p53 mutations in transitional cell carcinomas of the urinary bladder in rats treated with N-butyl-N-(4-hydroxybutyl)-nitrosamine

Tsuneo Masui, Yimin Dong, Shinji Yamamoto, Nobuyasu Takada, Hayao Nakanishi, Ken Ichi Inada, Shoji Fukushima, Masae Tatematsu

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25 Citations (Scopus)

Abstract

Involvement of p53 gene alterations has been demonstrated in a variety of human neoplasias including urinary bladder carcinomas. N-Butyl-N-(4-hydroxybutyl)nitrosamine (BBN)-induced urinary bladder carcinogenesis models in rodents have been widely used to study carcinogenic processes in this organ. In the present study, transitional cell carcinomas induced in the urinary bladders of male F344 rats treated with 0.05% BBN for 16 or 32 weeks and then sacrificed at experimental week 32 were analyzed for mutational changes in the p53 and H-ras genes by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis and subsequent DNA sequencing. The total p53 mutation incidences were 3/10 (30%) and 8/12 (66.7%) in rats treated with BBN for 16 weeks followed by 16 weeks' non-treatment, or in rats treated with BBN for 32 weeks, respectively, while the H-ras mutation incidences were 0/10 (0%), and 1/12 (8.3%), respectively. The present results indicate that mutations in the p53 gene might be involved in the process of urinary bladder carcinogenesis by BBN as part of a multistep pathway. However, considering the decreasing tendency in lesions with p53 mutations after stopping BBN administration, a p53 mutation alone would not appear to be sufficient to give a marked selective advantage to mutant cells. No evidence of H-ras mutation involvement was gained even for the late course of rat urinary bladder carcinogenesis.

Original languageEnglish
Pages (from-to)105-112
Number of pages8
JournalCancer Letters
Volume105
Issue number1
DOIs
Publication statusPublished - 19-07-1996
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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