PURPOSE: Except hormonal agents and biologic response modifier, the biologic effects of chemotherapy and radiotherapy as anti-cancer therapy have the mechanism of DNA injury. They cause not only cancer cell necrosis, but also infertility, bone marrow suppression, secondary malignancy, and individual death. There are many reports to human genome or chromosomal injuries by radiation but few by chemotherapy. Therefore this study is designed for systemic evaluation of the frequency of chromosomal damage by chemotherapy. MATERIALS AND METHODS: We performed evaluation of chromosomal aberration, sister chromatid exchange, and mitotic index were examined in 3 patient with NSCLC. Two of them were stage IIIb and the other one was stage IV. Venous blood was taken from patients before chemotherapy and one day after last administration of combination chemotherapy. Microscopic examination for chromosomal aberration, chromatid aberration, and SCEs was done after cell culture and FPG stain. RESULTS: The incidence of chromatid break was 3 before chemotherapy and 26 after chemotherapy. The incidence of SCEs was 9.85 1.93 before chemotherapy and 40.47 7.12 after chemotherapy. CONCLUSION: Incidence of chromatid break and SCEs increased after combination chemotherapy.
Bone Marrow ; Carcinoma, Non-Small-Cell Lung ; Cell Culture Techniques ; Chromatids ; Chromosome Aberrations* ; DNA Damage ; Drug Therapy ; Drug Therapy, Combination ; Genome, Human ; Humans ; Incidence ; Infertility ; Mitotic Index ; Necrosis ; Radiotherapy ; Sister Chromatid Exchange

BACKGROUND AND OBJECTIVES: Apurinic/apyrimidinic endonuclease 1/redox effector factor-1 (APE1/Ref-1) is a multifunctional protein involved in the DNA base excision repair pathway, inflammation, angiogenesis, and survival pathways. We investigated serum APE1/Ref-1 in patients with coronary artery disease (CAD). SUBJECTS AND METHODS: Serum APE1/Ref-1 was measured with a sandwich enzyme-linked immunosorbent assay from 360 patients who received coronary angiograms. They were divided into two groups; a control (n=57) and a CAD group (n=303), the latter included angina (n=128) and myocardial infarction (MI, n=175). RESULTS: The levels of APE1/Ref-1 were higher in the CAD than the control (0.63+/-0.07 vs. 0.12+/-0.07 ng/100 microL, respectively; p<0.01). They were also higher in MI than angina (0.81+/-0.10 vs. 0.38+/-0.11 ng/100 microL, respectively; p<0.01) and different according to the thrombolysis in myocardial infarction (TIMI) flow (0.88+/-0.09 for TIMI flow 0, 1, 2 vs. 0.45+/-0.13 ng/100 microL for TIMI flow 3, p<0.01) in acute coronary syndrome. In correlation analysis, the levels of APE1/Ref-1 were positively correlated with Troponin I (r=0.222; p<0.0001) and N-terminal pro-B type natriuretic peptide (NT-proBNP, r=0.217; p<0.0001) but not high sensitivity to C-reactive protein. Also, they revealed a negative correlation with ejection fraction (EF, r=-0.221; p=0.002). However, there were no significant differences among the three groups, were divided by their levels of APE1/Ref-1, for major adverse cardiovascular events (death, recurrent MI, stroke, revascularization) (8.2 vs. 14.0 vs. 12.5%, p=ns). CONCLUSION: The levels of serum APE1/Ref-1 are elevated in CAD, and are higher in MI than in angina. They are correlated with Troponin I, NT-proBNP, and EF.
Acute Coronary Syndrome ; Biomarkers ; C-Reactive Protein ; Coronary Artery Disease* ; Coronary Vessels* ; DNA ; DNA Repair ; Enzyme-Linked Immunosorbent Assay ; Humans ; Inflammation ; Myocardial Infarction ; Stroke ; Troponin I