Abstract
Administration of CCl4 to 12–14 h starved Sprague Dawley male rats (220–240 g) at a dose of 5 ml of a 20% (v/v) olive oil solution/kg i.p. decreased the incorporation of14C-leucine into microsomal and nuclear proteins at 1 or 2 h after the hepatotoxin. Decreased amino acid incorporation capacity in nuclear but not in microsomal proteins returned to control values at 4 h after poisoning. Cycloheximide given i.p. at a dose of 1 mg/kg in saline either alone or before CCl4 also decreased to a similar or greater extent the incorporation of14C-leucine into both, microsomal and nuclear proteins at 1 h. The CCl4-induced decrease in amino acid incorporation was observable and significant even 1 h after CCl4 and involved histone and different non-histone nuclear protein fractions. Results suggest that decreased protein synthesis at the endoplasmic reticulum occurring in the very early stages of CCl4 poisoning might provoke temporary deficiencies in protein supplies to nuclei with as yet unknown consequences. However, some of the proteins involved have major regulatory properties in DNA expression.
References
Bancroft H (1960) Introducción a la estadística. Eudeba, Buenos Aires, pp 205–211
Bernacchi AS, Castro CR de, Toranzo EGD de, Marzi A, Ferreyra EC de, Fenos OM de, Castro JA (1980) Pyrazole prevention of CCl4-induced ultrastructural changes in rat liver. Br J Exp Pathol 61: 505–511
Castro JA (1984) Mechanistical studies and prevention of free radical cell injury. Proc IX International Congress of pharmacology. MacMillan, London, Vol 2, pp 243–250
Castro JA, Díaz Gómez MI (1976) Further studies on the mechanism of the carbon tetrachloride-induced polysome breakdown. Res Commun Chem Pathol Pharmacol 13: 731–741
Castro JA, Díaz Gómez MI, Ferreyra EC de, Castro CR de, D’Acosta N, Fenos OM de (1973) Differences in the carbon tetrachloride-induced damage to components of the smooth and rough endoplasmic reticulum from rat liver. Biochem Biophys Res Commun 50: 337–343
Castro JA, Díaz Gómez MI, Castro CR de, Fenos OM de, Ferreyra EC de D’Acosta N (1975) Carbon tetrachloride-induced polysome breakdown. Relative importance of lipid peroxidation and of binding to ribosomal components in the process. Res Commun Chem Pathol Pharmacol 10: 93–104
Castro JA, Ferreyra EC de, Castro CR de, Fenos OM de, Díaz Gómez MI, Gram TE, Reagan RL, Guarino AM (1977) Studies on the role of protein synthesis in cell injury by toxic agents: I. Effect of cycloheximide administration on several factors modulating carbon tetrachloride-induced liver necrosis. Toxicol Appl Pharmacol 41: 305–320
Clawson GA, MacDonald JR, Woo CH (1987) Early hypomethylation of 2-O-ribose moieties in hepatocyte cytoplasmic ribosomal RNA underlies the protein synthetic defect produced by CCl4. J Cell Biol 105: 705–711
Darnell J, Lodish H, Baltimore D (1986) Assembly of organelles. In: Molecular cell biology. Scientific American Books Inc, New York, pp 911–983
de Castro CR, Bernacchi AS, Ferreyra EC de, Fenos OM de, Castro JA (1978) Carbon tetrachloride induced ultrastructural alterations in pancreatic acinar cells and in the hepatocytes. Similarities and differences. Toxicology 11: 289–296
de Castro CR, Bernacchi AS, Villarruel MC, Fernández G and Castro JA (1984) Carbon tetrachloride activation by highly purified liver mitochondrial preparations. Agents Actions 15 [5/6]: 664–667
Dianzani MV (1987) The role of free radicals in liver damage. Proc Nutr Soc 46: 43–52
Díaz Gómez MI, Castro JA, Ferreyra EC de, D’Acosta N, Castro CR de (1973) Irreversible binding of14C from14CCl4 to liver microsomal lipids and proteins from rats pretreated with compounds altering microsomal mixed-function oxygenase activity. Toxicol Appl Pharmacol 25: 534–541
Gravela E, Dianzani MU (1970) Studies on the mechanism of CCl4-induced polyribosomal damage. FEBS Lett 9: 93–96
Lowry O, Rosenbrough N, Farr A, Randall R (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193: 265–275
Olson MO, Starbuck WC, Busch H (1974) Nuclear proteins. In: Busch H (ed) The molecular biology of cancer. Academic Press, New York, pp 309–353
Shannon Moore M, Blobel G (1992) The two steps of nuclear import, targeting to the nuclear envelope and translocation through the nuclear pore require different cytosolic factors. Cell 69: 939–950
Silver PA (1991) How proteins enter the nucleus. Cell 64: 489–497
Slater RF (1982) Activation of carbon tetrachloride, chemical principles and biological significance. In: McBrien DC, Slater TF (eds) Free radicals, lipid peroxidation and cancer. Academic Press, New York, pp 243–270
Smuckler EA (1976) Alterations produced in the endoplasmic reticulum by carbon tetrachloride. Panminerva Med 18: 292–303
Smuckler EA, Arcasoy M (1969) Structural and functional changes of the endoplasmic reticulum of hepatic parenchymal cells. Int Rev Exp Pathol 7: 305–418
Smuckler EA, Koplitz M (1969) The effects of carbon tetrachloride and ethionine on RNA synthesis in vivo and in isolated rat liver nuclei. Arch Biochem Biophys 132: 62–79
Steele WJ, Busch H (1963) Studies on acidic nuclear proteins of the Walker tumor and liver. Cancer Res 23: 1153–1163
Villarruel MC, Fernández G, Aguilar EG, Castro JA (1987) Early biochemical alterations in liver mitochondria from carbon tetrachloride poisoned rats. J Appl Toxicol 7: 173–177
Viviani A, Lutz WK, Schlatter C (1978) Time course of the induction of aryl hydrocarbon hydroxylase in rat liver nuclei and microsomes by phenobarbital, 3-methylcholantrene, 2,3,7,8-tetrachlorodibenzo-p-dioxin, dieldrin and other inducers. Biochem Pharmacol 27: 191–194
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Galelli, M., Gómez, M.I.D. & Castro, J.A. Decreased incorporation of14C-leucine in different liver nuclear protein fractions at early stages of carbon tetrachloride poisoning in the rat. Arch Toxicol 68, 206–209 (1994). https://doi.org/10.1007/s002040050056
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/s002040050056