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- 저자 : 한순영 ( Soon Young Han ) (검색결과 31 건)
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미성숙 동물에서 에스트로겐성 물질에 대한 자궁비대반응시험
한순영(Soon Young Han),김형식(Hyung Sik Kim),이동하(Dong Ha Lee),오세동(Se Dong Oh),김태성(Tae Sung Kim),박귀례(Kui Lea Park) 한국환경성돌연변이발암원학회 2000 한국환경성돌연변이·발암원학회지 Vol.20 No.1
자궁내 반응에 대한 용량 의존적인 효과를 검색하기 위해 에스트로겐 agonist 및 antagonist를 사용하여 미성숙 랫드에서 uterotrophic assay를 실시하였다. 김(2000) 등은 이미 난소절제랫드를 이용한 3-day uterotrophic assay에서 에스트로겐성 물질에 대한 검색 시험을 실시한 바 있다. 양성대조물질인 17-ethinyl estradiol (EE)을 미성숙랫드에 매일 3일간 피하 투여하였으며, EE의 에스트로겐 활성을 차단하기 위한 항에스트로겐성 물질인 ZM189, 154은 EE와 병행 투여했다. 본 시험 결과 EE 1.0 ㎍/㎏이상 투여군에서는 자궁 비대와 fluid 저류등이 대조군에 비해 육안적으로 뚜렷하게 나타났다. 자궁무게(wet 및 blotted)는 용량 의존적으로 증가하였으며 특히, EE 1.0 ㎍/㎏ 이상에서는 유의성 있는 증가를 나타내었다. 또한 질무게 증가도 자궁무게 증가와 일치 하였다. 0.3 ㎍/㎏을 투여한 후 ZM189, 154 0.1 ㎎/㎏ 및 1.0 ㎎/㎏ 투여와 비교할 때 EE에 의해 유도된 에스트로겐 활성이 용량 의존적으로 감소되었으나 유의성 있는 결과는 ZM189, 154 1.0 ㎎/㎏군에서만 나타났다. 본 연구결과 EE는 uterotrophic assay에서 자궁 무게(wet와 blotted)를 용량 의존적으로 증가시켰으며, ZM189, 154 1.0 ㎎/㎏은 EE의 에스트로겐 활성을 유의하게 감소시켰다. 따라서 미성숙 랫드를 이용한 3-day uterotrophic assay는 내분비계 장애물질 검색 시험법으로 우수하다는 것을 알 수 있었다. To investigate the dose-response effects of uterine response, uterotrophic assay was performed in immature female rat using a range of estrogen agonist and antagonist. We have previously reported that 3-day uterotrophic assay using ovariectomized (OVX) rats was a sensitive screening method to detect estrogen-like<br/> compounds (Kim et al., 2000). This study was conducted exactly as described by the OECD protocol. A positive control substance, 17-ethinyl estradiol (EE), was daily administered by subcutaneous injection for three consecutive days to immature rats at various doses. Additionally, a pure anti-estrogenic material, ZM 189,154 was administered to EE groups immediately after EE administration to determine the anti-estrogenic effects. In EEtreated groups, uterine enlargement and retention of fluid were markedly observed at doses higher than 1.0 ㎍/kg/day. The uterine wet and blotted weight was increased dose-dependently, and statistical significance was observed at 1.0 ㎍/kg/day and above. A similar dose-response relationship was also observed for vagina weight. Moreover, the uterine responses (uterine and vagina weights increase) of EE (0.3 ㎍/kg/day) were blocked by ZM189,154 in a dose-dependent manner. However, statistical significance was observed only in the ZM189,154 1.0 ㎍/kg/day. These findings indicate that the 3-day uterotrophic assay using immature rats is an effective in vivo short-term system for the screening of estrogen agonists and antagonists.
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랫드 자궁비대반응시험(Uterotrophic assay)을 이용한 phthalate esters의 에스트로겐성 작용 연구
한순영 ( Soon Young Han ),문현주 ( Hyun Ju Moon ),김형식 ( Hyung Sik Kim ),김철규 ( Cheul Kue Kim ),신재호 ( Jae Ho Shin ),오세동 ( Se Dong Oh ),장성재 ( Seung Jae Jang ),박귀례 ( Kui Lea Park ) 한국응용약물학회 2000 Biomolecules & Therapeutics(구 응용약물학회지) Vol.8 No.2
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이진영 ( Jin Young Lee ),강미선 ( Mi Sun Kang ),김지명 ( Ji Myoung Kim ),곽승준 ( Seung Jun Kwack ),한의식 ( Eui Sik Han ),한범석 ( Beom Seok Han ),박순희 ( Sue Nie Park ),강태석 ( Tae Seok Kang ),한순영 ( Soon Young Han ) 한국동물실험대체법학회 2010 동물실험대체법학회지 Vol.4 No.1
Repeated dose toxicity testing in rodents is used to have information on potential target organs in terms of toxicity, and the NOAEL (no-observed-adverse-effect-level). ECVAM and ICCVAM have not validated any non-animal methods for assessing chronic toxicity endpoints or repreated exposure target organ toxicity because in vivo systems often poorly resemble in vitro cell culture systems. However, recently ECVAM recommended a proposed approach for the assessment of repeated dose toxicity in vitro. We applied ECVAM`s proposal to assess target organ toxicity using liver and kidney cell lines. In order to predict liver and kidney target organ toxicities, we used three kinds of kidney toxicants(HgCl2, CH3HgCl, CdCl2) and two kinds of liver toxicants(acetaminophen, CuCl2) in human hepatoma(HepG2) cells, human renal tubular epithelial(HK-2) cells and human embryonic kidney(HEK293) cells. We performed cytotoxicity assays, mitochondria damage and calcium influx tests to predict target organ toxicity. Cell viability and cell proliferation were assessed by NRU assay and MTT assays, respectively. Mitochondria potential and cell calcium concentration([Ca2+]i) were estimated by a fluorescence microscopy using JC-1 dye and a fluorometer using Fluo-4/AM dye, respectively. The cytotoxicity of nephrotoxicants(HgCl2, CH3HgCl, CdCl2) from the result of NRU and MTT assay was higher in the kidney cells than in the liver cells. Also, the cytotoxicity of hepatotoxicants(acetaminophen, CuCl2) was higher in the liver cells than in the kidney cells. Mitochondria potential and [Ca2+]i show compatability with cytotoxicity results in the kidney cells but not in the liver cells. The results demonstrated that nephrotoxicants can predict target organ toxicity by in vitro tests like NRU, MTT assay, mitochondria potential and [Ca2+]i. However, hepatotoxicants can predict target organ toxicity by cytotoxicity assays like NRU and MTT assays but not by mitochondria potential and [Ca2+]i.
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연구논문 : ECVAM 등의 국제 독성시험법 국내 확립 및 적용
이진영 ( Jin Young Lee ),강미선 ( Mi Sun Kang ),김지명 ( Ji Myoung Kim ),곽승준 ( Seung Jun Kwack ),한의식 ( Eui Sik Han ),한범석 ( Beom Seok Han ),박순희 ( Sue Nie Park ),강태석 ( Tae Seok Kang ),한순영 ( Soon Young Han ) 한국동물실험대체법학회 2010 동물실험대체법학회지 Vol.4 No.1
Repeated dose toxicity testing in rodents is used to have information on potential target organs in terms of toxicity, and the NOAEL (no-observed-adverse-effect-level). ECVAM and ICCVAM have not validated any non-animal methods for assessing chronic toxicity endpoints or repreated exposure target organ toxicity because in vivo systems often poorly resemble in vitro cell culture systems. However, recently ECVAM recommended a proposed approach for the assessment of repeated dose toxicity in vitro. We applied ECVAM`s proposal to assess target organ toxicity using liver and kidney cell lines. In order to predict liver and kidney target organ toxicities, we used three kinds of kidney toxicants(HgCl2, CH3HgCl, CdCl2) and two kinds of liver toxicants(acetaminophen, CuCl2) in human hepatoma(HepG2) cells, human renal tubular epithelial(HK-2) cells and human embryonic kidney(HEK293) cells. We performed cytotoxicity assays, mitochondria damage and calcium influx tests to predict target organ toxicity. Cell viability and cell proliferation were assessed by NRU assay and MTT assays, respectively. Mitochondria potential and cell calcium concentration([Ca2+]i) were estimated by a fluorescence microscopy using JC-1 dye and a fluorometer using Fluo-4/AM dye, respectively. The cytotoxicity of nephrotoxicants(HgCl2, CH3HgCl, CdCl2) from the result of NRU and MTT assay was higher in the kidney cells than in the liver cells. Also, the cytotoxicity of hepatotoxicants(acetaminophen, CuCl2) was higher in the liver cells than in the kidney cells. Mitochondria potential and [Ca2+]i show compatability with cytotoxicity results in the kidney cells but not in the liver cells. The results demonstrated that nephrotoxicants can predict target organ toxicity by in vitro tests like NRU, MTT assay, mitochondria potential and [Ca2+]i. However, hepatotoxicants can predict target organ toxicity by cytotoxicity assays like NRU and MTT assays but not by mitochondria potential and [Ca2+]i.
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항안드로겐성 물질이 성 성숙 이전 단계의 정소에서 미치는 영향 연구
홍진,한순영,문현주,강태석,강일현,김태성,김승희,권기성,Hong Jin,Han Soon-Young,Moon Hyun-Ju,Kang Tae-Seok,Kang Il-Hyun,Kim Tae-Sung,Kim Seung-Hee,Kwon Ki-Sung 환경독성보건학회 2006 환경독성보건학회지 Vol.21 No.3
The experiments investigated whether early exposure to testosterone propionate (TP) during prepuberty alters testis development in Sprague-Dawley male rats. We performed Hershberger assay using the stimulated weanling male rats by OECD protocols, cDNA microarray, and Western blot. TP was subcutaneously injected to uncastrated Sprague-Dawley male rat of 22 days old for 10 consecutive days at doses of 0.4, 0.8, 1.0, 1.2, 1.6 mg/kg per day. At necropsy, the following tissues were removed and weighed: combined testes, epididymides (Epi), Cowper's glands (COW), levator am, and bulbocavernosus muscles (LABC), seminal vesicles, together with coagulating gland (SV) and ventral prostate (VP). We found that TP increased the weights of Epi, VP, SV, COW, and LABC, while testis was decreased in a dose-dependent manner. In cDNA microarray analysis of testis, there were significant reductions in the expression of cytochrome P450 11A (CYP11A), the rate-limiting enzyme of steroidogenesis. Taken together these results, TP exposure before puberty in male rats may produce the delay in testis development by inhibiting the CYP11A gene expression.
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방사선 조사 인삼이 랫드의 수태능 및 일반 생식독성에 미치는 영향에 관한 연구
박귀례(Kui Lea Park),한순영(Soon-Young Han),김판기(Pan Gyi Kim),이유미(You-Mie Lee),신재호(Jae-Ho Shin),장성재(Seung Jae Jang) 한국독성학회 2001 Toxicological Research Vol.17 No.2
Korean ginseng products have been fumigated with ethylene oxide (EO) for sterilization and prolongation of storage periods. However, there had been controversies indicating that the consumption of food treated with EO might cause harmful effects in human. Since, in Korea the use of EO gas for food treatment was banned in 1991. Since then, irradiation technique has been developed as an alternative. This study was carried out to investigate the effects of irradiated ginseng on fertility, and reproductive and developmental toxicity. Either EO gas fumigated or gamma-irradiated ginseng was administered to male rats by oral gavage for 63 days during the premating period. Female rats were administered from 14 days before mating to day 20 of gestation or to day 21 of lactation. The exposure amount of irradiation used was 5, 10 and 30 kGy, respectively. There were no treatment related changes of dams in clinical signs, and parturition. No treatment related changes in food consumption, body/organ weights, male/female reproductive and fertility performances were observed. F1 fetuses showed no external abnormality. Reflex/sensory functions, physical/behavioral development, and reproductive performance of F1 rats were not adversary affected. The results of this study show that gamma-irradiated ginseng, up to 30 kGy, has no adverse effects on the fertility, reproduction and development in Wistar rats.
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재조합 인간상피세포 성장인자(rhEGF, DWP401)가 랫트의 수태능, 태자와 신생자 발달 및 모체기능에 미치는 영향
박귀례(Kui Lea Park),한순영(Soon-Young Han),신재호(Jae-Ho Shin),이유미(Yoo Mie Lee),김판기(Pan Gyi Kim),장성재(Seung Jae Jang) 대한약학회 2001 약학회지 Vol.45 No.2
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 mcg/kg/day, respectively, 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 form 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, of skeletal malformation of fetuses, growth and development, behavior, and/or reproductive performance of F1 animals. At the highest dose(1,000mcg/kg), the mean body weights of F0 animals were significantly increased in males and females at 3 or 2 weeks after treatment, respectively. 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 siginificantly increased in both sexes of 1,000mcg/kg. At the highest dose(1,000mcg/kg), there was a statistically significant increase of pregnancy period and the number of dead fetuses. Moreover, siginificant increase of mean fatal body weight and decrease of number of live fetuses, which related to the difficult delivery were observed in highest dose group. In F1 examination, no adverse effects on external, visceral, and skeletal malformation, physical and functional development, behavior, or reproductive ability of F1 animals were observed in any group. Also there was no significant difference between control and treated groups in copulation or fertility indices of F1 animals. These results indicate that rhEGF had no adverse effect on fertility and reproductive ability of Sprague-Dawley rats.
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재조합 인간상피세포 성장인자(rhEGF, DWP401)의 배, 태자 발달 독성 연구
박귀례(Kui Le Park),한순영(Soon Young Han),신재호(Jae Ho Shin),이유미(Yoo Mie Lee),박희정(Hee Jung Park),장성재(Seung Jae Jang) 대한약학회 1998 약학회지 Vol.42 No.5
Effect of recombinant human epidermal growth factor (rhEGF, DWP401) on fetal external, visceral and skeletal malformation during organogenesis was examined. Pregnant Sprauge-Dawley rats were administered with 0.2, 1 and 5mg/kg/day subcutaneously on gestation day 6 through 16. Dams were sacrified at 20th day of gestation. Materal body weight, food consumption and clinical observation were not changed. Significant dose-dependent increase of relative and absolute liver weight were observed in the treatment group, whereas other organ weights were not changed. Placental weight of 1 and 5mg/kg/day group and number of resorption in 5mg/kg/day treatment group were significantly increased. External and visceral malformation of fetuses were not observed with treatment. However, skeletal variations(increase of asymmetry sternebrae, decrease of dumb-bell and asymmetry sternbrae at 5mg/kg/day, and fused stemebrae at 5mg/kg/day) were observed. These results showed that rhEGF (DWP401) may not have embryo and/or fetal developmental toxicity effect in rats.
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