Assessment of DNA base oxidation and glutathione level in patients with type 2 diabetes

Mutat Res. 2002 Aug 29;505(1-2):75-81. doi: 10.1016/s0027-5107(02)00143-4.

Abstract

The first aim of the present study was to examine the relationship between reduced glutathione (GSH) level, a powerful cellular antioxidant, and oxidative damage to DNA; and secondly, to see the effect of glycemic control on oxidative DNA damage in type 2 diabetics. We determined GSH level and, using the comet assay, formamidopyrimidine DNA glycosylase (Fpg)-sensitive sites which indicates oxidised guanine in freshly isolated blood from age-matched type 2 diabetics and controls. We found significant differences between men and women in the control group for both GSH and Fpg-sensitive sites. Therefore, we compared the controls and type 2 diabetics separately in men and women. GSH level of whole blood was found to be lower, Fpg-sensitive sites in leukocytes was found to be higher in the both type 2 diabetic men and women, as compared with their respective controls. When the diabetic group was divided into two groups as well-controlled diabetics and poorly-controlled diabetics with respect to glycosylated haemoglobine levels, it was found that Fpg-sensitive sites was significantly higher in the poorly-controlled diabetics than in the well-controlled diabetics in both the men and women. GSH level was lower in the poorly-controlled diabetics but not significantly. Fpg-sensitive sites were found to be moderately correlated with both glycosylated haemoglobine and GSH, and weakly correlated with glucose. Data indicate that decreased GSH level may be a contributory factor for enhanced oxidative DNA damage in type 2 diabetics; and chronic hyperglycemia derived from poorly-controlled diabetic conditions may induce oxidative DNA damage in these patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Comet Assay
  • DNA / blood*
  • DNA Damage*
  • DNA-Formamidopyrimidine Glycosylase
  • Diabetes Mellitus, Type 2 / genetics
  • Diabetes Mellitus, Type 2 / metabolism*
  • Female
  • Glutathione / blood*
  • Glycated Hemoglobin / analysis
  • Guanine / chemistry
  • Humans
  • Hyperglycemia / genetics
  • Hyperglycemia / metabolism
  • Male
  • Middle Aged
  • N-Glycosyl Hydrolases / pharmacology
  • Oxidation-Reduction
  • Oxidative Stress
  • Reactive Oxygen Species

Substances

  • Glycated Hemoglobin A
  • Reactive Oxygen Species
  • Guanine
  • DNA
  • N-Glycosyl Hydrolases
  • DNA-Formamidopyrimidine Glycosylase
  • Glutathione