Induction of 8-Hydroxydeoxyguanosine Formation in DNA by Fructose and Glucose in the Presence of Copper

Abstract

Summary The effects of glucose and fructose in the presence or absence of iron or copper on the formation of 8-hydroxydeoxyguanosine (8-OHdG) in calf-thymus DNA were examined. Glucose (5 and 10 mM) and fructose (10-200 µM) increased 8-OHdG formation 1.9-2.8 times and 3.0-8.3 times compared to the control, respectively. In the presence of fructose (200 µM), copper (50 µM) was found to increase 8-OHdG formation 46.2 times compared to the control, and 3.8 times compared to the iron (50 µM)-treated value. The stimulatory potency of 8-OHdG formation by fructose (200 µM) in the presence of copper (50 µM) was much stronger than that by glucose (10 mM) in the presence of iron (50 µM) or of copper (50 µM). Sorbitol, 3-deoxyglucosone and methylglyoxal in the presence or absence of copper had no or weaker stimulating effects on 8-OHdG formation than fructose in the presence or absence of copper. These results suggest that fructose in the presence of copper has the potential to dramatically induce oxidative DNA damage.

DNA-bound metal ions: recent developments

“…The enhanced ability of the fructose/Cu(II) system to cause oxidative damage is suggested to proceed by a mechanism where fructose (a reducing sugar) reduces DNA-bound Cu(II) to produce a · fructose (enediol radical anion)-DNACu + complex. This complex can react subsequently with H 2 O 2 to produce a DNA-Cu + -OOH complex, regenerating fructose (50). This study is significant because it connects DNA-bound Cu(II) with many of the observations associated with diabetes, including elevated fructose levels, release of metal ions from intracellular stores [including Cu(II)], and elevated levels of 8-OH-dG.…”