Significant correlation of nitric oxide synthase activity and p53 gene mutation in stage I lung adenocarcinoma

Hisao Fujimoto, Ji Ichiro Sasaki, Mitsuhiro Matsumoto, Moritaka Suga, Yukio Ando, Richard Iggo, Mitsuhiro Tada, Hideyuki Saya, Masayuki Ando

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Nitric oxide (NO) and its derivatives can directly cause DNA damage and mutation in vitro and may play a role in the multistage carcinogenic process. It has been reported that NO induces mutation in the p53 tumor suppressor gene; we therefore analyzed the relationship between NO synthase (NOS) activity and p53 gene status in early-stage lung adenocarcinoma. Surgical samples were classified into two categories: 14 lung adenocarcinomas with high NOS activity (> 25 pmol/min/g tissue, category A), and 16 with low NOS activity (< 25 pmol/min/g tissue, category B). A yeast functional assay for p53 mutations disclosed a red colony that corresponded to a mutation in the p53 gene in 8 cases (57.1%) in category A and 3 cases (18.8%) in category B, the frequency being significantly higher in the former (P < 0.05). A p53 DNA sequence analysis revealed that 5 of the 8 p53 mutation-positive samples in category A had a G:C-to-T:A transversion, which is reported to he a major target of NO. The mechanism of carcinogenesis of adenocarcinoma is not fully understood, but these results suggest that an excess of endogenously formed NO may induce a p53 gene mutation containing mainly G:C-to-T:A transversion in the early stage of lung adenocarcinoma. Our results suggest that NO has potential mutagenic and carcinogenic activity, and may play important roles in human lung adenocarcinoma.

Original languageEnglish
Pages (from-to)696-702
Number of pages7
JournalJapanese Journal of Cancer Research
Volume89
Issue number7
DOIs
Publication statusPublished - 07-1998

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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