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

Abstract

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. 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. 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. TAS was significantly decreased (905 +/- 112 micromol/l) in patients on a "loose diet" (group A) as compared to those when restored to their diet (group B) (1,340 +/- 112 micromol/l, p < 0.001) and controls (1,558 +/- 115 micromol/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. 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.