Abstract
-
1.
14C-labelled trichloroethylene was injected i.p. into male mice (10 μmole/g of b.w.). The radioactivity irreversibly bound to hepatic protein reached highest levels after 6 h: 2 nmole/mg in cytosol protein, 4.4 nmole/mg in mitochondrial protein, and 7.6 nmole/mg in microsomal protein.
-
2.
The commercial trichloroethylene contained radioactive impurities binding to proteins without metabolic activation. Purification by various extractions removed 60–70% of those materials. In aerobic incubates of mice hepatic microsomes and NADPH the covalent binding rate of the purified trichloroethylene was 1.4 nmole/mg protein in 60 min. The activity of rat liver microsomes was approximately 40% less. Covalent binding increased 2-fold with microsomes of mice pretreated with phenobarbital.
Similar content being viewed by others
References
Bonse, G., Henschler, D.: Chemical reactivity, biotransformation, and toxicity of polychlorinated aliphatic compounds. CRC Rev. Toxicology 4, 395–409 (1976)
Browning, E.: Toxicity and metabolism of industrial solvents, pp. 189–212. Amsterdam: Elsevier 1965
Carlson, G. P.: Enhancement of the hepatotoxicity of trichloroethylene by inducers of drug metabolism. Res. Comm. Chem. Pathol. Pharmacol. 7, 637–640 (1974)
Daniel, J. W.: The metabolism of 36Cl-labelled trichloroethylene and tetrachloroethylene in the rat. Biochem. Pharmacol. 12, 795–802 (1963)
D.H.E.W., National Cancer Institute: Carcinogenesis bioassay of trichloroethylene, Carcinogenesis Technical Report Series, No. 2. Washington, D.C.: U.S. Gouvernment Printing Office 1976
Fishbein, L.: Industrial mutagens and potential mutagens. I. Halogenated aliphatic derivatives. Mutation Res. 32, 267–308 (1976)
Greim, H., Bonse, G., Radwan, Z., Reichert, D., Henschler, D.: Mutagenicity in vitro and potential carcinogenicity of chlorinated ethylenes as a function of metabolic oxirane formation. Biochem. Pharmacol. 24, 2013–2017 (1975)
Henschler, D.: Gesundheitsschädliche Arbeitsstoffe, Toxikologisch-arbeitsmedizinische Begründung von MAK-Werten, Trichloräthylen. Weinheim: Verlag Chemie 1975
Moslen, M. T., Reynolds, E. S., Szabo, S.: Correlation between the chemically induced potentiation of trichloroethylene hepatotoxicity and its metabolism. Fed. Proc. 35, 934 (1976)
Powell, J. F.: Trichloroethylene: Absorption, elimination and metabolism. Brit. J. industr. Med. 2, 142–145 (1945)
Recknagel, R. O., Glende, R. A.: Carbon tetrachloride: An example of lethal cleavage. CRC Rev. Toxicology 3, 263–297 (1973)
Reiner, O., Uehleke, H.: Bindung von Tetrachlorkohlenstoff an reduziertes mikrosomales Cytochrom P-450 und an Häm. Hoppe-Seyler's Z. physiol. Chem. 353, 1048–1052 (1971)
Reynolds, E. S., Moslen, M. T., Boor, P. J., Bailey, K., Szabo, S.: Trichloroethylene-induced deactivation of liver endoplasmic reticulum and glutathione depletion. Toxicol. appl. Pharmacol. 39, 173 (1977)
Uehleke, H.: The model system of microsomal drug activation and covalent binding to endoplasmic proteins. In: Experimental model systems in toxicology and their significance in man. Proc. Europ. Soc. for the Study of Drug Toxicity. XV, 119–129 (1973)
Uehleke, H., Hellmer, K. H., Tabarelli, S.: Binding of 14C-carbon-tetrachloride to microsomal proteins in vitro and the formation of CHCl3 by reduced microsomes. Xenobiotica 3, 1–11 (1973a)
Uehleke, H., Hellmer, K. H., Tabarelli-Poplawski, S.: Metabolic activation of halothane and its covalent binding to liver endoplasmic proteins in vitro. Naunyn-Schmiedeberg's Arch. Pharmacol. 279, 39–52 (1973b)
Uehleke, H., Poplawski, S., Bonse, G., Henschler, D.: Spectral evidence for 2,2,3-trichloro-oxirane formation during microsomal trichloroethylene oxidation. Naunyn-Schmiedeberg's Arch. Pharmacol. 293, R64 (1976), and Arch. Toxicol. 37, 95–105 (1977a)
Uehleke, H., Werner, Th.: A comparative study on the irreversible binding of labelled halothane, trichlorofiuoromethane, chloroform, and carbon tetrachloride to hepatic protein and lipids in vitro and in vivo. Arch. Toxicol. 34, 289–308 (1975)
Uehleke, H., Werner, Th., Greim, H., Krämer, M.: Metabolic activation of haloalkanes and in vitro tests for mutagenicity. Xenobiotica 7, No 7 (1977b)
Van Duuren, B. L., Banerjee, S.: Covalent interaction of metabolites of the carcinogen trichloroethylene in rat hepatic microsomes. Cancer Res. 36, 2419–2422 (1976)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Uehleke, H., Poplawski-Tabarelli, S. Irreversible binding of 14C-labelled trichloroethylene to mice liver constituents in vivo and in vitro. Arch. Toxicol. 37, 289–294 (1977). https://doi.org/10.1007/BF00330820
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00330820