MENDOZA-NÚÑEZ, V.M., RUIZ-RAMOS, M., SÁNCHEZ-RODRÍGUEZ, M.A., RETANA-UGALDE, R. and MUÑOZ-SÁNCHEZ, J.L. Aging-Related Oxidative Stress in Healthy Humans. Tohoku J. Exp. Med., 2007, 213 (3), 261-268 Oxidative stress has been reported to increase with aging; however, the scientifi c evidence is controversial. We therefore aimed to analyze the relationship between aging and some markers of oxidative stress. A crosssectional and comparative study was carried out in a sample of 249 healthy subjects: (i) 25-29 years (n = 22); (ii) 30-39 years (24); (iii) 40-49 years (30); (iv) 50-59 years (48); (v) 60-69 years (60), and (vi) 70 years (65). We measured lipoperoxides and total antioxidant status in plasma and superoxide dismutase and glutathione peroxidase activities in erythrocytes. There was an age-related increase in lipoperoxides, which was evident in the comparison of the group of 25-29 years (0.22 ± 0.11 μ mol/l) with the group of 60-69 years (0.38 ± 0.18 μ mol/l, p < 0.01) and 70 years (0.42 ± 0.19, p < 0.001). Conversely, the total antioxidant status showed an age-related decrease (25-29 years, 1.4 ± 0.31 mmol/l vs 60-69 years, 1.1 ± 0.21 and 70 years, 1.1 ± 0.22, p < 0.05 for each). In erythrocytes, glutathione peroxidase activity showed an age-related decrease (25-29 years, 7,966 ± 1,813 UI/l vs 60-69 years, 6,193 ± 2,235 and 70 years, 6,547 ± 2,307, p < 0.001 for each), whereas superoxide dismutase activity was similar in all age groups. Importantly, there was no age-related change in oxidative stress markers in subjects of < 60 years. These fi ndings suggest that age of 60 years may be associated with increased oxidative stress.aging; oxidative stress; superoxide dismutase; lipoperoxides; antioxidant enzymes

These results suggest that ROS generation might be the cause of cytotoxicity, which seems to be related to initial genetic damage rather than to lipid peroxidation. HeLa cells showed to be more sensitive than normal cells.

Copper [Cu(II)] is an ubiquitous transition and trace element in living organisms. It increases reactive oxygen species (ROS) and free-radical generation that might damage biomolecules like DNA, proteins, and lipids. Furthermore, ability of Cu(II) greatly increases in the presence of oxidants. ROS, like hydroxyl (.OH) and superoxide (.O(2)) radicals, alter both the structure of the DNA double helix and the nitrogen bases, resulting in mutations like the AT-->GC and GC-->AT transitions. Proteins, on the other hand, suffer irreversible oxidations and loss in their biological role. Thus, the aim of this investigation is to characterize, in vitro, the structural effects caused by ROS and Cu(II) on bacteriophage lambda DNA or proteins using either hydrogen peroxide (H(2)O(2)) or ascorbic acid with or without Cu(II). Exposure of DNA to ROS-generating mixtures results in electrophoretic (DNA breaks), spectrophotometric (band broadening, hypochromic, hyperchromic, and bathochromic effects), and calorimetric (denaturation temperature [T(d)], denaturation enthalpy [DeltaH], and heat capacity [C(p)] values) changes. As for proteins, ROS increased their thermal stability. However, the extent of the observed changes in DNA and proteins were distinct, depending on the efficiency of the systems assayed to generate ROS. The resulting effects were most evident when Cu(II) was present. In summary, these results show that the ROS, .O2 and .OH radicals, generated by the Cu(II) systems assayed deeply altered the chemical structure of both DNA and proteins. The physiological relevance of these structural effects should be further investigated.

Human natural killer (NK) cells are considered professional cytotoxic cells that are integrated into the effector branch of innate immunity during antiviral and antitumoral responses. The purpose of this study was to examine the peripheral distribution and expression of NK cell activation receptors from the fresh peripheral blood mononuclear cells of 30 breast cancer patients prior to any form of treatment (including surgery, chemotherapy, and radiotherapy), 10 benign breast pathology patients, and 24 control individuals. CD3−CD56dimCD16bright NK cells (CD56dim NK) and CD3−CD56brightCD16dim/− NK cells (CD56bright NK) were identified using flow cytometry. The circulating counts of CD56dim and CD56bright NK cells were not significantly different between the groups evaluated, nor were the counts of other leukocyte subsets between the breast cancer patients and benign breast pathology patients. However, in CD56dim NK cells, NKp44 expression was higher in breast cancer patients (P = .0302), whereas NKp30 (P = .0005), NKp46 (P = .0298), and NKG2D (P = .0005) expression was lower with respect to healthy donors. In CD56bright NK cells, NKp30 (P = .0007), NKp46 (P = .0012), and NKG2D (P = .0069) expression was lower in breast cancer patients compared with control group. Only NKG2D in CD56bright NK cells (P = .0208) and CD56dim NK cells (P = .0439) showed difference between benign breast pathology and breast cancer patients. Collectively, the current study showed phenotypic alterations in activation receptors on CD56dim and CD56bright NK cells, suggesting that breast cancer patients have decreased NK cell cytotoxicity.

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