Reduced DNA-dependent protein kinase activity is associated with lung cancer

Reduced DNA repair capacity of carcinogen-induced DNA damage is now thought to significantly influence inherent susceptibility to lung cancer. DNA-dep endent protein kinase (DNA-PK) is a serine-threonine kinase activated by th e presence of double-strand breaks in DNA that appears to play a major role in non-homologous recombination and transcriptional control. The purpose o f this study was to determine whether DNA-PK activity varies among individu als and how this affects lung cancer risk. DNA-PK activity in peripheral mo nonuclear cells from individuals with lung cancer (n = 41) was compared wit h lung cancer-free controls (n = 41), Interindividual variability was seen within each group, however, significant differences (P = 0.03) in DNA-PK ac tivity between cases and controls were seen when comparing the distribution of enzyme activity among these two groups. The percentages of cases and co ntrols with DNA-PK activity in the ranges 2.5-5.0 and 7.6-10.0 units were 3 9 versus 20% and 7 versus 29%, respectively. The enzyme activity in periphe ral mononuclear cells reflected that seen in bronchial epithelial cells, on e progenitor cell for lung cancer, supporting the use of peripheral mononuc lear cells for larger population-based studies of DNA-PK activity. Its role as a potential modifier for lung cancer risk was supported by the fact tha t cell growth in bronchial epithelial cells exposed to bleomycin was direct ly associated with enzyme activity. The results of this study demonstrate t hat reduced DNA-PK repair activity is associated with risk for lung cancer.