We have developed a new strategy for the evaluation of the mutagenicity of a damaged DNA precursor (deoxyribonucleoside 5-triphosphate) in Escherichia coli. 8-Hydroxydeoxyguanosine triphosphate (8-OH-dGTP) and 2-hydroxydeoxyadenosine triphosphate (2-OHdATP) were chosen for this study because they appear to be formed abundantly by reactive oxygen species in cells. We introduced the oxidatively damaged nucleotides into competent E. coli and selected mutants of the chromosomal lacI gene. Both damaged nucleotides induced lacI gene mutations in a dose-dependent manner, whereas unmodified dATP and dGTP did not appear to elicit the mutations. The addition of 50 nmol of 8-OHdGTP and 2-OH-dATP into an E. coli suspension induced 12-and 9-fold more substitution mutations than the spontaneous event, respectively. The 8-OH-dGTP induced A⅐T 3 C⅐G transversions, and the 2-OH-dATP elicited G⅐C 3 T⅐A transversions. These results indicate that the two oxidatively damaged nucleotides are mutagenic in vivo and suggest that 8-OH-dGTP and 2-OH-dATP were incorporated opposite A and G residues, respectively, in the E. coli DNA. This new method enables the evaluation and comparison of the mutagenic potentials of damaged DNA precursors in vivo.
The expression of vascular endothelial growth factor was one of the most important prognostic factors in completely resected non-small-cell lung cancer, especially in squamous cell carcinoma.
The detection of lymph nodal micrometastasis by cytokeratin and p53 protein immunohistochemical staining will be helpful to predict the recurrence and prognosis of patients with completely resected stage 1 NSCLC.
The detection of lymph nodal micrometastatic tumor cells provides an accurate assessment of tumor staging and has powerful prognostic implications for completely resected stage I NSCLC patients.
Detection of p53 mutations may help in the selection of NSCLC patients suitable for appropriate investigational therapeutic strategies in view of improving their survival and quality of life.
RESULTS. Thirty-one of 115 NSCLC specimens (27%) showed negative p16 staining.
Department of Surgery II, School of Medicine,The frequency of negative p16 expression was significantly higher in squamous University of Occupational and Environmental cell carcinoma (39.5%) than in adenocarcinoma (20.3%) (P Å 0.026). There were Health, Kitakyushu, Japan.no statistically significant differences in the p16 status with respect to age, gender, smoking history, histologic differentiation, or stage of the disease. The KaplanMeier survival curves demonstrated that patients with negative p16 expression survived for a significantly shorter period of time than those with positive p16 expression (P Å 0.043). p16 status was a significant prognostic factor, especially in patients with early stage disease (Stages I-II) (P Å 0.039).
CONCLUSIONS.A lack of p16 INK4 expression in NSCLC was observed more frequently in squamous cell carcinoma than in adenocarcinoma, and also was found to be closely related to prognosis, especially in patients with early stage squamous cell carcinoma.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.