Altered DNA repair capacity and bleomycin sensitivity as risk markers for non-small cell lung cancer

DNA repair capacity in human peripheral blood lymphocytes was monitored by the repair rate of bleomycin-induced DNA damage using an alkaline single-ce ll gel electrophoresis assay (comet assay). DNA repair capacity, after 15 m in repair time, in lymphocytes of non-small cell lung cancer patients (n = 160) and controls (n = 180) was 67% and 79.3%, respectively (p < 0.0004), B leomycin sensitivity defined as the tail moment of bleomycin-treated periph eral blood lymphocytes, without allowing rime for DNA repair, was significa ntly higher in lung cancer patients than in tumor-free hospital controls (p < 0.0001), There was no correlation, in either patient or control group, b etween the bleomycin sensitivity and DNA repair capacity with age or gender . The median values of DNA repair capacity and sensitivity in controls were used as the cut-off points for calculating odds ratios (OR), After adjustm ent for age, gender and smoking status, the cases vs. controls had reduced DNA repair capacity (OR = 2.1; 95% confidence limit [CL] 1.1-4.0) and incre ased bleomycin sensitivity (OR = 4; 95% CL 2.2-7.4). For current smokers, t he adjusted risk associated with bleomycin sensitivity was 2.3 (95% CL 1.1- 4.9). We conclude that our standard comet assay as a phenotypical repair te st has sufficient sensitivity and rapidity allowing application to both nat ive and cryopreserved lymphocytes. Bleomycin sensitivity and DNA repair cap acity were found to be 2 independent susceptibility markers for non-small c ell lung cancer, confirming similar investigations with different marker en d points. The latter were much more time consuming than the method used in our study. Thus, the comet assay is more suitable for screening large numbe rs of individuals in epidemiological studies. Validation of this assay in l arge prospective studies for the identification of subjects at high risk fo r non-small cell lung cancer is now warranted. (C) 2001 Wiley-Liss, Inc.