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

研究成果: Article査読

50 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)696-702
ページ数7
ジャーナルJapanese Journal of Cancer Research
89
7
DOI
出版ステータスPublished - 07-1998
外部発表はい

All Science Journal Classification (ASJC) codes

  • 腫瘍学
  • 癌研究

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