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

D H Auckley1, R E Crowell, E R Heaphy

  • 1Division of Pulmonary, Critical Care and Allergy, University of New Mexico and the New Mexico Veterans Health Care System, Albuquerque, NM 87108, USA.

Carcinogenesis
|April 27, 2001
PubMed

Insights

Reduced DNA repair capacity, specifically DNA-dependent protein kinase (DNA-PK) activity, is linked to increased lung cancer risk. Lower DNA-PK activity in individuals correlates with a higher susceptibility to developing lung cancer.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Genetics

Background:

  • Reduced DNA repair capacity for carcinogen-induced DNA damage is a key factor in inherent susceptibility to lung cancer.
  • DNA-dependent protein kinase (DNA-PK) is a critical enzyme involved in DNA double-strand break repair and transcriptional control.

Purpose of the Study:

  • To investigate interindividual variations in DNA-PK activity.
  • To determine the association between DNA-PK activity levels and lung cancer risk.

Main Methods:

  • DNA-PK activity was measured in peripheral mononuclear cells (PMNs) from lung cancer patients (n=41) and healthy controls (n=41).
  • Enzyme activity in PMNs was correlated with activity in bronchial epithelial cells.
  • The effect of DNA-PK activity on bronchial epithelial cell growth after bleomycin exposure was assessed.

Main Results:

  • Significant differences in DNA-PK activity distribution were observed between lung cancer cases and controls (P=0.03).
  • Fewer cases than controls exhibited high DNA-PK activity (7-10 units), while more cases had low to moderate activity (2.5-5.0 units).
  • DNA-PK activity in PMNs accurately reflected that in bronchial epithelial cells, validating PMNs as a suitable biomarker.

Conclusions:

  • Reduced DNA-PK activity is associated with an increased risk of lung cancer.
  • DNA-PK activity may serve as a potential modifier of lung cancer risk.
  • Peripheral mononuclear cells are a viable surrogate for studying DNA-PK activity in population-based lung cancer research.

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