Spontaneous and 2-nitropropane induced levels of 8-hydroxy-2'-deoxyguanosine in liver DNA of rats fed iron-deficient or manganese- and copper-deficient diets

Rats (Wistar, female, 4 weeks old) were fed iron-deficient (Fe^–;2.2 µg Fe/g) or manganese- and copper-deficient (Mn.Cu^–;0.3 µg Mn/g, 0.4 ug Cu/g) diets for 8 weeks to determinethe oxidative damage of DNA by element deficiency. After feedingof the diets, 2-nitropropane (2-NP, 80 mg/kg body weight) wasadministered i. p. as an inducer of 8-hydroxy-2'-deoxyguanosine(8-OH-dG) to the element-deficient rats. The hemoglobin concentrationof rats in the Fe- group showed an induction of severe anemia(8.4 g/100 ml whole blood). In the Mn.Cu^– group, Mn-super-oxidedismutase (SOD) activities of plasma and Cu.Zn-SOD activitieswere significantly lower than that of the normal diet group.However, total SOD activities of plasma were not depressed severelyin contrast to that of the liver in the Mn.Cu^– group.Background (spontaneous) levels of 8-OH-dG in normal diet groupwere 0.96 + 0.37/105 deoxyguanosine (dG), however, significantlyhigher levels were detected in the Fe^– group (1.56±0.19,P < 0.01). Conversely, a lower (but not significant) levelof 8-OH-dG than the normal diet group were detected in the Mn.Cu^–group (0.78 ±0.08). Six hours after 2-NP treatment,8-OH-dG levels in liver DNA were significantly induced to 1.44+ 0.24 in the normal diet fed group 1.89±0.22 in theFe^– and 1.08±0.12 in the Mn.Cu^– groups. Comparedto the normal diet group, these induced levels of 8-OH-dG inthe Fe-group were significantly higher (P < 0.05), and thatin Mn. Cu^– group were significantly lower (P < 0.05).The high levels of 8-OH-dG in severe iron deficiency might bethe results of (i) an increase of hydroxyl radical generationby accumulated copper in hepatocytes; or (ii) a depression ofenzymatic activity for removing 8-hydroxy-2' -deoxyguanosinein DNA, which is dependent on divalent cations. On the otherhand, the low level of 8-OH-dG in manganese and copper deficiencymight be the result of a decrease of lipid peroxidation whichhas been suggested to be an intermediator from active oxygenspecies to hydroxyl radical.