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 an d mutation in vitro and may play a role in the multistage carcinogenic process. Tt has been reported that NO induces mutation in the p53 tum or suppressor gene; me therefore analyzed the relationship between NO synthase (NOS) activity and p53 gene status in early-stage lung adenoc arcinoma. Surgical samples were classified into two categories: 14 lun g adenocarcinomas with high NOS activity (>25 pmol/min/g tissue, categ ory A), and 16 with low NOS activity (<25 pmol/min/g tissue, category B). ii 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 sig nificantly 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 h ad a G:C-to-T:A transversion, which is reported to be a major target o f NO. The mechanism of carcinogenesis of adenocarcinoma is not fully u nderstood, but these results suggest that an excess of endogenously fo rmed NO may induce a p53 gene mutation containing mainly G:C-to-T:A tr ansversion in the early stage of lung adenocarcinoma. Our results sugg est that NO has potential mutagenic and carcinogenic activity, and may play important roles in human Lung adenocarcinoma.