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.

Abstract

Rats (Wistar, female, 4 weeks old) were fed iron-deficient (Fe-; 2.2 micrograms Fe/g) or manganese- and copper-deficient (Mn.Cu-; 0.3 microgram Mn/g, 0.4 microgram Cu/g) diets for 8 weeks to determine the oxidative damage of DNA by element deficiency. After feeding of the diets, 2-nitropropane (2-NP, 80 mg/kg body weight) was administered i.p. as an inducer of 8-hydroxy-2'-deoxyguanosine (8-OH-dG) to the element-deficient rats. The hemoglobin concentration of rats in the Fe- group showed an induction of severe anemia (8.4 g/100 ml whole blood). In the Mn.Cu- group, Mn-superoxide dismutase (SOD) activities of plasma and Cu.Zn-SOD activities were significantly lower than that of the normal diet group. However, total SOD activities of plasma were not depressed severely in contrast to that of the liver in the Mn.Cu- group. Background (spontaneous) levels of 8-OH-dG in normal diet group were 0.96 +/- 0.37/10(5) deoxyguanosine (dG), however, significantly higher levels were detected in the Fe- group (1.56 +/- 0.19, P < 0.01). Conversely, a lower (but not significant) level of 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 the Fe- and 1.08 +/- 0.12 in the Mn.Cu- groups. Compared to the normal diet group, these induced levels of 8-OH-dG in the Fe- group were significantly higher (P < 0.05), and that in Mn.Cu- group were significantly lower (P < 0.05). The high level of 8-OH-dG in severe iron deficiency might be the results of: (i) an increase of hydroxyl radical generation by accumulated copper in hepatocytes; or (ii), a depression of enzymatic activity for removing 8-hydroxy-2'-deoxyguanosine in DNA, which is dependent on divalent cations. On the other hand, the low level of 8-OH-dG in manganese and copper deficiency might be the result of a decrease of lipid peroxidation which has been suggested to be an intermediator from active oxygen species to hydroxyl radical.