Different mutation status of the beta-catenin gene in carcinogen-induced colon, brain, and oral tumors in rats.
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.
Suzui
M
M
Department of Internal Medicine, Gifu University School of Medicine, Gifu, Japan.
Sugie
S
S
Mori
H
H
Okuno
M
M
Tanaka
T
T
Moriwaki
H
H
D015112:4-Nitroquinoline-1-oxide / Q000633:toxicity; D000818:Animals; D000880:Anthraquinones / Q000633:toxicity; D001932:Brain Neoplasms / Q000139:chemically induced / Q000235:genetics*; D002273:Carcinogens / Q000633:toxicity*; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000235:genetics*; D003598:Cytoskeletal Proteins / Q000235:genetics*; D005819:Genetic Markers; D008297:Male; D008746:Methylazoxymethanol Acetate / Q000031:analogs & derivatives* / Q000633:toxicity; D009062:Mouth Neoplasms / Q000139:chemically induced / Q000235:genetics*; D009154:Mutation; D009607:Nitrosourea Compounds / Q000633:toxicity; D009928:Organ Specificity; D016133:Polymerase Chain Reaction; D015363:Quinolones / Q000633:toxicity; D051381:Rats; D011916:Rats, Inbred F344; D015534:Trans-Activators; D051176:beta Catenin
C120195:4-nitroquinolone-1-oxide; D000880:Anthraquinones; D002273:Carcinogens; C495268:Ctnnb1 protein, rat; D003598:Cytoskeletal Proteins; D005819:Genetic Markers; D009607:Nitrosourea Compounds; D015363:Quinolones; D015534:Trans-Activators; D051176:beta Catenin; D015112:4-Nitroquinoline-1-oxide; D008746:Methylazoxymethanol Acetate; C030667:methylazoxymethanol; C061208:1-hydroxyanthraquinone