Different mutation status of the beta-catenin gene in carcinogen-induced colon, brain, and oral tumors in rats.

Abstract

Mutations in the region corresponding to the N-terminal phosphorylation sites (codons 1-51) of the rat beta-catenin gene (Ctnnb1) were investigated in rat colon tumors induced by 1-hydroxyanthraquinone (1-HA) plus methylazoxymethanol (MAM) acetate, by using polymerase chain reaction (PCR)-single-strand conformation polymorphism (SSCP) analysis. The beta-catenin gene was also screened for mutations in rat brain and oral tumors induced by ethyl nitrosourea (ENU) and 4-nitroquinoline 1-oxide (4-NQO), respectively. In colon tumors, beta-catenin gene mutations were found in two of three adenomas (67%) and 26 of 28 adenocarcinomas (93%), with a total incidence of 90% (28 of 31 adenomas plus adenocarcinomas). Eight (29%) were (34)G-->T (second position), eight (29%) were (32)G-->A (first position), five (18%) were (34)G-->A (first position), five (18%) were (41)C-->T (second position), one (4%) was (34)G-->A (second position), and one (4%) was (32)A-->G (second position), mutations, resulting in the substitutions of Gly(34)-->Val, Asp(32)-->Asn, Gly(34)-->Arg, Thr(41)-->Ile, Gly(34)-->Glu, and Asp(32)-->Gly, respectively. The (34)G-->T (second position) mutations found in this study were unique compared to those found in other carcinogen-induced rat colon carcinogenesis models. In contrast, beta-catenin gene mutations were not found in either the brain or oral tumors. These results suggest that mutations in the beta-catenin gene in rat tumors occur in specific tissues or organ sites and in a carcinogen-specific manner. Thus, the mutation spectrum in the beta-catenin gene is organ- and chemical carcinogen-specific.

• Authors: M Suzui, S Sugie, H Mori, M Okuno, T Tanaka, H Moriwaki
• Journal: Molecular carcinogenesis (Mol Carcinog) Vol. 32 Issue 4 Pg. 206-12 (Dec 2001) ISSN: 0899-1987 [Print] United States
• PMID: 11746832 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2001 Wiley-Liss, Inc.

Chemical References

• 4-nitroquinolone-1-oxide
• Anthraquinones
• Carcinogens
• Ctnnb1 protein, rat
• Cytoskeletal Proteins
• Genetic Markers
• Nitrosourea Compounds
• Quinolones
• Trans-Activators
• beta Catenin
• 4-Nitroquinoline-1-oxide
• Methylazoxymethanol Acetate
• methylazoxymethanol
• 1-hydroxyanthraquinone

Topics

• 4-Nitroquinoline-1-oxide (toxicity)
• Animals
• Anthraquinones (toxicity)
• Brain Neoplasms (chemically induced, genetics)
• Carcinogens (toxicity)
• Colonic Neoplasms (chemically induced, genetics)
• Cytoskeletal Proteins (genetics)
• Genetic Markers
• Male
• Methylazoxymethanol Acetate (analogs & derivatives, toxicity)
• Mouth Neoplasms (chemically induced, genetics)
• Mutation
• Nitrosourea Compounds (toxicity)
• Organ Specificity
• Polymerase Chain Reaction
• Quinolones (toxicity)
• Rats
• Rats, Inbred F344
• Trans-Activators
• beta Catenin