• Title/Summary/Keyword: Fetal Dose

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Inhibition of Cellular Proliferation by CURCUMAE LONGAE Rhizoma Extracts on MCF-7 (강황(薑黃) 추출물이 유방암 세포주 MCF-7 증식 억제에 미치는 영향)

  • Jung, Sun;Kim, Hyung-Woo;Park, Ji-Eun;Kim, Young-Gyun;Cho, Su-In
    • The Korea Journal of Herbology
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    • v.21 no.1
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    • pp.71-77
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    • 2006
  • Objectives : This investigation was undertaken to evaluate the anti-proliferation of CURCUMAE LONGAE Rhizoma extracts using MCF-7, human breast cancer cells. Methods : MCF-7 cells were cultured in Dulbecco's modified Eagle's medium/F12 supplemented with 10% fetal bovine serum and antibiotics. At varying times after extract treatment, cells were harvested with scraper and processed for analysis of proliferation, cytotoxicity. Results : The extract of CURCUMAE LONGAE Rhizoma strongly inhibits the proliferation of MCF-7 cells in a dose and time-dependent manner. Sulforhodamine B assay showed that the addition of ethanol extract of CURCUlVIAE LONGAE Rhizoma reduced the viability of MCF-7 cells in a dose-dependent manner. Conclusion : So, it can be concluded that CURCUMAE LONGAE Rhizoma have an inhibitive effect on MCF-7 human breast cancer cells.

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Fertility Study of KTC-1, a New Semisynthetic Rifamycin Derivative, in Rats. (새로운 반합성 Rifamucin 유도체 KTC-1의 랫트 수태능력 시험)

  • 김종춘;정문구;노정구
    • Toxicological Research
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    • v.12 no.1
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    • pp.93-99
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    • 1996
  • The effect of KTC-1, a new semisynthetic rifamycin antituberculous drug, on general toxicity, reproductive capability and fetal development was investigated in Sprague-Dawley rats. Male rats were administered KTC-1 with mashed feed from 63 days before mating to the end of mating period, and female rats were given from 14 days before mating to day 7 of gestation at dose levels of 0, 375, 750, and 1,500 ppm. The females were sacrificed on day 21 of gestation for examination of their fetuses. At 1,500 ppm, a reduction in body weight gain and testis atrophy were observed in male rats. Histological examination revealed testicular atrophy, absence or decrease of germinal cells, and vacuolization of Sertoli cells in testis. A reduction in body weight gain, a decrease in food consumption were found in female rats. In addition, decreases in the number of corpora lutea, iraplantations, and the litter size of live fetuses were seen. Mating, fertility, and pregnancy performances were also affected. There were no external abnormalities observed by examination of fetuses. At 750 ppm, a reduction in the body weight gain of male and female rats and decreases in the number of implantations and litter size were found. At 375 ppm, no treatment-related effects were observed. The results suggest that the no-effect dose levels (NOELs) of KTC-1 are 375 ppm for males and females on general toxicity, 750 ppm for males and females on reproductive capability, and 375 ppm for fetuses on embryonic development.

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Photodynamic Therapy with Photofrin Reduces Invasiveness of U87 Malignant Human Glioma Cells (교모세포종 세포주 U87에서 Photofrin을 사용한 광역학 치료가 종양 침습성에 미치는 영향)

  • Woo, Hye Kyung;Cho, Kyung-Keun;Rha, Hyung Kyun;Lee, Kyung Jin;Park, Sung Chan;Cho, Jung Ki;Park, Hea Kwan;Kang, Joon Ki;Choi, Chang Rak
    • Journal of Korean Neurosurgical Society
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    • v.30 no.sup2
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    • pp.189-196
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    • 2001
  • Objective : We tested the hypothesis that photodynamic therapy(PDT) with Photofrin inhibits tumor invasion of U87 human glioma cells using several in vitro assay to measure tumor invasiveness. The effects of PDT on cell growth, directional migration and cell invasion were investigated. Material and Method : Tumor cells were treated with Photofrin at various doses and at a fixed optical(632nm) dose of $100mJ/cm^2$. Cytotoxicity was tested using the MTT method. Invasion assays including the matrigelartificial basement membrane barrier migration and spheroid confrontation with confocal microscopic analysis were used to study the relationship between PDT and invasiveness. Result : U87 cells showed a dose dependent cytotoxic response to increasing Photofrin dose. Data from the matrigel artificial basement membrane assay indicate that PDT inhibits the U87 cell migration dose dependently. Low doses of subcytotoxic PDT treatment, such as 2.5ug/ml Photofrin dose, also appeared to significantly inhibit migration of U87 cells(p<0.05). In co-cultures between U87 cell spheroids and brain aggregates, progressive invasion with destruction of the brain aggregate occurs. The extent of tumor cell infiltration and proportion or intact brain aggregate remaining after 24h differs in Photofrin PDT treated versus Photofrin only control, with changes suggestive of a dose-response effect. Conclusion : our data indicate that PDT with Photofrin significantly inhibits the invasiveness of U87 cells, and this inhibition is dose dependent.

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Teratogenic and Embryotoxic Effects of Clomiphene Citrate in Developing Mice

  • Ara, Chaman;Asmatullah, Asmatullah
    • Asian-Australasian Journal of Animal Sciences
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    • v.24 no.8
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    • pp.1053-1059
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    • 2011
  • The objective of this study was to assess the teratogenic and embryotoxic effects of clomiphene citrate in mice. The pregnant mice were administered a single dose of clomiphene citrate at different concentrations i.e 1.0, 2.0, 4.0 and 6.0 ${\mu}g/g$ BW on day 8 of gestation. Fetuses recovered on day 18 of gestation were analyzed on morphological, morphometric and histological basis. Morphological observations showed defects like open eyelids, anophthalmia, fore and hindlimb micromelia, meromelia, amelia, sacral hygroma, hydrocephaly, hemorrhagic spots, kyphosis and clubbed feet. Morphometric analysis indicated a significant (p<0.001) reduction in fetal body weight, crown rump length, head circumference, eye circumference, forelimb and hindlimb lengths and tail size against controls. The histological observations showed brain defects like hydrocephaly, enlarged ventricles and undifferentiated neuroglial cells in cerebellum. Cleft palate, underdeveloped pharynx and atrophy of jaw muscles were the common anatomical defects of pharyngeal region. It is concluded that the concentrations of clomiphene citrate used during the present study proved teratogenic in mice fetuses.

Morphological study on effect of radiation in developing mouse brain after fetal exposure (태아시기의 방사선 노출에 의한 마우스 뇌 발달에 미치는 영향에 관한 형태학적 연구)

  • Lee, Jong-hwan;Oh, Heon;Kim, Se-ra;Lee, Hae-june;Kim, Tae-hwan;Lee, Yun-sil;Kim, Sung-ho
    • Korean Journal of Veterinary Research
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    • v.41 no.3
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    • pp.395-400
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    • 2001
  • The present study analyze the morphological aspects of the cerebrum of mice with prenatal exposure to high and low dose (0.5, 1, 2 Gy) of $\gamma$-radiation on gestation day 12 or 16. The animal were allowed to give birth and the offspring were sacrificed at postnatal days 28 for gross and microscopic examination of cerebrum. Their body weight, brain weight, brain length, brain width, cortical thickness and area of cingulum bundle were examined. The histological and planimetric analysis were performed observing coronal sections. The gross malfomation (microcephaly) and abnormality of cortical architecture were prominent after exposure to 2 Gy on day 12 of gestation. significant dose-related reductions in body weight, brain weight, brain size were found in all irradiated groups. A significant change was found in thickness of the cerebral cortex and area of the cingulum bundle in the groups exposed to 0.5 Gy or more. There was no difference a lamina patter of six layers in cerebral cortex between the control and irradiated groups, but cell packing density increased significantly in the group exposed to 1 Gy or more. These results suggested that dose as low as 0.5 Gy could cause a morphologically reduce change in developing mouse cerebrum and exposure on day 12 of gestation to $\gamma$-irradiation is a particularly sensitive phase in causing malformation and abnormality of central nerve system.

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Studies on the Reproductive and Developmental Toxicity of Herbal Medicine Containing Aristolochic Acids

  • Sohn, K-H;Rhee, G-S;Kim, S-S;Kim, S-H;Kwack, S-J;Chae, S-Y;Park, C-H;Kim, B-H;Kil, K-S;Choi, K-S;Park, K-L
    • Proceedings of the Korean Society of Embryo Transfer Conference
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    • 2002.11a
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    • pp.110-110
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    • 2002
  • Rapidly progressive interstitial renal fibrosis has recently been reported in young women who have been on a slimming regimen including chinese herbs. Aristolochic acid, suspected as the causal factor of this renal disease, is a well known carcinogen. It has been known that Madouling (Aristolochiae fructus) contains aristolochic acid. The objective of this study was to investigate the effects of Madouling, Madouling-tang, which are the extract mixture from 10 different chinese herbs including Madouling, and aristolochic acid on reproductive and developmental toxicity. Female rats were administered orally with the extracts of Madouling, madouling-tang, and aristolochic acid from 14 days before mating to day 17 of gestation. Madouling (8mg/kg) decreased fertility in the 8mg/kg group, but Madouling-tang and aristolochic acids did not. Significant decrease of mean fetal body weights were observed in the 16mg/kg group of aristolochic acids. External, visceral and skeletal malformation of fetuses were not observed with treatment. Histopathological examination showed the discrete damage of kidney in the 8mg/kg group of Madouling and 16mg/kg groups of aristolochic acid. In whole embryo culture, Madouling and Madouling-tang caused the retardation of growth and development of embryo in the dose of 1 $\mu$g/ml and 0.02 $\mu\textrm{g}$/kg, respectively while aristolochic acids showed the similar effect in the dose of 300 $\mu\textrm{g}$/kg. These results indicate that Madouling, up to 0.05mg/kg (prescription dose to human) has no adverse effects on the fertility, reproduction and development of Sprague-Dawley rats.

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Fertility and Reproductive & Developmental Toxicity Study on Recombinant Human Epidermal Growth Factor (rhEGF, DWP401) in Rats (재조합 인간상피세포 성장인자(rhEGF, DWP401)가 랫드의 수태능, 태자와 신생자 발달 및 모체기능에 미치는 영향)

  • 박귀례;한순영;신재호;이유미;김판기
    • YAKHAK HOEJI
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    • v.45 no.2
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    • pp.190-204
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    • 2001
  • This study was conducted to investigate for its effects on reproductive and developmental toxicity of recombinant human epidermal growth factor (rhEGF) in Sprague-Dawley rats. Male rats were administered rhEGF at doses of 1, 10, 100, and 1000$\mu$g/kg/day, respective1y, by subcutaneous injection from 63 days before and throughout to mating period until the day before sacrifice. Female rats were administered rhEGF at the same doses from 14 days before mating to day 20 of gestation or to day 21 of lactation. We examined the male and female fertility indices and maternal toxicity of F0 parental animals. Also, we examined the external, visceral, or skeletal malformation of fetuses, growth and development, behavior, and/or reproductive performance of F1 animals. At the highest dose (1,000 $\mu$g/kg), the mean body weights of F0 animals were significantly increased in males and females at 3 or 2 weeks after treatment, respective1y. No clinical signs and food intakes were observed at any time during the experimental period by rhEGF treatment. In autopsy examination, the relative and absolute liver weights significantly increased in both sexes of 1,000 $\mu$g/kg. At the highest dose (1,000 $\mu$g/kg), there was a statistically significant increase of pregnancy period and the number of dead fetuses. Moreover, significant increase of mean fetal body weight and decrease of number of live fetuses, which related to the difficult dilivery were observed in highest dose group. In Fl examination, no adverse effects on external, visceral, and skeletal malformation, physical and functional development, behavior or reproductive ability of Fl animals were observed in any group. Also, there was no significant difference between control and treated groups in copulation or fertility indices of Fl animals. These results indicate that rhEGF had no adverse effect on fertility and reproductive ability of Sprague-Dawley rats.

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Effect of ionizing radiation on cultured submandibular gland (SG) cells of mouse (전리 방사선 조사에 의한 마우스 배양 악하선 세포의 변화)

  • Lee, Song-Jae
    • The Journal of Korean Society for Radiation Therapy
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    • v.4 no.1
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    • pp.71-77
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    • 1990
  • The present study was undertaken to investigate effects of ionizing radiation on DNA synthesis and chromosomal abnormality in cultured submandibular gland(SG) cells. SG cells from C57BL/6N Crj mice were cultured in Dulbecco's modified Eagle's medium (DME) supplemented with $10\%$ fetal bovine serum, antibiotics and fungizone. The cultured SG cells were irradiated with graded doses of gamma ray ($^{60}Co$) at a dose rate of 58.4rad/min. The effect of irradiation of $^{60}Co$ on DNA synthesis in cultured cells was evaluated by measuring the incorporation of 3H-TdR. Using conventional chromosome techniques and Giemsa staining methods, chromosomal abnormalities in cultured SG cells, induced by irradiation of $^{60}Co$ werw examined. Cytological observations were carried out by a light microscope with high resolving power. The results obtained were as follows : 1. DNA synthesis of SG cells was quantitatively dependent on a radiation dose compare to control. 2. A polyploids and few chromosome-type break, such as single and double breaks, deltions and triradial figures were more predominantly in irradiated SG cells than in control. This increase of chromosomal abnormality was in the proposition to the irradiation doses.

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Effects of Di(n-butyl) Phthalate on the Developing Immune System of Fetal and Neonatal SD Rats (Di(n-butyl) Phthalate가 태자와 신생자 SD Rat의 면역계 발생에 미치는 영향)

  • 정승태;엄준호;박재현;정형진;황인창;김동섭;하광원;김형수
    • Toxicological Research
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    • v.17 no.2
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    • pp.115-121
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    • 2001
  • Some of endocrine disruptors with sexual hormone-like effects have been increasingly reported to be immunotoxic in many species in recent several years. Phthalate esters have possible effects on the endocrine system. Prenatal exposure to di(n-butyl) phthalate (DBP) has been reported to impair the androgen-dependent development of the male reproductive tract in rat. Therefore, the immunomodulatory effect of DBP was investigated in the developing immune system of fetal and neonatal Sprague-Dawley rats. Timed-bred pregnant SD rats were given to the doses of 0, 250, 500, and 750 mg DBP/kg$\cdot$ body weight /day by gavage once a day from gestational day (GD) 5 to 18. On GD19 or GD22/postnatal day one (PD1), the dams were euthanized, and the changes in organ weights and thymus phenotypes were examined for their offsprings. At 750 mg DBP/kg$\cdot$b.w./day in maternal exposure group, GD19 fetuses showed decreases in body weight. The spleen/body weight ratios were reduced in GD 19 fetuses from the dams exposed to 500 and 750 mg DBP/kg$\cdot$b.w./day. There were no significant changes in thymus and spleen cellularities though these cellularities showed a tendency to decrease in a dose dependent way. In the DBP-exsposed GD22/PD1 offsprings, the body weights, the relative organ weights and the cellularities did not exhibit alteration. Additionally, the percentages of CD3$^{+}$(CD4$^{+}$CD8$^{+}$, CD4$^{+}$CD8$^{-}$, CD4$^{-}$CD8$^{+}$, and CD4$^{-}$CD8$^{-}$) and CD3$^{-}$(CD4$^{+}$CD8$^{+}$, CD4$^{+}$CD8$^{-}$, CD4$^{-}$CD8$^{+}$, and CD4$^{-}$CD8$^{-}$) thymocyte subsets were not changed in any DBP-treated group. The proliferative responses of splenic T cells to Con A and B cells to LPS were decreased in all DBP-exposed GD22/PD1 offsprings.

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The effect of yacon (Samallanthus sonchifolius) ethanol extract on cell proliferation and migration of C6 glioma cells stimulated with fetal bovine serum

  • Lee, Kang Pa;Choi, Nan Hee;Kim, Jin Teak;Park, In-Sik
    • Nutrition Research and Practice
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    • v.9 no.3
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    • pp.256-261
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    • 2015
  • BACKGROUND/OBJECTIVES: Yacon (Samallanthus sonchifolius), a common edible plant grown throughout the world, is well known for its antidiabetic properties. It is also known to have several other pharmacological properties including anti-inflammatory, anti-oxidant, anti-allergic, and anti-cancer effects. To date, the effect of yacon on gliomas has not been studied. In this study, we investigated the effects of yacon on the migration and proliferation of C6 glioma cells stimulated by fetal bovine serum (FBS). MATERIALS/METHODS: Cell growth and proliferation were determined by evaluating cell viability using an EZ-Cytox Cell Viability Assay Kit. FBS-induced migration of C6 glioma cells was evaluated by performing the scratch wound healing assay and the Boyden chamber assay. We also used western blot analysis to determine the expression levels of extracellular signal-regulated kinase 1/2 (ERK1/2), a major regulator of migration and proliferation of glioma cells. Matrix metallopeptidase (MMP) 9 and TIMP-1 levels were measured by performing reverse transcription PCR. RESULTS: Yacon ($300{\mu}g/mL$) reduced both the FBS-induced proliferation of C6 glioma cells and the dose-dependent migration of the FBS-stimulated C6 cells. FBS-stimulated C6 glioma cells treated with yacon (200 and $300{\mu}g/mL$) showed reduced phosphorylation of ERK1/2 and inhibition of MMP 9 expression compared to those shown by the untreated FBS-stimulated C6 cells. In contrast, yacon (200 and $300{\mu}g/mL$) induced TIMP-1 expression. CONCLUSIONS: On the basis of these results, we suggest that yacon may exert an anti-cancer effect on FBS-stimulated C6 glioma cells by inhibiting their proliferation and migration. The most likely mechanism for this is down-regulation of ERK1/2 and MMP9 and up-regulation of TIMP-1 expression levels.