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Titolo:
beta-catenin mutation in rat colon tumors initiated by 1,2-dimethylhydrazine and 2-amino-3-methylimidazo[4,5-f]quinoline, and the effect of post-initiation treatment with chlorophyllin and indole-3-carbinol
Autore:
Blum, CA; Xu, MR; Orner, GA; Fong, AT; Bailey, GS; Stoner, GD; Horio, DT; Dashwood, RH;
Indirizzi:
Oregon State Univ, Linus Pauling Inst, Corvallis, OR 97331 USA Oregon State Univ Corvallis OR USA 97331 ng Inst, Corvallis, OR 97331 USA Oregon State Univ, Dept Environm & Mol Toxicol, Corvallis, OR 97331 USA Oregon State Univ Corvallis OR USA 97331 Toxicol, Corvallis, OR 97331 USA Ohio State Univ, Sch Publ Hlth, Columbus, OH 43210 USA Ohio State Univ Columbus OH USA 43210 h Publ Hlth, Columbus, OH 43210 USA St Francis Med Ctr, Dept Pathol, Honolulu, HI 96817 USA St Francis Med Ctr Honolulu HI USA 96817 t Pathol, Honolulu, HI 96817 USA
Titolo Testata:
CARCINOGENESIS
fascicolo: 2, volume: 22, anno: 2001,
pagine: 315 - 320
SICI:
0143-3334(200102)22:2<315:BMIRCT>2.0.ZU;2-D
Fonte:
ISI
Lingua:
ENG
Soggetto:
HETEROCYCLIC AMINES; C-MYC; CANCER; TARGET; EXPRESSION; PATHWAY; GENES; ANTICARCINOGENS; CARCINOMAS; MOUSE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
37
Recensione:
Indirizzi per estratti:
Indirizzo: Dashwood, RH Oregon State Univ, Linus Pauling Inst, Corvallis, OR 97331 USA Oregon State Univ Corvallis OR USA 97331 allis, OR 97331 USA
Citazione:
C.A. Blum et al., "beta-catenin mutation in rat colon tumors initiated by 1,2-dimethylhydrazine and 2-amino-3-methylimidazo[4,5-f]quinoline, and the effect of post-initiation treatment with chlorophyllin and indole-3-carbinol", CARCINOGENE, 22(2), 2001, pp. 315-320

Abstract

Carcinogens 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and 1,2-dimethylhydrazine (DMH) induce colon tumors in the rat that contain mutations in beta -catenin, but the pattern of mutation differs from that found in human colon cancers. In both species, mutations affect the glycogen synthase kinase-3 beta consensus region of beta -catenin, but whereas they directly substitute critical Ser/Thr phosphorylation sites in human colon cancers, the majority of mutations cluster around Ser33 in the rat tumors. Two dietary phytochemicals, chlorophyllin and indole-3-carbinol, given post-initiation, shifted the pattern of beta -catenin mutations in rat colon tumors induced by IQ and DMH. Specifically, 17/39 (44%) of the beta -catenin mutations in groups given carcinogen plus modulator were in codons 37, 41 and 45, and substituted critical Ser/Thr residues directly, as seen in human colon cancers, None of the tumors from groups given carcinogen alone had mutations in these codons. Interestingly, many of the mutations that substituted critical Ser/Thr residues in beta -catenin were from a single group given DMH and 0.001% chlorophyllin, in which a statistically significant increase in colon tumor multiplicity was observed compared with the group given DMH only. Thesetumors had marked over-expression of cyclin DI, c-myc and c-jun mRNA and c-Myc and c-Jun proteins were strongly elevated compared with tumors containing wild-type beta -catenin, The results indicate that the pattern of beta -catenin mutations in rat colon tumors can be influenced by exposure to dietary phytochemicals administered postinitiation, and that the mechanism might involve the altered expression of beta -catenin/Tcf/Lef target genes.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 02/04/20 alle ore 00:01:34