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January 1971, Vol 24, No. 1 >
Article | January 1971

Ultrastructural Changes in Skeletal Muscle Induced by Colchicine

Omkar N. Markand, MD, FRCPC; Anthony N. D'Agostino, MD
[+] Author Affiliations

Accepted for publication Aug 4,1970.

Reprint requests to Department of Neurology, University of Texas (Southwestern) Medical School, 5323 Harry Hines Blvd, Dallas 75235 (Dr. Markand).


Arch Neurol. 1971;24(1):72-82. doi:10.1001/archneur.1971.00480310100010
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COLCHICINE arrests mitotic division of many plant and animal cells by interfering with the formation of the mitotic spindle.1-7 Cellular division is arrested at metaphase, bizarre and abnormal nuclear configurations occur, and the cell often dies. Colchicine also has a profound effect on nonmitotic differentiating cells. It induces the formation of cytoplasmic filaments in the interphase HeLa cells in vitro8 and neurofibrillary tangles in tissue cultures of rat neurons.9 Neurofibrillary change has recently been noted in the brainstem and spinal cord of rabbits after intracisternal injection of colchicine.10 The variable effects of colchicine apparently depend on its binding to the subunit protein of microtubules.11

Although colchicine consistently causes severe ascending paralysis in experimental animals, a thorough morphological study of skeletal muscle has not been undertaken. Ferguson12 reported delayed paralysis of the hindlimbs in acute toxicity experiments in rats and prominent muscle atrophy in

REFERENCES

1 +
Amoroso EC:  Colchicine and tumour growth . Nature 135:266-267, 1935;.
2 +
Brown WO, Seed L:  Effect of colchicine on human tissues . Amer J Clin Path 15:189-195, 1945;.
3 +
Gaulden ME, Carlson JG:  Cytological effects of colchicine on the grasshopper neuroblast in vitro with reference to origin of the spindle . Exp Cell Res 2:416-433, 1951;.
4 +
Inoue S:  The effect of colchicine on the microscopic and submicroscopic structure of the mitotic spindle . Exp Cell Res 2( (suppl) ):305-314,1952;.
5 +
Eigsti OJ, Dustin P Jr: Colchicine: In Agriculture, Medicine, Biology and Chemistry . Ames, Iowa, Iowa State College Press, 1955;.
6 +
Dustin P Jr:  New aspects of pharmacology of antimitotic agents . Pharmacol Rev 15:449-480, 1963;.
7 +
Taylor EW:  The mechanism of colchicine inhibition of mitosis: I. Kinetics of inhibition and binding of 3H-colchicine . J Cell Biol 25( (suppl) ):145-160, 1965;.
8 +
Robbins E, Gonatas NK:  Histochemical and ultrastructural studies on HELA cell cultures exposed to spindle inhibitors with special reference to the interphase cell . J Histochem Cytochem 12:704-711, 1964;.
9 +
Peterson E, Murray M:  Serial observations in tissue cultures on neurotoxic effects of colchicine . Anat Rec 154:401, 1966;.
10 +
Wisniewski H, Terry RD:  Experimental colchicine encephalopathy: I. Induction of neurofibrillary degeneration . Lab Invest 17:577-587, 1967;.
11 +
Borisy SG, Taylor EW:  The mechanism of action of colchicine, colchicine binding to sea urchin eggs and the mitotic apparatus . J Cell Biol 34:535-548, 1967;.
12 +
Ferguson FC Jr:  Colchicine: I. General pharmacology . J Pharmacol Exp Ther 106:261-270, 1952;.
13 +
Godman GC, Murray MR:  Influence of colchicine on the form of skeletal muscle in tissue cultures . Proc Soc Exp Biol Med 84:668-672, 1953;.
14 +
Godman GC:  The effect of colchicine on the striated muscle in tissue culture . Exp Cell Res 8:488-499, 1955;.
15 +
Bischoff R, Holtzer H:  The effect of mitotic inhibitors on myogenesis in vitro . J Cell Biol 36:111-127, 1968;.
16 +
Kontos HA:  Myopathy associated with chronic colchicine toxicity . New Eng J Med 266:38-39, 1962;.
17 +
Anderson PJ, Song SK, Slotwiner P:  The fine structure of spheromembranous degeneration of skeletal muscle induced by vincristine. J . Neuropath Exp Neurol 26:15-24, 1967;.
18 +
Bowden DH, Goyer RA:  Drug-induced muscle necrosis with massive taurinuria . Arch Path 74:137-141, 1962;.
19 +
Price HM, Pease DC, Pearson CM:  Selective actin filament and Z-band degeneration induced by plasmocid . Lab Invest 11:549-562, 1962;.
20 +
D'Agostino AN:  An electron microscopic study of skeletal and cardiac muscle of the rat poisoned by plasmocid . Lab Invest 12:1060-1071, 1963;.
21 +
Sternberg SS, Philips FS, Cronin AA, et al:  Toxicological studies of calvacin . Cancer Res 23:1036-1044, 1963;.
22 +
Anderson PJ, Song SK:  Skeletal muscle necrosis secondary to calvacin . J Neuropath Exp Neurol 25:149, 1966;.
23 +
Jasmin G, Gareau R:  Histopathological study of muscle lesions produced by paraphenylenediamine in rats . Brit J Exp Path 42:592-596, 1961;.
24 +
D'Agostino AN, Chiga M:  Morphological changes in cardiac and skeletal muscles induced by corticosteroids . Ann NY Acad Sci 138:73-81, 1966;.
25 +
Spiro AJ, Shy GM, Gonatas NK:  Myotubular myopathy . Arch Neurol 14:1-14, 1966;.
26 +
Wechsler W:  Comparative electron microscopic studies on various forms of muscle atrophies and dystrophies in animals and man . Ann NY Acad Sci 138:113-137, 1966;.
27 +
Milhorat AT, Shafiq SA, Goldstone L:  Changes in muscle structure in dystrophic patients, carriers and normal siblings seen by electron microscopy: Correlation with levels of CPK . Ann NY Acad Sci 138:246-292, 1966;.
28 +
Shy GM, Gonatas NK, Perez M:  Two childhood myopathies with abnormal mitochondria . Brain 89:133-158, 1966;.
29 +
Pearce GW:  Electron microscopy in the study of muscular dystrophy , in Bourne GH, Golarz MN (eds): Muscular Dystrophy in Man and Animals . New York, Hafner Publishing Co, 1964;.
30 +
D'Agostino AN, Ziter FA, Rallison ML, et al:  Familial myopathy with abnormal muscle mitochondria . Arch Neurol 18:388-401, 1968;.
31 +
Markand ON, North RR, D'Agostino AN, et al:  Benign sex-linked muscular dystrophy: Clinical and pathological features . Neurology 19:617-633, 1969;.
32 +
Terry RD, Wisniewski H, Johnson AB:  Studies on the formation of autophagic vacuoles in neurons treated with spindle inhibitors (colchicine and vinblastine) . J Neuropath Exp Neurol 29:142-143, 1970;.
33 +
Chou SM:  Myxovirus-like structures in a case of human chronic polymyositis . Science 158:1453-1455, 1967;.
34 +
Shelanski ML, Taylor EW:  Isolation of a protein subunit from microtubules . J Cell Biol 34:549-554, 1967;.
35 +
Forsheit AB, Hayashi T:  The effect of colchicine on contractile proteins . Biochim Biophys Acta 147:546-551, 1967;.
36 +
Remmer H, Merker HJ:  Effects of drugs on the formation of smooth endoplasmic reticulum and drug-metabolizing enzymes . Ann NY Acad Sci 123:79-97, 1965;.
37 +
Steiner JW, Miyai K, Philips M:  Electron microscopy of membrane-particle arrays in liver cells of ethionine-intoxicated rats . Amer J Path 44:169-214,1964;.
38 +
Stenger RJ:  Concentric lamellar formations in hepatic parenchymal cells of carbon tetrachloridetreated rats . J Ultrastruct Res 14:240-253, 1966;.
39 +
Huxley HE:  Evidence for the continuity between the central elements of the triads and extra cellular space in frog sartorius muscle . Nature 202:1067-1071, 1964;.
40 +
Sandow A:  Excitation-contraction coupling in skeletal muscles . Pharmacol Rev 17:265-320, 1965;.

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1 +
Amoroso EC:  Colchicine and tumour growth . Nature 135:266-267, 1935;.
2 +
Brown WO, Seed L:  Effect of colchicine on human tissues . Amer J Clin Path 15:189-195, 1945;.
3 +
Gaulden ME, Carlson JG:  Cytological effects of colchicine on the grasshopper neuroblast in vitro with reference to origin of the spindle . Exp Cell Res 2:416-433, 1951;.
4 +
Inoue S:  The effect of colchicine on the microscopic and submicroscopic structure of the mitotic spindle . Exp Cell Res 2( (suppl) ):305-314,1952;.
5 +
Eigsti OJ, Dustin P Jr: Colchicine: In Agriculture, Medicine, Biology and Chemistry . Ames, Iowa, Iowa State College Press, 1955;.
6 +
Dustin P Jr:  New aspects of pharmacology of antimitotic agents . Pharmacol Rev 15:449-480, 1963;.
7 +
Taylor EW:  The mechanism of colchicine inhibition of mitosis: I. Kinetics of inhibition and binding of 3H-colchicine . J Cell Biol 25( (suppl) ):145-160, 1965;.
8 +
Robbins E, Gonatas NK:  Histochemical and ultrastructural studies on HELA cell cultures exposed to spindle inhibitors with special reference to the interphase cell . J Histochem Cytochem 12:704-711, 1964;.
9 +
Peterson E, Murray M:  Serial observations in tissue cultures on neurotoxic effects of colchicine . Anat Rec 154:401, 1966;.
10 +
Wisniewski H, Terry RD:  Experimental colchicine encephalopathy: I. Induction of neurofibrillary degeneration . Lab Invest 17:577-587, 1967;.
11 +
Borisy SG, Taylor EW:  The mechanism of action of colchicine, colchicine binding to sea urchin eggs and the mitotic apparatus . J Cell Biol 34:535-548, 1967;.
12 +
Ferguson FC Jr:  Colchicine: I. General pharmacology . J Pharmacol Exp Ther 106:261-270, 1952;.
13 +
Godman GC, Murray MR:  Influence of colchicine on the form of skeletal muscle in tissue cultures . Proc Soc Exp Biol Med 84:668-672, 1953;.
14 +
Godman GC:  The effect of colchicine on the striated muscle in tissue culture . Exp Cell Res 8:488-499, 1955;.
15 +
Bischoff R, Holtzer H:  The effect of mitotic inhibitors on myogenesis in vitro . J Cell Biol 36:111-127, 1968;.
16 +
Kontos HA:  Myopathy associated with chronic colchicine toxicity . New Eng J Med 266:38-39, 1962;.
17 +
Anderson PJ, Song SK, Slotwiner P:  The fine structure of spheromembranous degeneration of skeletal muscle induced by vincristine. J . Neuropath Exp Neurol 26:15-24, 1967;.
18 +
Bowden DH, Goyer RA:  Drug-induced muscle necrosis with massive taurinuria . Arch Path 74:137-141, 1962;.
19 +
Price HM, Pease DC, Pearson CM:  Selective actin filament and Z-band degeneration induced by plasmocid . Lab Invest 11:549-562, 1962;.
20 +
D'Agostino AN:  An electron microscopic study of skeletal and cardiac muscle of the rat poisoned by plasmocid . Lab Invest 12:1060-1071, 1963;.
21 +
Sternberg SS, Philips FS, Cronin AA, et al:  Toxicological studies of calvacin . Cancer Res 23:1036-1044, 1963;.
22 +
Anderson PJ, Song SK:  Skeletal muscle necrosis secondary to calvacin . J Neuropath Exp Neurol 25:149, 1966;.
23 +
Jasmin G, Gareau R:  Histopathological study of muscle lesions produced by paraphenylenediamine in rats . Brit J Exp Path 42:592-596, 1961;.
24 +
D'Agostino AN, Chiga M:  Morphological changes in cardiac and skeletal muscles induced by corticosteroids . Ann NY Acad Sci 138:73-81, 1966;.
25 +
Spiro AJ, Shy GM, Gonatas NK:  Myotubular myopathy . Arch Neurol 14:1-14, 1966;.
26 +
Wechsler W:  Comparative electron microscopic studies on various forms of muscle atrophies and dystrophies in animals and man . Ann NY Acad Sci 138:113-137, 1966;.
27 +
Milhorat AT, Shafiq SA, Goldstone L:  Changes in muscle structure in dystrophic patients, carriers and normal siblings seen by electron microscopy: Correlation with levels of CPK . Ann NY Acad Sci 138:246-292, 1966;.
28 +
Shy GM, Gonatas NK, Perez M:  Two childhood myopathies with abnormal mitochondria . Brain 89:133-158, 1966;.
29 +
Pearce GW:  Electron microscopy in the study of muscular dystrophy , in Bourne GH, Golarz MN (eds): Muscular Dystrophy in Man and Animals . New York, Hafner Publishing Co, 1964;.
30 +
D'Agostino AN, Ziter FA, Rallison ML, et al:  Familial myopathy with abnormal muscle mitochondria . Arch Neurol 18:388-401, 1968;.
31 +
Markand ON, North RR, D'Agostino AN, et al:  Benign sex-linked muscular dystrophy: Clinical and pathological features . Neurology 19:617-633, 1969;.
32 +
Terry RD, Wisniewski H, Johnson AB:  Studies on the formation of autophagic vacuoles in neurons treated with spindle inhibitors (colchicine and vinblastine) . J Neuropath Exp Neurol 29:142-143, 1970;.
33 +
Chou SM:  Myxovirus-like structures in a case of human chronic polymyositis . Science 158:1453-1455, 1967;.
34 +
Shelanski ML, Taylor EW:  Isolation of a protein subunit from microtubules . J Cell Biol 34:549-554, 1967;.
35 +
Forsheit AB, Hayashi T:  The effect of colchicine on contractile proteins . Biochim Biophys Acta 147:546-551, 1967;.
36 +
Remmer H, Merker HJ:  Effects of drugs on the formation of smooth endoplasmic reticulum and drug-metabolizing enzymes . Ann NY Acad Sci 123:79-97, 1965;.
37 +
Steiner JW, Miyai K, Philips M:  Electron microscopy of membrane-particle arrays in liver cells of ethionine-intoxicated rats . Amer J Path 44:169-214,1964;.
38 +
Stenger RJ:  Concentric lamellar formations in hepatic parenchymal cells of carbon tetrachloridetreated rats . J Ultrastruct Res 14:240-253, 1966;.
39 +
Huxley HE:  Evidence for the continuity between the central elements of the triads and extra cellular space in frog sartorius muscle . Nature 202:1067-1071, 1964;.
40 +
Sandow A:  Excitation-contraction coupling in skeletal muscles . Pharmacol Rev 17:265-320, 1965;.

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