dG Ratio Research Articles

Lithium Slag and Solid Waste-Based Binders for Cemented Lithium Mica Fine Tailings Backfill.

To mitigate the adverse effects of fine-grained lithium mica tailings and other solid wastes generated from the extraction of lithium ore mining, as well as the limitations of traditional cement-based binders for lithium mica fine tailings, this study explores the feasibility of using a binder composed of ordinary Portland cement, lithium slag, fly ash, and desulfurization gypsum to stabilize lithium fine tailings into cemented lithium tailings backfill. Compared with traditional cementitious binders, an extensive array of experiments and analyses were conducted on binders formed by various material proportion combinations, employing uniaxial compressive strength tests, microstructural morphology, grayscale analyses, and flowability tests. The results show the following: (1) In this study, an LSB binder exhibiting superior mechanical properties compared to traditional cementitious binders was identified, with an optimal OPC:LS:FA:DG ratio of 2:1:1:1. (2) In the context of cemented lithium mica fine tailings, the LSB-CLTB material exhibits higher unconfined compressive strength and lower self-weight compared to OPC-CLTB materials. At a binder content of 10 wt%, the UCS values achieved by the LSB-CLTB material at curing periods of 7 days, 14 days, and 28 days are 0.97 MPa, 1.52 MPa, and 2.1 MPa, respectively, representing increases of 40.6%, 34.5%, and 44.8% over the compressive strength of OPC-based materials under the same conditions. (3) The LSB binder not only exhibits enhanced pozzolanic reactivity but also facilitates the infilling of detrimental pores through its inherent particle size and the formation of AFt and C-(A)-S-H gels via hydration reactions, thereby effectively improving the compressive strength performance of fine-grained tailings backfill.

Vicarious Radiometric Calibration of the Multispectral Imager Onboard SDGSAT-1 over the Dunhuang Calibration Site, China

The multispectral imager (MII), onboard the Sustainable Development Science Satellite 1 (SDGSAT-1), performs detailed terrestrial change detection and coastal monitoring. SDGSAT-1 was launched at 2:19 UTC on 5 November 2021, as the world’s first Earth science satellite to serve the United Nations 2030 Sustainable Development Agenda. A vicarious radiometric calibration experiment was conducted at the Dunhuang calibration site (Gobi Desert, China) on 14 December 2021. In-situ measurements of ground reflectance, aerosol optical depth (AOD), total columnar water vapor, radiosonde data, and diffuse-to-global irradiance (DG) ratio were performed to predict the top-of-atmosphere radiance by the reflectance-, irradiance-, and improved irradiance-based methods using the moderate resolution atmospheric transmission model. The MII calibration coefficients were calculated by dividing the top-of-atmosphere radiance by the average digital number value of the image. The radiometric calibration coefficients calculated by the three calibration methods were reliable (average relative differences: 2.20% (reflectance-based vs. irradiance-based method) and 1.43% (reflectance-based vs. improved irradiance-based method)). The total calibration uncertainties of the reflectance-, irradiance-, and improved irradiance-based methods were 2.77–5.23%, 3.62–5.79%, and 3.50–5.23%, respectively. The extra DG ratio measurements in the latter two methods did not improve the calibration accuracy for AODs ≤ 0.1. The calibrated MII images were verified using Landsat-8 Operational Land Imager (OLI) and Sentinel-2A MultiSpectral Instrument (MSI) images. The retrieved ground reflectances of the MII over different surface types were cross-compared with those of OLI and MSI using the FAST Line-of-sight Atmospheric Analysis of Hypercubes software. The MII retrievals differed by <0.0075 (7.13%) from OLI retrievals and <0.0084 (7.47%) from MSI retrievals for calibration coefficients from the reflectance-based method; <0.0089 (7.57%) from OLI retrievals and <0.0111 (8.65%) from MSI retrievals for the irradiance-based method; and <0.0082 (7.33%) from OLI retrievals and <0.0101 (8.59%) from MSI retrievals for the improved irradiance-based method. Thus, our findings support the application of SDGSAT-1 data.

Oxidative DNA Damage Is Increased in Living Kidney Donors

BackgroundLong-term consequences of donor nephrectomy might be reduced kidney function, increased risk for cardiovascular disease, and impaired quality of life. The purpose of the current cross-sectional study was to evaluate the relationship between clinical, laboratory, and donation-specific outcomes of living kidney donors and systemic oxidative DNA damage. MethodsWe conducted a cross-sectional study and assessed retrospectively pre- and postdonation data from 60 donors who donated between 2010 and 2015. Plasma malondialdehyde levels and 8-hydroxy-2′-deoxyguanosine/deoxyguanosine ratio (8-OHdG/dG ratio) were determined as oxidative stress markers. Catalase, carbonic anhydrase, and paraoxonase (PON) activities were measured as antioxidants. ResultsApproximately 3 years after donation, the hypertensive donor ratio was 12%, and 11% of the donors had glomerular filtration rate <60 mL/min/1.73 m2. Mean serum urea (P = .001) and serum creatinine levels (P = .001) were increased; creatinine clearance level (126.2 ± 35.5 vs 94.6 ± 26.8, P = .001) was decreased in the postdonation period. There was a significant positive correlation between predonation serum urea and 8-0HdG/dG ratio (r = 0.338, P = .016) and predonation serum creatinine and 8-0HdG/dG ratio (r = 0.442, P = .001), while there was a significant negative correlation between serum creatinine and PON activity (r = −0.545, P < .001). ConclusionOur data have demonstrated that kidney donors exhibit increased oxidative DNA damage and decreased antioxidant activity. We propose that predonation serum creatinine is positively correlated with 8-0HdG/dG ratio and negatively correlated with antioxidant PON activity. This is the first study to demonstrate that plasma oxidative DNA damage increases in healthy kidney donors.

Levels of leukocyte oxidative DNA damage (8-OHdG), serum coenzyme Q10 and lipid peroxidation in the formation attacks of patients with multiple sclerosis

Multiple sclerosis (MS) is a demyelinating disease&#x0D; of the nervous system. Evidence about oxidative stress plays an important role&#x0D; in the pathogenesis of MS is increasing day by day. In our study, we aimed to&#x0D; investigate the effect of oxidative DNA damage and oxidative stress in the&#x0D; pathogenesis of MS disease. Blood samples were obtained from during an attack&#x0D; (Group 1), between attacks (Group 2) of MS patients (20 male and 10 female) and&#x0D; 30 healthy volunteers (Group 3). Malondialdehyde (MDA) levels as indicator of&#x0D; oxidized lipids were detected using fluorescence dedector with high pressure&#x0D; liquid chromatograph (HPLC). DNA was extracted from leukocytes of control and&#x0D; patients with MS and then we measured 8-hydroxy- 2' -deoxyguanosine (8-OHdG) and deoxyguanosin (dG) by using HPLC method with electrochemical and&#x0D; UV detector, respectively. Measurement of oxidized coenzyme Q10 (CoQ10) and&#x0D; reduced CoQ (CoQ10H) was performed by using UV detector with HPLC method. Serum&#x0D; MDA level of group 1 was significantly higher than those in group 2 and group 3&#x0D; (p&amp;lt; 0.001). 8- OHdG/106 dG ratio&#x0D; of group 1 was significantly higher than those in group 2 and group 3 (p&amp;lt;&#x0D; 0.001). CoQ10/CoQ10H rates of group 1 were significantly increased compared&#x0D; with group 2 and group 3 (p&amp;lt;0.001). In conclusion, we observed that&#x0D; oxidative DNA damage, lipid and mitochondria oxidative damage were high in&#x0D; blood of patients with MS. It seems that oxidative stress acts a play role the&#x0D; pathogenesis of MS patients as well as induces attacks.&#x0D; &#x0D;

CHANGES OF 8-OXO-2'-DEOXYGUANOSINE LEVEL IN MOUSE LIVER CELLS DNA IN CASE OF ACUTE TOXIC STRESS

The changes of the 8-oxo-2'-deoxyguanosine (8-oxo-dG)/dG ratio in the DNA of laboratory mice hepatocytes under the influence of toxic stress were studied. It was shown that the injection of carbon tetrachloride causes the growth of 8-oxo-dG level. A rapid increase in the level of 8-oxo-dG in DNA occurs during the first day of the experiment at short-term toxic stress. Subsequently, 48 hours after the initial injection, the level of 8-oxo-dG decreases to the control values. This change in the value of the biomarker can be attributed to the activation of the reparative and antioxidant systems. The subsequent injection results again in an increase of 8-oxo-dG level, and the latter only increases thereafter. This reflects the exhaustion of the reparative potential of the organism and accompanies the progress of inflammation and pathological change of the liver tissue.

In Vitro Formation of 8-hydroxy-2-deoxyguanosine (8-OHdG) in Calf Thymus DNA upon Treatment of 2-deoxyguanosine with Propyl Gallate and 2,6-di-tert-butyl-p-benzoquinone

Oxidative DNA damage caused by propyl gallate (PG) and 2,6-di- tert -butyl- p -benzoquinone (BHT-quinone, a metabolite of butylated hydroxytoluene (BHT)) was analyzed from the 8-hydroxy-2 ¢ -deoxyguanosine (8-OHdG) formation in calf thymus DNA and DNA base, 2 ¢ -deoxyguanosine (dG). PG in the presence of CuCl 2 increased the 8-OHdG formation in calf thymus DNA by around 9.17 times as compared to the control (untreated DNA). In the presence of CuCl 2 at 1.28×10 -5 M, the 8-OHdG per dG ratio resulting from the reaction of dG with PG at various concentrations (20–150 ppm) ranged from 75.50 to 312.06 8-OHdG per 10 5 dG. The 8-OHdG formation increased when the PG concentration was increased from 20 ppm to 80 ppm, and then, it began to plateau around 80 ppm. On the other hand, BHT-quinone increased the formation of 8-OHdG in the presence of CuCl 2 by 0.05 times as compared to the control (untreated DNA). LC-MS/MS analysis was used to identify the molecular structure of 8-OHdG, which had a base peak (M +. + 1) at m/z = 284 and two main fragments at m/z = 167.9 and m/z = 139.9.

Correlations between Oxidative DNA Damage, Oxidative Stress and Coenzyme Q10 in Patients with Coronary Artery Disease

The correlation of coronary artery disease (CAD) with pro-oxidant/antioxidant balance and oxidative DNA damage was investigated.Seventy-seven patients with CAD and 44 healthy individuals as control were included in this study. The comparative ratios of ubiquinol-10/ubiquinone-10, 8-hydroxy-2'-deoxyguanosine/deoxyguanosine and the level of MDA measured by HPLC and the activities of GPX and SOD by colorimetric approach in blood samples obtained from patients with CAD were unraveled.8-OHdG/dG ratios, serum MDA level and GPX activity were found significantly elevated level in serum of CAD patients compared to control group. The SOD activity was observed in stable levels in CAD patients. Ubiquinol-10/ubiquinone-10 ratio was significantly lower in patients with CAD than the controls.The positive correlation was observed between 8-OHdG/dG ratios in both MDA levels and GPX activity, while the significant negative correlation was seemed between the ratio of 8-OHdG/dG and ubiquinol-10/ ubiquinone-10 as well as MDA levels and ubiquinol-10/ ubiquinone-10 ratio.We conclude that, both the disruption of pro-oxidant/antioxidant balance and oxidative stress in DNA may play an important role in the pathogenesis of coronary artery disease.

Accelerated atherosclerosis in haemodialysis patients; correlation of endothelial function with oxidative DNA damage

Accelerated atherosclerosis is the major cause of mortality in patients on chronic haemodialysis (HD). The aim of this study was to evaluate the relationship between oxidative DNA damage [8-hydroxy-2'-deoxyguanosine/deoxyguanosine ratio (8-OHdG/dG ratio)], oxidative stress biomarkers and endothelial function in HD patients as an indicator of atherosclerosis. Forty-four chronic HD patients without known atherosclerotic disease and 55 age- and sex-matched healthy individuals were included in the study. Plasma malondialdehyde (MDA) levels and 8-OHdG/dG ratio were determined as oxidative stress markers. Superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities were measured as antioxidants. Endothelial function was assessed by ultrasonography. 8-OHdG/dG ratio and MDA levels were higher in HD patients than controls while SOD and GPx activities were lower in HD patients compared to controls. Flow-mediated dilatation FMD% in HD patients were lower than the control group (7.28 ± 0.79 versus 11.18 ± 0.82, P < 0.001). There was a significant negative correlation between FMD% and 8-OHdG/dG ratio (r = -0.678, P < 0.01) and MDA levels (r = -0.517, P < 0.01), while there was a significant positive correlation between FMD% and SOD (r = 0.538, P < 0.01) and GPx levels (r = 0.720, P < 0.01). Our data have demonstrated that HD patients exhibit increased oxidative DNA damage and decreased antioxidant activity. We propose that endothelial function is negatively correlated with 8-OHdG/dG ratio and positively correlated with antioxidant enzymes. To our knowledge, this is the first study to demonstrate the inverse relationship between endothelial function and plasma oxidative DNA damage in HD patients.

Assessment of deoxynivalenol metabolite profiles in UK adults

Deoxynivalenol (DON) requires no activation for toxicity, though susceptibility may reflect individual variations in detoxification. This study reports the measurement of un-metabolised urinary DON (free DON) and DOM-1 in samples previously analysed for the combined measure of free DON+DON-glucuronide (fD+DG), with a concentration >5ng/ml, for 34 UK adults. Four consecutive daily urine samples were analysed from twenty-two individuals, whilst from 12 individuals only a single sample was analysed. The mean (median) concentration of urinary fD+DG in this sub-set was 17.8ng/ml (13.8ng/ml), range 5.0–78.2ng/ml. In 23/34 (68%) individuals, free DON was detected, mean 2.4ng/ml; range 0.5–9.3ng/ml. Urinary DOM-1 was detected in 1/34 (3%) of individuals; present at ∼1% of urinary fD+DG concentration for that individual. The concentration of fD+DG combined was significantly correlated with urinary free DON (p<0.001, R2=0.65), but not with the percentage of free DON to fD+DG (p=0.615, R2=0.01), suggesting that the level of DON exposure did not affect the metabolism to DG within the range observed. In this survey most individuals had no detectable urinary DOM-1 and 68% did not detoxify all of the ingested DON to DON-glucuronide. This study needs to be extended to understand whether the fD / DG ratio provides a phenotypic measure of DON susceptibility.

The citrus flavonoid naringenin stimulates DNA repair in prostate cancer cells

As part of a systematic study of the effects of phytochemicals beyond antioxidation on cancer prevention, we investigated whether naringenin (NR), a citrus flavonoid, stimulates DNA repair following oxidative damage in LNCaP human prostate cancer cells. The 8-hydroxydeoxyguanosine (8-OH-dG) to deoxyguanosine (dG) ratio was measured after cells were treated with 200 μmol/L of ferrous sulfate in serum-free medium followed by NR exposure for 24 h in growth medium. The results demonstrated that exposure to 10–80 μmol/L of NR led to a significant decrease in the ratio of 8-OH-dG to 10 6 dG. Because cells were treated with NR after ferrous sulfate was removed, we conclude that we demonstrated an effect on DNA repair beyond antioxidation. In support of this conclusion, we determined the induction of mRNA expression over time after oxidative stress followed by NR administration of three major enzymes in the DNA base excision repair (BER) pathway: 8-oxoguanine-DNA glycosylase 1 (hOGG1), apurinic/apyrimidinic endonuclease and DNA polymerase β (DNA poly β). hOGG1 and DNA poly β mRNA expression in cells after 24-h exposure to NR was increased significantly compared with control cells without NR. The intracellular concentration of NR after exposure to 80 μmol/L was 3 pmol/mg protein, which is physiologically achievable in tissues. In conclusion, the cancer-preventive effects of citrus fruits demonstrated in epidemiological studies may be due in part to stimulation of DNA repair by NR, which by stimulating BER processes may prevent mutagenic changes in prostate cancer cells.

Convenient Syntheses of Dibenzo[c,p]chrysene and Its Possible Proximate and Ultimate Carcinogens: In Vitro Metabolism and DNA Adduction Studies

Dibenzo[c,p]chrysene (DB[c,p]C) is the only hexacyclic polycyclic aromatic hydrocarbon having two fjord regions, both in different chemical environments. Its environmental presence and relative tumorigenic potency are not known due to the lack of synthetic standards. We report here the synthesis of dibenzo[c,p]chrysene (1), its proximate carcinogens, i.e., trans-1,2-dihydroxy-1,2-dihydro-DB[c,p]C (2) and trans-11,12-dihydroxy-11,12-dihydro-DB[c,p]C (3), and possible ultimate carcinogens, i.e., anti-trans-1,2-dihydroxy-3,4-epoxy-1,2,3,4-tetrahydro-DB[c,p]C (4) and anti-trans-11,12-dihydroxy-13,14-epoxy-11,12,13,14-tetrahydro-DB[c,p]C (5). The syntheses of 1 and the appropriately methoxy-substituted DB[c,p]C (12 and 27), key intermediates for the synthesis of its proximate and ultimate metabolites, were tried first using a Suzuki cross-coupling reaction. However, the cyclization of olefins (10 and 11) gave poor yields of the desired products. An alternate method was thus developed employing a photochemical approach. The in vitro metabolism of DB[c,p]C was established with the S9 fraction of liver homogenate from phenobarbital/beta-naphthoflavone-induced Sprague-Dawley rats. The major dihydrodiol formed was identified as the fjord region 11,12-dihydroxy-11,12-dihydro-DB[c,p]C, while the major and minor phenols were identified as 11-hydroxy-DB[c,p]C and 12-hydroxy-DB[c,p]C, respectively. Further, the DNA adduction studies with the calf thymus DNA led to a mixture of dA and dG adducts for both fjord region diol epoxides (4 and 5). Interestingly, the dA to dG ratio for 1,2-dihydroxy-3,4-epoxide was much higher (3.2) compared to that of 11,12-dihydroxy-13,14-epoxide (0.5).

Increased 8-Hydroxy-2′-Deoxyguanosine in Leukocyte DNA in Leber’s Hereditary Optic Neuropathy

This study was conducted to test the hypothesis that oxidative stress is involved in the pathogenesis of Leber's hereditary optic neuropathy (LHON). The level of 8-hydroxy-2'-deoxyguanosine (8-OHdG), an oxidized DNA base common in cells undergoing oxidative stress, was measured in leukocyte DNA from patients with LHON and normal control subjects. The 8-OHdG and deoxyguanosine (dG) content in leukocyte DNA from 25 patients with LHON with an 11778 mitochondrial (mt)DNA mutation, 14 asymptomatic maternal relatives, and 27 unrelated normal control subjects were measured using high-performance liquid chromatography and electrochemical detection methods. The mean 8-OHdG/10(5) dG ratio from leukocyte DNA was 1.34 +/- 0.99 in patients with LHON, 1.00 +/- 0.91 in their asymptomatic maternal relatives, and 0.31 +/- 0.20 in normal control subjects, respectively. There was a statistically significant difference in the mean 8-OHdG/10(5) dG ratio between patients with LHON and normal control subjects and between asymptomatic maternal relatives and normal control subjects. The difference between patients with LHON and asymptomatic maternal relatives did not reach statistical significance. Patients with LHON with an 11778 mtDNA mutation had higher oxidative DNA damage. Oxidative stress has a key role in the pathogenesis of LHON.

Oxidative DNA damage in human sperm influences time to pregnancy.

Oxidative stress and related DNA damage in human sperm may be important for fecundity and pregnancy outcome. We studied the level of oxidative DNA damage in terms of 7-hydro-8-oxo-2'-deoxyguanosine (8-oxodG) in sperm DNA among 225 first-pregnancy planners. Over the six menstrual cycle follow-up time, after cessation of contraception, 135 pregnancies were conceived. The likelihood of pregnancy occurring in a single menstrual cycle was inversely associated with the 8-oxodG level (P < 0.01). The odds ratio of pregnancy in each of the first three or all six follow-up menstrual cycles was 0.42 (0.23-0.78; 95% CI) and 0.61 (0.36-0.91) per unit increase in the log 8-oxodG/100 000 dG ratio after adjustment for potential confounders, (including sperm concentration) respectively. The intra-individual coefficient of variation of 8-oxodG in 2-6 monthly repeated sperm samples from 116 men was 19% for the 8-oxodG/dG ratio, whereas the inter-individual coefficient of variation was 49%. The 8-oxodG level was not significantly associated with smoking, consumption of alcohol or caffeine, exposure to welding fumes or the plasma levels of sex hormones. The data suggest that oxidative damage to sperm DNA influences fecundity and the level of damage is relatively constant within an individual and not influenced by smoking.

Protective Effects of Boysenberry Anthocyanins on Oxidative Stress in Diabetic Rats

The protective effects of major boysenberry anthocyanins (BoAnt) against oxidative stress were investigated in streptozotocin (STZ)-induced diabetic rats. Increases in the concentration of plasma thiobarbituric acid reactive substances (TBARS), and in the liver 8-hydroxy deoxyguanosine (8-OH dG)/deoxyguanosine (dG) ratio and also in the liver GSSG/GSH ratio, which were all observed in STZ-injected rats, were restored or tended to be restored to the level of the control rats when a diet with BoAnt was given to the diabetic animals. The susceptibility of the liver homogenate of the diabetic rats to the oxidation by AAPH was relieved when BoAnt was fed to them. These results suggested that BoAnt was effective in protecting the development of in vivo oxidation involved with diabetes.

Mitochondrial DNA Mutations and Oxidative Damage in Skeletal Muscle of Patients with Chronic Uremia

Abundant evidence has been gathered to suggest that mitochondrial DNA (mtDNA) sustains many more mutations and greater oxidative damage than does nuclear DNA in human tissues. Uremic patients are subject to a state of enhanced oxidative stress due to excess production of oxidants and a defective antioxidant defense system. This study was conducted to investigate mtDNA mutations and oxidative damage in skeletal muscle of patients with chronic uremia. Results showed that large-scale deletions between nucleotide position (np) 7,900 and 16,300 of mtDNA occurred at a high frequency in muscle of uremic patients. Among them, the 4,977-bp deletion (mtDNA⁴⁹⁷⁷) was the most frequent and most abundant large-scale mtDNA deletion in uremic skeletal muscle. The proportion of mtDNA⁴⁹⁷⁷ was found to correlate positively with the level of 8-hydroxy 2′-deoxyguanosine (8-OHdG) in the total DNA of skeletal muscle (r = 0.62, p < 0.05). Using long-range PCR and DNA sequencing, we identified and characterized multiple deletions of mtDNA in skeletal muscle of 16 of 19 uremic patients examined. The 8,041-bp deletion, which occurred between np 8035 and 16,075, was flanked by a 5-bp direct repeat of 5′-CCCAT-3′. Some of the deletions were found in more than 1 patient. On the other hand, we found that the mean 8-OHdG/10⁵dG ratio in the total cellular DNA of muscle of uremic patients was significantly higher than that of the controls (182.7 ± 63.6 vs. 50.9 ± 21.5, p = 0.05). In addition, the mean 8-OHdG/10⁵dG ratio in muscle mtDNA of uremic patients was significantly higher than that in nuclear DNA (344.0 ± 56.9 vs. 146.3 ± 95.8, p = 0.001). Moreover, we found that the average content of lipid peroxides in mitochondrial membranes of skeletal muscle of uremic patients was significantly higher than that of age-matched healthy subjects (23.76 ± 6.06 vs. 7.67 ± 0.95 nmol/mg protein; p < 0.05). The average content of protein carbonyls in the mitochondrial membranes prepared from uremic skeletal muscles was significantly higher than that in normal controls (24.90 ± 4.00 vs. 14.48 ± 1.13 nmol/mg protein; p < 0.05). Taken together, these findings suggest that chronic uremia leads to mtDNA mutations together with enhanced oxidative damage to DNA, lipids, and proteins of mitochondria in skeletal muscle, which may contribute to the impairment of mitochondrial bioenergetic function and to skeletal myopathy commonly seen in uremic patients.

OXIDATIVE DNA DAMAGE IN MALE WISTAR RATS EXPOSED TO DI- n -BUTYL PHTHALATE

Dialkyl phthalate esters are used in the plastic industry and widely distributed in the environment. Previously, it has been shown that di- n -butyl phthalate (DBP) produces testicular atrophy and liver enlargement in rodents, and the mechanisms behind this could involve reactive oxygen species (ROS). In this study, oxidative DNA damage was measured in terms of the premutagenic modified nucleoside 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-oxodG) in nuclear DNA from liver, kidneys, and testes from rats exposed to DBP in the perinatal or preadult period. In one experiment, pregnant rats were administered 0 or 0.5 g DBP/kg/d by gavage from d 7 after conception to d 17 after delivery and organs from male offspring were analyzed. In a second experiment, 25-d-old rats were administered 0, 0.5, or 2 g DBP/kg/d by gavage for 10 d. After perinatal exposure, body and organ weights were unchanged. The 8-oxodG/10 6 dG ratio in liver DNA increased significantly in the exposed group. In contrast, the 8-oxodG/10 6 dG ratio was significantly decreased in kidney DNA, whereas it remained unchanged in the testis. After preadult exposure (postnatal d 25 to 34) the testes weight of the exposed animals were significantly decreased and severe atrophy of the seminiferous tubules was observed. The body weight of the animals in the high-dose group was significantly decreased compared to the control. The 8-oxodG levels in liver, kidney, and testis DNA remained unchanged. Although ROS has been suspected of being involved in the formation of testicular atrophy in phthalate-exposed rats, no apparent sign of oxidative DNA damage was found after phthalate exposure perinatally or during the preadult stage. With respect to phthalate-induced oxidative DNA damage in the liver, it appears that the developmental stage during exposure is important.

A longitudinal evaluation of oxidative stress in trauma patients.

The purpose of this study was to determine the course of oxidative stress in trauma patients as measured by antioxidant disappearance and modulation of DNA damage. The study also explored the role of injury severity and the effect of changes in plasma lipoprotein concentration as the result of hemodilution on lipid-soluble plasma antioxidant concentrations. The study population included 17 adult male trauma patients in an urban level-1 trauma hospital and 12 healthy adult male controls. Blood was collected immediately after admission in the emergency room, and on days 2, 3, 4, 6, and 8 of admission. Plasma antioxidant concentrations and total cholesterol concentrations were evaluated. DNA damage was evaluated using the ratio of 8-hydroxydeoxyguanosine to deoxyguanosine (8OhdG to dG). Admission data were compared with data from controls. Plasma antioxidant concentrations (except alpha-tocopherol) significantly decreased by 9.9% to 34.3% in the 24 hours after trauma and remained depressed throughout day 8. Repeated measures regression analysis for trend showed a significant increase in unadjusted alpha-tocopherol from day 1 to day 8 (p < .008). No other unadjusted antioxidant or plasma cholesterol showed a significant change. After individually adjusting antioxidant concentrations by total cholesterol, only gamma-tocopherol (22.2%) and lycopene (22.6%) were decreased (p < .04) in the 24 hours after trauma. Repeated measures regression analysis for trend for the cholesterol-adjusted antioxidants showed a significant decrease from day 1 to day 8 for cholesterol-adjusted alpha-carotene (p < .007) and beta-carotene (p < .007). Trauma patients were divided into more and less severely injured groups based on Injury Severity Score (ISS). Decreases in antioxidant concentration from day 1 to day 2 were found for the patients in the more injured group, with no significant differences from day 1 to day 2 in the less severely injured group. Cholesterol-adjusted gamma-to copherol (29.7%, p < .003) and lycopene (32.7%, p < .05) decreased from day 1 to day 2 in the more severely injured group. Using repeated measures regression analysis for trend, the only antioxidant that was significantly different in the high versus low ISS groups from day 1 through day 6 was cholesterol-adjusted lutein-zeaxanthin (p < .02). Compared with controls, trauma patients had significantly lower (27.3% to 64.9%) concentrations of all cholesterol-adjusted antioxidants at day 1 except for lycopene. Trauma patients had higher leukocyte 8OhdG to dG ratios at admission (42.6%, p < .05), but 8OhdG to dG ratios tended to decrease over the 24 hours after trauma (p < .07). This decrease was greater in the 3 trauma patients with an admission 8OhdG to dG ratio greater than 6 x 10(-5) (59.3% versus 0.05%, p < .03). The difference in antioxidant concentrations between trauma patients and controls may have been associated with oxidative stress or with a poorer diet. The difference between antioxidant concentrations and cholesterol-adjusted antioxidant concentrations is likely caused by hemodilution or by changes in plasma lipid levels as a result of trauma. Therefore, individually adjusting lipid-soluble antioxidant concentrations by total cholesterol concentrations is important in trauma patients. Leukocyte 8OhdG to dG ratios were already elevated in trauma patients on admission but returned nearly to control levels 24 hours later, indicating short-term responsiveness to DNA oxidation in trauma patients and an extensive capacity for DNA repair within 24 hours.

Receptor-mediated ethinylestradiol-induced oxidative DNA damage in rat testicular cells.

Estrogenic chemicals are suspected of affecting cancer risk and male reproduction, possibly involving oxidative DNA damage. In this study, formation of 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-oxodG), was measured in testicular cells from rats after 17 alpha-ethinylestradiol (EE) exposure in vivo and in vitro after incubation with EE with or without an antiestrogen. In vivo, preadult (30-35 days) and adult (110-120 days) Wistar rats received 0, 2.8, or 56 mg EE/kg body weight as intraperitoneal injections (n=6). After 1 or 4 h, the 8-oxodG/10(6) dG ratio was measured in the liver, kidneys, and testes. Testes DNA analysis revealed an age-related effect (adult animals had a higher ratio than the young animals) and a concentration effect in preadult rats (increased EE-concentration caused increased ratio), but no time effect. No differences were found in the liver or kidneys. In vitro, testicular cells were isolated and incubated with EE concentrations ranging from 0.1 to 1000 nM. The results indicated an increase in 8-oxodG/10(6) dG from 0 to 10 nM estrogen. At 1000 nM, the level was close to control level. Coincubation of 10 nM EE (maximum damage) with an estrogen antagonist, ICI 182.780, abolished the effect at 10 nM, indicating that the damaging effect is estrogen receptor mediated.

Interrelationship of DOC Distribution in Metabolic Network to Growth Yield in Batch Culture

Oxidative assimilation of dissolved organic carbon (DOC) includes the interrelated processes of catabolism and anabolism. It has been demonstrated that energy uncoupling is a dominant characteristic of substrate-sufficient batch culture. However, the interrelationship of DOC distribution between catabolism and anabolism to the observed growth yield (\iY\Dobs\N) has not yet been clear for substrate-sufficient batch cultures. In this study, the DOC distribution between catabolism and anabolism was described using a ratio of the DOC channeled into carbon dioxide (\iS\DCO2\N) to the DOC converted into biomass (\iS\dg). Based on a balanced oxidative reaction of DOC, a \iS\DCO2\N/\iS\i\dg-dependent \iY\Dobs\N model was developed for substrate-sufficient batch culture, and was verified with experimental and literature data. The model showed a reducing trend of growth yield an increasing \iS\DCO2/\iS\i\dg ratio. It appears that the imbalance between catabolism and anabolism induced by substrate excess leads to non-growth-associated DOC consumption, which is responsible for the observed reduction of \iY\Dobs\N under substrate-sufficient conditions.

Melatonin protects against age-related DNA damage in the brains of female senescence-accelerated mice.

We investigated whether melatonin reduces the age-related susceptibility of brain to oxidative DNA damage. Brain tissues and blood samples were obtained in the middle of dark period of the daily light:dark cycle from female senescence-accelerated mice (SAM-P/6) at ages 4, 8, and 12 months. Serum melatonin concentrations and the contents of deoxyguanosine (dG) and 8-hydroxydeoxyguanosine (8-OHdG) in DNA extracted from these brain homogenates were measured by high-performance liquid chromatography. Contents of 8-OHdG showed a significant age-related increase (P < 0.001) while that of dG did not. The 8-OHdG:dG ratio also exhibited a significant age-related increase (P < 0.001). Serum melatonin concentration decreased markedly between 8 (159.7 +/- 4.5 pg/mL) and 12 (46.8 + 4.5 pg/mL) months of age (P < 0.0001). Oral melatonin administration (2 microg/mL in water) starting at 8 months of age, which produced a significant increase in serum melatonin concentration at 12 months (187.6 +/- 18.3 pg/mL) compared with untreated animals (P < 0.0001) also resulted in significant decreases in brain 8-OHdG contents and 8-OHdG:dG ratios. These results indicate that administration of a physiologic dose of melatonin to SAM-P 6 mice may prevent the age-related oxidative DNA damage in the brain.