PCB 153, a non-dioxin-like tumor promoter, selects for beta-catenin (Catnb)-mutated mouse liver tumors

Julia Strathmann; Michael Schwarz; Job C Tharappel; Howard P Glauert; Brett T Spear; Larry W Robertson; Klaus E Appel; Albrecht Buchmann

doi:10.1093/toxsci/kfl041

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PCB 153, a non-dioxin-like tumor promoter, selects for beta-catenin (Catnb)-mutated mouse liver tumors

Journal article

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PCB 153, a non-dioxin-like tumor promoter, selects for beta-catenin (Catnb)-mutated mouse liver tumors

Julia Strathmann, Michael Schwarz, Job C Tharappel, Howard P Glauert, Brett T Spear, Larry W Robertson, Klaus E Appel and Albrecht Buchmann

Toxicological sciences, Vol.93(1), pp.34-40

09/2006

DOI: 10.1093/toxsci/kfl041

PMID: 16782779

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Abstract

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 [PB])-like inducers of cytochrome P-450. Since we have previously shown that tumor promotion by PB leads to clonal outgrowth of beta-catenin (Catnb)-mutated but not Ha-ras-mutated mouse liver tumors, we were interested to know whether the non-dioxin-like tumor promoter 2,2',4,4',5,5'-hexachlorobiphenyl (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 ip injections of 300 mumol/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 approximately 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 PB, a prototypical tumor promoter in rodent liver.

Immunohistochemistry

Animals

Polychlorinated Biphenyls - toxicity

Base Sequence

Liver Neoplasms, Experimental - chemically induced

Male

Liver Neoplasms, Experimental - genetics

Mice

Mutation

DNA Primers

beta Catenin - genetics

Carcinogens - toxicity

Details

Title: Subtitle: PCB 153, a non-dioxin-like tumor promoter, selects for beta-catenin (Catnb)-mutated mouse liver tumors
Creators: Julia Strathmann - Department of Toxicology, University of Tuebingen, 72074 Tuebingen, Germany
Michael Schwarz
Job C Tharappel
Howard P Glauert
Brett T Spear
Larry W Robertson
Klaus E Appel
Albrecht Buchmann
Resource Type: Journal article
Publication Details: Toxicological sciences, Vol.93(1), pp.34-40
Publisher: United States
DOI: 10.1093/toxsci/kfl041
PMID: 16782779
ISSN: 1096-6080
eISSN: 1096-0929
Grant note: P42 ES013661 / NIEHS NIH HHS ES 013661 / NIEHS NIH HHS ES 07380 / NIEHS NIH HHS
Language: English
Date published: 09/2006
Academic Unit: Occupational and Environmental Health; Iowa Superfund Research Program
Record Identifier: 9984002406102771

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