• Development and Reproduction
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• v.6 no.1
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• pp.45-54
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• 2002

Reproductive activity of golden hamsters(Mesocricetus auratus) is regulated by the photoperiod. They are sexually active in summer and inactive in winter. Melatonin, a pineal hormone, has been known to mediate sexual activities in seasonal breeding animals. Melatonin receptor was recently identified in several animal species including hmm. But little has been known about it in relation to the reproductive activities of golden hamsters. By using reverse transcription polymerase chain reaction(RT-PCR) methods, a portion of the melatonin receptor gene(309 nucleotides) was identified in golden hamsters. The nucleotide sequence of the melatonin receptor and the amino acid sequence deduced were compared to those reported in other animals. Melatonin receptors were obviously detected in hypothalamus, pituitary containing pars tuberalis, blood, and spleen. Although the testicular weights and the levels of reproductive hormones were dramatically affected by photoperiods, the expression of melatonin receptor was not markedly changed by them. These results suggest that the action of melatonin in regulating reproduction might be mainly due to the affinity of melatonin receptor rather than the density fi melatonin receptor.

• Archives of Pharmacal Research
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• v.25 no.2
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• pp.197-201
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• 2002

${\beta}-lonone$ has been reported to induce the cytochrome P45O (P45O) 2B1 in rats. In this study, the effects of ${\beta}-ionone$ and an isomer, ${\alpha}-ionone$, on liver P45O IA and 2B expression in Sprague Dawley rats were investigated . Subcutaneous administration of ${\alpha}-$ and ${\beta}-lonone$ 72 and 48hr prior to sacrificing the animals induced the liver microsomal P45O 1A and 2B proteins. P45O 2Bl induction was associated with the accumulation of its corresponding mRNA. 1 Induction by ${\beta}-lonone$ was much higher than that by ${\alpha}-ionone$-ionone in both the mRNA and protein levels. When the route of administration was compared, P45O 2B was induced more strongly after oral administration compared to that after subcutaneous injection. A single oral dose of 100, 300 and 600 mg/kg of ${\alpha}-$ and ${\beta}-lonone$ for 24 h induced P45O 2B1 -selective pentoxyresorufin Odepentylase activity comparably in a dose-dependent manner In addition, ${\alpha}-$ and ${\beta}-lonone$ induced the P45O 1A and 2B proteins. These results suggest that ${\alpha}-$ and ${\beta}-lonone$ might be potent P45O 2Bl inducers in rats, and that both ionones may be useful for examining the role of metabolic activation in chemical-induced toxicity where metabolic activation is required.

• Toxicological Research
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• v.35 no.3
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• pp.257-270
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• 2019

Silver nanoparticles (AgNPs) have been widely used in a variety of applications in innovative development; consequently, people are more exposed to this particle. Growing concern about toxicity from AgNP exposure has attracted greater attention, while questions about nanosilver-responsive genes and consequences for human health remain unanswered. By considering early detection and prevention of nanotoxicology at the genetic level, this study aimed to identify 1) changes in gene expression levels that could be potential indicators for AgNP toxicity and 2) morphological phenotypes correlating to toxicity of HepG2 cells. To detect possible nanosilver-responsive genes in xenogenic targeted organs, a comprehensive systematic literature review of changes in gene expression in HepG2 cells after AgNP exposure and in silico method, connection up- and down-regulation expression analysis of microarrays (CU-DREAM), were performed. In addition, cells were extracted and processed for transmission electron microscopy to examine ultrastructural alterations. From the Gene Expression Omnibus (GEO) Series database, we selected genes that were up- and down-regulated in AgNPs, but not up- and down-regulated in silver ion exposed cells, as nanosilver-responsive genes. HepG2 cells in the AgNP-treated group showed distinct ultrastructural alterations. Our results suggested potential representative gene data after AgNPs exposure provide insight into assessment and prediction of toxicity from nanosilver exposure.

• Journal of The Korean Society of Clinical Toxicology
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• v.4 no.1
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• pp.7-16
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• 2006

Purpose: As basic information of antioxidant treatments for the patient with paraquat intoxication, in human peripheral lymphocytes, the cytotoxicity of paraquat was measured, and to evaluate the antioxidant effect of vitamin C and deferoxamine against this cytotoxicity, malondialdehyde (MDA), superoxide dismutase (SOD) activity and total antioxidant status (TAS) were measured. Methods: From 10 healthy adults, after obtaining a consent, 20ml peripheral blood was collected. Experimental groups were divided to (1) control group, the group treated with an identical amount of saline, (2) P group: the group treated with paraquat only, (3) PV group: the group treated with paraquat followed by vitamin C 30 minutes later, (4) PD group: the group treated with paraquat followed by deferoxamine 30 minutes later, (5) PVD group: the group treated with paraquat followed by vitamin C 30 minutes later and subsequently deferoxamine one hour later, and (6) PDV group: the group treated with paraquat followed by deferoxamine 30 minutes later and subsequently vitamin C 1 hour later, and thus to total 6 groups. In each group, 10 samples of peripheral blood was assigned and $100{\mu}M\;paraquat,\;100{\mu}M$ vitamin C, and $100{\mu}M$ deferoxamine were used as reagent. Lymphocytes were isolated, cultured, and cytotoxicity was measured by the Microculture Tetrazolium method (MTT assay), MDA and SOD activity, and TAS concentration were measured. Results: In regard to the cytotoxicity measured in each group, their cytotoxicity was decreased in the group treated with antioxidants, in comparison with the group treated with paraquat only. In the cases that the order of the treatment of these two antioxidants was altered, viability in the PDV group $(1.077{\pm}0.121)$ was increased more that the PVD group $(0.888{\pm}0.152)$ statistically significantly (p=0.018). Concerning the amount of MDA, in comparison with the P group $(6.78{\pm}0.93{\mu}mol/L)$, after the treatment of each antioxidant, the concentration of MDA was decreased statistically significantly (p<0.05). In the group treated with two antioxidants together, in comparison with the group treated only with one antioxidant, the amount of MDA was increased statistically significantly $(PV:\;3.96{\pm}0.98{\mu}mol/L,\;PD:\;4.92{\pm}1.50{\mu}mol/L,\;PVD:\;3.22{\pm}0.83{\mu}mol/L,\;and\;PDV:\;3.42{\pm}0.95{\mu}mol/L,\;p=0.007)$. The concentration of SOD measured in the blood in each group after the administration of paraquat, in comparison with the control group, a pattern of the elevation of SOD activity and subsequent decrease was detected, however, it was not statistically significant. In the comparison of the groups treated with antioxidants, in comparison with the P group $(1419.9{\pm}265.9{\mu}mol/L)$, SOD activity was decreased statistically significantly in only the PDV group $(1176.4{\pm}238.9{\mu}mol/L)$ (p=0.017). In regard to TAS measured in each group, in comparison with the P group $(0.87{\pm}0.05{\mu}mol/L)$, in all groups treated with the antioxidants, the PV group was $1.00{\pm}0.03{\mu}mol/L$ (p=0.005), the PD group was $9.01{\pm}0.24{\mu}mol/L$ was $4.64{\pm}3.98{\mu}mol/L$ (P=0.005), and the PDV group was $9.41{\pm}0.27{\mu}mol/La$ (p=0.005), and thus total antioxidant activity was increased statistically significantly In a multiple comparison test, the PDV group showed the highest total antioxidant activity (p<0.0001). Conclusion: The result of the assessment of the antioxidant effect of vitamin C and deferoxamine on paraquat-induced cytotoxicity showed that in regard to cytotoxicity, SOD activity and TAS measurement, the best result was observed in the PDV group. Therefore, it was found that vitamin C and deferoxamine were effective antioxidants for the paraquat-induced cytotoxicity, and it suggests that the administration of deferoxamine followed by vitamin C may improve their antioxidant effect more.

• KOREAN JOURNAL OF CROP SCIENCE
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• v.64 no.4
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• pp.422-431
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• 2019

Severe droughts in spring have occurred frequently in Korea in recent years, exerting a critical impact on corn yield. Therefore, it is necessary to find physiological and/or molecular indicators of the response to drought stress in maize plants. In this study, we investigated the effects of water-deficit stress on two Korean elite F₁ maize hybrids, Ilmichal and Gwangpyeongok, by withholding water for 10 days at tassel initiation. The water deficit drastically reduced the relative leaf water content, leaf number, leaf area, and stem length, leading to dry matter reduction. Moreover, it reduced the SPAD values and stomatal conductance of leaves in drought-stressed plants of both hybrids. Importantly, the number of leaves and SPAD value were non-destructive and easy to investigate in response to water-deficit stress, suggesting that they may be useful indicators for screening drought-tolerant genetic resources. We detected more than 100 spots that were differentially accumulated under drought stress. Of these spots, a total of 21 protein spots (≥1.5-fold) from drought-exposed maize leaves were successfully analyzed by MALDI-TOF-TOF mass spectrometry. Functional annotation using Gene Ontology analysis revealed that most of the identified proteins were involved in carbohydrate metabolism, stress response fatty acid catabolism, photosynthesis, energy metabolism, and transport. The protein expression levels were increased in both Ilmichal and Gwangpyeongok, except for triosephosphate isomerase, fructose-bisphosphate aldolase, and an uncharacterized protein. The lactoylglutathione lyase delta (3,5)-delta (2,4)-dienoyl-CoA isomerase was overexpressed in Gwangpyeongok only. The results obtained from this study suggest that the drought-specific genes may be useful as molecular markers for screening drought-tolerant maize genotypes.

• Journal of Microbiology and Biotechnology
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• v.18 no.3
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• pp.523-531
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• 2008

Radiotherapy is currently applied in the treatment of human cancers. We studied whether genistein would enhance the radiosensitivity and explored its precise molecular mechanism in cervical cancer cells. After co-treatment with genistein and irradiation, the viability, cell cycle analysis, and apoptosis signaling cascades were elucidated in CaSki cells. The viability was decreased by co-treatment with genistein and irradiation compared with irradiation treatment alone. Treatment with only ${\gamma}$-irradiation led to cell cycle arrest at the $G_1$ phase. On the other hand, co-treatment with genistein and ${\gamma}$-irradiation caused a decrease in the $G_1$ phase and a concomitant increase up to 56% in the number of $G_2$ phase. In addition, co-treatment increased the expression of p53 and p21, and Cdc2-tyr-15-p, supporting the occurrence of $G_2/M$ arrest. In general, apoptosis signaling cascades were activated by the following events: release of cytochrome c, upregulation of Bax, down regulation of Bcl-2, and activation of caspase-3 and -8 in the treatment of genistein and irradiation. Apparently, co-treatment downregulated the transcripts of E6*I, E6*II, and E7. Genistein also stimulated irradiation-induced intracellular reactive oxygene, species (ROS) production, and co-treatment-induced apoptosis was inhibited by the antioxidant N-acetylcysteine, suggesting that apoptosis has occurred through the increase in ROS by genistein and ${\gamma}$-irradiation in cervical cancer cells. Gamma-irradiation increased cyclooxygenase-1 (COX-2) expression, whereas the combination with genistein and ${\gamma}$-irradiation almost completely prevented irradiation-induced COX-2 expression and $PGE_2$ production. Co-treatment with genistein and ${\gamma}$-irradiation inhibited proliferation through $G_2/M$ arrest and induced apoptosis via ROS modulation in the CaSki cancer cells.

• Environmental Mutagens and Carcinogens
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• v.18 no.2
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• pp.71-76
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• 1998

Exposure to environmental toxicants can cause cellular problems including the interference of DNA repair processes which may lead to the development of cancer. The existence of toxicant-induced DNA repair abnormality was investigated using mice exposed in vivo to genotoxic chemicals and then challenging their exposed lymphocytes in vitro with bleomycin. The repair of bleomycin-induced DNA damage as estimated by the frequency of chromosome aberrations was determined. Our data indicates that the observed aberration frequencies after in vivo exposure to N-methyl-N'-nitro-N-nitnsoguanidine (MNNG) and in vitro challenge with bleomycin are consistently higher than expected. The enhanced response is not due to the induction of chromosome damage by 25 or 50 mg/kg MNNG since the chemical did not cause chromosome aberrations in lymphocytes of these mice. The observed response after the combined exposure to benzo[a]pyrene (BP) and bleomycin was significantly lower than expected with low in vivo doses of BP (50 mg/kg) and then significantly higher than expected with the high doses (200 mg/kg). We interpret our data to indicate that in vivo exposure to genotoxic agents can cause abnormal DNA repair activities. The response is, however, independent of the clastogenic activities of the inducing chemicals, but dependent upon the inducing agents and on the exposure doses.

• Journal of Pharmacopuncture
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• v.19 no.4
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• pp.319-328
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• 2016

Objectives: Advancements in nanotechnology have led to nanoparticle (NP) use in various fields of medicine. Although the potential of NPs is promising, the lack of documented evidence on the toxicological effects of NPs is concerning. A few studies have documented that homeopathy uses NPs. Unfortunately, very few sound scientific studies have explored the toxic effects of homeopathic drugs. Citing this lack of high-quality scientific evidence, regulatory agencies have been reluctant to endorse homeopathic treatment as an alternative or adjunct treatment. This study aimed to enhance our insight into the impact of commercially-available homeopathic drugs, to study the presence of NPs in those drugs and any deleterious effects they might have, and to determine the distribution pattern of NPs in zebrafish embryos (Danio rerio). Methods: Homeopathic dilutions were studied using high-resolution transmission electron microscopy with selected area electron diffraction (SAED). For the toxicity assessment on Zebrafish, embryos were exposed to a test solution from 4 - 6 hours post-fertilization, and embryos/larvae were assessed up to 5 days post-fertilization (dpf ) for viability and morphology. Toxicity was recorded in terms of mortality, hatching delay, phenotypic defects and metal accumulation. Around 5 dpf was found to be the optimum developmental stage for evaluation. Results: The present study aimed to conclusively prove the presence of NPs in all high dilutions of homeopathic drugs. Embryonic zebrafish were exposed to three homeopathic drugs with two potencies (30CH, 200CH) during early embryogenesis. The resulting morphological and cellular responses were observed. Exposure to these potencies produced no visibly significant malformations, pericardial edema, and mortality and no necrotic and apoptotic cellular death. Conclusion: Our findings clearly demonstrate that no toxic effects were observed for these three homeopathic drugs at the potencies and exposure times used in this study. The embryonic zebrafish model is recommended as a well-established method for rapidly assessing the toxicity of homeopathic drugs.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.3931-3936
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• 2012

Background: Epidemiological studies evaluating the association of two variants rs9340799 and rs2234693 on estrogen receptor 1 (ESR1) with prostate risk have generated inconsistent results. Methods: A meta-analysis was here conducted to systematically evaluate the relationship of these two variants with prostate cancer susceptibility. Results: For rs9340799, heterozygosity of T/C carriers showed a significant increased prostate cancer risk with a pooled odds ratio (OR) of 1.34 (95% CI = 1.06-1.69) while homozygote C/C carriers showed an increased but not statistically significant association with prostate cancer risk (pooled OR = 1.29, 95% CI = 0.94-1.79). Compared to the homozygous TT carriers, the allele C carriers showed a 31% increased risk for prostate cancer (pooled OR = 1.31, 95% CI = 1.06-1.63). No significant association between the rs2234693 and prostate cancer risk was found with the pooled OR of 1.15 (95% CI = 0.97-1.39, T/C and C/C vs. T/T) under the dominant genetic model. Compared to the homozygote T/T carriers, the heterozygous T/C carriers did not show any significantly different risk of prostate cancer (pooled OR = 1.13, 95% CI = 0.94-1.36) and the homozygous C/C carriers also did not show a significant change for prostate cancer risk compared to the wide-type T/T carriers (pooled OR = 1.26, 95% CI = 0.98-1.62). Conclusion: These data suggested that variant rs9340799, but not rs2234693, on ESR1 confers an elevated risk of prostate cancer.

• Molecular & Cellular Toxicology
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• v.3 no.3
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• pp.198-207
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• 2007

[ $^{18}F$ ]-fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET) scan has been found to reflect tumor aggressiveness and prognosis in various types of cancer. In this study, the gene expression profiles of glial tumors were evaluated to determine whether glial tumors with high $^{18}F$-FDG uptake have more aggressive biological potential than with low uptake. Surgical specimens were obtained from the 12 patients with glial tumors (4 males and 8 females, age range 42-68 years). The tumor samples were divided into two groups based on the $^{18}F$-FDG uptake PET scan findings: high $^{18}F$-FDG uptake (n=4) and low $^{18}F$-FDG uptake (n=8). The pathological tumor grade was closely correlated with the $^{18}F$-FDG uptake pattern: Glial tumors with high $^{18}F$-FDG uptake were pathologically Edmondson-Steiner grade III, while those with low uptake were grade II. The total RNA was extracted from the frozen tissues of all glial tumors (n=12), and adjacent non-cancerous tissue (n=3). The gene expression profiles were evaluated using cDNA microarray. The glial tumors with high $^{18}F$-FDG uptake showed increase expression of 15 genes compared to those with low uptake (P<0.005). Nine genes were down-regulated. Gene expression is closely related to cell survival, cell-to-cell adhesion or cell spreading; therefore, glial tumors with high $^{18}F$-FDG uptake appear to have more aggressive biological properties than those with low uptake.