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-cell gel electrophoresis assay (comet assay). DNA repair capacity, after 15 min 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). Bleomycin sensitivity defined as the tail moment of bleomycin-treated peripheral blood lymphocytes, without allowing time for DNA repair, was significantly higher in lung cancer patients than in tumor-free hospital controls (p < 0.0001). There was no correlation, in either patient or control group, between 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 adjustment 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 increased bleomycin sensitivity (OR = 4; 95% CL 2.2-7.4). For current smokers, the 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 test has sufficient sensitivity and rapidity allowing application to both native and cryopreserved lymphocytes. Bleomycin sensitivity and DNA repair capacity were found to be 2 independent susceptibility markers for non-small cell lung cancer, confirming similar investigations with different marker end 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 numbers of individuals in epidemiological studies. Validation of this assay in large prospective studies for the identification of subjects at high risk for non-small cell lung cancer is now warranted.
Division of Toxicology and Cancer Risk Factors, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany.
N
N
Rajaee-Behbahani
P
P
Schmezer
A
A
Risch
W
W
Rittgen
K W
KW
Kayser
H
H
Dienemann
V
V
Schulz
P
P
Drings
S
S
Thiel
H
H
Bartsch
D000328:Adult; D000367:Age Factors; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy*; D016022:Case-Control Studies; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects; D004260:DNA Repair; D019008:Drug Resistance, Neoplasm; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007091:Image Processing, Computer-Assisted; D008175:Lung Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy*; D008214:Lymphocytes / Q000378:metabolism; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D012307:Risk Factors; D012737:Sex Factors; D012907:Smoking; D013997:Time Factors