• Title/Summary/Keyword: DNA Damage

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Gender-Specific Changes of Plasma MDA, SOD, and Lymphocyte DNA Damage during High Intensity Exercise (고강도 운동 시 성별에 따른 혈장 MDA, SOD 및 임파구 DNA 손상 변화)

  • Cho, Su-Youn;Chung, Young-Soo;Kwak, Yi-Sub;Roh, Hee-Tae
    • Journal of Life Science
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    • v.21 no.6
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    • pp.838-844
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    • 2011
  • The purpose of this study was to investigate gender-specific changes of plasma MDA, SOD, and lymphocyte DNA damage during high intensity exercise. In this study, 17 healthy male and 18 healthy female college students ran on a treadmill at 85%$VO_{2max}$ until the point of all-out. Blood-collecting was carried out five times (Rest, Ex-Exha, R0.5h, R4h and R24h), and with the collected blood, plasma malondialdehyde (MDA), superoxide dismutase (SOD), and lymphocyte DNA damage were analyzed. Plasma MDA and SOD concentration increased significantly at the Ex-Exha (p<0.05), and there were no significant differences in gender. For the degree of lymphocyte DNA damage, all %DNA in the tail, tail length and tail moment increased significantly at the Ex-Exha (p<0.05), and %DNA in the tail and tail length were significantly higher in the male group than in the female group (p<0.05). These results suggest that acute high intensity exercise not only causes oxidative stress but also brings about lymphocyte DNA damage. In addition, it was found that males showed higher DNA damage than females in terms of oxidative stress subject to high intensity exercise. Nevertheless, further subsequent studies are required in order to better understand the mechanism behind DNA damage varying with gender, in a way that takes into consideration physical fitness, hormonal level, exercise intensity and duration - additional factors which might affect DNA damage.

DNA Damage Protection and Anti-inflammatory Activity of Different Solvent Fractions from Aruncus dioicus var. kamtschaticus

  • Zhang, Qin;Kim, Hye-Young
    • Korean Journal of Plant Resources
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    • v.27 no.6
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    • pp.714-719
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    • 2014
  • This study investigated DNA damage protection and anti-inflammatory activity of different solvent fractions from Aruncus dioicus var. kamtschaticus (A. dioicus) aerial parts water extract. As for DNA damage protection, distilled water ($H_2O$) fraction displayed the most powerful protection for DNA damage at a concentration of 1 mg/ml. As for anti-inflammatory activity, dichloromethane ($CH_2Cl_2$) fraction exhibited the highest NO inhibition activity, ranging from 61% to 19% ($10-40{\mu}g/ml$). Furthermore, the levels of pro-inflammatory cytokines mRNA expressions and intracellular reactive oxygen species (ROS) were employed to verify the anti-inflammatory activity of the $CH_2Cl_2$ fraction on further researches. It could be concluded that A. dioicus had a significantly effect of DNA damage protection and anti-inflammatory activity which also as an essential edible vegetable and medicinal species.

Effect of Some Natural Products on the DNA Damaging Activity of 4NQO (4-nitroquinoline n-oxide) and Daunorubicin (Daunorubicin과 4NQO의 DNA damaging activity에 대한 천연물질의 영향)

  • 이완희;이행숙;권혁일;박진서;최수영;이길수
    • Environmental Mutagens and Carcinogens
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    • v.19 no.2
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    • pp.112-115
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    • 1999
  • The action mechanism of the inhibitory effect of some natural products on the DNA strand break and DNA damage was investigated in vitro and in vivo. In the E. coli chromosomal DNA strand break experiment in vitro, three mushroom water extracts were effective on the DNA strand breaking by daunorubicin. Phellinus linteus water extract inactivated daunorubicin, a DNA strand breaking agent, but did not protect DNA from daunorubicin-induced DNA strand breaking. Agaricus blazei water extract inhibited DNA strand breaking action of daunorubicin not only by daunorubicin inactivation, but also by DNA protection from daunorubicin. An inhibitory effect of Ganoderma lucidum water extract on the DNA strand break was based on the DNA protection rather than daunorubicin inactivation. In vivo mutagen assay system (SOS-chromotest), among three mushroom water extracts Phellinus linteus water extract was the most effective one on the inhibition of DNA damage by 4-NQO. The results suggest that all three mushroom water extracts inhibit daunorubicin-induced DNA damage and in vivo DNA damaging action of 4-NQO by the reaction of mutagen inactivation or DNA protection from the mutagen.

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Chronological Switch from Translesion Synthesis to Homology-Dependent Gap Repair In Vivo

  • Fujii, Shingo;Isogawa, Asako;Fuchs, Robert P.
    • Toxicological Research
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    • v.34 no.4
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    • pp.297-302
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    • 2018
  • Cells are constantly exposed to endogenous and exogenous chemical and physical agents that damage their genome by forming DNA lesions. These lesions interfere with the normal functions of DNA such as transcription and replication, and need to be either repaired or tolerated. DNA lesions are accurately removed via various repair pathways. In contrast, tolerance mechanisms do not remove lesions but only allow replication to proceed despite the presence of unrepaired lesions. Cells possess two major tolerance strategies, namely translesion synthesis (TLS), which is an error-prone strategy and an accurate strategy based on homologous recombination (homology-dependent gap repair [HDGR]). Thus, the mutation frequency reflects the relative extent to which the two tolerance pathways operate in vivo. In the present paper, we review the present understanding of the mechanisms of TLS and HDGR and propose a novel and comprehensive view of the way both strategies interact and are regulated in vivo.

GENE-SPECIFIC OXIDATIVE DNA DAMAGE IN HELICOBACTER PYLORI INFECTED HUMAN GASTRIC MUCOSA

  • Jinhee Chol;Yoon, Sun-Hee;Kim, Ja-Eun;Rhee, Kwang-Ho;Youn, Hee-Sang;Chung, Myung-Hee
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2002.05a
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    • pp.84-84
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    • 2002
  • Abstract To study the status of oxidative DNA damage in Helicobacter pylori infection in more details, gene-specific oxidative DNA damage was investigated by examining oxidative DNA damage to individual genes. This was done by determining the loss of PCR product of a targeted gene before and after gastric mucosal DNA was treated with 8-hydroxyguanine glycosylase, which cleaves DNA at the 8-hydroxyguanine residues.(omitted)

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Protective Effect of Garlic (Allium sativum L.) Extracts Prepared by Different Processing Methods on DNA Damage in Human Leukocytes (마늘의 조리방법에 따른 DNA 손상 보호 효과의 비교)

  • Kim, Jung-Mi;Jeon, Gyeong-Im;Park, Eun-Ju
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.39 no.6
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    • pp.805-812
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    • 2010
  • DNA damage including base modifications, loss of base and breaks in DNA strands can occur by exposure to irradiation, smoking and several components of food. Unrepaired DNA damage is known to lead to cellular dysfunction, cell death, cancer, and other diseases such as arteriosclerosis and diabetes. The protective effect of garlic on oxidative stress induced DNA damage has been reported recently. In this study, we investigated the protective effect of garlic extracts prepared by different processing methods (raw garlic extracts, RGE; grilled garlic extracts, GGE; pickled garlic extracts, PGE) on leukocytic DNA damage using comet assay. Human leukocytes were incubated with ethanol and methanol extract of garlic at various concentrations (1, 5, 10, 50 ${\mu}g$/mL), followed by oxidative stimuli (200 ${\mu}M$ $H_2O_2$ or 200 ${\mu}M$ 4-hydroxynonenal (HNE)). The methanol and ethanol extracts of RGE, GGE, and PGE showed inhibitory activities of DNA damage induced by $H_2O_2$ or HNE. Especially methanol extract of RGE ($ED_{50}$; 13.3 ${\mu}g$/mL) had a higher antigenotoxic effect on $H_2O_2$ induced DNA damage than those of GGE (23.5 ${\mu}g$/mL) or PGE (24.5 ${\mu}g$/mL). HNE induced DNA damage tended to be effectively inhibited by the lower concentration of all garlic extracts. Therefore, garlic might have protective effects against oxidative DNA damage regardless of processing methods (raw, grilled, pickled) which are the general consumed forms of garlic in Korea.

Evaluation of Oxidative DNA Damage Using an Alkaline Single Cell Gel Electrophoresis (SCGE) Comet Assay, and the Protective Effects of N-Acetylcysteine Amide on Zearalenone-induced Cytotoxicity in Chang Liver Cells

  • Kang, Changgeun;Lee, Hyungkyoung;Yoo, Yong-San;Hah, Do-Yun;Kim, Chung Hui;Kim, Euikyung;Kim, Jong Shu
    • Toxicological Research
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    • v.29 no.1
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    • pp.43-52
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    • 2013
  • Zearalenone (ZEN) is a non-steroidal estrogenic mycotoxin produced by several species of Fusarium that are found in cereals and agricultural products. ZEN has been implicated in mycotoxicosis in farm animals and in humans. The toxic effects of ZEN are well known, but the ability of an alkaline Comet assay to assess ZEN-induced oxidative DNA damage in Chang liver cells has not been established. The first aim of this study was to evaluate the Comet assay for the determination of cytotoxicity and extent of DNA damage induced by ZEN toxin, and the second aim was to investigate the ability of N-acetylcysteine amide (NACA) to protect cells from ZEN-induced toxicity. In the Comet assay, DNA damage was assessed by quantifying the tail extent moment (TEM; arbitrary unit) and tail length (TL; arbitrary unit), which are used as indicators of DNA strand breaks in SCGE. The cytotoxic effects of ZEN in Chang liver cells were mediated by inhibition of cell proliferation and induction of oxidative DNA damage. Increasing the concentration of ZEN increased the extent of DNA damage. The extent of DNA migration, and percentage of cells with tails were significantly increased in a concentration-dependent manner following treatment with ZEN toxin (p < 0.05). Treatment with a low concentration of ZEN toxin (25 ${\mu}M$) induced a relatively low level of DNA damage, compared to treatment of cells with a high concentration of ZEN toxin (250 ${\mu}M$). Oxidative DNA damage appeared to be a key determinant of ZEN-induced toxicity in Chang liver cells. Significant reductions in cytolethality and oxidative DNA damage were observed when cells were pretreated with NACA prior to exposure to any concentration of ZEN. Our data suggest that ZEN induces DNA damage in Chang liver cells, and that the antioxidant activity of NACA may contribute to the reduction of ZEN-induced DNA damage and cytotoxicity via elimination of oxidative stress.

The effect of carrot juice, ${\beta}$-carotene supplementation on lymphocyte DNA damage, erythrocyte antioxidant enzymes and plasma lipid profiles in Korean smoker

  • Lee, Hye-Jin;Park, Yoo-Kyoung;Kang, Myung-Hee
    • Nutrition Research and Practice
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    • v.5 no.6
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    • pp.540-547
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    • 2011
  • High consumption of fruits and vegetables has been suggested to provide some protection to smokers who are exposed to an increased risk of numerous cancers and other degenerative diseases. Carrot is the most important source of dietary ${\beta}$-carotene. Therefore, the objective of this study was to investigate whether carrot juice supplementation to smokers can protect against lymphocyte DNA damage and to compare the effect of supplementationof capsules containing purified ${\beta}$-carotene or a placebo (simple lactose). The study was conducted in a randomized and placebo-controlled design. After a depletion period of 14 days, 48 smokers were supplemented with either carrot juice (n = 18), purified ${\beta}$-carotene (n = 16) or placebo (n = 14). Each group was supplemented for 8 weeks with approximately 20.49 mg of ${\beta}$-carotene/day and 1.2 mg of vitamin C/day, as carrot juice (300 ml/day) or purified ${\beta}$-carotene (20.49 mg of ${\beta}$-carotene, 1 capsule/day). Lymphocyte DNA damage was determined using the COMET assay under alkaline conditions and damage was quantified by measuring tail moment (TM), tail length (TL), and% DNA in the tail. Lymphocyte DNA damage was significantly decreased in the carrot juice group in all three measurements. The group that received purified ${\beta}$-carotene also showed a significant decrease in lymphocyte DNA damage in all three measurements. However, no significant changes in DNA damage was observed for the placebo group except TM (P = 0.016). Erythrocyte antioxidant enzyme was not significantly changed after supplementation. Similarly plasma lipid profiles were not different after carrot juice, ${\beta}$-carotene and placebo supplementation. These results suggest that while the placebo group failed to show any protective effect, carrot juice containing beta-carotene or purified ${\beta}$-carotene itself had great antioxidative potential in preventing damage to lymphocyte DNA in smokers.

The Level of UVB-induced DNA Damage and Chemoprevention Effect of Paeoniflorin in Normal Human Epidermal Kerationcytes

  • Lim, Jun-Man;Park, Mun-Eok;Lee, Sang-Hwa;Kang, Sang-Jin;Cho, Wan-Goo;Rang, Moon-Jeong
    • Molecular & Cellular Toxicology
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    • v.1 no.2
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    • pp.111-115
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    • 2005
  • Ultraviolet (UV) radiation to mammalian skin is known to alter cellular function via generation of Reactive Oxygen Species (ROS), DNA damage and DNA lesions, such as pyrimidine dimmers and photoproducts, which could lead to DNA mutation if they are not repaired. In this study, we have investigated the reduction of DNA damage and of apoptosis with a particular attention to genetic effect of paeoniflorin in Normal Human Epidermal Keratinocytes (NHEK). After UVB irradiation from $10\;to\;500mJ/cm^{2}$ to NHEK, Mean Tail Moments (MTM) were increased with UVB dose increase. The greatest amount of strand breaks was induced at $500mJ/cm^{2}$ of UVB. Even at the lowest dose of UVB ($10mJ/cm^{2}$), change in MTM was detected (P<0.0001). Pretreated cell with 0.1% paeoniflorin maximally reduced the level of DNA damage to about 21.3%, compared to untreated cell. In the lower concentrations less than 0.01% of paeoniflorin, MTM had a small increase but paeoniflorin still had reductive effects of DNA damage. We measured the apoptosis suppression of paeoniflorin with annexin V flous staining kit. As we observed under the fluorescence microscopy to detect apoptosis in the irradiated cell, the fluorescence intensity was clearly increased in the untreated cell, but decreased in treated cells with paeoniflorin. These results suggest that paeoniflorin reduces the alteration of cell membranes and prevents DNA damage. Therefore, the use of paeoniflorin as a free radical scavenger to reduce the harmful effects of UV lights such as chronic skin damage, wrinkling and skin cancer can be useful to prevent the formation of photooxidants that result in radical damage.

Smoking Related DNA Damage in Human Lymphocytes Assessed by the Comet Assay (단세포전기영동법으로 평가한 흡연자의 백혈구 DNA손상)

  • 선수진;정해원;한정호
    • Environmental Mutagens and Carcinogens
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    • v.22 no.2
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    • pp.83-89
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    • 2002
  • The single cell gel electrophoresis (comet) assay is one of the useful tools for the study of genetic damage in humans exposed to environmental mutagens and carcinogens. This study was undertaken to evaluate the status of DNA damage in peripheral lymphocytes depending on their sex, age, smoking habits, and other factors in normal healthy Korean population. The 99 volunteers included in the study and out of these, 36 volunteers were smoker and 63 volunteers were non-smoker aged between 20-59 years. All individual answered a questionnaire that assessed their general information including smoking habits and the extent of the environmental tobacco smoke (ETS) exposure, and blood samples were obtained. There was a statistically significant difference in the extent of DNA damage between smoker and non-smoker (p<0.001). A significant difference was also observed between male and female (p<0.001) and amongst the different group of age (p<0.005), however, correlation analysis showed that only smoking habit was a significant factor for DNA damage. No significant effect of smoking duration, number of cigarettes smoking a day, SPY (smoke pack years) in smokers and environmental tobacco smoke exposure in non-smokers on the status of DNA damage was observed.

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