• Environmental Mutagens and Carcinogens
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• v.23 no.3
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• pp.99-102
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• 2003

IARC classified areca quid as a human carcinogen. Areca quid chewed in Taiwan includes Piper betle inflorescence, which contains high concentrations of safrole (15 mg/fresh weight). Safrole is a documented rodent hepatocarcinogen, and chewing areca quid may contribute to human exposure (420 $\mu$m in saliva). The carcinogenicity of safrole is mediated through 1'-hydroxysafrole formation, followed by sulfonation to an unstable sulfate that reacts to form DNA adducts. Using human liver microsomes and Escherichia coli membranes expressing bicistronic human P450s, CYP2E1 and CYP2C9 were identified as the main P450s involved in the activation of safrole. We have demonstrated the presence of stable safrole-dGMP adducts in human oral tissues following areca quid chewing using $^{32}$ P-postlabeling and HPLC mass spectrometry methods. By studying 88 subjects with a known AQ chewing history and 161 matched controls, we have demonstrated that the presence of safrole-DNA adducts in peripheral blood cells was correlated to AQ chewing, and CYP2E1 seemed to play an important role in the modulation of safrole-DNA adduct formation. We have also shown that safrole can form stable safrole-DNA adducts as well as oxidative damages in rodent liver. However, the stable safrole-DNA adducts may represent a more significant initial lesion as compared to the rapidly repaired safrole-induced 8-hydroxy-2'-deoxyguanosine. This oxidative DNA damage is mediated through the formation of hydoryxchavicol, the major safrole metabolite in human urine. Hydroxychavicol may have gone through two-electron oxidation to the o-quinone; then via one-electron reduction to semiquinone radicals to generate oxidative DNA damage. However, these reactive metabolites can be efficiently conjugated by GSH. These data suggest that safrole may contribute to the initiation of oral carcinogenesis through safrole-DNA adduct and not oxidative DNA damage. In addition, CYP2E1 may modulate this adduct formation.

• Food Science of Animal Resources
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• v.25 no.4
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• pp.494-499
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• 2005

In the present study, we investigate the protective effect of antioxidant strain Lactobacillus gasseri KACC 91155, isolated from Korean infant feces(Obstetrics & Gynecology, Suwon, Korea) on the oxidative stress damage on the Jurkat T cells. To estimate the extent of cellular lipid peroxidation inhibition, MDA(malondialdehyde) production was measured Furthermore, cell viability was detected by the MTT assay, DNA damage was tested by the comet assay. Cell grown in medium with or without L gasseri lysate$(100\~1,000{\mu}g)$ were treated with $H_2O_2,\;Fe^{2+}$ as an oxidative stimulus. From the result obtained, the supplementation of Jurkat T cells with L. gasseri lysate significantly decreased in MDA production (1,250 vs. 835 nmol/mg protein), and DNA damage(31.6 vs. 22.6 tail moment). Also L gasseri increase cell viability against oxidative damage. We concluded that the L. gasseri KACC 91155 showed a protective effect against oxidative stress.

• Journal of Applied Biological Chemistry
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• v.61 no.2
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• pp.109-117
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• 2018

Recently, cancer incidence in modern society is increasing sharply. DNA damage is caused by intrinsic or extrinsic factors in the human body, cells protect themselves by defense mechanism against DNA damage. Also, Aberrant DNA and deficient DNA repair are closely associated with various diseases, including aging and cancer. Researchers are interested in search for proper materials to inhibition for DNA damage. As knew the side effects of synthetic antioxidant, some researches have been conducted about cancer prevention materials derived from nature. Root of Smilax china, in Liliaceae, is used detoxification and tumor treatments traditionally. However, studies on the inhibitory effect of DNA damage haven't progressed. In this study, antioxidant activity and protective effects on oxidative DNA damage of S. china root were confirmed, relationship between those activities and contents of phenolic compounds in plants were established. S. china root effectively removed 1,1-diphenyl-2-picryl-hydrazyl radicals and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid radicals. The quantification and identification of phenolic compounds were confirmed by high performance liquid chromatography analysis, its antioxidant activity was associated with some phenolic compounds. In addition, protective effects against hydroxyl radicals and ferrous ion-induced oxidative DNA damage were confirmed in plasmid DNA. In the cellular levels, S. china root suppressed the expression of ${\gamma}$-H2AX and p53 protein in NIH 3T3. Besides, S. china root suppressed H2AX and p53 mRNA levels. In conclusion, S. china root had the effect on DNA protection and antioxidant.

• Archives of Pharmacal Research
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• v.29 no.2
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• pp.159-164
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• 2006

The protective properties of Satureja hortensis L. on the rat lymphocytes DNA lesions were tested. Lymphocytes were isolated from blood samples taken from healthy rats. DNA breaks and resistance to $H_{2}O_{2}$-induced damage were measured with the comet assay. Rat lymphocytes were incubated in S. hortensis ethanolic extract (SHE) (0.05, 0.1, 0.5, 1.0, and 2.5 mg/mL), essential oil (SHEO)(0.05, 0.1, 0.5, 1.0, and 2.5 ${mu}L/mL$), $H_{2}O_{2}$ (50, 100, and 200 ${\mu}M$), a combination of $H_{2}O_{2}$ (200 mM) with either SHE (1.0, 2.5 mg/mL) or SHEO (1.0, 2.5 ${\mu}L/mL$) at $4^{\circ}C$ for 30 min, and the extent of DNA migration was measured using a single-cell microgel electrophoresis technique under alkaline conditions. Treatment of rat lymphocytes with SHE or SHEO resulted in significant reduction of $H_{2}O_{2}$-induced DNA damage compared to controls. SHE exhibited a significant (P<0.01) inhibitory effect on oxidative DNA damage at 2.5 mg/mL. SHEO (1.0 and 2.5 ${\mu}L/mL$) also showed significant inhibitory effects (P<0.01) on $H_{2}O_{2}$ induced chromosomal damage. In conclusion both the ethanolic extract and the essential oil of the plant reversed the oxidative damage to rat lymphocytes induced by hydrogen peroxide.

• BMB Reports
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• v.35 no.3
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• pp.297-301
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• 2002

Membrane lipid peroxidation processes yield products that may react with DNA and proteins to cause oxidative modifications. The oxyR gene product regulates the expression of enzymes and proteins that are needed for cellular protection against oxidative stress. Upon exposure to tert-butylhydroperoxide (t-BOOH) and 2,2'-azobis (2-amidinopropane) hydrochloride (AAPH), which induce lipid peroxidation in membranes, the Escherichia coli oxyR overexpression mutant was much more resistant to lipid peroxidation-mediated cellular damage, when compared to the oxyR deletion mutant in regard to growth kinetics, viability, and DNA damage. The deletion of the oxyR gene in E. coli also resulted in increased susceptibility of superoxide dismutase to lipid peroxidation-mediated inactivation. The results indicate that the peroxidation of lipid is probably one of the important intermediary events in free radical-induced cellular damage. Also, the oxyR regulon plays an important protective role in lipid peroxidation-mediated cellular damage.

• Toxicological Research
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• v.17 no.4
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• pp.249-253
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• 2001

Fumonisin B1, a mycotoxin, is thought to induce esophageal cancer in humans and apoptosis in animal cells by inhibiting ceramide synthase. Dumonisin Bl may also generate reactive oxygen species directly or indirectly, leading to DNA damage and lipid peroxidation. In this study, a DNA fragmentation assay, dichlorofluorescein (DCF) analysis, and single cell gel electrophoresis (SCGE) were used to investigate the involvement of cellular free radicals, specifically hydrogen peroxide, in the DNA damaging activity of fumonisin B1. From an in vitro DNA fragmentation assay, E. coli DNA, damage by fumonisin Bl was increased by the addition of superxide dismutase (SOD) and decreased by catalase. SCGE and DCF analysis in vivo showed that the nuclear DNA damage and intracellular free radicals in cultured rat hepatocytes treated with fumonisin B1 were increased with the concentration of fumonisin Bl . DNA damage and free radical generation were inhibited by the addition of catalase. Fumonisin Bl , in the presence of SOD, produces hydrogen peroxide causing oxidative DNA damage and protein malfunction, leading to genotoxicity and cytotoxicity of the toxin.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.16
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• pp.6967-6972
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• 2015

Background: Cigarette smoking and tobacco chewing are common modes of consuming tobacco all over the world. Parents need to be aware that germ cell integrity is vital for birth of healthy offspring as biological parenting begins much before birth of a child and even before conception. The present study was conducted to determine the etiology of non-familial sporadic heritable retinoblastoma (NFSHRb), by evaluating oxidative sperm DNA damage in fathers due to use of tobacco (smoking and chewing). Materials and Methods: We recruited 145 fathers of NFSHRb children and 53 fathers of healthy children (controls) in the study. Tobacco history was obtained by personal interview. Seminal reactive oxygen species (ROS) in semen, sperm DNA fragmentation index (DFI) and 8 hydroxy 2' deoxyguanosine (8-OHdG) levels in sperm were evaluated. The RB1 gene was screened in genomic blood DNA of parents of children with NFSHRb and controls. Odds ratios (ORs) derived from conditional logistic regression models. Results: There was significant difference in the levels of ROS (p<0.05), DFI (p<0.05) and 8-OHdG (p<0.05) between tobacco users and non-users. The OR of NFSHRb for smokers was 7.29 (95%CI 2.9-34.5, p<0.01), for tobacco chewers 4.75 (2.07-10.9, p<0.05) and for both 9.11 (3.79-39.2; p<0.01). Conclusions: This study emphasizes the adverse effect of tobacco on the paternal genome and how accumulation of oxidative damage in sperm DNA may contribute to the etiology of NFSHRb. In an ongoing parallel study in our laboratory, 11 of fathers who smoked underwent. Meditation and yoga interventions, showed significant decline in levels of highly mutagenic oxidised DNA adducts after 6 months. Thus our lifestyle and social habits impact sperm DNA integrity and simple interventions like yoga and meditation are therapeutic for oxidative damage to sperm DNA.

• Journal of Nutrition and Health
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• v.46 no.2
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• pp.126-136
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• 2013

This study was conducted in order to investigate the association between hypertension and oxidative stress-related parameters and to evaluate these parameters in subclinical hypertensive patients and normotensive subjects living in Korea. We attempted to determine whether oxidative stress-related parameters would differ between two groups of 227 newly-diagnosed, untreated (systolic blood pressure (BP) ${\geq}$ 130 mmHg and diastolic BP ${\geq}$ 85 mmHg) and 130 normotensive subjects (systolic BP < 120 mmHg and diastolic BP < 80 mmHg). General characteristics of the subjects were collected using a simple questionnaire. From subjects' blood, degree of DNA damage in lymphocytes, the activities of erythrocyte superoxide dismutase, catalase, and glutathione peroxidase, level of plasma total radical-trapping antioxidant potential (TRAP), glutathione, and anti-oxidative vitamins, as well as plasma lipid profiles and conjugated diene (CD) were analyzed. Evaluation of the associations of oxidative stress-related parameters with blood pressure of the subjects was performed using Pearson partial correlation and multivariate logistic regression analysis after adjusting for confounding factors. Several oxidative stress-related parameters were higher in subclinical hypertensive patients than in normotensive subjects. Plasma levels of ${\alpha}$-tocopherol, ${\beta}$-carotene, TRAP, and activity of GSH-px were significantly lower in subclinical hypertensive patients than in normotensive subjects. Increased levels of DNA damage, lipid peroxidation, triglyceride, total cholesterol, and LDL-cholesterol were observed in subclinical hypertensive patients. These results confirm an association between blood pressure and oxidative stress-related parameters and suggest that the pathogenic role of oxidative stress in hypertension might be significant.

• Journal of Ginseng Research
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• v.33 no.4
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• pp.305-310
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• 2009

Phenanthrene, one of the polycyclic aromatic hydrocarbons, has been known to be toxic to the environment. In this investigation, the protective effect of red ginseng on phenanthrene-induced oxidative DNA damage was evaluated using Comet assay in A549 cells. Red ginseng's cytoprotective effect on phenanthrene-induced hemolysis was also investigated. This study's findings show that oxidative DNA damage and hemolysis were significantly prevented by red ginseng treatment. Notably, it was found that pulverizing red ginseng into ultra-fine particles even enhanced its protective effects against DNA damage and hemolysis. The results suggest that particle size reduction seems to effectively enhance red ginseng's pharmacological efficacies.

• Nutritional Sciences
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• v.8 no.4
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• pp.262-267
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• 2005

Reactive oxygen species can be generated in the skin by hair dyeing. The aim of this study was to find out the effects of the oxidative-type hair dye application in young women on the antioxidant systems. We investigated the lipid peroxide levels, glutathione (GSH) levels, and the antioxidant enzyme activities including superoxide dismutase (SOD), glutathione peroxidase (GSHPx) in plasma and erythrocytes and catalase (CAT) in erythrocytes, and DNA damages in lymphocytes. Also, plasma concentrations of antioxidant vitamins, vitamin A and E, were measured and the correlations between various antioxidant parameters and oxidative damages were evaluated The antioxidant enzyme activities in plasma (GSHPx) and in erythrocytes (SOD and CAT) were decreased significantly after hair dyeing. 1be lipid peroxide and GSH levels were not affected in both plasma and erythrocytes. No significant difference was found in the concentrations of both vitamin A and E between before and after hair dyeing. However, DNA damages expressed as the tail extent moment (TEM) and tail length (TL) were significantly (p<0.001) increased. The plasma vitamin E concentration was correlated with DNA damages (TEM: r=-0.590, p<0.01 and TL: r=-0.533. p<0.01) and RBC SOD activity (r=0.570, p<0.05). In turn, RBC SOD activity was significantly correlated with both plasma MDA levels (r=-0.412, p<0.05) and DNA damages (TM: r=-0.546, p<0.01, TL: r=-0.493, p<0.01). Our results demonstrated that the exposure to hair dyeing produced lymphocyte DNA damage and modification of the antioxidant enzyme activities. Also, there were very strong associations between plasma vitamin E concentration, RBC SOD activity and DNA damage induced by hair dyeing. It suggests that the antioxidant status of a subject is likely to be related to the extent of the harmful effects caused by hair dyeing.