We determined relationship among DNA damage, nitric oxide (NO) and antioxidant defense in leukocytes of patients with Type 1 DM. DNA damage was evaluated as strand breakage and formamidopyrimidine DNA glycosylase (Fpg)-sensitive sites by the comet assay in DNA from leukocytes of the subjects. Nitrite level, as a product of NO, superoxide dismutase (SOD) activity and glutathione peroxidase (G-Px) activity of the leukocytes were measured by spectrophotometric kits. Serum glucose level and glycosylated haemoglobin (HbA(1c)) were higher in the patients, as expected. Differences in measured parameters between controls and patients were assessed in men and women separately. There was no significant difference between patient and control groups in neither men nor women for nitrite level. Strand breakage and Fpg-sensitive sites were found to be increased, SOD and G-Px activities of the leukocytes were found to be decreased in both men and women of patient group as compared to their respective controls. Significant correlations were determined between strand breakage and HbA(1c) (r 0.37, P < 0.05); Fpg-sensitive sites and HbA(1c) (r = 0.59, P < 0.01); Fpg-sensitive sites and glucose (r = 0.45, P < 0.02); Fpg-sensitive sites and SOD (r = -0.48, P < 0.02); HbA(1c), and SOD (r = -0.50, P < 0.02). In conclusion, impaired antioxidant defense in leukocytes of patients with Type I DM may be one of the responsible mechanisms for increased DNA damage in those patients. (C) 2003 Elsevier Science B.V. All rights reserved.