• Journal of Nutrition and Health
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• v.34 no.4
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• pp.401-408
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• 2001

The spontaneous frequency of genetic damage and the possible relationship of this damage to total radical-trapping antioxidant potential(TRAP) and antioxidant vitamins, including plasma levels of $\alpha$-carotene, $\beta$-carotene, cryptoxanthin, retinol, $\alpha$-tocopherol and ${\gamma}$-tocopherol in humans were investigated in 57 subjects using two indices of genetic damage, SCE & HFC frequency. The mean of SCE and HFC frequencies were weakly correlated with plasma TRAP(r=-0.305, p<0.1 for SCEs: r=-0.297, p<0.1 for HFCs, respectively), but those were strongly negatively correlated with plasma $\beta$-carotence(r=-0.385, p<0.01 for SCEs : r=-0.392, p<0.01 for HFCs) and cryptoxanthin(r=-0.312, p<0.05 for SCEs : r=0.335, p<0.05 for HFCs, respectively) levels in the subjects. However, those DNA damage markers including SCE and HFC did not correlate with either plasma $\alpha$-carotene, $\alpha$-tocopherol or retinol concentrations. The mean of SCE and HFC frequencies were positively correlated with plasma ${\gamma}$-tocopherol level(r=0.421, p<0.01 for SCEs : r=0.399, p<0.01 for HFCs, respectively). These findings indicate that increased cytogenetic DNA changes, as determined by SCE and HFC frequencies are possibly associated with generation of free radicals in lymphocytes and decreased plasma antioxidant vitamin($\beta$-carotene and cryptoxanthin) status in the subjects. (Korean J Nutrition 34(4) : 401~08, 2001)

• Molecules and Cells
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• v.19 no.2
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• pp.167-179
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• 2005

The cells of metazoans respond to DNA damage by either arresting their cell cycle in order to repair the DNA, or by undergoing apoptosis. This response is highly conserved across species, and many of the genes involved in this DNA damage response have been shown to be inactivated in human cancers. This suggests the importance of DNA damage response with regard to the prevention of cancer. The DNA damage checkpoint responses vary greatly depending on the developmental context, cell type, gene expression profile, and the degree and nature of the DNA lesions. More valuable information can be obtained from studies utilizing whole organisms in which the molecular basis of development has been well established, such as Drosophila. Since the discovery of the Drosophila p53 orthologue, various aspects of DNA damage responses have been studied in Drosophila. In this review, I will summarize the current knowledge on the DNA damage checkpoint response in Drosophila. With the ease of genetic, cellular, and cytological approaches, Drosophila will become an increasingly valuable model organism for the study of mechanisms inherent to cancer formation associated with defects in the DNA damage pathway.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.2199-2206
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• 2012

Background: Our objective was to evaluate the MTHFR C677T-A1298C polymorphisms in patients with breast cancer and in individuals with no history of cancer, to compare the levels of genetic damage and apoptosis under folic acid (FA) deficiency between patients and controls, and to assess associations with breast cancer. Methods: Genetic damage was marked by micronucleated binucleated cells (MNBN) and apoptosis was estimated by cytokinesis-block micronucleus assay (CBMN). PCR-RFLP molecular analysis was carried out. Results: The results showed significant associations between the MTHFR 677TT or the combined MTHFR C677T-A1298C and breast cancer risk (OR = 2.51, CI = 0.85 to 7.37, p = 0.08; OR = 4.11, CI = 0.78 to 21.8, p < 0.001). The MNBN from the combined MTHFR C677T-A1298C was higher and the apoptosis was lower than that of the single variants (p < 0.05). At 15 to 60 nmol/L FA, the MNBN in cases with the TTAC genotype was higher than controls (p < 0.05), whereas no significant difference in apoptosis was found between the cases and controls after excluding the genetic background. Conclusions: Associations between the combined MTHFR C677T-A1298C polymorphism and breast cancer are possible from this study. A dose of 120 nmol/L FA could enhance apoptosis in cases with MTHFR C677T-A1298C. Breast cancer individuals with the TTAC genotype may be more sensitive to the genotoxic effects of FA deficiency than controls.

• YAKHAK HOEJI
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• v.35 no.6
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• pp.522-529
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• 1991

The purpose of this research is to evaluate effects of chloramphenicol, phenobarbital and progesterone on damage of DNA, RNA and protein which was induced by dimethylnitrosamine. $N,N-Di[^{14}C]$ methyl-nitrosamine (DMN) was used as a damaging agent and levels of DNA, RNA and protein damage in liver, brain and pancreas were compared with a control group. Pretreatment of mice with chloramphenicol increased protein damage in pancreas two times more than the control level. Liver RNA damage was increased up to 5.8 times and brain DNA damage up to 6.95 times by treatment of phenobarbital but brain RNA damage was decreased significantly down to 21% of the control group. The damage of liver RNA was significantly decreased by treatment of progesterone, although liver protein damage, pancreas RNA damage and pancreas protein damage were increased.

• Molecules and Cells
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• v.22 no.2
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• pp.220-227
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• 2006

Oxidative alteration of mitochondrial cytochrome c has been linked to disease and is one of the causes of proapoptotic events. We have investigated the modification of cytochrome c by $H_2O_2$. When cytochrome c was incubated with $H_2O_2$, oligomerization of the protein increased and the formation of carbonyl derivatives and dityrosine was stimulated. Radical scavengers prevented these effects suggesting that free radicals are implicated in the $H_2O_2$-mediated oligomerization. Oligomerization was significantly inhibited by the iron chelator, deferoxamine. During incubation of deoxyribose with cytochrome c and $H_2O_2$, damage to the deoxyribose occurred in parallel with the release of iron from cytochrome c. When cytochrome c that had been exposed to $H_2O_2$ was analyzed by amino acid analysis, the tyrosine, histidine and methionine residues proved to be particularly sensitive. These results suggest that $H_2O_2$-mediated cytochrome c oligomerization is due to oxidative damage resulting from free radicals generated by a combination of the peroxidase activity of cytochrome c and the Fenton reaction of free iron released from the oxidatively-damaged protein.

• Toxicological Research
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• v.22 no.4
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• pp.423-429
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• 2006

Recent reports on the photocarcinogenicity and photogerotoxicity of many compounds led to an increasing awareness for the need of a standard approach to test for photogenotoxicity. The comet assay has been recently validated as a sensitive and specific test system for the quantification of DNA damage. Thus, the objectives of this study are to investigate the utility of photo-comet assay for detecting photo-mutagens, and to evaluate its ability to predict rodent photo-carcinogenicity. Photo-comet assays were performed using L5178Y $Tk^{+/-}$ mouse lymphoma cells on five test substances (8-methoxypsoralen, chlorpromazine, lomefloxacin, anthracene and retinoic acid) that demonstrated positive results in photocarcinogenicity tests. For the best discrimination between the test substance-mediated DNA damage and the undesirable DNA damage caused by direct UV absorption, a UV dose-response of the cells in the absence of the test substances was firstly fnalized. Out of 5 test substances, positive comet results were obtained for chlorpromazine, lomefloxacin, anthracene and retinoic acid while 8-methoxypsoralen found negative. An investigation into the predictive value of this photo-comet assay for determining the photocarcinogenicity showed that photo-comet assay has relatively high sensitivity. Therefore, the photo-comet assay with mammalian cells seems to be a good and sensitive predictor of the photocarcinogenic potential of new substances.

• Structural Engineering and Mechanics
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• v.65 no.3
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• pp.303-314
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• 2018

Shear walls are a typical member under a complex stress state and have complicated mechanical properties and failure modes. The separated-elements model Genetic Evolutionary Structural Optimization (GESO), which is a combination of an elastic-plastic stress method and an optimization method, has been introduced in the literature for designing such members. Although the separated-elements model GESO method is well recognized due to its stability, feasibility, and economy, its adequacy has not been experimentally verified. This paper seeks to validate the adequacy of the separated-elements model GESO method against experimental data and demonstrate its feasibility and advantages over the traditional elastic stress method. Two types of reinforced concrete shear wall specimens, which had the location of an opening in the middle bottom and the center region, respectively, were utilized for this study. For each type, two specimens were designed using the separated-elements model GESO method and elastic stress method, respectively. All specimens were subjected to a constant vertical load and an incremental lateral load until failure. Test results indicated that the ultimate bearing capacity, failure modes, and main crack types of the shear walls designed using the two methods were similar, but the ductility indexes including the stiffness degradation, deformability, reinforcement yielding, and crack development of the specimens designed using the separated-elements model GESO method were superior to those using the elastic stress method. Additionally, the shear walls designed using the separated-elements model GESO method, had a reinforcement layout which could closely resist the actual critical stress, and thus a reduced amount of steel bars were required for such shear walls.

• Smart Structures and Systems
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• v.33 no.2
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• pp.165-175
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• 2024

Rotating beams play a crucial role in representing complex mechanical components that are prevalent in vital sectors like energy and transportation industries. These components are susceptible to the initiation and propagation of cracks, posing a substantial risk to their structural integrity. This study presents a two-stage methodology for detecting the location and estimating the size of an open-edge transverse crack in a rotating Euler-Bernoulli beam with a uniform cross-section. Understanding the dynamic behavior of beams is vital for the effective design and evaluation of their operational performance. In this regard, modal parameters such as natural frequencies and eigenmodes are frequently employed to detect and identify damages in mechanical components. In this instance, the Frobenius method has been employed to determine the first two natural frequencies and corresponding eigenmodes associated with flapwise bending vibration. These calculations have been performed by solving the governing differential equation that describes the motion of the beam. Various parameters have been considered, such as rotational speed, beam slenderness, hub radius, and crack size and location. The effect of the crack has been replaced by a rotational spring whose stiffness represents the increase in local flexibility as a result of the damage presence. In the initial phase of the proposed methodology, a damage index utilizing the slope of the beam's eigenmode has been employed to estimate the location of the crack. After detecting the presence of damage, the size of the crack is determined using a Genetic Algorithm optimization technique. The ultimate goal of the proposed methodology is to enable the development of more suitable and reliable maintenance plans.

• Steel and Composite Structures
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• v.36 no.1
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• pp.31-45
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• 2020

The purpose of this study is to develop an effective iterative two-stage method (ITSM) for structural damage identification of offshore platform structures. In each iteration, a new damage index, Modal Energy-Based Damage Index (MEBI), is proposed to help effectively locate the potential damage elements in the first stage. Then, in the second stage, the beetle antenna search (BAS) algorithm is used to estimate the damage severity of these elements. Compared with the well-known particle swarm optimization (PSO) algorithm and genetic algorithm (GA), this algorithm has lower computational cost. A modal energy based objective function for the optimization process is proposed. Using numerical and experimental data, the efficiency and accuracy of the ITSM are studied. The effects of measurement noise and spatial incompleteness of mode shape are both considered. All the obtained results show that under these influences, the ITSM can accurately identify the true location and severity of damage. The results also show that the objective function based on modal energy is most suitable for the ITSM compared with that based on flexibility and weighted natural frequency-mode shape.

• Molecular & Cellular Toxicology
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• v.1 no.1
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• pp.26-31
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• 2005

The detection and the regulation of man-made synthetic chemicals and the establishment of toxicity that may pose a genetic hazard in our environment are subjects of great concern because of its close correlation between environmental contamination and human health. Since the tens of thousands of man-made chemicals that have been introduced into the environment in the last few decades must also be tested for their damaging effect on DNA, the agents that cause this damage must be identified.