Frameshift mutation in codon 176 of the p53 gene in rat esophageal epithelial cells transformed by benzo[a]pyrene dihydrodiol. Mol Carcinog 1995 Oct;14(2):84-93
Date
10/01/1995Pubmed ID
7576103DOI
10.1002/mc.2940140204Scopus ID
2-s2.0-0028849305 (requires institutional sign-in at Scopus site) 15 CitationsAbstract
Mutations in the p53 tumor suppressor gene have been associated with exposure to environmental chemical carcinogens. Cultured rat esophageal epithelial cells were transformed in vitro by treatment with benzo[a]pyrene dihydrodiol (BP-DHD). A BP-DHD-transformed cell line and control cell lines were analyzed for mutations in the p53 gene and in the Ha-ras gene by single-strand conformation polymorphism analysis of polymerase chain reaction-amplified products and direct DNA sequencing. The deletion of one cytosine in codons 174-176 (TGCCCCCAC-->TGCCCCAC) of the p53 gene was found only in the BP-DHD-transformed cell line. The BP-DHD-transformed cells were highly invasive and tumorigenic when transplanted into syngeneic rats, whereas control lines either were nontumorigenic or formed epithelial cysts. BP-DHD-transformed cells and control lines were negative for mutations in the Ha-ras gene. Our results suggest that the tumorigenic potential of the BP-DHD-transformed cell line is associated with a frameshift mutation in codon 176 of the p53 gene but not with mutations in the Ha-ras gene. The G/C-rich codons 174-176 in the rat p53 gene may be specific targets for BP-DHD.
Author List
Wang D, You L, Sneddon J, Cheng SJ, Jamasbi R, Stoner GDMESH terms used to index this publication - Major topics in bold
AnimalsBase Sequence
Cell Adhesion
Cell Division
Cell Transformation, Neoplastic
Cells, Cultured
DNA Primers
Dihydroxydihydrobenzopyrenes
Epithelial Cells
Esophagus
Frameshift Mutation
Genes, p53
Genes, ras
Molecular Sequence Data
Mutagens
Neoplasms, Experimental
Polymorphism, Single-Stranded Conformational
Rats
Tumor Suppressor Protein p53
