8‐hydroxy‐2‐desoxyguanosine serum concentrations as a marker of DNA damage in patients with classical galactosaemia

Abstract

Abstract Background: Classical galactosaemia is caused by a deficiency of galactose‐1‐phosphate uridyl transferase, resulting in high galactose (Gal), galactose‐1‐phosphate (Gal‐1‐P) and galactitol blood levels. Galactose/lactose restriction intake is the only treatment. 8‐hydroxy‐2‐desoxyguanosine (8‐OHdG) is a marker of oxidized DNA damage. Aim: Since galactosaemia outcome is closely related to restriction of Gal intake, we aimed to evaluate correlations between Gal‐1‐P, total antioxidant status (TAS) and 8‐OHdG blood levels in galactosaemic patients on poor or strict diet. Methods: Venous blood samples were obtained from galactosaemic patients (n = 11) on poor diet (group A) and after 30 d on strict diet (group B). Twenty‐eight healthy children were the controls. Gal‐1‐P and TAS were evaluated in their blood spectrophotometrically and 8‐OHdG with an immunoassay. Results: TAS was significantly decreased (905±112 µmol/l) in patients on a “loose diet” (group A) as compared to those when restored to their diet (group B) (1340±112 µmol/l, p<0.001) and controls (1558±115 µmol/l, p<0.001). As expected, Gal‐1‐P levels were remarkably increased in group A. 8‐OHdG level was twofold higher (0.25±0.03 ng&ml) in group A than that of group B (0.11±0.04 ng/ml) and threefold higher than that of the controls (0.08±0.02 ng/ml). TAS and Gal‐1‐P inversely correlated to 8‐OHdG (r= − 0.802, p<0.001), whereas Gal‐1‐P positively correlated to 8‐OHdG (r=0.820, p<0.001) in all the groups. Conclusion: a) Low TAS and high Gal‐1‐P levels are implicated with high 8‐OHdG blood levels in galactosaemic patients; b) 8‐OHdG may be a sensitive biomarker of DNA damage in patients with classical galactosaemia.