Significant correlation of nitric oxide synthase activity and p53 gene mutation in stage I lung adenocarcinoma.
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 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.
Fujimoto
H
H
First Department of Internal Medicine, Kumamoto University School of Medicine.
Sasaki
J
J
Matsumoto
M
M
Suga
M
M
Ando
Y
Y
Iggo
R
R
Tada
M
M
Saya
H
H
Ando
M
M
D000230:Adenocarcinoma / Q000201:enzymology / Q000235:genetics*; D000368:Aged; D004247:DNA / Q000737:chemistry; D005260:Female; D016158:Genes, p53; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000378:metabolism*
D009569:Nitric Oxide; D004247:DNA; D019001:Nitric Oxide Synthase