Open AccessSignificant Correlation of Nitric Oxide Synthase Activity and p53 Gene Mutation in Stage I Lung Adenocarcinoma
Author(s) -
Fujimoto Hisao,
Sasaki Jiichiro,
Matsumoto Mitsuhiro,
Suga Moritaka,
Ando Yukio,
Iggo Richard,
Tada Mitsuhiro,
Saya Hideyuki,
Ando Masayuki
Publication year - 1998
Publication title -
japanese journal of cancer research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 0910-5050
DOI - 10.1111/j.1349-7006.1998.tb03273.x
Subject(s) - transversion , adenocarcinoma , carcinogenesis , mutation , carcinogen , biology , mutation frequency , nitric oxide synthase , gene mutation , cancer research , microbiology and biotechnology , gene , tumor suppressor gene , lung cancer , nitric oxide , cancer , genetics , pathology , endocrinology , medicine
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.