• Toxicological Research
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• v.29 no.4
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• pp.249-255
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• 2013

Erythritol is a sugar alcohol that is widely used as a natural sugar substitute. Thus, the safety of its usage is very important. In the present study, short-term genotoxicity assays were conducted to evaluate the potential genotoxic effects of erythritol. According to the OECD test guidelines, the maximum test dose was 5,000 ${\mu}g$/plate in bacterial reverse mutation tests, 5,000 ${\mu}g/ml$ in cell-based assays, and 5,000 mg/kg for in vivo testing. An Ames test did not reveal any positive results. No clastogenicity was observed in a chromosomal aberration test with CHL cells or an in vitro micronucleus test with L5178Y $tk^{+/-}$ cells. Erythritol induced a marginal increase of DNA damage at two high doses by 24 hr of exposure in a comet assay using L5178Y $tk^{+/-}$ cells. Additionally, in vivo micronucleus tests clearly demonstrated that oral administration of erythritol did not induce micronuclei formation of the bone marrow cells of male ICR mice. Taken together, our results indicate that erythritol is not mutagenic to bacterial cells and does not cause chromosomal damage in mammalian cells either in vitro or in vivo.

• Molecules and Cells
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• v.45 no.11
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• pp.792-805
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• 2022

Repairing damaged DNA and removing all physical connections between sister chromosomes is important to ensure proper chromosomal segregation by contributing to chromosomal stability. Here, we show that the depletion of non-SMC condensin I complex subunit H (NCAPH) exacerbates chromosome segregation errors and cytokinesis failure owing to sister-chromatid intertwinement, which is distinct from the ultra-fine DNA bridges induced by DNA inter-strand crosslinks (DNA-ICLs). Importantly, we identified an interaction between NCAPH and GEN1 in the chromatin involving binding at the N-terminus of NCAPH. DNA-ICL activation, using ICL-inducing agents, increased the expression and interaction between NCAPH and GEN1 in the soluble nuclear and chromatin, indicating that the NCAPH-GEN1 interaction participates in repairing DNA damage. Moreover, NCAPH stabilizes GEN1 within chromatin at the G2/M-phase and is associated with DNA-ICL-induced damage repair. Therefore, NCAPH resolves DNA-ICL-induced ultra-fine DNA bridges by stabilizing GEN1 and ensures proper chromosome separation and chromosome structural stability.

• YAKHAK HOEJI
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• v.49 no.3
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• pp.249-254
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• 2005

The ethanol extracts of the mixed vegetables (Bioactive Vegetables, BV) and the mixed fruits (Bioactive Fruits, BF) were evaluated for their in vivo antioxidant activities. Four weeks treatment of oral administration was performed to mice. A $KBrO_3$ as a potent oxidant was used to induce the oxidative stress for in vivo experiment. BV and BF were shown to possess the significant inhibitory effect of lipid peroxidation as measured by the level of malondialdehyde (MDA) formation although the potencies were not higher than those of well-known antioxidants such as vitamin C, trolox and quercetin. Furthermore, BV and BF inhibited DNA damage assessed by single cell gel electrophoresis (comet assay) and reduced the micronucleated reticulocyte (MNRET) formation of peripheral blood. Antioxidants tested also revealed potent inhibitory activities higher than BV and BF. These antigenotoxic activity profiles were similar to that of abovementioned inhibition of lipid peroxidation. Therefore, BV and BF having mild antioxidant activity as functional food candidates may be useful natural antioxidants by the inhibiting of lipid peroxidation and the protecting oxidative DNA and chromosomal damage.

• Toxicological Research
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• v.24 no.4
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• pp.321-328
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• 2008

Smoke flavors based on the thermal decomposition of wood have been applied to a variety of food products as an alternative for traditional smoking. Despite its increasing use, the available genotoxicity data on wood smoke flavors (WSF) are still controversial. Thus, potential genotoxic effects of WSF in four short-term in vitro genotoxicity assays were investigated, which included the Ames assay, chromosomal aberration assay, micronucleus test and the alkaline comet assay. WSF did not cause any mutation in the Ames assay using five tester strains at six concentrations of 0.16, 0.31, 0.63, 1.25, 2.5 and 5 ${\mu}l/plate$. To assess clastogenic effect, the in vitro chromosomal aberration assay was performed using Chinese hamster lung cells. No statistically significant increase in the number of metaphases with structural aberrations was observed at the concentrations of 1.25, 2.5, and 5 ${\mu}l/ml$. The in vitro comet assay and micronucleus test results obtained on L5178Y cells also revealed that WSF has no genotoxicity potential, although there was a marginal increase in micronuclei frequencies and DNA damage in the respective micronucleus and comet assays. Taken together, based on the results obtained from these four in vitro studies, it is concluded that WSF is not a mutagenic agent in bacterial cells and causes no chromosomal and DNA damage in mammalian cells in vitro.

• Korean Journal of Microbiology
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• v.29 no.6
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• pp.392-396
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• 1991

Mu d1(Ap lac) bacteriophage can be used to search for genes which are members of a common regulatory network without having to know the functions of the genes in advance. Aim was for obtaining the loci in the SOS network as well as temperature inducible loci. For this purpose, recA441 allele was used. This allele encodes a thermosensitive recA gene product; thus, the recA441 allele can be activated upon temperature upshift without by external DNA damage. Approximately 10, 000 colonies were screened, and then searched for the colonies which expressed .betha.-galactosidase higher level at 42.deg.C than at 30.deg.C. The strains identified fell into two dlasses; (i) ones in which the increased expression was $recA^{+}$ $lexA^{+}$ -dependent, that is, din(damage-inducible) genes which were due to the activation of recA441 allele and (ii) ones in which the increased expression was $recA^{+}$ $lexA^{+}$ -independent and only temperature-inducible, tin genes. Rough mapping position was obtained for these genes.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.1773-1777
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• 2016

Diagnostic and therapeutic radiation fields are planned so as to reduce side-effects while maximising the dose to site but effects on healthy tissues are inevitable. Radiation causes strand breaks in DNA of exposed cells which can lead to chromosomal aberrations and cause malfunction and cell death. Several researchers have highlighted the damaging effects of high dose radiation but still there is a lacuna in identifying damage due to low dose radiation used for diagnostic purposes. Blood is an easy resource to study genotoxicity and to estimate the effects of radiation. The micronucleus assay and chromosomal aberration can indicate genetic damage and our present aim was to establish these with lymphocytes in an in vitro model to predict the immediate effects low dose radiation. Blood was collected from healthy individuals and divided into 6 groups with increasing radiation dose i.e., 0Gy, 0.10Gy, 0.25Gy, 0.50Gy, 1Gy and 2Gy. The samples were irradiated in duplicates using a LINAC in the radiation oncology department. Standard protocols were applied for chromosomal aberration and micronucleus assays. Metaphases were stained in Giemsa and 200 were scored per sample for the detection of dicentric or acentric forms. For micronuclei detection, 200 metaphases. Giemsa stained binucleate cells per sample were analysed for any abnormality. The micronuclei (MN) frequency was increased in cells exposed to the entire range of doses (0.1-2Gy) delivered. Controls showed minimal MN formation ($2.0%{\pm}0.05$) with triple MN ($5.6%{\pm}2.0$) frequency at the lowest dose. MN formation increased exponentially with the radiation dose thereafter with a maximum at 2Gy. Significantly elevated numbers of dicentric chromosomes were also observed, even at doses of 0.1-0.5Gy, compared to controls, and acentric chromosomes were apparent at 2Gy. In conclusion we can state that lymphocytes can be effectively used to study direct effect of low dose radiation.

• Korean Journal of Food Science and Technology
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• v.47 no.1
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• pp.87-94
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• 2015

High voltage pulsed electric fields (PEF) treatment is one of the more promising nonthermal technologies to fully or partially replace thermal processing. The objective of this research was to investigate the microbial inactivation mechanisms of PEF treatment in terms of intra- and extracellular changes in the cells. Saccharomyces cerevisae cells treated with PEF showed cellular membrane damage. This resulted in the leakage of UV-absorbing materials and intracelluar ions, which increased with increasing treatment time and electric fields strength. This indicates that PEF treatment causes cell death via membrane damage and physical rupture of cell walls. We further confirmed this by Phloxine B staining, a dye that accumulates in dead cells. Using scanning and transmission electron microscopy, we observed morphological changes as well as disrupted cytoplasmic membranes in PEF treated S. cerevisae cells. In addition, PEF treatment led to damaged chromosomal DNA in S. cerevisiae.

• Molecular & Cellular Toxicology
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• v.5 no.3
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• pp.257-264
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• 2009

Gardenia yellow, extracted from gardenia fruit, has been widely used as a coloring agent for foods, and thus, safety of its usage is of prime importance. In the current study, short-term genotoxicity assays were conducted to evaluate the potential genotoxic effects of gardenia yellow. The gardenia yellow used was found to contain 0.057 mg/g of genipin, a known biologically active compound of the gardenia fruit extract. Ames test did not reveal any positive results. No clastogenicity was detected by a chromosomal aberration test, even on evaluation at the highest feasible concentration of gardenia yellow. Gardenia yellow was also shown to be non-genotoxic using an in vitro comet assay and a micronucleus test with L5178Y cells, although a marginal increase in DNA damage and micronuclei frequency was reported in the respective assays. Additionally, in vivo micronucleus test results clearly demonstrated that oral administration of gardenia yellow did not induce micronuclei formation in the bone marrow cells of male ICR mice. Taken together, our results indicate that gardenia yellow is not mutagenic to bacterial cells, and that it does not cause chromosomal damage in mammalian cells, either in vitro or in vivo.

• Radiation Oncology Journal
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• v.11 no.2
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• pp.193-203
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• 1993

In understanding radiosensitivity a new concept of inherent radiosensitivity based on individuality and heterogeneity within a population has recently been explored. There has been some discussion of possible mechanism underlying differences in radiosensitivity between cells. Ataxia telangiectasia (AT), a rare autosomal recessive genetic disorder, is characterized by hypersensitivity to ionizing radiation and other DNA damaging agents at the cellular level. There have been a lot of efforts to describe the cause of this hypersensitivity to radiation. At the cellular level, chromosome repair kinetics study would be an appropriate approach. The purpose of this study was to better understand radiosensitivity En an approach to investigate kinetics of induction and repair of $G_2$ chromatic bleaks using normal, AT heterozygous (ATH), and AT homozygous lymphoblastoid cell lines. In an attempt to estimate initial damage, $9-{\beta}-D-arabinosyl-2-fluoroadenine,$ an inhibitor of DNA synthesis and repair, was used in this study. It was found from this study that radiation induces higher chromatid breaks in AT than in normal and ATH cells. There was no significant differences of initial chromatid breaks between normal and ATH cells. Repair kinetics was the same for all. So the higher level of breaks in AT $G_2$ cells is thought to be a reflection of the increased initial damage. The amount of initial damage correlated well with survival fraction at 2 Gy of cell survival curve following radiation. Therefore, the difference of radiosensitivity in terms of $G_2$ chromosomal sensitivity is thought to result from the difference of initial damage.

• Clinical and Experimental Reproductive Medicine
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• v.47 no.2
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• pp.94-100
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• 2020

The inverse correlation between maternal age and pregnancy rate represents a major challenge for reproductive endocrinology. The high embryo ploidy error rate in failed in vitro fertilization (IVF) cycles reflects genetic misfires accumulated by older oocytes over time. Despite the application of different follicular recruitment protocols during IVF, gonadotropin modifications are generally futile in addressing such damage. Even when additional oocytes are retrieved, quality is frequently poor. Older oocytes with serious cytoplasmic and/or chromosomal errors are often harvested from poorly perfused follicles, and ovarian vascularity and follicular oxygenation impact embryonic chromosomal competency. Because stimulation regimens exert their effects briefly and immediately before ovulation, gonadotropins alone are an ineffective antidote to long-term hypoxic pathology. In contrast, the tissue repair properties (and particularly the angiogenic effects) of platelet-rich plasma (PRP) are well known, with applications in other clinical contexts. Injection of conventional PRP and/or its components (e.g., isolated platelet-derived growth factors as a cell-free substrate) into ovarian tissue prior to IVF has been reported to improve reproductive outcomes. Any derivative neovascularity may modulate oocyte competence by increasing cellular oxygenation and/or lowering concentrations of intraovarian reactive oxygen species. We propose a mechanism to support intrastromal angiogenesis, improved follicular perfusion, and, crucially, embryo ploidy rescue. This last effect may be explained by mRNA upregulation coordinated by PRP-associated molecular signaling, as in other tissue systems. Additionally, we outline an intraovarian injection technique for platelet-derived growth factors and present this method to help minimize reliance on donor oocytes and conventional hormone replacement therapy.