FRAMESHIFT MUTATION IN CODON-176 OF THE P53 GENE IN RAT ESOPHAGEAL EPITHELIAL-CELLS TRANSFORMED BY BENZO[A]PYRENE DIHYDRODIOL

被引:16
作者
WANG, DA
YOU, L
SNEDDON, J
CHENG, SJ
JAMASBI, R
STONER, GD
机构
[1] OHIO STATE UNIV, COLL MED, DEPT PREVENT MED, COLUMBUS, OH 43210 USA
[2] CHINESE ACAD MED SCI, CANC INST HOSP, BEIJING 100037, PEOPLES R CHINA
[3] BOWLING GREEN STATE UNIV, DEPT MED TECHNOL, BOWLING GREEN, OH 43403 USA
关键词
BENZO[A]PYRENE DIHYDRODIOL; RAT ESOPHAGEAL EPITHELIAL CELLS; NEOPLASTIC TRANSFORMATION; P53; GENE;
D O I
10.1002/mc.2940140204
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 CIC-rich codons 174-176 in the rat p53 gene may be specific targets for BP-DHD. (C) 1995 Wiley-Liss, Inc.
引用
收藏
页码:84 / 93
页数:10
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