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 |
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Authors: | Adachi, Shuichi Takemoto, Kazuo Hirosue, Toshiko Hosogai, Yuutaro |
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Affiliation: | Department of Public Health, Saitama Medical School Irumagun, Saitama 350-04 1Department of Food Hygiene, Kagawa Nutrition College Sakado, Saitama 35002, Japan |
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Abstract: | 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.Cugroup (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. |
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