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. 1998 Jul;89(7):696–702. doi: 10.1111/j.1349-7006.1998.tb03273.x

Significant Correlation of Nitric Oxide Synthase Activity and p53 Gene Mutation in Stage I Lung Adenocarcinoma

Hisao Fujimoto 1, Ji‐ichiro Sasaki 1,2, Mitsuhiro Matsumoto 1,✉, Moritaka Suga 1, Yukio Ando 1, Richard Iggo 3, Mitsuhiro Tada 4, Hideyuki Saya 2, Masayuki Ando 1
PMCID: PMC5921893  PMID: 9738975

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 9 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 be 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.

Keywords: key words, Nitric oxide, Nitric oxide synthase, p53, Lung adenocarcinoma, Yeast functional assay

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