Szukałam czegoś o DCA i znalazłam taki artykulik... doświadzenie było robione na komórkach wątrobowych myszy i szczurów... wychodzi, że DCA może mieć związek z rakiem wątroby...
Dichloroacetic acid induction of peroxisome proliferation in cultured hepatocytes
Jennie L. Everhart, David T. Kurtz, JoEllyn M. McMillan, Ph.D. *
Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina,Charleston, SC 29425
*Correspondence to JoEllyn M. McMillan, Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, 171 Ashley Ave., Charleston, SC 29425. Tel.: (803) 792-8827
Funded by:
Department of Energy; Grant Number: DE-FC02-98CH10902
Keywords
Dichloroacetate � Hepatocytes � Peroxisomes � Carcinogenesis
Abstract
Trichloroethylene is a widespread industrial solvent and one of the most common environmental contaminants. Trichloroethylene causes hepatocarcinoma in the B6C3F1 mouse in a dose-dependent manner. Trichloroethylene's hepatocarcinogenicity is thought to be mediated through its metabolites trichloroacetate and dichloroacetate. Although the mechanism of action is not well understood, hepatic tumors are thought to arise as a result of excessive peroxisome-dependent active oxygen production or secondary to enhanced cell replication. The peroxisome proliferative activity of trichloroacetate has been replicated in cultured rodent hepatocytes, while that of dichloroacetate has not been demonstrated. The present experiments were designed to characterize the peroxisome proliferative response to dichloroacetate in hepatocyte cultures from male B6C3F1 mice and male Long Evans rats. The cultured hepatocytes were treated after attachment with 0.1, 0.5, 1.0, 2.0, or 4.0 mM dichloroacetate for 72 hours. Peroxisome proliferation was assessed by measuring palmitoyl-CoA oxidation and by immunoquantitation of peroxisomal bifunctional enzyme. Palmitoyl CoA oxidation increased in a concentration-dependent manner, with maximal induction of 5.5- and 5-fold in mouse and rat hepatocytes, respectively, after treatment with 2.0 mM dichloroacetate. Peroxisomal bifunctional enzyme protein levels also increased in a concentration-dependent manner in both rat and mouse hepatocytes in response to dichloroacetate exposure. These results indicate that the peroxisomal response observed in vivo in response to dichloroacetate administration can be reproduced in primary cultures of rat and mouse hepatocytes treated with dichloroacetate. Further studies using this model system will help elucidate mechanisms of dichloroacetate-induced hepatocarcinogenesis. © 1998 John Wiley & Sons, Inc. J Biochem Mol Toxicol 12: 351-359, 1998
Received: 14 January 1998; Revised: 27 April 1998; Accepted: 11 May 1998