Plasma 8-hydroxydeoxyguanosine Research Articles

The effects of iodine 131 treatment on chromosomal and oxidative DNA damage in papillary thyroid carcinoma

Papillary thyroid carcinoma (PTC) is a common endocrine cancer with a good prognosis. Radioactive iodine is thought to be useful for individuals who have had a total or almost total thyroidectomy, but its effects are still controversial. The effects of radioactive iodine-131 (I-131) treatment on oxidative and chromosomal damage in PTC patients were examined in this study, which was carried out with 16 patients newly diagnosed with PTC and 20 healthy control subjects with similar age and gender. Blood samples were taken from patients with PTC at five sampling times (before total thyroidectomy, after total thyroidectomy, and seven days, six months, and one year after treatment) and from control subjects. The cytokinesis block micronucleus cytome (CBMN-cyt) assay parameters in peripheral blood lymphocytes of patients with PTC and controls were evaluated and plasma 8-hydroxydeoxyguanosine (8-OHdG) levels were measured. Furthermore, genome instability and oxidative DNA damage in peripheral blood lymphocytes and plasma of patients with PTC were evaluated before total thyroidectomy (n=16), after total thyroidectomy (before I-131 treatment) (n=16), seven days (n=10), six months (n=5), and one year after treatment (n=5). The numbers of CBMN-cyt assay parameters (micronucleus; MN and nucleoplasmic bridges; NPB) and 8-OHdG levels in patients with PTC were determined to be significantly higher than in those of the control subjects and these values significantly decreased after total thyroidectomy (before I-131 treatment). While the number of MN, apoptotic, and necrotic cells increased after I-131 treatment, it significantly decreased after six months and one year after treatment. The results achieved in this study suggest that I-131 treatment may pose a threat to cells and that radioactive iodine therapy should be avoided (if possible) for patients with PTC after total thyroidectomy.

Effects of catechin and copper or their combination in diet on productive performance, egg quality, egg shelf-life, plasma 8-OHdG concentrations and oxidative status in laying quail (Coturnix coturnix japonica)

ABSTRACT The aim of this study was to determine the effects of catechin and copper supplementations to quail diet on performance, egg quality and lipid peroxidation, plasma 8-hydroxydeoxyguanosine (8-OHdG) concentrations and oxidative status. In this study, 300 quails, 10-week old, were divided into 4 groups with 5 replicates. The dietary treatments were a control diet and a control diet supplemented with 3000 mg/kg of green tea catechins (Cat), 80 mg/kg of copper proteinate (CuP), or 3000 mg/kg of Cat + 80 mg/kg of CuP (combination; Cat + CuP) for 8 weeks. Plasma 8OHdG and enzyme activities did not change. Egg weight and specific gravity of Cat group were lower than that of the control group (p < 0.001). Egg yolk colour increased by dietary catechin (p = 0.001). The MDA concentrations in egg yolk, plasma and tissue decreased by dietary catechin; and kidney MDA concentrations also decreased by all treatments (p < 0.05). Consequently, dietary catechin had a negative effect on egg-specific gravity and a positive effect on egg yolk colour without affecting internal egg quality parameters. However, dietary catechin and copper, without causing DNA damage, reduced lipid peroxidation in egg and organism and has a positive effect on egg lipid peroxidation.

Anti-inflammatory and antioxidant role of resveratrol on nicotine-induced lung changes in male rats.

Male albino rats of Wistar strain were injected intraperitoneally with nicotine or/and resveratrol for 4 weeks. Serum Interleukin-2, Interleukin-6, alpha-fetoprotein and tumor necrosis-alpha, as well as plasma 8-hydroxydeoxyguanosine of nicotine-treated rats were increased significantly. Myeloperoxidase, xanthine oxidase, nitric oxide, lipid peroxidation and total oxidative status of the lung in nicotine-treated rats were increased significantly, which were brought down to normal in resveratrol co-treated group. Endogenous antioxidant status as the activity of superoxide dismutase, catalase, glutathione peroxidase, and glucose-6-phosphate dehydrogenases were found to be decreased significantly in the lung of the nicotine-treated group, which were significantly raised in resveratrol-administered groups. The non-enzymatic antioxidants as total antioxidant and thiol levels were decreased significantly as the effect of nicotine that was effectively enhanced by resveratrol treatment. The lung of nicotine-treated rats showed severe congestion of the alveolar lung tissues with scattered congestion per bronchiolar and perivascular cells, as well as, inflammatory cells were observed. The data suggested that resveratrol exerts its protective effect by modulating the extent of oxidative status and improving the enzymatic/non-enzymatic antioxidant defense system, moreover, decreases the pathological changes in animals against the lung damage caused by nicotine.

Mitochondrial dysfunction in Kennedy's disease: a new pharmacological target?

Mitochondrial impairment and elevated oxidative stress have been implicated in the pathogenesis of Kennedy's disease. However, there is still no study describing the mitochondrial nutrient management in patients with Kennedy's disease. We assessed the clinical and electrophysiological features in a patient with Kennedy's disease. This patient was diagnosed by genetic analysis. We also measured the plasma 8-hydroxydeoxyguanosine (8-OHdG) levels of the patient and his family members using commercial enzyme-linked immunosorbent assay (ELISA). Treatment with intravenous L-carnitine (2 g/day) for the patient was started on admission, followed by two weeks. Routine laboratory tests revealed a severe elevation of creatine kinase (CK) (606.5 U/L; normal value: 15-170 U/L). Sequencing of the first exon of androgen receptor (AR) revealed an increased number of CAG repeat (50; the normal range from 10-36) in the patient. Plasma 8-OHdG level in the patient was relatively elevated (34.68±1.01 ng/mL) compared with the female carriers and non-carriers. Two weeks after L-carnitine treatment, we observed a reduction of approximately 40% in CK level (391 U/L) in the patient. Oxidative stress resulting from mitochondrial dysfunction could be involved in Kennedy's disease. Targeting the mitochondrial dysfunction in Kennedy's disease may have significant therapeutic potential.

Protective effect of resveratrol on sodium fluoride-induced oxidative stress, hepatotoxicity and neurotoxicity in rats

Protective effect of resveratrol on sodium fluoride-induced oxidative stress, hepatotoxicity and neurotoxicity were studied in rats. A total of 28 Wistar albino male rats were used. Four study groups were randomly formed with seven animals in each. The groups were treated for 21days with distilled water (control group), with water containing 100ppm fluoride (fluoride group), with resveratrol (12.5mg/kg i.p., resveratrol group), or with 100ppm fluoride+12.5mg/kg resveratrol i.p. (fluoride+resveratrol group). At the end of the trial, blood samples were collected by cardiac puncture and tissue samples were taken simultaneously. The total antioxidant and oxidant status in plasma and tissues as well as plasma 8-hydroxydeoxyguanosine levels were measured. Histopathological analyses of rat liver and brain tissues were performed in all groups to identify any changes. In the fluoride group, the total oxidant levels increased in plasma, liver and brain and total antioxidant levels decreased, as did the plasma 8-hydroxy-deoxyguanosine levels. These changes were prevented by co-administration of resveratrol. In addition, fluoride-associated severe histopathological changes in brain and liver tissues were not observed in the fluoride+resveratrol group. Consequently, these data suggested that resveratrol had beneficial effects in alleviating fluoride-induced oxidative stress.

Associations of neonatal lead, cadmium, chromium and nickel co-exposure with DNA oxidative damage in an electronic waste recycling town

ObjectiveThis study aimed to evaluate the effects of toxic heavy metal co-exposure on DNA oxidative damage in neonates from a primitive e-waste recycling region, Guiyu town, China. MethodsOur participants included 201 pregnant women: 126 from Guiyu town and 75 from Jinping district of Shantou city, where no e-waste recycling and dismantling activities existed. Structured interview questionnaires were administered to the pregnant women and umbilical cord blood (UCB) samples were collected after delivery. The UCB concentrations of lead, cadmium, chromium, and nickel were analyzed by graphite furnace atomic absorption spectrometry (GFAAS). Levels of UCB plasma 8-hydroxydeoxyguanosine (8-OHdG, a DNA oxidative damage biomarker) were determined by enzyme-linked immunosorbent assay. ResultsOur results suggested that UCB lead and cadmium concentrations in neonates of Guiyu were significantly higher than those of Jinping (lead: median 110.45ng/mL vs. 57.31ng/mL; cadmium: median 2.50ng/mL vs. 0.33ng/mL, both P<0.001). Parents' residence in Guiyu, and parents' work related to e-waste recycling were the risk factors associated with neonate's UCB lead and cadmium levels. No significant difference of UCB plasma 8-OHdG levels was found between Guiyu and the control area. After adjusting for potential confounders, cord plasma 8-OHdG concentrations (ng/mL) were positively associated with blood cadmium (β=0.126ng/mL, 95% CI: 0.055 to 0.198ng/mL), chromium (β=0.086ng/mL, 95% CI: 0.014 to 0.158ng/mL) and nickel (β=0.215ng/mL, 95% CI: 0.113 to 0.317ng/mL) concentrations. ConclusionsThe primitive e-waste recycling and dismantling activities may contribute to the elevated umbilical cord blood toxic heavy metal levels in neonates born in Guiyu. Exposures to cadmium, chromium and nickel were associated with increased oxidative DNA damage in neonates.

Cardiovascular Changes in Atherosclerotic ApoE-Deficient Mice Exposed to Co60 (γ) Radiation

BackgroundThere is evidence for a role of ionizing radiation in cardiovascular diseases. The goal of this work was to identify changes in oxidative and nitrative stress pathways and the status of the endothelinergic system during progression of atherosclerosis in ApoE-deficient mice after single and repeated exposure to ionizing radiation.Methods and ResultsB6.129P2-ApoE tmlUnc mice on a low-fat diet were acutely exposed (whole body) to Co60 (γ) (single dose 0, 0.5, and 2 Gy) at a dose rate of 36.32 cGy/min, or repeatedly (cumulative dose 0 and 2 Gy) at a dose-rate of 0.1 cGy/min for 5 d/wk, over a period of 4 weeks. Biological endpoints were investigated after 3–6 months of recovery post-radiation. The nitrative stress marker 3-nitrotyrosine and the vasoregulator peptides endothelin-1 and endothelin-3 in plasma were increased (p<0.05) in a dose-dependent manner 3–6 months after acute or chronic exposure to radiation. The oxidative stress marker 8-isoprostane was not affected by radiation, while plasma 8-hydroxydeoxyguanosine and L-3,4-dihydroxyphenylalanine decreased (p<0.05) after treatment. At 2Gy radiation dose, serum cholesterol was increased (p = 0.008) relative to controls. Percent lesion area increased (p = 0.005) with age of animal, but not with radiation treatment.ConclusionsOur observations are consistent with persistent nitrative stress and activation of the endothelinergic system in ApoE−/− mice after low-level ionizing radiation exposures. These mechanisms are known factors in the progression of atherosclerosis and other cardiovascular diseases.

MicroRNA Expression in Response to Controlled Exposure to Diesel Exhaust: Attenuation by the Antioxidant N -Acetylcysteine in a Randomized Crossover Study

Background: Adverse health effects associated with diesel exhaust (DE) are thought to be mediated in part by oxidative stress, but the detailed mechanisms are largely unknown. MicroRNAs (miRNAs) regulate gene expression post-transcriptionally and may respond to exposures such as DE.Objectives: We profiled peripheral blood cellular miRNAs in participants with mild asthma who were exposed to controlled DE with and without antioxidant supplementation.Methods: Thirteen participants with asthma underwent controlled inhalation of filtered air and DE in a double-blinded, randomized crossover study of three conditions: a) DE plus placebo (DEP), b) filtered air plus placebo (FAP), or c) DE with N-acetylcysteine supplementation (DEN). Total cellular RNA was extracted from blood drawn before exposure and 6 hr after exposure for miRNA profiling by the NanoString nCounter assay. MiRNAs significantly associated with DEP exposure and a predicted target [nuclear factor (erythroid-derived 2)-like 2 (NRF2)] as well as antioxidant enzyme genes were assessed by reverse transcription–quantitative polymerase chain reaction (RT-qPCR) for validation, and we also assessed the ability of N-acetylcysteine supplementation to block the effect of DE on these specific miRNAs. 8-hydroxy-2´-deoxyguanosine (8-OHdG) was measured in plasma as a systemic oxidative stress marker.Results: Expression of miR-21, miR-30e, miR-215, and miR-144 was significantly associated with DEP. The change in miR-144 was validated by RT-qPCR. NRF2 and its downstream antioxidant genes [glutamate cysteine ligase catalytic subunit (GCLC) and NAD(P)H:quinone oxidoreductase 1 (NQO1)] were negatively associated with miR-144 levels. Increases in miR-144 and miR-21 were associated with plasma 8-hydroxydeoxyguanosine 8-OHdG level and were blunted by antioxidant (i.e, DEN).Conclusions: Systemic miRNAs with plausible biological function are altered by acute moderate-dose DE exposure. Oxidative stress appears to mediate DE-associated changes in miR-144.

Consumption of cranberry beverage protected against oxidative damage, inflammation and bacteria adhesion in healthy humans

We studied the health benefits of acute cranberry beverage consumption on oxidative damage, inflammation, and anti‐bacterial adhesion activity of urine in healthy humans. Six males and 6 females (18–35 yr old; BMI 19–25 kg/m^2) consumed 15.2 oz placebo, cranberry extract beverage (CEB) and low calorie cranberry juice cocktail (LCJC) in a randomized, cross‐over, double‐blind, placebo‐controlled experimental design. Washout between beverages was 1 week. Blood was collected at 0, 2, 4, 8 and 24 h after beverage consumption for measuring oxidative and inflammatory biomarkers. Urine was collected at 0, 0–3, 3–6, 6–9, 9–12 and 24 h post‐intervention. Consumption of CEB elevated (P &lt; 0.05) blood superoxide dismutase (SOD) and glutathione peroxidase (GPx), and decreased (P &lt; 0.05) plasma nitric oxide (NO) compared to placebo. LCJC consumption increased (P &lt; 0.05) SOD and reduced‐glutathione (GSH), and decreased (P &lt; 0.05) NO. Neither cranberry beverage significantly changed concentrations of plasma 8‐hydroxydeoxyguanosine, inflammatory cytokines and total antioxidant capacity. At 0–3 h, participants who consumed cranberry beverages had higher (P &lt; 0.05) ex vivo anti‐adhesion activity against P‐fimbriated E. coli compared to placebo. An acute dose of cranberry beverages reduced oxidative and inflammatory biomarkers and improved inhibition of bacterial adhesion by urine. Funded by Ocean Spray Cranberries Inc.

The association of plasma prorenin level with an oxidative stress marker, 8-OHdG, in nondiabetic hemodialysis patients

Circulating prorenin contributes to the pathogenesis of tissue damage leading to cardiovascular disease (CVD) in hypertension and diabetic mellitus (DM) by activating the tissue renin-angiotensin-aldosterone (RAS) system; however, little is known about its roles in hemodialysis (HD) patients. We evaluated plasma prorenin level and prorenin receptor [(P)RR] expression in peripheral blood mononuclear cells (PBMCs) in 49 nondiabetic HD (non-DM-HD) patients. Then we investigated the association between plasma prorenin level or (P)RR expression level in PBMCs and CVD-predictive biomarkers. The plasma prorenin level increased in non-DM-HD patients [147.1±118.9pg/ml (standard value <100pg/ml)]. The (P)RR mRNA expression level in PBMCs also increased 1.41±0.39-fold in non-DM-HD patients compared with that in healthy control subjects (p<0.001). Although plasma prorenin level did not correlate with plasma BNP level and plasma high-sensitivity C-reactive protein level, it significantly correlated with plasma 8-hydroxydeoxyguanosine (8-OHdG) level (r=0.535, p<0.001). The plasma prorenin level did not correlate with plasma renin activity (PRA), plasma angiotensin I (AT I) level, plasma angiotensin II (AT II) level and plasma aldosterone (Ald) level. PRA, plasma AT I level, plasma AT II level and plasma Ald level did not correlate with the level of any CVD predictive biomarker. (P)RR expression level in PBMCs did not correlate with the level of any CVD predictive biomarker. The plasma prorenin level and (P)RR expression level in PBMCs increased, and the plasma prorenin level was associated with plasma 8-OHdG level independent of circulating RAS in non-DM-HD patients.

Pigmented Potato Consumption Alters Oxidative Stress and Inflammatory Damage in Men ,

Pigmented potatoes contain high concentrations of antioxidants, including phenolic acids, anthocyanins, and carotenoids. These bioactive compounds have been implicated in the inhibition or prevention of cellular oxidative damage and chronic disease susceptibility. We assessed the effects of pigmented potato consumption on oxidative stress and inflammation biomarkers in adult males. Free-living healthy men (18-40 y; n = 12/group) consumed 150 g of cooked white- (WP), yellow- (YP), or purple-flesh potatoes (PP) once per day for 6 wk in a randomized study. Blood was collected at baseline and wk 6 to analyze total antioxidant capacity (TAC), DNA damage as assessed by plasma 8-hydroxydeoxyguanosine (8-OHdG), protein oxidation, lipid peroxidation, C-reactive protein (CRP), inflammatory cytokines, lymphoproliferation, NK cytotoxicity, and phenotypes. Potatoes were analyzed for TAC, phenolic acids, anthocyanins, and carotenoids. Compared with the WP group, the YP group had higher concentrations of phenolic acids (P < 0.002) and carotenoids (P < 0.001), whereas the PP group had higher concentrations of phenolic acids (P < 0.002) and anthocyanins (P < 0.001). Men who consumed YP and PP tended to have lower (P < 0.08) plasma IL-6 compared with those consuming WP. The PP group tended to have a lower plasma CRP concentration than the WP group (P = 0.07). The 8-OHdG concentration was lower in men who consumed either YP or PP compared with WP. Pigmented potato consumption reduced inflammation and DNA damage in healthy adult males. This offers consumers an improved nutritional choice in potato consumption.

Erythropoietin enhances hydrogen peroxide-mediated dilatation of canine coronary collateral arterioles during myocardial ischemia in dogs in vivo

We have previously demonstrated that endothelium-derived hydrogen peroxide (H(2)O(2)) plays an important role in the canine coronary microcirculation as an endothelium-derived hyperpolarizing factor in vivo. However, it remains to be examined whether endogenous H(2)O(2) is involved in the dilatation of coronary collaterals during myocardial ischemia in vivo and, if so, whether erythropoietin (EPO) enhances the responses. Canine subepicardial native collateral small arteries (CSA; ≥ 100 μm) and arterioles (CA; <100 μm) were observed using an intravital microscope. Experiments were performed after left anterior descending coronary artery ischemia (90 min) under the following eight conditions (n = 5 each): control, EPO, EPO+catalase, EPO+N-monomethyl-l-arginine (l-NMMA), EPO+l-NMMA+catalase, EPO+l-NMMA+iberiotoxin [Ca(2+)-activated K(+) (K(Ca)) channel blocker], EPO+l-NMMA+apamin+charybdotoxin (K(Ca) channel blocker), and EPO+wortmannin (phosphatidylinositol 3-kinase inhibitor). Myocardial ischemia caused significant vasodilatation in CA but not in CSA under control conditions, which was significantly decreased by catalase in CA. After EPO, the vasodilatation was significantly increased in both sizes of arteries and was significantly decreased by catalase. The enhancing effect of EPO was reduced by l-NMMA but not by catalase in CSA and was reduced by l-NMMA+catalase in CA, where the greater inhibitory effects were noted with l-NMMA+catalase, l-NMMA+iberiotoxin, L-NMMA+apamin+charybdotoxin, or wortmannin. EPO significantly ameliorated ischemia-induced impairment of myocardial Akt phosphorylation, which was abolished by l-NMMA+catalase or wortmannin. EPO also ameliorated oxidative stress and myocardial injury, as assessed by plasma 8-hydroxydeoxyguanosine and troponin-T, respectively. These results indicate that EPO enhances H(2)O(2)-mediated dilatation of coronary collateral arterioles during myocardial ischemia in dogs in vivo.

Increased Plasma Levels of 8-Hydroxydeoxyguanosine Are Associated with Development of Colorectal Tumors

Increased oxidative stress is generally thought to be associated with tumorigenesis. In this cross-sectional study, we evaluated plasma 8-hydroxydeoxyguanosine (8-OHdG) levels in patients with colorectal adenoma and cancer, as a surrogate marker of oxidative damage to deoxyribonucleic acid (DNA). We collected blood samples from 58 patients with adenoma, 32 with early cancer, 25 with advanced cancer, and 36 without polyps or cancer (as controls), and measured plasma levels of 8-OHdG by enzyme-linked immunosorbent assay. Univariate analysis by logistic regression showed that an increased level of 8-OHdG was a significant risk for adenoma [odds ratio (OR) 1.393, 95% confidence interval (CI) 1.008–1.926, p = 0.045]. In patients with early cancer, univariate analysis revealed significant differences for age, body mass index (BMI), systolic blood pressure, and 8-OHdG level. Subsequent multivariate analysis revealed that 8-OHdG [OR 1.627, 95% CI 1.079–2.453, p = 0.020] and BMI [OR 1.283, 95% CI 1.038–1.585, p = 0.021] were significant risk factors for early cancer. However, 8-OHdG was not a significant risk factor for advanced cancer. Our results suggest that an increased plasma level of 8-OHdG is associated with development of colorectal adenoma and cancer.

Abstract 5516: Cardioprotective Effects of Hydrogen Peroxide and Erythropoietin During Acute Coronary Occlusion in Canine Coronary Native Collateral Microvessels in vivo

Background: We have previously demonstrated that endothelium-derived hydrogen peroxide (H 2 O 2 ) is an endothelium-derived hyperpolarizing factor (EDHF) in canine coronary autoregulation in vivo. The aim of this study was to examine the role of H 2 O 2 during acute coronary occlusion with recombinant human erythropoietin (EPO) in the collateral vasodilatation of coronary microcirculation in vivo. Methods and Results: Canine subepicardial native collateral coronary small arteries (CSA, ≥100 μ m) and arterioles (CA, &lt;100 μ m) were observed by an intravital microscope under cyclooxygenase blockade. Experiments were performed after LAD occlusion (90 min) under the following 8 conditions (n=5, each); control, low-dose EPO (100 IU/kg, L-EPO), high-dose EPO (1000 IU/kg, H-EPO), H-EPO+catalase (a H 2 O 2 decomposer), H-EPO+NO synthase inhibitor (L-NMMA), H-EPO+L-NMMA+catalase, H-EPO+L-NMMA+tetraethylammonium (TEA, a K Ca channels blocker) and H-EPO+ wortmannin (PI3K inhibitor). Ischemia caused a significant collateral arteriolar vasodilatation of control, which was significantly inhibited by catalase. After H-EPO, the vasodilatation was significantly increased in both-sized arteries (CSA 6±1%, CA 22±4%) compared with control (CSA 1±1%, CA 16±3%) or L-EPO (CSA 2±1%, CA 18±3%) associated with increase in collateral blood flow (microsphere technique). H-EPO+catalase significantly decreased the vasodilatation in CA (12±2%). The vasodilatation was markedly attenuated after H-EPO+L-NMMA+catalase (CSA −4±1%, CA 6±1%), H-EPO+L-NMMA+TEA (CSA −5±1%, CA 6±1%) and H-EPO+ wortmannin (CSA −5±1%, CA 6±1%). In the control group, expression of Akt phosphorylation in the ischemic LAD area was significantly decreased compared with the H-EPO group. In H-EPO+L-NMMA+catalase or H-EPO+wortmannin group, expression of Akt phosphorylation was further decreased compared with H-EPO or L-NMMA+H-EPO group. Plasma 8-hydroxydeoxyguanosine from coronary sinus as a myocardial oxidative stress marker (HPLC-ECD method) significantly decreased in H-EPO compared with control. Conclusions: H 2 O 2 and EPO play an important collaborative role in native collateral vasodilatation in response to acute coronary occlusion in canine coronary microcirculation in vivo.

Mechanical stimulation of gingiva reduces plasma 8-OHdG level in rat periodontitis

Objective Gingival cells respond to periodontal pathogens by generating reactive oxygen species, and such a condition would increase circulating oxidative stress. Improvement of gingival inflammation by toothbrushing may offer clinical benefits on not only periodontal health but also the circulatory conditions. We examined the effects of mechanical stimulation on the plasma 8-hydroxydeoxyguanosine level in a rat periodontitis model. Design In this experiment, male Wistar rats ( n = 18) were divided into three groups. The control group received topical application of pyrogen-free water to the gingival sulcus for 8 weeks, while the other two groups received topical application of bacterial pathogens (lipopolysaccharide and proteases). After 4 weeks, half of the rats in the experimental groups received daily mechanical stimulation with an electric toothbrush for 4 weeks. Results Rats treated with bacterial pathogens presented periodontal tissue damage and increased plasma levels of 8-hydroxydeoxyguanosine. Mechanical stimulation by toothbrushing decreased gingival inflammation and oxidative DNA damage indicated by a decrease in plasma 8-hydroxydeoxyguanosine. Conclusions Mechanical stimulation of periodontally involved gingiva reduced 8-hydroxydeoxyguanosine in plasma and may contribute to a reduction in circulating oxidative stress associated molecules.

Oxidative DNA Damage Estimated by Plasma 8‐hydroxydeoxyguanosine (8‐OHdG): Influence of 4, 4'‐methylenebis (2‐chloroaniline) Exposure and Smoking

Oxidative DNA damage may play an important role in the human carcinogenic process. Recently, we reported a case of bladder cancer among 4, 4'-methylenebis (2-chloroaniline) (MBOCA)-exposed workers. By measuring the plasma level of 8-hydroxydeoxyguanosine (8-OHdG), we investigated the association between oxidative DNA damage and MBOCA exposure. In addition, we examined the effects of different confounders on the plasma level of 8-OHdG. We undertook a cross-sectional survey at four MBOCA-producing factories in Taiwan (158 subjects). Plasma 8-OHdG levels and urinary MBOCA concentrations were measured by liquid chromatography coupled with tandem mass spectrometry (LC/MS/MS). Personal characteristics were collected by questionnaire. The workers were classified according to their job titles as exposed (n=57) or unexposed (n=101) groups as well as classified according to urinary MBOCA levels as high urinary MBOCA (>20 microg/g creatinine) (n=45) or low urinary MBOCA (n=108) groups. Neither the MBOCA-exposed workers nor the high urinary MBOCA workers had a significant increase in the mean plasma 8-OHdG level, even after adjustment for potential confounders. Age and gender were significantly positively correlated with plasma 8-OHdG levels. Smokers among high urinary MBOCA workers also had significantly higher 8-OHdG levels than non-smokers among high urinary MBOCA workers. Our study provides evidence that smoking rather than MBOCA exposure induces elevation of plasma 8-OHdG levels among workers exposed to MBOCA, indicating that oxidative DNA damage does not play an important role in the carcinogenic processes of MBOCA.