랫드에서 신경줄기세포의 분화기전에 관한 연구

Thesis(doctoral)--서울대학교 대학원 :수의학과 수의공중보건학전공,2005.Docto

Apoptosis Induced by BARODON？ in Human Gastric Cancer Cells

BARODON?is a multi-purpose, high functional alkali solution made by mixing and liquid- ionizing silicon, calcium, sodium, borax, organic carbon chemicals and silver. In this study, we have investigated the apoptotic potential and mechanistic insights of BARODON?in human gastric cancer cell line (AGS cells). In MTT assay, BARODON?reduced cell viability in AGS cells. Morphological features of apoptosis with marked cytoplasmic vacuolation and appearance of apoptotic peaks in flow cytometry were observed in AGS cells with BARODON?treatment. In addition, BARODON?induced apoptosis of stomach cancer cell is related to bax up-regulation, caspase 7 protease activation and subsequent cleavage of poly (ADP-ribose) polymerase (PARP). These results suggest that BARODON?can induce the apoptosis of AGS cells through modulation of bcl-2 family and the activation of intrinsic caspase cascades, indicating that it is potentially useful as a anti-cancer agent.N

Protective Effect of the Stem Bark of Syringa velutina on Bisphenol-A in the Human Breast Cancer Cell Line and Immature Rat

The inhibitory activity against bisphenol-A (BPA), one of well-known endocrine disrupters was examined with the water extracts prepared from the Stem Bark of Syringa velutina (SBS). In this study, we have investigated the effect of SBS on the toxicity caused by BPA in human breast cancer cell line, MCF-7 cells and immature Sprague-Dawley rats. In the estrogen receptor-mediated proliferation assay using MCF-7 cells, BPA (16 ng/ml) induced the cell proliferation, but the water extract of SBS inhibited BPA-induced cell proliferation in a dose-dependent manner. These results are associated with PARP degradation and specific cleavage of anti-apoptotic protein Bcl-2 of apoptotic regulatory factors. Additionally, the BPA (400 mg/100 g) significantly induced the increase of the uterine and virginal weights, while SBS (50 mg/100 g) showed the inhibitory action against BPA, i.e. caused the increase of estrogen-related organ weights in immature rat uterotrophic assay. Taken together, the present data suggest that SBS may have anti-toxicity activities against BPA in vitro and in vivo systems. SBS may be capable of inhibiting adverse effects of BPA such as reproductive disorder.N

Eye Irritation, Skin Irritation and Skin Sensitization Tests for Nonspecific Immunostimulator BARODON/sup (R)/

Two local irritation and skin sensitization studies of nonspecific immunostimulator, BAR-ODON/sup (R)/ were carried out with New Zealand White rabbits and Hartley guinea pigs. In skin irritation test of male New Zealand White rabbits, body weights were not significantly changed and there were no responses after treatment for 24 or 72 hours and the Primary irritation index (P.1.1.) was0. And, in the eye irritation test, there were chemosis in some of rabbits. One of 3 rabbits in washing group was detected chemosis after 24 and 72 h following treatment and 2 of 6 rabbits in non-washing group were detected chemosis after 24h and 7 days following treatment. Therefore, total score is4after 24 h and2after 72 h following treatment by conforming articlesome blood vessel are clearly hyperemic. However evaluation value is non-irritant because M.O.I. (Mean ocular irritation index) score is below during the all experimental period and no significance through individuals and exposure time. In skin sensitization, the score of skin reaction was graded 1 with 0% sensitization rate. Taken together, these results indicate that BARODON/sup (R)/ may be non-irritant material.N

Mutagenicity Studies on Nonspecific Immunostimulator BARODON？

A nonspecific immunostimulator BARODON/sup (R)/ was tested for mutagenicity using Ames Salmonella tester strains TA98, TA1 00, TA 102, TA 1535 and TA 1537 with or without metabolic activation (59 mix). None of the fresh species showed mutagenicity. In the reverse mutation test using Salmonella phimurium TA98, TA100, TA102, TA1535 and TA1537 did not increase the number of revertants at all doses tested (5, 2.5 or 1.25 mg/ml). Chromosome aberration test was carried out in Chinese hamster lung (CHL) cell line. The cells were treated with BARODON/sup (R)/ (1, 0.5 or 0.25 mg/ml), while positive control group was treated with Mitomycin C (0.1 mg/ml). The results show that there is no statistically significant difference between positive control and treatment groups. In mouse micronucleus test, there was significant increase in the ratio of micronucleated polychromatic erythrocyte (MNPCE) in the high dose group (10% BARODON/sup (R)/), while there is no significance between control and low (2.5% BARODON/sup (R)/) or middle (5% BARODON/sup (R)/) dose groups. Taken together, this results suggest that below 5% BARODON/sup (R)/ might not have mutagenic potential in vitro and vivo systems.N

Subcutaneous Toxicity Study of Saposhnikovia divaricata (Turcz.) Schischk in Rats

To evaluate influence of Saposhnikovia divaricata (Turcz.) Schischk extract on rat,Saposhnikovia divaricata (Turcz.) Schischk extract was diluted with 0.9% saline (100 mg/ml/kg,10 mg/ml/kg, and 1 mg/ml/kg, respectively), and each of diluted test material extract was daily treatedsubcutaneously for 4 weeks and single-treated subcutaneously for 2 weeks. There were no significan-ces in body weight analysis, urinary analysis, and ophthalmological test. However, in serum biochemi-cal analysis and hematological analysis, we found some significances in high and middle dose groupcompared with control group. These significances in serum biochemical analysis and hematologicalanalysis may be not induced by test material, because it was not found to be significant from controlgroup in histopathological examination. Therefore, it was concluded that NOEL (No Observed EffectLevel) of test material extract may be higher than all treatment doses used in this study, and Saposh-nikovia divaricata (Turcz.) Schischk extract may be a non-toxic material.N

Toxicity study of GC-100X in rats and beagles

Because cleaning products are part of our everyday lives, it is essential that they should not present significant risks to health. However, many petrochemicals in most soaps and detergents can be absorbed through the scalp and skin and, over time, accumulate in the organs and tissues. This accumulation may result in brain, nerve, and liver damage. Therefore, it is interested in developing non-harmful detergent. According to Korea Research Institute of Chemical Technology, GC-100X may be non-harmful and non-corrosive alkaline ionic water (pH 12). It is composed of hydroxyl radicals and supplemented with xylitol. To evaluate influence of GC-100X on rats and beagles, GC-100X was diluted with distilled water (25%, 50%, and 100% solution respectively). Each of diluted GC-100X was daily treated per oral. In body weight analysis, urinary analysis, ophthalmological test and autopsy, we did not find any significance, but in serum biochemical analysis and hematological analysis, we found some significances in middle dose group compared with control group. These significances in serum biochemical analysis and hematological analysis may be not induced by GC-100X, because it was not found to be significant from control group in histopathological examination. Thus, it is concluded that NOEL(No Observed Effect Level) of GC-100X may be higher than all treatment doses used in this study, and GC-100X may be a non-toxic detergent.N

Single and Four-Week Subcutaneous Toxicity Studies of a Bee Venom Extracts (F1, F3) In Rats

This study was performed to evaluate single and repeated-dose toxicities of BeVenom Extracts (F1, F3) in Spraque-Dawley. F1 was injected subcutaneously to rat at dose levels of0, 0.0002, 0.002, 0.02 mg/kg/day for single-dose toxicity study and repeated-dose toxicity study. F3was injected subcutaneously to rat at dose level of 0, 0.003, 0.03, 0.3 mg/kg/day for single-dose toxic-ity study and repeated-dose toxicity study. In both studies, there were no dose related changes inmortality, clinical sign, body weight change, food and water consumption, opthalmoscopy, organweights, urine analysis, biochemical examination, and hematological findings of all animals treatedwith Bee Venom (F1, F3). Gross and histopathological findings revealed no evidence of specific toxic-ity related to Bee Venom (F1, F3). These results suggest that the subcutaneous NOEL (No ObservedEffect Level) of Bee Venom (F1, F3) may be over F1 - 0.02 mg/kg, F3 - 0.3 mg/kg.N

Antigenicity Study of Nonspecific Immunostimulator BARODONⓡ

The antigenicity of nonspecific immunostimulator BARODONⓡ, a newly developed drug, was investigated by tests for passive cutaneous anaphylaxis (PCA) and active systemic anaphylaxis (ASA) in mice and guinea pigs. In ASA test using guinea pigs, there were no significant clinical symptoms in all individuals of low(0.3%) and high(3%) dose of both groups treated with only BARODONⓡ and cotreated with BARODONⓡ and adjuvant group. In PCA test, blue spots of Evan's were observed from 26 to 210 in homologous group and from 22～25 dilution rate in heterologous group of BSA treated positive control group. However, intradermal sensitization with antiserum obtained from low (0.3%) and high (3%) dose of BARODONⓡ only treatment group and treated-with-adjuvant group, followed by intravenous injection of respective antigen and Evan's blue mixture (1:1) showed no blue spot observed. In conclusion, BARODONⓡ, as showed in ASA and PCA test, did not cause anaphylatic shock when treated 3 and 10 times higher than clinically intended dose, nor induce IgE, so that might not have antigenic properties in mice and guinea pigs.N