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Frameshift mutation in codon 176 of the p53 gene in rat esophageal epithelial cells transformed by benzo[a]pyrene dihydrodiol
Author(s) -
Wang Dian,
You Liang,
Sneddon Jeff,
Cheng ShuJun,
Jamasbi Roubadeh,
Stoner Gary D.
Publication year - 1995
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.2940140204
Subject(s) - frameshift mutation , biology , microbiology and biotechnology , gene , mutation , cell culture , gene mutation , benzo(a)pyrene , genetics , carcinogen
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 (TGAC → 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. ©1995 Wiley‐Liss, Inc.