Inhibitory effects of retinoic acid on the proliferation of pre-neoplastic and hepatoma cells in rat liver

정자영(Ja Young Jeong),이영순(Yong Soon Lee) 한국예방수의학회 1998 예방수의학회지 Vol.22 No.3

본 연구는 retinoic acid(RA)가 간발암화 과정에 미치는 조절효과와 간암세포 및 정상 간세포의 증식성에 미치는 효과를 조사하기 위하여 수행하였다. 간 발암물질로는 diethylnitrosamine(DEN, 200mg/kg, i.p.)과 2-acetylaminofluorene(AAF, 15mg/kg, i.g.)을 사용하였다. Ⅰ군은 DEN과 AAF를 투여하였고, 3주에 간부분 절제술(partial hepatectomy, PH)을 해 주었다. Ⅱ군은 DEN, AAF, PH 그리고 RA(1.5mg/kg, i.m.)를 처치하였다. Ⅲ군은 Ⅱ군의 처치에서 AAF를 제외시켰다. Ⅳ군은 PH와 RA를, 그리고 V군은 PH만 처치하였다. 모든 랫드는 8주. 16주, 32주에 부검하여 조사하였으며, 간암세포와 정상 간세포의 증식성 평가는 5-bromo-2’-deoxyuridine(BrdU)의 표지, proliferating cell nuclear antigen(PCNA)의 발현, 그리고 핵당 silver-binding nucleolar organizer regions(AgNORs)의 갯수 등을 조사하였다. 또한 c-myc 종양단백의 발현 역시 평가하였다. 결과로서, 부검 8주에 GST-p 면역염색 후 조사한 전암병변의 수와 면적은 Ⅱ군에서 Ⅰ군보다 유의적으로 감소되었다(p<0.01). 종양발생율에 있어서도 RA의 억제효과가 16주 및 32주에서 확인되었다. 또한 PCNA와 BrdU에 대한 면역조직화학적 염색결과에서는 Ⅱ군에서 정상 간세포의 증식능이 Ⅰ군보다 더 크게 나타났다. c-myc 종양단백의 발현은 정상부위보다 종양성 병변에서 유의적으로 높게 발현되었지만, Ⅱ군의 종양성 병변에서는 8주(p<0.01)와 32주(p<0.01)에서 Ⅰ군에 비하여 유의적으로 감소되었다. 결론적으로, 이러한 결과는 DEN-AAF-PH로 유발한 간발암화 과정에서 RA투여에 의하여 발암 억제효과가 확인 되었으며, 이 억제효과는 매우 강력하여 AAF의 암 촉진 효과를 충분히 차단할 만큼 큰 것으로 조사되었다. 간발암화 과정중 RA의 억제효과는 전암성 간세포의 증식 억제, 정상 간세포의 증식 촉진 그리고 c-myc 종양단백 발현의 감소에서 기인되는 것으로 사료된다.

비유전독성 간발암물질인 Cloibrate 의 F344 랫드에 있어서 경구 아급성독성시험

정자영(Ja Young Jeong),이국영(Kook Kyung Lee),신동환(Dong Hwan Shin),한범석(Beom Seok Han),김대중(Dae Joong Kim),강태석(Tae Seok Kang),김기상(Ki Sang Kim),장동덕(Dong Deuk Jang),김창옥(Chang Ok Kim),김효정(Hyo Jung Kim),김지희(Jee He 한국응용약물학회 1995 Biomolecules & Therapeutics(구 응용약물학회지) Vol.3 No.1

Clofibrate, a peroxisome proliferator, is hepatocarcinogenic in rats in a dose-dependent manner. A total of 70 male and female F344 rats, 5-week-old, were divided into three groups. Rats were fed clofibrate at 0, 0.25, or 0.5% in diet for 30 days. All rats were anesthetized with CO₂, blood samples were taken by cardiac puncture for hematology and clinical chemistry, and the rats were killed by exsanguination. Livers, kidenys, pancreas, adrenal glands, spleen, heart, lungs, thyroid gland, reproductive organs, and digestive organs were removed, weighed, later processed, and embedded with paraplast for histological examination. The relative liver and kidney weights with respect to final body weight in the clofibrate-treated group were significantly increased compared with those of control group at all dose levels (p<0.01). It has been suggested that clofibrate may influence on hepatotoxicity by increases in peroxisomal proliferation.

비판적 사고력 평가 관점과 기준

정자영 ( Ja Young Jeong ) 한국언어문화학회 2011 한국언어문화 Vol.0 No.44

Researcher elucidate the structure of critical thinking through analysis and systematization for the concept and the sub-factors of critical thinking, and describe the point of view and the criteria for assessment of critical thinking through literature review. Critical thinking which is the main goal of the Korean language and the power means of learners set at the level as the goal, in the situation what was uncertain the implications and the concrete reality of critical thinking, what was not set the teaching-learning method and the true assessment system which was substantially intended to learners` critical thinking. The detailed description of critical thinking` structure can be approached the essence of critical thinking. When based on a thoughtful understanding of critical thinking, we can advance teaching-learning reflected the sub-factors and the characteristic of critical thinking, furthermore critical thinking of learners can improve more and more. Because the attribute of thinking is abstract and thinking is working syntagmatically by many factors, a study is a limit. But through literature review in the analysis and conceptualization process of critical thinking, the substance of critical thinking can become distinct more and more. The plans and practices that critical thinking of learners can promote at the chalkface can be established till substance and factors of critical thinking are the foundation. Therefore researcher classify skills and disposition with critical thinking to promote increased understanding about the concept and the structure of critical thinking. And the subcategory of critical thinking skills was classified as conceptualization, analysis, synthesis, inference, judgment. And the subcategory of critical thinking disposition was classified as pursuit of truth, value of ground, intellectual independence, openness of thinking, carefulness of thinking, self-reflection. A study extract the core characteristics of critical thinking so that establish the point of view and the criteria for substantive assessment of critical thinking.

Flowcytometric quantitative analysis and immunoblotting patterns of the c-myc oncoprotein in hepatocarclnogenesis

정자영(Ja Young Jeong),이영순(Yong Soon Lee) 한국예방수의학회 1998 예방수의학회지 Vol.22 No.3

본 연구는 화학적 간발암화 과정에서 c-myc 종양단백의 immunoblotting 패턴과 유세포 측정기를 이용한 정량분석을 수행하였다. 또한 종양성 간세포의 증식성 평가를 위하여 핵당 silver-binding nucleolar organizer regions(AgNORs)를 조사하였다. 실험군은 세 군으로 나누었으며, Ⅰ군은 대조군, Ⅱ군은 암 유발 물질 투여군으로, 2,2’-dihydroxy-di-n-propylnitrosamine(DHPN, 0.1% in d.w.)과 N-ethyl-N-hydroxyethylnitrosamine(EHEN, 0.15% in d. w.)을 1주 동안씩 각각 처치하였다. 암유발 및 촉진군으로 Ⅲ군은 암유발 물질 투여후, 촉진을 위하여 3’-methycholanthracene(3’-MC, 10mg/kg, i.p., twice a week)와 DL-serine (0.05% in d.w.)을 5주 동안 처치하였다. 모든 동물은 8, 12 그리고 20주에 희생시켜 조사하였다. 면역형광 염색은 붉은 색의 핵에 녹색의 둥근 점이 산재되어 관찰되었다. Dual-parametric FCM으로 분석한 c-myc 퍼센트는 Ⅰ군에서 18%, Ⅱ군에서 21~23% 그리고 Ⅲ군에서는 24~26%로 조사되었으며, 부검시간과 처치에 따른 유의차는 인정되지 않았다. c-myc 종양단백의 immunoblotting 조사에서는, 발암물질을 처치하지 않은 Ⅰ군에서 68 kDa의 강한 하나의 밴드가 관찰되었다. 그러나 발암물질 처치군인 Ⅲ군에서는 68 kDa 밴드 이외에 65 kDa의 밴드가 새롭게 나타났다. Ⅱ군의 AgNORs의 평균수는 암병변에서 정상부위에 비하여 8주 (p<0.05), 12주(p<0.01)에서 유의성 높게 나타났다. Ⅲ군에서도 역시 전암병변에서 8주 (p<0.05), 12주 (p<0.05) 그리고 20주(p<0.01)에서 유의성 높게 관찰되었다. 결론적으로 유세포 측정기로 측정한 c-myc 종양단백의 함량 측정방법은 간편하고, 단순하며 신속한 방법이었다. 발암물질을 처치한 간에서 immunoblotting한 c-myc 종양단백은 68 kDa이 약해지고, 새롭게 65 kDa이 합성되어 나타났다. 따라서 발암물질에 의하여 새롭게 합성된 p65c-myc는 발암물질의 투여 결과이며, 발암물질에 의한 구조적 변성에서 기인된 것으로 사료된다. 한편 핵당 AgNORs의 평가는 종양성 간세포 또는 증식성 세포의 평가를 가능하게 해주는 것으로 조사되었다.

랫드의 간암 발생과정에서 분리한 자연살해세포의 활성측정 및 특성연구

정자영,이국경,길광섭,이영순,Jeong, Ja-young,Lee, Kuk-kyung,Kil, Jwang-sup,Lee, Yong-soon 대한수의학회 1999 大韓獸醫學會誌 Vol.39 No.1

The purposes of this study were to set up the method of the natural killer(NK) cell activity assay using the flow cytometer and to examine the characteristics and distribution of the NK cell during rat hepatocarcinogenesis. Forty five male 6 week-old specific pathogen free(SPF) Sprague-Dawley rats were randomly divided into three groups. Group I was the non-treated control and given normal diet and water. Group II was treated with diethylnitrosamine(DEN, 200mg/kg, i.p.) and partial hepatectomy. Group III was treated with DEN, partial hepatectomy and 0.05% phenobarbital sodium in water from 3 to 16 weeks. All animals were examined the morphology of the large granular lymphocyte(LGL), the LGL percent of the total lymphocytes and the LGL conjugation rate with YAC-1 cell in peripheral blood, spleen and liver. Moreover, activity of the LGL isolated from peripheral blood lymphocytes was determined using the flow cytometer. As results, LGL were observed in the peripheral blood, spleen and liver. LGL were observed the relatively faintly staining basophilic cytoplasm with granules, and eccentric, often kidney-shaped nuclei in Giemsa stain. Its size was $11{\sim}13{\mu}m$. LGL percentage of the isolated lymphocytes in peripheral blood, spleen and liver were 1.8~2.3%, 1.3~1.4% and 0.87~0.99%, respectively. LGL conjugation rate with YAC-1 cell was shown to be peripheral blood(9.3~10.3 %) > spleen(7.7~8.7%) > liver(5.6~7.0%). The activity of the LGL isolated from peripheral blood lymphocytes in Group I, II and III was 33.7%, 30.5% and 35.4%, respectively. However, all values were not significantly between groups.

간과 선장의 암유발과정에서 혈액화학효소 및 DNA ploidy pattern 의 변화에 대한 조사

정자영,장동덕,조재천,이영순,Jeong, Ja-Young,Jang, Dong-Deuk,Cho, Jae-Cheon,Lee, Yong-Soon 한국수의병리학회 1998 한국수의병리학회지 Vol.2 No.2

This study was carried out to investigate on the serum chemistry and the DNA ploidy changes in carcinogenesis of the rat liver and kidney. Sixty male Sprague-Dawley rats were divided into two groups. Group I was non-treated control. Group II was given initiators (2,2'-dihydroxy- di-N-propylnitrosamine, 0.1% in drinking water(d.w.) for 1 week and N-ethyl-N-hydroxy-ethylnitrosamine; 0.15% in d.w. for 1 week) and promoters (3'methyl-cholanthrene; 3'MC, l0mg/kg, intraperitoneally(i.p.) twice a week and DL-serine; 0.05% in d.w. for 5 weeks, from 3 to 8 weeks). All examinations were performed at 12 and 20 weeks RBC, HGBCp<0.05) and PCVCp<0.01) significantly decreased in Group II at 20 weeks. Activities of ALT, AST(p<0.05) and GGT(p<0.01) were significantly increased in Group II at 20 weeks. Flow cytometric analysis showed hepatocyte nuclei from normal livers were predominantly tetraploid(66~67%) and then diploid(28~30%). Most of hepatocyte nuclei from carcinogen-treated rats were diploid (52~68%) and less were tetraploid(28~42%). Neoplastic liver nodules and hepatocellular carcinoma contained almost exclusively diploid nuclei. Renal cell nuclei from normal kidney were predominantly diploid(88~93%), those from carcinogen-treated rats had an abnormal DNA-content peak(aneuploidy, 6-7%), near the tetraploidy area. These results suggest that diploidy may be an effective screening marker of the liver carcinogenesis. Aneuploidy may be an useful marker in assessment of the experimental renal carcinogenesis.

택사(Alismatis Rhizoma) 추출물의 급성 경구투여 독성 연구

석지현,노항식,정자영,하헌용,Seok, Ji-Hyun,Roh, Hang-Sik,Jeong, Ja-Young,Ha, Hun-Yong 대한한방안이비인후피부과학회 2013 한방안이비인후피부과학회지 Vol.26 No.4

Objectives : This study was carried out to evaluate the acute oral toxicity of Alismatis Rhizoma in Sprague-Dawley(SD) rats. Methods : male and female rats were administered orally with Alismatis Rhizoma water extract of 1,000 mg/kg (low dosage group), 2,000 mg/kg(middle dosage group) and 4,000 mg/kg(high dosage group). We daily observed number of deaths, clinical signs and gross findings for 7 days. After 7 days, we measured body and organs weight. Also we analyzed hematological changes. Results : No dead SD rats and no clinical signs were found during the experiment period. Also other specific changes were not found between control and treated groups in hematology and serum biochemistry. In addition no significant changes of gross body and individual organs weight. Conclusions : These results suggest that water soluble extract of Alismatis Rhizoma has not acute oral toxicity and oral $LD_{50}$ value was over 4,000 mg/kg in SD rats.

백선피(Dictamnus dasycarpus Turcz) 추출물의 급성 경구투여 독성 연구

석지현,노항식,정자영,하헌용,Seok, Ji-Hyun,Roh, Hang-Sik,Jeong, Ja-Young,Ha, Hun-Yong 대한한방안이비인후피부과학회 2014 한방안이비인후피부과학회지 Vol.27 No.1

Objectives : This study was carried out to evaluate the acute oral toxicity of Dictamnus dasycarpus Turcz in Sprague-Dawley(SD) rats. Methods : Male and female rats were administered orally with Dictamnus dasycarpus Turcz water extract of 1,000 mg/kg(low dosage group), 2,000 mg/kg(middle dosage group) and 4,000 mg/kg(high dosage group). We daily observed number of deaths, clinical signs and gross findings for 7 days. After 7 days, we measured body and organs weight. Also we analyzed hematological changes. Results : No dead SD rats and no clinical signs were found during the experiment period. Also other specific changes were not found between control and treated groups in hematology. But we found out subtle changes in body weight and individual organ weight of the female group. In addition specific changes were observed in serum biochemical value of female group. Conclusions : These results suggest that water soluble extract of Dictamnus dasycarpus Turcz has not acute oral toxicity and oral $LD_{50}$ value was over 4,000 mg/kg in SD rats. Also Dictamnus dasycarpus Turcz is expected to be sensitive with respect to the female.

택사(Alismatis Rhizoma) 추출물의 반복 경구투여 독성 연구

노항식,석지현,정자영,이종권,김태성,최혜경,하헌용,Roh, Hang-Sik,Seok, Ji-Hyun,Jeong, Ja-Young,Lee, Jong-Kwon,Kim, Tae-Sung,Choi, Hye-Kyung,Ha, Hun-Yong 대한한방안이비인후피부과학회 2014 한방안이비인후피부과학회지 Vol.27 No.1

Objectives : This study was carried out to evaluate the repeated dose oral toxicity of Alismatis Rhizoma in Sprague-Dawley(SD) rats. Methods : Male and female rats were administered orally with Alismatis Rhizoma water extract of 500 mg/kg(low dosage group), 1,000 mg/kg(middle dosage group) and 2,000 mg/kg(high dosage group). We daily observed number of deaths, clinical signs and gross findings for 14 days(twice a day). After 14 days, we measured body and organs weight. Also we analyzed hematological changes. Results : No dead SD rats and no clinical signs were found during the experiment period. Also other specific changes were not found between control and treated groups in hematology and serum biochemistry. In addition no significant changes of gross body and individual organs weight. Conclusions : These results suggest that water soluble extract of Alismatis Rhizoma has not repeated dose oral toxicity and oral LD50 value was over 2,000 mg/kg in SD rats. As a result, we can determine Alismatis Rhizoma is a relatively safe substance.

미성숙 랫드 자궁비대반응시험을 이용한 DEHA의 내분비계 장애작용 평가

박기대,한범석,정자영,오재호,조완섭,조민정,최미나,김성준,김승희,Park, Ki-Dae,Han, Beom-Seok,Jeong, Ja-Young,Oh, Jae-Ho,Cho, Wan-Seob,Cho, Min-Jeong,Choi, Mi-Na,Kim, Sung-Joon,Kim, Seung-Hee 한국환경보건학회 2007 한국환경보건학회지 Vol.33 No.5

This study was aimed to investigate the estrogenic activity of Di-(2-ethylhexyl) adipate (DEHA) using immatured type uterotrophic assay. SD rats were treated with DEHA (40, 200, 1000mg/kg/day), estradiol-3-benzoate (EB) $(1{\mu}g/kg/day)$ as positive control on the assay. In immatured-type uterotrophic assay, relative organ weights of kidney and reproductive organs such as ovary at high-dose group were significantly increased compared to those of vehicle control group. DEHA did not influence the levels of serum FSH and LH, and uterine morphological changes such as luminal epithelial height, myometrial thickness and numbers of uterine gland, and BrdU indices. In these results, there was no significant variation by DEHA treatment, suggesting that DEHA appears not to be a endocrine disrupter with estrogenic activity.