• Asian Pacific Journal of Cancer Prevention
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• 제16권12호
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• pp.4803-4812
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• 2015

Chronic alcohol and tobacco abuse plays a crucial role in the development of different liver associated disorders. Intake promotes the generation of reactive oxygen species within hepatic cells exposing their DNA to continuous oxidative stress which finally leads to DNA damage. However in response to such damage an entangled protective repair machinery comprising different repair proteins like ATM, ATR, H2AX, MRN complex becomes activated. Under abnormal conditions the excessive reactive oxygen species generation results in genetic predisposition of various genes (as ADH, ALDH, CYP2E1, GSTT1, GSTP1 and GSTM1) involved in xenobiotic metabolic pathways, associated with susceptibility to different liver related diseases such as fibrosis, cirrhosis and hepatocellular carcinoma. There is increasing evidence that the inflammatory process is inherently associated with many different cancer types, including hepatocellular carcinomas. The generated reactive oxygen species can also activate or repress epigenetic elements such as chromatin remodeling, non-coding RNAs (micro-RNAs), DNA (de) methylation and histone modification that affect gene expression, hence leading to various disorders. The present review provides comprehensive knowledge of different molecular mechanisms involved in gene polymorphism and their possible association with alcohol and tobacco consumption. The article also showcases the necessity of identifying novel diagnostic biomarkers for early cancer risk assessment among alcohol and tobacco users.

• 농업과학연구
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• 제49권2호
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• pp.307-316
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• 2022

The misuse of pesticides has resulted in environmental pollution, which directly or indirectly affects all life on earth. Chlorpyrifos is a chlorinated organophosphorus pesticide that is commonly used in agriculture. The aim of this study was to investigate the effects of chlorpyrifos on the fertilization function of boar spermatozoa. Sperm samples from boars were subjected to varying concentrations of chlorpyrifos from 10 to 200 µM for two incubation periods, 30 min or 2 hrs. The boar spermatozoa were then evaluated for motility, motion kinematics, viability, acrosome integrity, chromatin stability, and generation of intracellular reactive oxygen species (ROS). There was a significant percentage reduction in sperm motility and motion kinematic parameters after both incubation periods (p < 0.05). The proportion of viable spermatozoa decreased after incubation for 30 min and 2 hrs in a dose-dependent manner (p < 0.05). A significantly lower percentage of normal acrosomes was observed in spermatozoa exposed to 200 µM chlorpyrifos over both incubation periods, compared to the controls. The damage to sperm DNA was significantly higher when the exposure time to chlorpyrifos was longer. There was a significant increase in the ROS levels in spermatozoa incubated with chlorpyrifos for 2 hrs (p < 0.05). From the results of the present study, it is concluded that direct exposure of boar spermatozoa to chlorpyrifos altered boar sperm characteristics, suggesting potential toxicity that may affect the male reproductive function.

• Biomolecules & Therapeutics
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• 제17권2호
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• pp.113-124
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• 2009

Aging is a multifaceted biological process that affects all organs and organ systems of the body. This review provides an up-to-date analysis of this highly exciting, rapidly changing field of science. The aging process is largely under genetic control but is highly responsive to diverse environmental influences. The genes that control aging are those that are involved with cell maintenance, cell damage and repair. The environmental factors that accelerate aging are those that influence either damage of cellular macromolecules, or interfere with their repair. Prominent among these are chronic inflammation, chronic infection, some metallic chemicals, ultraviolet light, and others that heighten oxidative stress. Other environment factors slow the aging process. Included among these agents are resveratrol and vitamin D. In addition, dietary restriction and exercise have been found to extend human lifespan. The various mechanisms whereby all these agents exert their influence on aging include epigenetic modification, chromatin maintenance, protection of telomeres, and anti-oxidant defense, among others. The complex process of aging remains under continued, intense investigation.

• BMB Reports
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• 제57권2호
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• pp.98-103
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• 2024

The mammalian sirtuin family (SIRT1-SIRT7) has shown diverse biological roles in the regulation and maintenance of genome stability under genotoxic stress. SIRT7, one of the least studied sirtuin, has been demonstrated to be a key factor for DNA damage response (DDR). However, conflicting results have proposed that Sirt7 is an oncogenic factor to promote transformation in cancer cells. To address this inconsistency, we investigated properties of SIRT7 in hepatocellular carcinoma (HCC) regulation under DNA damage and found that loss of hepatic Sirt7 accelerated HCC progression. Specifically, the number, size, and volume of hepatic tumor colonies in diethylnitrosamine (DEN) injected Sirt7-deficient liver were markedly enhanced. Further, levels of HCC progression markers and pro-inflammatory cytokines were significantly elevated in the absence of hepatic Sirt7, unlike those in the control. In chromatin, SIRT7 was stabilized and colocalized to damage site by inhibiting the induction of γH2AX under DNA damage. Together, our findings suggest that SIRT7 is a crucial factor for DNA damage repair and that hepatic loss-of-Sirt7 can promote genomic instability and accelerate HCC development, unlike early studies describing that Sirt7 is an oncogenic factor.

• 한국식품영양과학회지
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• 제20권2호
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• pp.111-120
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• 1991

가열유 섭취에 따른 동물체내에서의 과산화적 손상에 대한 연구와 VE의 식이중 첨가수준에 따라 가열유로 인한 과산화적 손상에 대한 항산화적 방어현상을 관찰하기 위하여 열화된 가열유(산가 4.02, carbonyl가 27.9, peroxide value 52.7)를 하루 총열량의 10%, 그리고 $dl-{\alpha}-tocopheryl acetate$의 양을 달리하여 (0, 40, 200mg/kg of diet : HOF group, HO group, HOE group) tube feeding하면서 0, 3, 6주간씩 사육하였다. 실험종료후 쥐를 휘생시켜 간장을 적출하여 과산화적 손상으로부터 생체를 보호하는 생체내 항산화적 해독기전에 관여하는 효소계인 superoxide dismutase(SOD), glutathione peroxidase(GPX)와 비효소적 방어계인 microsome 대의 VE를 측정함과 동시에 조직의 손상이나 노화의 독성이 되는 지질과산화량을 측저 였고 또한 mitochondria를 비롯한 세포내 각 소기관들의 손상을 전자현미경적으로 관찰하였다. SOD활성도는 가열유 투여군이 대조군에 비해 다소 높았고 GPX활성도 및 VE함량0] 낮았으며 POV는 현저하게 높았다. 전자현미경적 관찰에서는 mitochondria내막과 cristae가 소실되고 핵막과 chromatin이 불규칙 하였다. 가열유 투여군에서 VE첨가수준을 각각 달리했을때 VE가 부족한 HOF식이군은 HO군, HOE군에 비해 s SOD활성이 높았고, GPX활성 및 VE함량이 현저히 저하되었으며, POV가 높았으며, 세포내 mitochon ndria등을 비롯한 소기관들의 손상이 더욱 현저하게 나타났으나, VE를 다량 첨가한 HOE식이군에서는 HO군, HOF식이군에 비해 이러한 과산화적 손상이 경하게 나타냈다. 또 이러한 현상은 3주때보다 6주에서 더 뚜렷하게 나타났다.

• Restorative Dentistry and Endodontics
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• 제21권1호
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• pp.385-402
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• 1996

Cytotoxicity of dental restorative materials using cell culture technique has been extensively studied by various quantitative assays. The aim of this study was to investigate the microstructural change of damaged L292 cells which could not observed with light microscope. Cytotoxic effect of ZOE, Prisma APH (Densply International Inc., U.S.A.), Clearfil FII(Kuraray Co., Japan), Fuji II(GC Co., Japan) and Fuji II LC(GC Co., Japan) on cultured L292 cells were observed. Irreversible cell damage and cytolysis were found in ZOE and Fuji II groups. In Clearfil FII, mild to moderate cell damage was observed. APH group showed variable cytotoxicity. Moderate cell damage was found in Fuji II LC group. Cytotoxic effect were as follows : A condensation of the chromatin occureds along or adjacent to the inner membrane of the nuclear envelops. The nuclear envelope remained resonably intact but the contents were partially or completely lost. The cell nucleus contains clusters of markedly electron-dense interchromatin granules. The rough endoplasmic reticulum were dilated. In some mitochondira, matrix was disoriented and fused cristae were discernible. Mitochondiral swelling and woolly appearance were recognized. Large vacuoles and autolysosmes were found in cytoplasm. Some breaks of the cytoplasmic membrane and even cytolysis could be seen in dying cells.

• 대한의생명과학회지
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• 제7권4호
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• pp.181-190
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• 2001

This study was designed to investigate the effects of reactive oxygen species (ROS) on DNA stability in human spermatozoa. To verify human spermatozoa were incubated with xanthine-xanthine oxidase (X 100$\mu$M-XO 50 mlU ~ 400 mIU), $H_2O_2$ (125 $\mu$M ~ 1 mM), sodium nitroprusside (SNP 0.1 $\mu$M ~ 100 $\mu$M) or lymphocyte. Otherwise, spermatozoa were incubated under low $O_2$ (5%) condition. Damage of sperm DNA was analyzed by single cell electrophoresis (Comet assay) and flow cytometry after acridine orange staining. In the presence of ROS, there was increase in DNA damage. The rate of DNA single strand breakage (9.0$\pm$1.0% ~ 46.0$\pm$4.6%) and DNA fragmentation (7.51$\pm$1.0% ~ 29.5$\pm$4.6%) were similar regardless of the kinds of ROS and exposure time. DNA damage in the lower $O_2$ condition (5%) was lower than ambient $O_2$ condition (20%). Taken together, it suggested that sperm DNA might be damaged by ROS. In the presence of ROS, increase in DNA damage and chromatin instability was obvious in spite of short exposure. Although present study reconfirmed that sperm incubation in the low concentration of ROS have the benefit m the induction of capacitation and Ah, the increase in DNA damage by ROS and possible genetic problem should be considered before the human trials.

• Clinical and Experimental Reproductive Medicine
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• 제45권3호
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• pp.101-109
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• 2018

In an age when a small quantity of sperm can lead to pregnancy through in vitro fertilization or intracytoplasmic sperm injection, selecting healthy sperm is important. Sperm DNA fragmentation (SDF) is known to be higher in infertile men. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) and the alkaline comet test are SDF tests that directly measure DNA damage and have shown closer correlations with assisted reproduction results than indirect tools such as the sperm chromatin structure assay or the sperm chromatic dispersion test. It is difficult; however, to endorse a single test as the best test overall; instead, it is best to select a testing method based on each patient's clinical condition and goals. In a couple struggling with infertility, if the male partner has a high level of SDF, he should aim to decrease SDF through lifestyle modifications, antioxidant treatment, and ensuring an appropriate duration of abstinence, and physicians need to treat the underlying diseases of such patients. If sperm DNA damage continues despite the patient's and physician's efforts, other methods, such as micromanipulation-based sperm selection or testicular sperm extraction, should be used to select healthy sperm with nuclear DNA integrity.

• Parasites, Hosts and Diseases
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• 제42권4호
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• pp.205-208
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• 2004

Neutrophils are important effector cells against protozoan extracellular parasite Entamoeba histolytica, which causes amoebic colitis and liver abscess in human beings. Apoptotic cell death of neutrophils is an important event in the resolution of inflammation and parasite's survival in vivo. This study was undertaken to investigate the ultrastructural aspects of apoptotic cells during neutrophil death triggered by Entamoeba histolytica. Isolated human neutrophils from the peripheral blood were incubated with or without live trophozoites of E. histolytica and examined by transmission electron microscopy (TEM). Neutrophils incubated with E. histolytica were observed to show apoptotic characteristics, such as compaction of the nuclear chromatin and swelling of the nuclear envelop. In contrast, neutrophils incubated in the absence of the amoeba had many protrusions of irregular cell surfaces and heterogenous nuclear chromatin. Therefore, it is suggested that Entamoeba-induced neutrophil apoptosis contribute to prevent unwanted tissue inflammation and damage in the amoeba-invaded lesions in vivo.

• Molecules and Cells
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• 제41권4호
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• pp.362-372
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• 2018

High mobility group box 2 (HMGB2) is an abundant, chromatin-associated, non-histone protein involved in transcription, chromatin remodeling, and recombination. Recently, the HMGB2 gene was found to be significantly downregulated during senescence and shown to regulate the expression of senescent-associated secretory proteins. Here, we demonstrate that HMGB2 transcription is repressed by p21 during radiation-induced senescence through the ATM-p53-p21 DNA damage signaling cascade. The loss of p21 abolished the downregulation of HMGB2 caused by ionizing radiation, and the conditional induction of p21 was sufficient to repress the transcription of HMGB2. We also showed that the p21 protein binds to the HMGB2 promoter region, leading to sequestration of RNA polymerase and transcription factors E2F1, Sp1, and p300. In contrast, NF-Y, a CCAAT box-binding protein complex, is required for the expression of HMGB2, but NF-Y binding to the HMGB2 promoter was unaffected by either radiation or p21 induction. A proximity ligation assay results confirmed that the chromosome binding of E2F1 and Sp1 was inhibited by p21 induction. As HMGB2 have been shown to regulate premature senescence by IR, targeting the p21-mediated repression of HMGB2 could be a strategy to overcome the detrimental effects of radiation-induced senescence.