OXIDATIVE DAMAGE TO DNA IN PATIENTS WITH CYSTIC-FIBROSIS

Patients with cystic fibrosis (CF) may be more susceptible to oxidative-cell. injury due to impaired absorption of dietary-antioxidants. In addition, recurring pulmonary infections regularly subject them to oxidative stress. Our objective was to determine whether the concentration of urinary 8-hydroxydeoxyguanosine (oh(8)dG), a marker of free radical-induced DNA damage, is elevated in CF patients and to correlate its excretion with clinical status. The first morning void of urine was collected from 13 CF patients and 10 control children of similar age. To determine clinical status, forced expiratory volume (FEV(1)) and forced ventilatory capacity (FVC) and a Taussig-Schwachman score were obtained for each patient. Urinary oh(8)dG was measured by high performance liquid chromatography (HPLC) with electrochemical detection and the concentration normalized against creatinine concentration. The mean concentration (+/- SD) of urinary oh(8)dG was significantly higher in the CF group (2.78 +/- 1.21 vs. 1.51 +/- 0.38 nmol/mmol creatinine). A significant positive correlation was found between urinary oh(8)dG concentration and plasma alpha-tocopherol concentration in the CF patients (r = 0.947, p = 0.0001), suggesting that vitamin E might be involved in the excretion of oh(8)dG. However, no correlation was found between urinary oh(8)dG in CF and markers of lung function or the qualitative index of clinical status. These results confirm that patients with CF are susceptible to oxidative-induced DNA damage, although this appears to be independent of clinical status. Increased DNA damage may explain, in part, why CF patients have a higher incidence of malignancy compared to normal healthy age-matched controls.