Differences in phenotype and cell replicative behavior of hepatic tumors induced by dichloroacetate (DCA) and trichloroacetate (TCA)

Toxicology and Applied Pharmacology
A J Stauber, R J Bull

Abstract

Dichloroacetate (DCA) and trichloroacetate (TCA) are two hepatocarcinogenic by-products of water chlorination. To compare the effects of DCA and TCA on cell replication in the nodules and tumors they induce, male B6C3F1 mice were administered 2.0 g/L DCA or TCA in their drinking water for 38 or 50 weeks, respectively. The pretreated mice were then given water containing 0, 0.02, 0.5, 1.0, or 2.0 g/L DCA or TCA for two additional weeks to determine whether cell proliferation in the normal liver or tumors that had been induced by DCA or TCA was dependent on continued treatment. Prior to sacrifice the mice were subcutaneously implanted with mini-osmotic pumps to label DNA in dividing cells with 5-bromo-2'-deoxyuridine (BrdU). Serial sections of nodules/tumors and normal liver were stained immunohistochemically for BrdU, the oncoproteins c-Jun and c-Fos, and hematoxylin and eosin (H & E); or with Periodic acid-Schiff (PAS) stain, BrdU, and H & E, respectively. DCA and TCA transiently stimulated the division of normal hepatocytes relative to rates observed in the livers of control mice. However, at 40 and 52 weeks of treatment, replication of normal hepatocytes was substantially inhibited by DCA and TCA, respectively. Cell division ...Continue Reading

References

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Citations

Mar 10, 2009·Journal of Toxicology and Environmental Health. Part a·Richard J BullLinda K Teuschler
May 13, 2004·Toxicology·Hannu Komulainen
Apr 5, 2001·Journal of Applied Toxicology : JAT·J Kato-WeinsteinR J Bull
Aug 31, 2002·Environmental and Molecular Mutagenesis·Michael J PlewaElizabeth D Wagner
May 12, 2000·Environmental Health Perspectives·C W Chen
Feb 2, 2008·Environmental and Molecular Mutagenesis·Vincent James CoglianoFatiha El Ghissassi
Mar 4, 2006·Der Urologe. Ausg. A·K GolkaP J Goebell
Oct 30, 2008·Journal of Immunotoxicology·Ping CaiRolf Konig
Dec 5, 2017·Archives of Toxicology·J Christopher CortonJames E Klaunig
Dec 29, 1998·Toxicology·J Kato-WeinsteinR J Bull
Dec 3, 2003·Toxicology and Applied Pharmacology·Julian E A LeakeyWilliam T Allaben

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