181–199 (1966).
Palay, S., McGee-Russell, S. M., Gordon, S., Grillo, M.: Fixation of neural tissues for electron microscopy by perfusion with solutions of osmium tetroxide. J. Cell Biol. 12, 385–410 (1962).
Peachey, L.: Electron microscopic observations on the accumulation of divalent cations in intramitochondrial granules. J. Cell Biol. 20, 95–109 (1964).
—, Greif, R.: Alterations of mitochondrial structure induced by thyroid hormones “in vivo” and “in vitro”. Endocrinology 77, 61–77 (1965).
Peters, R. A.: Biochemistry of some toxic agents. II. Some recent work in the field of fluoroacetate compounds. Bull. Johns Hopk. Hosp. 97, 21–42 (1955).
—: Mechanism of the toxicity of the active constituent of Dichapetalum cymosum and related compounds. Advanc. Enzymol. 18, 113–160 (1957).
—, Shorthouse, M.: Note on the behavior of rat brain tissue treated with fluoroacetate “in vitro”. Biochem. Pharmacol. 15, 2130–2131 (1966).
Porter, K., Bruni, C.: An electron microscopic study of the early effect of 3′-Me-DAB on rat liver cells. Cancer Res. 19, 997–1009 (1959).
Potter, V. R., Busch, H.: Citric acid content of normal and tumor tissues “in vivo” following injection of fluoroacetate. Cancer Res. 10, 353–356 (1950).
Remmer, H., Merker, J.: Drug induced changes in liver endoplasmic reticulum: Associated with drug-metabolizing enzymes. Science 142, 1657 (1963).
Reynolds, E.: Liver parenchymal cell injury. III. The nature of calcium associated electronopaque masses in rat liver mitochondria following poisoning with carbon tetrachloride. J. Cell. Biol. 53, 75 (1965).
Schjeide, O. A., McCandless, R., Wilkens, M., Peterson, M., Alexander, G.: Effects of various factors on occurrence of mitochondrial inclusions. Exp. Cell Res. 32, 379–390 (1963).
Weiss, J.: Mitochondrial changes induced by potassium and sodium in the duodenal absorption cell as studied with the electron microscope. J. exp. Med. 102, 783–788 (1955).
Yates, J., Yates, R.: Some morphological effects of strychnine on the spinal cord: A light and electron microscopic study. Anat. Rec. 150, 279–291 (1964).
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Research supported by USPHS Grants HE 12751, NS 05665, and 00690.
Recipient of Career Research Development Award 1K3 GM 28064.—The authors would like to express their appreciation to Drs. E. M. Gal and R. A. Peters for supplying the samples of fluoroacetate and to Mr. J. Mascorro for technical assistance.
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Yates, R.D., Yates, J.C. An ultrastructural study of the effects of fluoroacetate on hepatocytes. Z. Zellforsch. 117, 65–72 (1971). https://doi.org/10.1007/BF00331101
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DOI: https://doi.org/10.1007/BF00331101