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ToxSci Advance Access published online on February 27, 2008
Toxicological Sciences, doi:10.1093/toxsci/kfn043
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© The Author 2008. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Tumor Promotion in Liver of Mice with a Conditional Cx26 Knockout

P. Marx-Stoelting*, J. Mahr*, T. Knorpp{dagger}, S. Schreiber*, M.F. Templin{dagger}, T. Ott{ddagger}, A. Buchmann* and M. Schwarz*

* Institute of Pharmacology and Toxicology, Department of Toxicology, University of Tübingen, Wilhelmstr. 56, 72074 Tübingen, Germany {ddagger} IZKF / Central Unit for Transgenic Animals, Ottfried-Mueller-Str. 27, 72076 Tübingen, Germany {dagger} NMI, Markwiesenstr. 55, 72770 Reutlingen, Germany

Corresponding Author: Dr. Michael Schwarz, Institute for Pharmacology and Toxicology, Wilhelmstr. 56, 72074 Tübingen, Email: michael.schwarz{at}uni-tuebingen.de, Tel.: 0049 7071 29 77398, Fax.: 0049 7071 29 2273

Received January 21, 2008; revision received February 19, 2008; accepted February 19, 2008


  Abstract

Connexin (Cx) 26 and 32 are the major gap junction proteins in liver. We recently demonstrated that Cx32 is essential for phenobarbital (PB)-mediated tumor promotion in mouse liver. To investigate whether Cx26 plays a similar role, an initiation-promotion experiment was conducted using mice with a liver-specific knockout of Cx26. Control and Cx26-deficient mice were injected a single dose of N-nitrosodiethylamine (DEN, 90µg/g b.wt.) at six weeks of age and groups of mice were subsequently kept on a PB (0.05%) containing or control diet for 35 weeks. At the end of the experiment, the carcinogenic response in the liver was monitored. Mice from PB-treatment groups showed strongly increased liver weights compared to mice treated with DEN alone, which was mostly due to a much higher tumor burden. The tumor response in PB-treated mice of both strains was quite similar, but the number of smaller tumors and of enzyme-altered neoplastic lesions was somewhat larger in PB-treated Cx26 knockout compared to wild-type mice while the volume fraction of enzyme-altered lesions was slightly reduced in PB-treated Cx26-deficient mice. There was no significant difference in tumor prevalence between Cx26 knockout and wild-type mice. Altogether our present data show that elimination of Cx26 has only minor effects on chemically induced mouse hepatocarcinogenesis, in striking contrast to the effects seen in Cx32 knockout mice.

Key Words: Connexin; Liver; Phenobarbital; Tumor promotion; β-Catenin.


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