• Biomolecules & Therapeutics
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• 제4권4호
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• pp.297-300
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• 1996

LBD-001, a recombinant human interferon $\gamma$ produced by genetically engineered yeast as a host system, was administered intraperitoneally to Sprague-Dawley male rats from premating to mating period at least for 60 days and to female rats from at least for 2 weeks before mating to early gestation period (from day 0 to 7 of gestation) at dose levels of $0.35\times10^6, 0.39\times10^6, and 1.38\times10^6$ I.U./kg/day. In the positive control group, ethynylestradiol ($EE_2$; 40 $\mu\textrm{g}$/kg/day) was subcutaneously administered only to female rats during the early gestation period. Effects of the test agents on reproductive performances of the male or female rats and embryonic development were as followings; (1) No significant changes by the treatment of LBD-001 were observed in general behaviors, body weight, food and water consumption, and necropsy of parent animals. However, significant decreases of body weight, food consumption, and water consumption were observed in ($EE_2$ -treated female rats. (2) Mating performances and fertility of parent animals were not significantly affected by the treatment of LBD-001. In ($EE_2$ -treated females, however, the fertility was completely inhibited. (3) No changes in resorption rate and external abnormality of F1 fetuses were observed by the treatment of LBD-001. The results show that LBD-001 at the dose of $1.38\times10^6$ I.U./kg/day or less does not affect general toxicity and reproductive function of parent animals and embryonic development of F1 fetuses.

• Journal of Environmental Health Sciences
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• 제30권2호
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• pp.71-78
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• 2004

This study was performed to evaluate developmental and estrogenic activity of bisphenol A (BPA) and butyl benzyl phthalate (BBP) to the second generation of Sprague-Dawley rats ingested during gestational or lactational periods. Rats were given BPA 20$\mu\textrm{g}$/kg BBP 100mg/kg of pregnancy or lactation periods. Maternal body weight and neonatal body weight were recorded. The rats were sacrificed on day 21 after birth. Reproductive organs of dam and neonate were utilized for receptor binding assay. The plasma concentrations of BPA and MBep, one of the major metabolites of BBP were analyzed with HPLC. The co-administration of BPA and BBP induced slow weight gain compared with single administration in dams. Also, such mixture induced low neonatal body weights in next generation. The dams treated with BPA and BBP during lactational periods showed significant organ weight changes in liver and spleen. The dams exposed during lactational periods showed significant organ weight changes not only in liver and spleen but also in kidney, uterus and ovary. The F1 female rats exposed during lactation periods showed significant organ weight changes in liver, spleen, ovary. The F1 male rats showed significant organ weight changes in liver, kidney, epididymis, vesicular glands, prostate. However, no clear synergistic effects of BPA and BBP were noted. There was no significantly different ER$\alpha$ expression pattern between control and treated groups. However, ER$\alpha$ expression were increased in F1 male testis and female uterus. PI male showed distinct ER$\alpha$ expression, especially in the group of lactational combined exposure. Synergistic ER$\alpha$ expression was found by combined treatment of BPA and BBP. We could not find any evidences of synergistic effects on BPA and/or BBP combined administration on dams and their fetuses, except in ER$\alpha$ expression of F1 male.

• Clinical and Experimental Reproductive Medicine
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• 제26권3호
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• pp.369-375
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• 1999

Objective: To evaluate the effect of serum obtained before and after treatment for endometriosis on in vitro fertilization and development of two cell mouse embryo. Design: Pretreatment and posttreatment comparoson of fertilization of mouse oocyte and embryo development in serum supplement from patients with endometriosis; result were compared using Stuent T-test analysis. Method: Infertility Clinic, Department of Obstetrics and Gynecology, Collage of Medicine, Won kwang university, Korea. Patients was chosed eleven consecutive women with endometriosis. Interventions was all patient underwent laparoscopic or conservative surgery. This was followed by a 6-month course of burserelin acetate $900{\mu}g/d$. Main outcome was measured total number of fertilization and embryo that was fertilization after 24 hours and reached blastocyst stage after 72 hours of incubation were compared before and after treatment. Result: Before treatment, 47% of the oocyte were fertilized and 31% of the embryo reached blastocyst stage. After treatment, Significantly more fertilized and Significantly more embryo developed to blastocyst on the stage I and II of endometriosis. Conclusion: The fertilization and embryo toxicity of serum samples from patients with endometriosis is lost after treatment.

• Clinical and Experimental Reproductive Medicine
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• 제24권3호
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• pp.325-333
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• 1997

The use of hormonal stimulation in human in vitro fertilization and embryo transfer (IVF-ET) leads to increased production of embryos for ET. So to avoid high pregnancies and to allow conception in future, unstimulated cycles, cryopreservation of spare embryos is desirable. One of the improvement of cryopreservation methods is vitrification. We cryopreserved mouse day 3 embryos by vitrification using the three different vitrification solution (EFS40, VS11 and VS3a). EFS40 solution is consisted of 40% (v/v) ethylene glycol, Ficol170 30% (w/v) and 0.5M sucrose and VS11 is 6.0M ethylene glycol and 1.8M glycerol. And VS3a is 6.5M glycerol and 6% (w/v) BSA (bovine serum albumin). First we tested the toxicity of three vitrification solution by exposure to these solution during 3 min. After washing by thawing solution, the survival rates of each groups are 95.5%, 90.9% and 84.4% (EFS40, VS11 and VS3a). High percentages of them developed to expanded blastocyst and hatching embryos in culture 48hrs 94.2%, 97.7%, 100% and 97.4% (no treatment group, EFS40, VS11 and VS3a). So there is no significant differences among the each group. Second, after thawing of vitirfied embryos, the survival rates of each groups are 96.8% (slow freeze), 94.1% (EFS40), 85.5% (VS11) and 80.0% (VS3a, P vs. no freeze or EFS40 is 0.01). Vitrified embryos exhibited a high rate of development in vitro after 48hrs culture. The percentages of each group to blastocyst and hatching embryos are 88.7% (no freeze), 91.8% (slow freeze), 93.4% (EFS40), 87.7% (VS11) and 73.0% (VS3a, P vs. other group is 0.01). The results suggest that there is no significant differences in exposure of various vitrification solution and day 3 mouse embryos can be vitrified in solution EFS40 and VS11 by simple procedure.

• Clinical and Experimental Reproductive Medicine
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• 제49권2호
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• pp.93-100
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• 2022

Objective: The impact of imatinib, a tyrosine kinase inhibitor, on ovarian follicles and several proteins related to follicular function and apoptosis was investigated in mice. Methods: Saline, cyclophosphamide (Cp; 50 or 75 mg/kg), or imatinib (7.5 or 15 mg/kg) was injected once intraperitoneally into female B6D2F1 mice (18 mice in each group). In multiple ovarian sections, the number of various types of follicles and the proportion of good-quality (G1) follicles were counted. The levels of six proteins (anti-Müllerian hormone [AMH], BCL-xL, BAX, acid sphingomyelinase [A-SMase], caspase-3, and α-smooth muscle actin [α-SMA]) within the whole ovaries were quantified using Western blots. Results: Compared to the saline group, a significant reduction of the primordial follicle count was observed in the group treated with imatinib 7.5 and 15 mg/kg, as well as in the group treated with Cp 75 mg/kg. Administration of Cp significantly decreased the proportion of G1 primordial follicles, but administration of imatinib did not. No differences in the AMH, anti-apoptotic BCLX-L, pro-apoptotic BAX, and A-SMase levels in the ovarian tissues were observed among the five groups. However, caspase-3 and α-SMA levels were significantly higher in the imatinib and Cp groups than in the saline group. Conclusion: The administration of imatinib to mice significantly reduced the primordial follicle count and increased the protein levels of caspase-3 and α-SMA. Our findings suggest that imatinib potentially exerts ovarian toxicity via apoptotic processes, similarly to Cp.

• Environmental Analysis Health and Toxicology
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• 제25권1호
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• pp.41-55
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• 2010

The aims of this study were to develop the suitable "system software" in chemical ranking and scoring (CRS) for the food hazardous chemicals associated with environmental emission and to suggest the priority lists of food contamination by environmental-origined pollutants. Study materials were selected with reference to the priority pollutants list for environment and food management from domestic and foreign research and the number of study materials is 103 pollutants (18 heavy metals, 10 PBTs, 10 EDs, and 65 organic compounds). The Food-CRS-Korea system consisted of the environmental fate model via multimedia, transfer environment to food model, and health risk assessment by contaminated food intake. We have established that health risks of excess cancer risks, hazard quotients (HQs) by chronic toxicity and HQs by reproductive toxicity convert to score, respectively. The creditable scoring system was designed to consider uncertainty of quantitative risk assessment based on VOI (Value-Of-Information). The predictability of the Food-CRS-Korea model was evaluated by comparing the presumable values and the measured ones of the environmental media and foodstuffs. The priority lists based on emissions with background-level-correction are 15 pollutants such as arsenic, cadmium, and etc. The priority lists based on environmental monitoring date are 17 pollutants including DEHP, TCDD, and so on. Consequently, we suggested the priority lists of 13 pollutants by considering the several emission and exposure scenarios. According to the Food-CRS-Korea system, arsenics, cadmium, chromes, DEHP, leads, and nickels have high health risk rates and reliable grades.

• Proceedings of the Korea Society of Environmental Toocicology Conference
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• 한국환경독성학회 2002년도 추계국제학술대회
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• pp.170-170
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• 2002

College of Pharmacy, Ewha womans University, Seoul, 120-750, Korea 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is the most potent halogenated aromatic hydrocarbon congener that induces expression of several genes including CYP1A1. Exposure to TCDD results in many toxic actions such as carcinogenesis, hepatotoxicity, immune suppression, and reproductive and developmental toxicity. Dramatic differences in dioxin toxicity have been observed between the sexes of some animal species, suggesting hormonal modulation of dioxin action. Many studies have been reported and propose several mechanisms of anti-estrogenic effects of TCDD. In contrast, the effect of estrogen on the regulation of CYP1A1 are not clear at present. There are several reports showing conflicting results. It seems that induction/inhibition of CYP1A1 may be dependent on cell-type and concentration. The purpose of this study was to investigate the regulation of TCDD-induced CYP1A1 gene expression by estradiol and its metabolites. We examined whether estradiol and its metabolites altered TCDD-mediated induction of CYP1A1 enzyme activity. 17 ${\beta}$ estradiol and 16 ${\alpha}$ estriol at non cytotoxic concentrations caused a significant concentration dependent decline of TCDD-induced EROD activity To determine whether reduced EROD activity reflected altered CYP1A1 mRNA expression, we measured CYP1A1 mRNA level by RT-PCR. And to examine whether estradiol and its metabolites have effects on TCDD-induced CYP1A1 gene expression at the transcription level, we also peformed transient transfection with an AhR responsive reporter plasmid containing the 5' flanking region of the human CYP1A1 gene to examine whether estradiol and its metabolites have effects on TCDD-induced CYP1A1 gene expression at the transcription level.

• Journal of Preventive Medicine and Public Health
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• 제45권6호
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• pp.353-363
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• 2012

Methylmercury is a hazardous substance that is of interest with regard to environmental health, as inorganic mercury circulating in the general environment is dissolved into freshwater and seawater, condensed through the food chain, ingested by humans, and consequently affects human health. Recently, there has been much interest and discussion regarding the toxicity of methylmercury, the correlation with fish and shellfish intake, and methods of long-term management of the human health effects of methylmercury. What effects chronic exposure to a low concentration of methylmercury has on human health remains controversial. Although the possibility of methylmercury poisoning the heart and blood vessel system, the reproductive system, and the immune system is continuously raised and discussed, and the carcinogenicity of methylmercury is also under discussion, a clear conclusion regarding the human health effects according to exposure level has not yet been drawn. The Joint FAO/WHO Expert Committee on Food Additives proposed to prepare additional fish and shellfish intake recommendations for consumers based on the quantified evaluation of the hazardousness of methylmercury contained in fish and shellfish, methylmercury management in the Korea has not yet caught up with this international trend. Currently, the methylmercury exposure level of Koreans is known to be very high. The starting point of methylmercury exposure management is inorganic mercury in the general environment, but food intake through methylation is the main exposure source. Along with efforts to reduce mercury in the general environment, food intake management should be undertaken to reduce the human exposure to methylmercury in Korea.

• Toxicological Research
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• 제12권2호
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• pp.203-211
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• 1996

Methanol has been widely used as an industrial solvent and environmental exposure to methanol would be expected to be increasing. In humans, methanol causes metabolic acidosis and damage to ocular system, and can lead to death in severe and untreated case. Clinical symptoms are attributed to accumulation of forrnic acid which is a metabolic product of methanol. In humans and primates, formic acid is accumulated after methanol intake but not in rodents due to the rapid metabolism of methanol. Neverthless, the developmental and reproductive toxicity were reported in rodents. Previous reports showed that perinatal exposure to ethanol produces a variety of damage in human central nervous system by direct neurotoxicity. This suggests that the mechanism of toxic symptoms by methanol in rodents might mimic that of ethanol in human. In the present study I hypothesized that methanol can also induce toxicity in neuronal cells. For the study, primary culture of rat hippocampal neurons and glias were empolyed. Hippocampal cells were prepared from the embryonic day-17 fetuses and maintained up to 7 days. Effect of methanol (10, 100, 500 and 1000 mM) on neurite outgrowth and cell viability was investigated at 0, 18 and 24 hours following methanol treatment. To study the changes in proliferation of glial cells, protein content was measured at 7 days. Neuronal cell viability in culture was not altered during 0-24 hours after methanol treatment. 10 and 100 mM methanol treatment significantly enhanced neurite outgrowth between 18-24 hours. 7-day exposure to 10 or 100 mM methanol significantly increased protein contents but that to 1000 mM methanol decreased in culture. In conclusion, methanol may have a variety of effects on growing and differentiation of neurons and glial cells in hippocampus. Treatment with low concentration of methanol caused that neurite outgrowth was enhanced during 18-24 hours and the numbers of glial cell were increased for 7 days. High concentration of methanol brought about decreased protein contents. At present, the mechanism responsible for the methanol- induced enhancement of neurite outgrowth is not clear. Further studies are required to delineate the mechanism possibly by employing molecular biological techniques.

• Molecular & Cellular Toxicology
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• 제2권1호
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• pp.35-47
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• 2006

2, 3, 7, 8-Tetrachlorodibenzo-p-dioxin (TCDD) are well known as the most toxic environmental compound in these days. Many researches are reported that dioxin produces multiple toxic effects, such as endocrine toxicity, reproductive toxicity, immunotoxicity and cancer. In this study, we carried to discover novel evidence for previously unknown gene expression patterns in human exposed to dioxin by using radioactive cDNA microarray. 548 workers who were divided into experimental and control groups according to their urinary Naphthol levels were enrolled in our study. Blood mRNA in human was isolated, and the gene expression profiles were analyzed by cDNA microarray. Gene expression analysis identified 52 genes which exhibited a significant change. In our study, most notably, genes involved in cell cycle, cell proliferation, signal transduction and apoptosis in human exposed to dioxin, such as CCND3, TSHR, and EFRN5, were up-regulated. In the current study, we observed gene expression of people that are exposed to dioxin using radioactive cDNA microarray. Through these results, we suggest when objects are exposed to toxic compounds, such as dioxin, the radioactive cDNA microarray may be using in sensitively detecting of cancerous change.