© 1994 Oxford University Press
research-article |
p53 mutation is frequent and might not give a growth advantage in rat bladder carcinogenesis in vivo
Department of Pathology and Microbiology and the Eppley Institute for Research on Cancer and Allied Diseases, University of Nebraska Medical Center 600 S. 42nd Street, Omaha, NE 68198-3135, USA
1To whom correspondence and reprint requests should be addressed
Abnormalities of the p53 gene are frequently observed in human tumors, including urinary bladder carcinoma, suggesting that p53 plays an important role in human carcinogenesis. However, its role in rat bladder carcinogenesis is unclear. In this study, we investigated the presence of p53 mutations in 122 urinary bladder tumors induced in F344 rats in the following carcinogenesis models: (i) 0.2% N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT; 6 weeks) in the diet followed by 3% or 5% sodium saccharin in the diet, 5% sodium ascorbate, 3.12% calcium saccharin (CaSac), 1.34% sodium chloride (NaCl), 5.2% CaSac plus 1.34% NaCl, or basal diet alone (72 weeks); and (ii) 0.2% FANFT, 0.05% N-(4-hydroxybutyl)nitrosamine in the drinking water, N-methyl-N-nitrosourea 20 mg/kg body wt, i.p. twice per week, or basal diet alone (4 weeks), followed by 3% uracil in the diet (20 weeks). Polymerase chain reaction-single-strand conformation polymorphism analysis and direct sequencing were performed for exons 5–8 in the ratp53 gene. We found nine tumors (7.4%) with p53 mutations. Two tumors had two mutations in the p53 gene. The tumors that had p53 mutations were relatively smaller than those that did not have p53 mutations. There were no mutation clusters among the treatments or hot-spots for p53 mutations. These results indicate that p53 mutation is infrequent in bladder carcinogenesis in rats, and when it does occur, it does not appear to provide a growth advantage.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  S. Sugiura, K. Ogawa, M. Hirose, F. Takeshita, M. Asamoto, and T. Shirai Reversibility of proliferative lesions and induction of non-papillary tumors in rat urinary bladder treated with phenylethyl isothiocyanate Carcinogenesis, March 1, 2003; 24(3): 547 - 553. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. Cohen Comparative Pathology of Proliferative Lesions of the Urinary Bladder Toxicol Pathol, October 1, 2002; 30(6): 663 - 671. [Abstract] [PDF]
|
|
|
|
|
|
C. C. R. Lee, T. Ichihara, S. Yamamoto, H. Wanibuchi, K. Sugimura, S. Wada, T. Kishimoto, and S. Fukushima Reduced expression of the CDK inhibitor p27KIP1 in rat two-stage bladder carcinogenesis and its association with expression profiles of p21WAF1/Cip1 and p53 Carcinogenesis, September 1, 1999; 20(9): 1697 - 1708. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Morimura, S. Yamamoto, T. Murai, S. Mori, T.-X. Chen, H. Wanibuchi, and S. Fukushima LOH and mutational analysis of p53 alleles in mouse urinary bladder carcinomas induced by N-butyl-N-(4-hydroxybutyl) nitrosamine Carcinogenesis, April 1, 1999; 20(4): 715 - 718. [Abstract] [Full Text] [PDF]
|
|