title: Frameshift mutation in codon 176 of the p53 gene in rat esophageal epithelial cells transformed by benzo[a]pyrene dihydrodiol.
abstract: 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.
authors.affiliation: Department of Preventive Medicine, College of Medicine, Ohio State University, Columbus 43210-1240, USA.
authors.forename: D
authors.initials: D
authors.lastname: Wang
authors.forename: L
authors.initials: L
authors.lastname: You
authors.forename: J
authors.initials: J
authors.lastname: Sneddon
authors.forename: S J
authors.initials: SJ
authors.lastname: Cheng
authors.forename: R
authors.initials: R
authors.lastname: Jamasbi
authors.forename: G D
authors.initials: GD
authors.lastname: Stoner
mesh_terms: D000818:Animals; D001483:Base Sequence; D002448:Cell Adhesion; D002455:Cell Division; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002478:Cells, Cultured; D017931:DNA Primers / Q000737:chemistry; D004101:Dihydroxydihydrobenzopyrenes; D004847:Epithelial Cells; D004947:Esophagus / Q000166:cytology; D016368:Frameshift Mutation; D016158:Genes, p53; D011905:Genes, ras; D008969:Molecular Sequence Data; D009153:Mutagens; D009374:Neoplasms, Experimental / Q000235:genetics; D018807:Polymorphism, Single-Stranded Conformational; D051381:Rats; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D017931:DNA Primers; D004101:Dihydroxydihydrobenzopyrenes; D009153:Mutagens; D016159:Tumor Suppressor Protein p53; C017228:benzo(a)pyrene 7,8-dihydrodiol