• Environmental Analysis Health and Toxicology
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• v.19 no.4
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• pp.335-344
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• 2004

Diesel exhaust particle (<2.5 ${\mu}{\textrm}{m}$, DEP$_{2.5}$) is known to be probarbly carcinogenic (IARC group 2A). DEP$_{2.5}$ contains organic compounds such as polycyclicaromatic hydrocarbon (PAH), heterocyclic compounds, phenols, and nitroarenes. Reactive oxygen species (ROS) are generated by DEP$_{2.5}$ without any biological activation system. Therefore, an alternative mechanism by which DEP$_{2.5}$ could be carcinogenic is known by the generation of oxidative DNA damage. The aim of this study was to investigate genotoxic effects of DEP$_{2.5}$ using single cell gel electrophoresis. In order to evaluate the mechanisms of DEP$_{2.5}$ genotoxicity, the rat micro-some mediated and DNA repair enzyme treated comet assays together with routine comet assay were performed. DEP$_{2.5}$ was collected from diesel engine bus and dichloromethane extract was obtained. The organic extract of DEP$_{2.5}$ revealed DNA damage itself in NIH/3T3 cells. And it showed both oxidative and microsome mediated DNA damages. Vitamin C as an model antioxidant reduced DNA damage in endonuclase III treated comet assay. One of flavonoid, galangin as a CYP1A1 inhibitor reduced DNA damage in the presence of S-9 mixture. Our results show that DEP$_{2.5}$ are genotoxic and a great source of oxidative stress, but antioxidants can significantly reduce oxidative DNA damages. And DEP$_{2.5}$ may contain indirect mutagens which can be inhibited by CYP inhibitors.d by CYP inhibitors.

• Proceedings of the Korean Society of Toxicology Conference
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• 2006.11a
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• pp.55-64
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• 2006

The fetal central nervous system (CNS) is sensitive to diverse environmental factors, such as alcohol, heavy metals, irradiation, mycotoxins, neurotransmitters, and DNA damage, because a large number of processes occur during an extended period of development. Fetal neural damage is an important issue affecting the completion of normal CNS development. As many concepts about the brain development have been recently revealed, it is necessary to compare the mechanism of developmental abnormalities induced by extrinsic factors with the normal brain development. To clarify the mechanism of fetal CNS damage, we used one experimental model in which 5-azacytidine (5AZC), a DNA damaging and demethylating agent, was injected to the dams of rodents to damage the fetal brain. 5AzC induced cell death (apoptosis)and cell cycle arrest in the fetal brain, and it lead to microencephaly in the neonatal brain. We investigated the mechanism of apoptosis and cell cycle arrest in the neural progenitor cells in detail, and demonstrated that various cell cycle regulators were changed in response to DNA damage. p53, the guardian of genome, played a main role in these processes. Further, using DNA microarray analysis, tile signal cascades of cell cycle regulation were clearly shown. Our results indicate that neural progenitor cells have the potential to repair the DNA damages via cell cyclearrest and to exclude highly affected cells through the apoptotic process. If the stimulus and subsequent DNA damage are high, brain development proceeds abnormally and results in malformation in the neonatal brain. Although the mechanisms of fetal brain injury and features of brain malformation afterbirth have been well studied, the process between those stages is largely unknown. We hypothesized that the fetal CNS has the ability to repair itself post-injuring, and investigated the repair process after 5AZC-induced damage. Wefound that the damages were repaired by 60 h after the treatment and developmental processes continued. During the repair process, amoeboid microglial cells infiltrated in the brain tissue, some of which ingested apoptotic cells. The expressions of genes categorized to glial cells, inflammation, extracellular matrix, glycolysis, and neurogenesis were upregulated in the DNA microarray analysis. We show here that the developing brain has a capacity to repair the damage induced by the extrinsic stresses, including changing the expression of numerous genes and the induction of microglia to aid the repair process.

• Clinical and Experimental Pediatrics
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• v.48 no.12
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• pp.1295-1309
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• 2005

Nowadays, the nutritional deficits are rarely seen in Korea. However, an increased availability of the highly palatable energy dense, nutrient-poor foods increases the risks of obesity and deficits of vitamins and minerals in the general population. Also, optimum intake of vitamins and minerals, which varies with age and genetic back ground, might not suffice the poor, young, obese, and elderly people. Young girls and individuals participating in weight reductions and aesthetic components are prone to micronutrient deficiencies because they restrict food intake and specific micronutrient rich foods. An inadequate intake of vitamins or minerals is associated with reduced physical performance and exercise capacity, increased obesity, decreased cognitive function, increased DNA damages such as single- and double-stranded breaks or oxidative DNA lesions, and accelerated aging process and increased neuronal damages with mitochondrial oxidative decay. Most of these deleterious effects of the deficit could be prevented by a one tablet of multivitamins with a good balanced diet. High dose B vitamins are frequently administered to overcome the metabolic inadequacy to the people with the less functional enzymes with increased Km values for their coenzymes due to the single gene mutation or due to the single nucleotide polymorphisms. And some certain antioxidant vitamins are also used in large quantities to overcome the oxidative stress and to repair the damages. In this review, new nutritional concepts of some vitamins and minerals, which are widely used and useful for the children, will be discussed.

• Proceedings of the Microbiological Society of Korea Conference
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• 2004.05a
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• pp.47-50
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• 2004

The defenses against free radical damage include specialized repair enzymes that correct oxidative damages in DNA, and detoxification systems such as superoxide dismutases. These defenses may be coordinated genetically as global responses. We hypothesized that the expression of the SOD and the DNA repair genes would inhibit DNA damage under oxidative stress. Therefore, the protection of E. coli mutants deficient in SOD and DNA repair genes $(sod^-\;xth^-\;and\;nfo^-)$ was demonstrated by transforming the mutant strain with a plasmid pYK9 which encoded Photobacterium leiognathi CuZnSOD and human AP endonuclease. The results show that survival rates were increased in $sod^+\;xth^-\;nfo^+$ cells compared to $sod^-\;xth^-\;ap^+,\;sod^-\;xth^-\;ap^-,\;and\;sod^+\;xth^-\;ap^-$ cells under oxidative stress generated from 0.1 mM Paraquat or 3 mM $H_2O_2$. The data suggested that, at least, SOD and DNA repair enzymes may have collaborate protection and repair of the damaged DNA. Additionally, both enzymes are required for protection against free radicals.

• The Korean Journal of Zoology
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• v.20 no.1
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• pp.41-48
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• 1977

Dose response of DNA repair synthesis induced by bleomycin was dose-dependent in lower doses, and maximum rate of it at 5 $\\mu$g/ml represents about 15% of total cells analyzed. At higher doses DNA-repair synthesis was reduced and the rate of it remained unchanged even prolonged treatment. Pretreatment with BUdR or IUdR was found to enhance DNA repair synthesis and also to interfere with semiconservative DNA synthesis at higher doses. Time dependence study showed that DNA repair synthesis occurred as long as for 24 hours after removal of bleomycin. These results seem to suggest that bleomycin is not to be an effective chemical in inducing excision repair and that damages induced in DNA by this drug might include not only strand breaks but other types of DNA damage.

• Nutrition Research and Practice
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• v.7 no.1
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• pp.34-42
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• 2013

This study investigated the effects of magnetized water supplementation on blood glucose, DNA damage, antioxidant status, and lipid profiles in streptozotocin (STZ)-induced diabetic rats. There were three groups of 4-week-old male Sprague-Dawley rats used in the study: control group (normal control group without diabetes); diabetes group (STZ-induced diabetes control); and magnetized water group (magnetized water supplemented after the induction of diabetes using STZ). Before initiating the study, diabetes was confirmed by measuring fasting blood glucose (FBS > 200 dl), and the magnetized water group received magnetized water for 8 weeks instead of general water. After 8 weeks, rats were sacrificed to measure the fasting blood glucose, insulin concentration, glycated hemoglobin level, degree of DNA damage, antioxidant status, and lipid profiles. From the fourth week of magnetized water supplementation, blood glucose was decreased in the magnetized water group compared to the diabetes group, and such effect continued to the 8th week. The glycated hemoglobin content in the blood was increased in the diabetes group compared to the control group, but decreased significantly in the magnetized water group. However, decreased plasma insulin level due to induced diabetes was not increased by magnetized water supplementation. Increased blood and liver DNA damages in diabetes rats did significantly decrease after the administration of magnetized water. In addition, antioxidant enzyme activities and plasma lipid profiles were not different among the three groups. In conclusion, the supplementation of magnetized water not only decreased the blood glucose and glycated hemoglobin levels but also reduced blood and liver DNA damages in STZ-induced diabetic rats. From the above results, it is suggested that the long-term intake of the magnetized water over 8 weeks may be beneficial in both prevention and treatment of complications in diabetic patients.

• Bulletin of the Korean Chemical Society
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• v.30 no.9
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• pp.2149-2151
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• 2009

• Proceedings of the Korean Nutrition Society Conference
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• 2000.06a
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• pp.132-132
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• 2000

• The Korean Journal of Zoology
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• v.20 no.2
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• pp.93-99
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• 1977

Dose response forDNA repair synthesis induced by various concentrations of MMC (0.05 $\\sim$ 0.5 $\\mu$g/ml) in HeLa $S_3$ cells was not dose-dependent and the amounts of it were relatively lower, representing $7\\sim9%$ of total DNA synthesizing cells in $0.1\\sim0.5 \\mug/ml$ concentrations. Time dependence study showed that MMC-induced DNA repair synthesis occurred as long as for 24 hours with similar incidences in all time courses. Pretreatment with BUdR was found to have a sensitization effect on MMC-induced DNA repair synthesis, but that with IUdR was not. Combined treatment with BUdR of IUdR and MMC suppressed remarkably the semiconservative DNA synthesis especially at later time course. These results seem to suggest that damages induced in DNA by MMC might be repaired by both fast and slow excision processes.

• Proceedings of the Korean Nuclear Society Conference
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• 2004.10a
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• pp.1212-1213
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• 2004

The plasmid was used pBR 322 and ${\varphi}X174$ RF DNA. In neutron experiment, damage of pBR 322 and ${\varphi}X174$ RF DNA were observed according to increasing concentration of BSH and neutron dose. Damage of plasmid DNA appeared obvious by increasing of BSH and neutron irradiation. In ${\gamma}-$ radiation experiment, it was carried out like above neutron experiment but damages of two plasmid appeared no differences from the control unlike neutron result.