ToxSci Advance Access published online on June 16, 2006
Toxicological Sciences, doi:10.1093/toxsci/kfl041
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1 University of Tuebingen, Department of Toxicology, Wilhelmstr. 56, 72074 Tuebingen, Germany
* To whom correspondence should be addressed. Polychlorinated biphenyls (PCBs) are ubiquitous environmental toxicants which act as liver tumor promoters in rodents and can be classified as either dioxin-like or non-dioxin (phenobarbital)-like inducers of cytochrome P-450. Since we have previously shown that tumor promotion by phenobarbital leads to clonal outgrowth of
Received April 11, 2006
Accepted June 15, 2006
Carcinogenicity
PCB 153, a non-dioxin-like Tumor Promoter, Selects for
Julia Strathmann 1,
Michael Schwarz 1,
Job C. Tharappel 2,
Howard P. Glauert 2,
Brett T. Spear 3,
Larry W. Robertson 4,
Klaus E. Appel 5,
and
Albrecht Buchmann 1 *
-Catenin (Catnb) Mutated Mouse Liver Tumors
2 Graduate Center for Nutritional Sciences, Immunology & Molecular Genetics, University of Kentucky, Lexington, KY 40506 USA
3 Department of Microbiology, Immunology & Molecular Genetics, University of Kentucky, Lexington, KY 40506 USA
4 University of Iowa, Occupational & Environmental Health, College of Public Health, 100 Oakdale Campus #219 IREH, Iowa City, IA 52242-5000 USA
5 Federal Institute for Risk Assessment, Center for Experimental Toxicology, Thielallee 88-92, 14195 Berlin, Germany
Albrecht Buchmann, E-mail: albrecht.buchmann{at}uni-tuebingen.de
Abstract 
-Catenin (Catnb) mutated, but not Ha-ras mutated, mouse liver tumors, we were interested to know whether the non-dioxin-like tumor promoter PCB 153 shows the same selective pressure during tumor promotion. Male B6129SF2/J mice were given a single injection of N-nitrosodiethylamine (90 mg/kg body weight) at 9 weeks of age, followed by 39 weeks of treatment with PCB 153 (20 biweekly i.p. injections of 300 µmol/kg body weight) or corn oil as a control. Animals were killed 15 weeks after the last PCB 153 injection and liver tumors were identified by immunohistochemical staining of glutamine synthetase (GS) and analyzed for Catnb, Ha-ras and B-raf mutations. Quantitative analyses revealed that GS-positive tumors were much larger and more frequent in livers from PCB 153 treated mice than in control animals, whereas GS-negative tumors were similar in both groups. Almost 90% (34/38) of all tumors from PCB 153 treated animals contained Catnb mutations, which compares to 
45% (17/37) of tumors in the control group. Ha-ras and B-raf mutated liver tumors were rare and not significantly different between treatment groups. These results clearly indicate that PCB 153 strongly selects for Catnb mutated, GS-positive liver tumors, which is similar to the known action of phenobarbital, a prototypical tumor promoter in rodent liver.-Catenin; Catnb mutations.
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