8-hydroxy-2--deoxyguanosine and Uterine-Neoplasms

The pathological mechanisms of gestational trophoblastic disease have not yet been clearly determined. It is thought that oxidative damage contributes to the process. The aim of this study was to determine the levels of coenzyme Q10 (CoQ 10), DNA damage, and lipid peroxidation in patients with hydatidiform mole.. The authors studied the levels of CoQ10, 8-hydroxydeoxyguanosine (8-OHdG), malondialdehyde (MDA) by high-performance liquid chromatography (HPLC), and the activity of glutathione peroxidase (GPX) by spectrophotometric method in blood obtained from patients with a complete hydatidiform mole (n=29), healthy pregnant women (n=29), and healthy non-pregnant women (n=29).. The 8-OHdG/dG ratio (2.8148 ± 0.81592) and MDA (10.8341 ± 4.64875 μmol) were significantly higher in patients with complete hydatidiform mole, while the ubiquinol-10/ubiquinone-10 ratio (0.2107 ± 0.15675) and GPX activity (43.4606 ± 18.31694 mU/mI) were lower (p < 0.001).. The authors suggest that both mitochondrial oxidative and oxidative DNA damage play important roles in the pathogenesis of complete hydatidiform mole. Therefore supplementation of CoQ10 prevents recurrent gestational trophoblastic disease.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Case-Control Studies; Chromatography, High Pressure Liquid; Deoxyguanosine; DNA Damage; Female; Glutathione Peroxidase; Humans; Hydatidiform Mole; Lipid Peroxidation; Malondialdehyde; Mitochondria; Oxidation-Reduction; Pregnancy; Ubiquinone; Uterine Neoplasms; Vitamins; Young Adult

Oxidative stress is known to be an important contributing factor in many chronic diseases. Spontaneously occurring benign oviduct leiomyomas are common tumors of the Japanese quail (Coturnix coturnix japonica), which makes it a good animal model for screening potential agents for testing in the prevention and treatment of human myoma uteri. Since dietary intake of selenium has been associated with a reduced risk of a variety of human cancers, we investigated the effects of selenium supplementation on the development of leiomyomas in the Japanese quail. Potential mechanisms of action of selenium include its antioxidant properties and modulation of heat shock protein 70 (Hsp70); therefore, we measured levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), 8-isoprostane levels, and Hsp70 expression in tissue specimens obtained from the quails. One hundred and eighty quails (8 mo old) were assigned to 3 treatment groups consisting of 60 birds in each group. Birds were fed either a basal diet containing 0.048 mg Se per kg or the basal diet supplemented with 0.2 mg or 0.4 mg of selenium (Selenomax, yeast-bound l-selenomethionine, 60%) per kg of diet. The animals were sacrificed after 250 days, and the tumors were identified. Selenium supplementation did not affect the number of leiomyomas as compared to control subjects (P > 0.05). However, the tumors in selenium fed birds were smaller than those found in control birds (P = 0.01). Serum Se increased (P = 0.01), whereas MDA and 8-isoprostane, 8-OHdG concentrations decreased (P = 0.01) with selenium supplementation (P = 0.01). Selenium supplementation decreased Hsp70 in the tissue of birds. The results indicate that dietary supplementation with selenium reduces the size of spontaneously occurring leiomyoma of the oviduct in the Japanese quail.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Anticarcinogenic Agents; Antioxidants; Coturnix; Deoxyguanosine; Dietary Supplements; Dinoprost; Female; Genital Neoplasms, Female; HSP70 Heat-Shock Proteins; Incidence; Leiomyoma; Liver; Malondialdehyde; Oviducts; Random Allocation; Selenium; Selenomethionine; Tumor Burden; Uterine Neoplasms; Yeast, Dried

The results of this work show a higher level of 8-hydroxy-2'-deoxyguanosine (8-OH-dG), a typical biomarker of oxidative stress, in uterine myoma tissues than in their respective tumor-free tissues. The level of this modified base was elevated in uterine tissues of premenopausal women when compared with postmenopausal ones. We have also found the correlation between the size of the tumor and the amount of 8-OH-dG. These results suggest that estrogen-produced 8-OH-dG may be one of the factors responsible for the formation of the myoma, and it may contribute to malignant transformation of myoma cells.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Biomarkers; Deoxyguanosine; Female; Humans; Leiomyoma; Middle Aged; Oxidative Stress; Postmenopause; Premenopause; Reference Values; Uterine Neoplasms; Uterus