Decreased Repair Activities of 1,N-Ethenoadenine and 3,N-Ethenocytosine in Lung Adenocarcinoma Patients

To assess the role of oxidative stress and lipid peroxidation (LPO) in the pathogenesis of lung cancer, we measured the levels of 1,Nethenoadenine ( A) and 3,N-ethenocytosine ( C) in the DNA by immunoaffinity/P postlabeling (33 cases). We also measured the capacity for A and C repair (by the nicking assay) in normal and tumor lung tissues, as well as in blood leukocytes of lung cancer patients (56 cases). Repair activities for A and C were also assayed in leukocytes of healthy volunteers, matched with cancer patients for age, sex, and smoking habit (25 individuals). Up to 10-fold variations among individuals were observed both in adducts level and repair activities. No differences in A and C levels between tumor and nonaffected lung tissues were recorded. However, leukocytes accumulated a significantly higher number of DNA adducts than the lung tissues. Repair activities for both A and C were significantly higher in tumor than in normal lung tissue. No significant differences in A and C repair activities were associated with age, sex, or smoking habit. However, a significant difference in repair capacity was observed between two histological types of lung cancer, squamous cell carcinoma (SQ) and adenocarcinoma (AD). In individuals suffering from lung AD, Aand C-repair activities in normal lung and blood leukocytes were significantly lower than in SQ patients. Moreover, in nonaffected lung tissue of AD patients, the ratio A/ C adducts was lower than in SQ patients. Differences have also been found between A and C repair activities of cancer patients and healthy volunteers. Repair capacity for A was significantly lower in blood leukocytes of lung cancer patients than in leukocytes of healthy volunteers (P 0.012). This difference was even larger between healthy volunteers and patients developing inflammation-related AD (P 0.00033). Repair activities for C were the same in leukocytes of healthy controls, all lung cancer patients, and SQ patients. However, individuals with ADs revealed significantly lower C-repair activity