Titre
Analysis of activated protooncogenes in B6C3F1 mouse liver tumors induced by ciprofibrate, a potent peroxisome proliferator
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Hegi, M. E.
Auteure/Auteur
Fox, T. R.
Auteure/Auteur
Belinsky, S. A.
Auteure/Auteur
Devereux, T. R.
Auteure/Auteur
Anderson, M. W.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
0143-3334
Statut éditorial
Publié
Date de publication
1993-01
Volume
14
Numéro
1
Première page
145
Dernière page/numéro d’article
9
Notes
Journal Article --- Old month value: Jan
Résumé
Liver tumors from B6C3F1 mice induced by the potent peroxisome proliferator ciprofibrate, a hypolipidemic drug, were evaluated for the presence of transforming genes by the nude mouse tumorigenicity assay. As reported earlier, the tumors were not activated by a point mutation in codon 61 of H-ras. Two of the eight tumors examined contained a mutation in codon 13 or an H-ras gene mutated in codon 117. Screening of another 23 ciprofibrate-induced liver tumors by oligonucleotide hybridization analysis and direct DNA sequencing resulted in the identification of three tumor DNA samples with point mutations in codon 117 of the H-ras gene. In addition, another tumor sample contained a K-ras gene with a mutation in codon 61. Mutations in these codons have been seen only rarely in chemically induced liver tumors from this mouse strain. Of 15 spontaneous B6C3F1 liver tumors screened in the same manner, one exhibited a K-ras gene activated by a mutation in codon 13 and a second contained an H-ras gene activated by a mutation in codon 117. These ras gene mutations have not been reported previously from spontaneous liver tumors. The frequency and spectrum of ras oncogene mutations characterized in ciprofibrate-induced liver tumors differ significantly from the frequency and pattern identified in spontaneously occurring liver tumors. The results of this study with a limited number of samples suggest that ras protooncogene activation or activation of other protooncogenes that can be detected by the nude mouse tumorigenicity assay are not frequent events in the mechanism of carcinogenicity of the peroxisome proliferator ciprofibrate. However, the lower frequency and distinct pattern of H-ras mutations observed in these tumors disprove the assumption of promotion of spontaneous hepatocarcinogenesis by ciprofibrate.
Sujets
PID Serval
serval:BIB_80452F6BECE0
PMID
Date de création
2008-01-25T12:06:00.140Z
Date de création dans IRIS
2025-05-20T23:35:17Z