• Title/Summary/Keyword: Dose response relationship

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Relationship between △FVC(% fall in FVC at the PC20 Dose of Methacholine) and Serum Eosinophil Cationic Protein(ECP) in 6-8 Year Old Children with Asthma (6-8세 천식 환아에서 △FVC(메타콜린 PC20에서의 강제폐활량의 감소율)와 혈청 호산구 양이온 단백의 관계)

  • Suh, Dong In;Yu, Jinho;Yoo Young;Kim, Do Kyun;Kang, Hee;Koh, Young Yull
    • Clinical and Experimental Pediatrics
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    • v.48 no.10
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    • pp.1126-1131
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    • 2005
  • Purpose : Bronchial hyperresponsiveness(BHR) is considered a hallmark of asthma. Increased levels of eosinophil cationic protein(ECP) have been identified in serum of asthma patients. Several studies have examined the relationship between serum ECP and bronchial responsiveness, expressed as methacholine $PC_{20}$ in asthmatic patients, with conflicting results. The aims of this study were to examine the relationship between serum ECP and ${\Delta}FVC$, another index of bronchial responsiveness, which reflects increased maximal airway response. Methods : Six to 8-year-old children with asthma(n=109) underwent methacholine bronchoprovocation testing. The $PC_{20}$ dose of methacholine and ${\Delta}FVC$ were calculated for each individual from the methacholine dose response curves. Serum ECP levels and blood total eosinophil counts were also measured. Results : Serum ECP correlated with ${\Delta}FVC$(r=0.217, P=0.023), as well as $PC_{20}$(r=-0.208, P=0.030). However, blood eosinophil counts failed to show any correlations with ${\Delta}FVC$(r=0.085, P=0.378) or $PC_{20}$(r=-0.148, P=0.125). ${\Delta}FVC$ did not correlate with $PC_{20}$(r=-0.079, P=0.417). Conclusion : Blood eosinophil activation is associated with both components of BHR including increased sensitivity and increased maximal response in 6-8 year old children with asthma.

Chromosomal Aberrations Induced by in Vitro Irradiation of $^{131}I$ ($^{131}I$의 체외 방사선조사에 의한 염색체이상)

  • Kim, Eun-Sil;Kim, Myung-Seon;Seo, Doo-Seon;Jeong, Nae-In;Rho, Seung-Ik;Lee, Jae-Yong;Kim, Chong-Soon;Han, Seung-Soo;Kim, Hee-Geun;Kang, Duck-Won;Song, Myung-Jae
    • The Korean Journal of Nuclear Medicine
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    • v.28 no.1
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    • pp.133-140
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    • 1994
  • Recently, there are many considerations and studies on biological effects of radiations in radiation workers, as well as in accidentally or therapeutically irradiated persons. The most practical and reliable method of dosimetry for radiation accidents is the scoring of gross chromosomal aberrations in human lymphocytes (Ydr) as a biological dosimetry. By the way, although usual doses of $^{131}I$ administered therapeutically for thyroid cancer are ranging from 100 mCi to 200 mCi, there are differences of absorbed doses and Ydr, ranging from 0.004 to 0.04, on equally administered $^{131}I$ due to variations in metabolic characteristics, stage of tumors and physical status of subjects. In this study, We exert to obtain the dose-response relationships of $^{131}I$, as a good guide to evaluating acute effects of accidental irradiations and radiation induced leukemia or solid tumor, by in vitro induction of chromosomal aberrations. we studied the relationship between radiation dose (D) and the frequency of chromosomal aberrations (Ydr) obserbed in peripheral lymphocytes that were irradiated in vitro with $^{131}I$ at doses ranging from 0.05 to 6.00 Gy. By scoring cells with unstable chromosomal aberrations (dicentric chromosomes and ring chromosomes) we obtained this linear-quadratic dose response equation Ydr=0.064351 $D^2$-0.13143 D+0.045684 This dose-response relationship may be useful for evaluating acute and chronic $^{131}I$ induced biological effects.

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Association between Metabolic Syndrome and Participation in Clean-up Work at the Hebei Spirit Oil Spill (허베이 스피리트호 원유유출시 방제작업과 대사증후군의 연관성)

  • Lee, Ik-Jin;Jang, Bong-Ki;Lee, Jong-Wha;Son, Bu-Soon;Cheong, Hae-Kwan;Ha, Mina;Choi, Young-Hyun;Park, Myungsook
    • Journal of Environmental Health Sciences
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    • v.41 no.5
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    • pp.335-348
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    • 2015
  • Objectives: We aimed to assess the risk of metabolic syndrome one year after the 2007 Hebei Spirit oil spill in Taean, Korea among people exposed to spilt oil during clean-up work. Methods: A total of 6,923 adults, including 3,019 males and 3,904 females, participated in the study. Health examinations and blood tests (total cholesterol, triglycerides, HDL, fasting blood sugar) were performed. A logistic regression model adjusting for age, gender, smoking history, drinking history, income, education, and marital status was used to estimate the risk of metabolic syndrome associated with the level of oil spill exposure. Results: The prevalence of metabolic syndrome was 24.9% among males and 18% among females. Compared with people living within 20 km of the coastline, the risk of metabolic syndrome among people living within 0.8 km of the coastline was significantly higher (male OR=1.696, 95% CI=1.320-2.178, female OR=1.992, 95% CI=1.549-2.561), including a significant dose-response relationship for distance from early contaminate coastline (p<0.001). The risk of metabolic syndrome was higher according to the increase of duration of cleaning work. The risk of metabolic syndrome among people who participated in the clean-up work for more than 116 days, compared with people who participated in the cleaning work for or less 14 days, was significantly higher (male OR=1.845, 95% CI=1.448-2.353, female OR=1.752, CI=1.378-2.228), with a significant dose-response relationship for days of clean-up work (p<0.001). Conclusion: This study showed that there is a significant association between exposure to the oil spill during the clean-up work, distance from early contaminate coastline and the risk of metabolic syndrome in a doseresponse manner.

Comparative Study on Biological Effects of Gamma-Radiation and Bisphenol A with Tradescantia Micronucleus Assay (자주달개비 미세핵 분석법을 이용한 비스페놀 에이 및 감마선의 생물학적 영향 비교 연구)

  • 신해식;송희섭;현성희;이진홍;김진규
    • Korean Journal of Environmental Biology
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    • v.20 no.2
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    • pp.158-164
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    • 2002
  • Some of synthetic chemicals can net as an endocrine disrupting substance in higher animals. Dioxins, DDT, PCBs and bisphenol A (BPA) are classified into endocrine disruptors and aye under a strict control in many countries. This research was designed to compare the clastogenic effects of BPA to those of ionizng radiation to establish the relaltive effectiveness of BPA by means of Tradescantia micronucleus assay. For the uptake of the BPA through the stems, groups of fresh cuttings of Tradescantia BNL 4430 weve placed in BPA solutions of 0 to 4 $\mu$M for 6 hours under continuous aeration. The other groups of the cuttings were irradiated with 0 to 0.5 Gy of gamma- rays. The frequencies of micronucleus showed a positive dose- response relationship in the range of 0 to 0.5 Gy, and a clear concentration-response relationship in the experimental range of BPA concentrations. By comparing the two experimental results, it is possible to estimate the BPA concentration and its equivalent radiation dose for a fixed value of MCN frequency. BPA of $ll.8\mu{M}$ can give rise to 53.3 MCN/100 tetrads, which is the same frequency induced by 25 cGy of gamma- rays. It is of biological importance that clinical symptoms start to develop after a whole body exposure to radiation higher than 25 cGy. The results indicate that the pollen mother cells are an excellent biological end- point for toxicity test of suspected endocrine disrupting chemicals such as bisphenol A, cotylphenol and nonylphenol.

Comparison of Blood Metal Concentration in Ohjeok-san(Wuji-san) Treated Rats - Dose-Response Relationship and Mechanism - (오적산을 투여한 흰쥐의 혈액중 금속농도 비교에 관한 연구 - 용량-반응관계와 기전을 중심으로 -)

  • 이정렬;이선동
    • The Journal of Korean Medicine
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    • v.23 no.1
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    • pp.67-82
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    • 2002
  • Objectives: In recent years, extensive focus has been laid on adulteration of herbal medicine with heavy metals. This may be mainly due to soil contamination by environmental pollution. The objective of this study is to identify the contents of various heavy metals in the blood from Ohjeok-san (Wuji-san) Decoction (OD) treated-rats. Methods: For this study, 13 kinds of metals including essential and heavy metals, i.e. A1, As, Cd, Co, Cr, Cu, Fe, Hg, Mn, Ni, Pb, Se and Zn were analyzed by a slight modification of EP A methods and the following results are obtained. Results: 1. There was no significant difference between the OD-treated groups and control group in liver, kidney, bone, brain and weight, especially no significant difference at the 5th and 10th days in weight and the amount of food intake. 2. The amount of each metal analyzed in the blood were as follows; A1: 2.3~3.07 mg/l, As: 2.90~3.66 mg/l, Cd: 0~0.001 mg/l, Co: 0~0.01 mg/l, Cr: 0.40~043 mg/l, Cu: 0.93~1.88 mg/l, Fe: 414.35~464.46 mg/l, Hg: 0.01 mg/l, Mn: 0.10~0.17 mg/l, Ni: 0.01 mg/l, Pb: 0.03~012 mg/l, Se: 0.73 mg/l, Zn: 3.41~4.13 mg/l by groups, respectively. In control and experimental group, Experimental I and other experimental II, III, IV, and V groups, there were no significant differences. 3. The amount of non-toxic metals (A1, Co, Cu, Fe, Mn, Se, Zn) were $64.1{\pm}7.71{\;}mg/l$ in the control group and 60.70~67.58 mg/l in the experimental groups I, II, III, IV and V. The amount of Toxic metals (As, Cd, Cr, Ag, Pb) were $0.68{\pm}0.21{\;}mg/l$ in the control group and 0.57 ~ 0.66mg/l in the experimental groups. The total amount of metals were 32.35 mg/l in the control group and 30.48~34.12 mg/l in the test groups I, II, III, IV and V, respectively. Conclusions: There was no significant difference of metal concentration in the blood from the OD-treated-rats compared to those of the control group even if higher dosage (1~8 times the dosage for a person) of OD was administered. This may be mainly due to a decoction treatment which contains only supernatants filtered from the herb-mass after boiling. This indicates the legal limitation for metal concentration in herbal medicine must be applied according to different treatment methods of herbal medicine.

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Development of a Noble Dosimetry Using Metaphase Analysis and Micronuclei Assay of Bone Marrow Cells in Mice (마우스 골수세포의 중기염색체 분석 및 미소핵 검사를 이용한 피폭선량 평가법의 개발)

  • Min, Jung-Jun;Bom, Hee-Seung;Kim, Young-Ho;Yoon, Hyun-Joong;Kim, Ji-Yeul
    • The Korean Journal of Nuclear Medicine
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    • v.34 no.1
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    • pp.74-81
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    • 2000
  • Purpose: The purpose of this study was to develop in vivo dosimetries using both chromosomal aberrations and micronuclei in mice to assess biological effects of radiations. Materials and Methods: Five each mice were irradiated with 0, 1, 2, 3, 4, 5, 10 Gy of Cs-137 gamma-rays. We scored numbers of chromosomal aberrations in metaphase spreads and numbers of micronuclei in bone marrow smears under light microscope, and obtained the dose-response relationships. We also examined the relationship between the two dose-response curves. Results: The frequency of both chromosomal aberrations and micronuclei increased with dose, in a linear-quadratic manner The delta, beta, and alpha coefficients were 0.0176, 0.0324, and 0.0567 for metaphase analysis (r=1.0, p<0.001) and 0.0019, 0.0073, and 0.0506 for micronuclei assay (r=1.0, p<0.001). The frequency of chromosomal aberrations and micronuclei in different radiation doses was significantly correlated (r=0.99, p<0.01). Conclusion: In vivo dosimetry using either metaphase analysis or micronucleus assay was feasible in mice. These methods could be useful to evaluate biological effects of radiation.

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Reduced Ovarian Cancer Incidence in Women Exposed to Low Dose Ionizing Background Radiation or Radiation to the Ovaries after Treatment for Breast Cancer or Rectosigmoid Cancer

  • Lehrer, Steven;Green, Sheryl;Rosenzweig, Kenneth E
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.6
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    • pp.2979-2982
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    • 2016
  • Background: High dose ionizing radiation can induce ovarian cancer, but the effect of low dose radiation on the development of ovarian cancer has not been extensively studied. We evaluated the effect of low dose radiation and total background radiation, and the radiation delivered to the ovaries during the treatment of rectosigmoid cancer and breast cancer on ovarian cancer incidence. Materials and Methods: Background radiation measurements are from Assessment of Variations in Radiation Exposure in the United States, 2011. Ovarian cancer incidence data are from the Centers for Disease Control and Prevention. Standardized incidence ratios (SIR) of ovarian cancer following breast cancer and rectosigmoid cancer are from Surveillance, Epidemiology, and End Results (SEER) data. Obesity data by US state are from the Centers for Disease Control and Prevention. Mean ages of US state populations are from the United States Census Bureau. Results: We calculated standardized incidence ratios (SIR) from Surveillance, Epidemiology, and End Results (SEER) data, which reveal that in 194,042 cases of breast cancer treated with beam radiation, there were 796 cases of ovarian cancer by 120+ months of treatment (0.41%); in 283, 875 cases of breast cancer not treated with radiation, there were 1,531 cases of ovarian cancer by 120+ months (0.54%). The difference in ovarian cancer incidence in the two groups was significant (p < 0.001, two tailed Fisher exact test). The small dose of scattered ovarian radiation (about 3.09 cGy) from beam radiation to the breast appears to have reduced the risk of ovarian cancer by 24%. In 13,099 cases of rectal or rectosigmoid junction cancer treated with beam radiation in the SEER data, there were 20 cases of ovarian cancer by 120+ months of treatment (0.15%). In 33,305 cases of rectal or rectosigmoid junction cancer not treated with radiation, there were 91 cases of ovarian cancer by 120+ months (0.27%). The difference in ovarian cancer incidence in the two groups was significant (p = 0.017, two tailed Fisher exact test). In other words, the beam radiation to rectum and rectosigmoid that also reached the ovaries reduced the risk of ovarian cancer by 44%. In addition, there was a significant inverse relationship between ovarian cancer in white women and radon background radiation (r = - 0.465. p = 0.002) and total background radiation (r = -0.456, p = 0.002). Because increasing age and obesity are risk factors for ovarian cancer, multivariate linear regression was performed. The inverse relationship between ovarian cancer incidence and radon background was significant (${\beta}=-0.463$, p = 0.002) but unrelated to age (${\beta}=-0.080$, p = 0.570) or obesity (${\beta}=-0.180$, p = 0.208). Conclusions: The reduction of ovarian cancer risk following low dose radiation may be the result of radiation hormesis. Hormesis is a favorable biological response to low toxin exposure. A pollutant or toxin demonstrating hormesis has the opposite effect in small doses as in large doses. In the case of radiation, large doses are carcinogenic. However, lower overall cancer rates are found in U.S. states with high impact radiation. Moreover, there is reduced lung cancer incidence in high radiation background US states where nuclear weapons testing was done. Women at increased risk of ovarian cancer have two choices. They may be closely followed (surveillance) or undergo immediate prophylactic bilateral salpingo-oophorectomy. However, the efficacy of surveillance is questionable. Bilateral salpingo-oophorectomy is considered preferable, although it carries the risk of surgical complications. The data analysis above suggests that low-dose pelvic irradiation might be a good third choice to reduce ovarian cancer risk. Further studies would be worthwhile to establish the lowest optimum radiation dose.

Effects of Exposure to Hexavalent Chromium on the Level of 8-Hydroxydeoxyguanosine and the Activities of Superoxide Dismutase and 8-Hydroxyguannine Endonuclease in Rat Lung (6가 크롬 폭로가 흰쥐 폐조직의 8-Hydroxydeoxyguanosine 농도 및 Superoxide Dismutase와 8-Hydroxyguanine Endonuclease의 활성에 미치는 영향)

  • Kim, Hun-Sik;Kim, Ro-Sa;Kim, Hyeon-Yeong;Jeong, Jae-Hwang;Kim, Heon
    • Journal of Preventive Medicine and Public Health
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    • v.32 no.1
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    • pp.101-107
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    • 1999
  • Objectives. To determine the effects of exposure to hexavalent chromium, 93 male Sprague-Dawley rats were exposed to hexavalent chromium solution. Methods. Rats were divided into 4 groups and exposed to 0.1ml of 0 mM, 0.4 mM, 2.0 mM, and 10.0 mM potassium chromate in the first experiment, and to 0.1 ml of 0 mM, 20 mM, 40 mM, and 80 mM in the second for consecutive 3 days by tracheal instillation. Three and 10 rats were the controls for the first and the second experiments, respectively. Lung tissues were then removed to measure the 8-hydroxydeoxyguanosine (8-OH-dG) level using the HPLC-ECD method, superoxide dismutase (SOD) activity using the cytochrome C method, and 8-hydroxyguanine endonuclease activity using the oligonucleotide nicking assay. Results. The results showed no significant linear relationship between chromium exposure level and 8-OH-dG level or 8-hydroxyguanine endonuclease activity. In the first experiment, 8-OH-dG level and 8-hydroxyguanine endonuclease activity increased in 0.4 mM group, and then decreased in 2.0 mM and 10.0 mM groups. The correlation coefficients between 8-OH-dG level and 8-hydroxyguanine endonuclease activity was statistically significant (P<0.01), and total SOD activity was elevated by chromium exposure in a dose-dependent manner (P<0.05). In contrast, there was no significant dose-response pattern or correlation in the secod experiment. Conclusions. Based on the fact that there was no linear relationship between chromium dose and 8-OH-dG level or activity of the repair enzyme, it seems unlikely that 8-OH-dG formation is the major mechanism of chromium carcinogenesis.

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Superovulation-Oocyte and Uterine Function (과배란-난자 및 자궁기능)

  • 문영석
    • Korean Journal of Animal Reproduction
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    • v.20 no.4
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    • pp.379-384
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    • 1997
  • Superovulation with exogenous gonadotropins creates a spectrum of pre or periovulatory hormonal changes with subsequent detrimental effects on oocyte quality, fertilization, embryo development, implantation and maintenance of pregnancy. Our recent study determined potential roles for insulin-like growth factor-1 (IGF-1) in uterine environment regulation and preimplant tation in the rat. The evidence indicates that IGF-l may play an important role in the main tenance of a receptive uterine environment for embryonic development and the regulation of decidualization. Embryonic loss and failure of implantations following superovulation may be partially attributed to disturbances in uterine IGF-l action as observed in this study. We investigated the effects of superovulatory doses of gonadotropins on frequency of chromosomal a abnormalities of mouse embryos. Chromosome a analysis of mouse zygotes and 8- to 16-cell stage embryos from spontaneously ovulated, 5, 10, and l 15 lU pregnant mare serum gonadotropin (PMSG) superovulated mice was carried out. Aneuploidy, polyploidy and structural chrom- osomal abnormalities were detected among the four groups. However, only polyploidy was correlated with superovulation. In 10 and 15 IV PMSG treated groups, the rate of polypoidy was 2.9% and 10.5%, respectively. Furthermore, there was a dose reponse relationship between the PMSG dose and the incidence of embryonic p polyploidy (P

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Intracellular Calcium Concentration in the Glutamate-induced Cytotoxicity in PCl2 Cell (Glutamate에 의한 세포내 칼슘농도변화와 세포독성과의 관계)

  • 황인영;신임철;송연숙;성민제;박혜지;이윷모;박철범;이명구;오기완
    • Toxicological Research
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    • v.18 no.4
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    • pp.355-362
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    • 2002
  • Pathophysiological elevation of intracellular calcium concentration ($[Ca^{2+}]_1$) in the neuron has been considered as an important responsible factor in the neuronal cell damages. However the mechanism of increase of $[Ca^{2+}]_1$ and the relationship between $[Ca^{2+}]_1$ level and cytotocixity have not been fully demonstrated. In the present study, real-time alteration of $[Ca^{2+}]_1$and cellular response (cell damages) in the pheochromocytoma cells (PC12) stimulated by glutamate were investigated. Glutamate dose dependently decreased cell viability determined propidium iodide fluorescence method and morphology change. Conversely related with cell damages, glutamate dose dependently increased the level of[Ca$^{2+}$$_{i}$ . To investigate the mechanism of glutamate-induced increase of $[Ca^{2+}]_1$,$[Ca^{2+}]_1$, was first measured in the cell cultured in calcium free media and in the presence of dantrolene, an inhibitor of calcium release from ryanodine receptor located in endoplasmic reticulum (ER). Similar to the increase$[Ca^{2+}]_1$ in the calcium-containing media, glutamate dose dependently increased $[Ca^{2+}]_1$ in the cell cultured in free calcium media. However pretreatment (2 hr) with 20~50 $\mu\textrm{M}$ dantrolene substantial lowered glutamate-induced increase of $[Ca^{2+}]_1$, suggesting that release of calcium from ER may be major sourse of increase of $[Ca^{2+}]_1$ in PC12 cells. Dantrolene-induced inhibition of $[Ca^{2+}]_1$ resulted in recovery of cytotoxicity by glutamate. Relevance of N-methy-D-aspartate (NMDA) receptor, a type of glutamte receptor on glutamate-induced incense of $[Ca^{2+}]_1$,$[Ca^{2+}]_1$ was also determined in the cells pretreated (2 hr) with NMDA receptor antagonist MK-80l. Glutamate-induced increase of $[Ca^{2+}]_1$ was reduced by MK-801 dose dependently. Furthermore, glutamate-induced cytotoxicity was also prevented by MK-80l. These results demonstrate that glutamte increase $[Ca^{2+}]_1$ dose dependently and thereby cause cytotoxicity. The increase of $[Ca^{2+}]_1$ may release from ER, especially through ryanodine receptor and/or through NMDA receptor Alteration of calcium homeostasis through disturbance of ER system and/or calcium influx through NMDA receptor could contribute glutamate-induced cell damages.s.