Assessment of In Vitro Assay System for Thyroid HormoneDisruptors Using Rat Pituitary GH3 Cells

Hee Jin Kim1,Hae Young Park1,Jeonga Kim1,Il Hyun Kang2,Tae Sung Kim2,Soon Young Han2,Tae Seok Kang2,Kui Lea Park2,Hyung Sik Kim1 한국독성학회 2006 Toxicological Research Vol.22 No.4

The development of in vitro assays has been recommended to screening and test-ing the potential endocrine disruptors (EDs). These assay systems focus only on identifying thethe thyroid hormone (TH) disruptors. The aim of this study was to evaluate a test system to detectTH disruptors using rat pituitary tumor GH3 cells. The test system is based on the TH-dependentincrease in growth rate. As expected, L-3,5,3-triiodothyronine (T3) markedly induced a morphologicalchange in GH 3 cells from flattened fibroblastic types to rounded or spindle-shaped types. T3 stimu-lated GH3 cell growth in a dose-dependent manner with the maximum growth-stimulating effect9 M. In addition, T3 increased the release of growth hor-mone and prolactin into the medium of the GH3 cells culture. Using this assay system, the TH-dis-rupting activities of bisphenol A (BPA) and its related compounds were examined. BPA,dimethylbisphenol A (DMBPA), and TCI-EP significantly enhanced the growth of GH3 cells in therange of 1 × 10-5M to 1 × 10-6M concentrations. In conclusion, this in vitro assay system might bestandardization before it can be used as a broad-based screening tool.

HPLC용 형광유도체화제인 1-(N,N-dimethylamino)pyrene-6-sulfonyl chloride를 이용한 GABA와 Glutamate의 HPLC분석에 관한 연구

이윤중,김용희,강동호,박귀례 성균관대학교 약학연구소 1991 成均藥硏論文集 Vol.3 No.1

Abstract-Fluorescent derivatives of amino acid neurotransmitter such as GABA and glutamate were synthesized using 1-(N,N-dimethylamino)pyrene-6-sulfonyl chloride (DAPS-Cl) as a derivatizing reagent. GABA and glutamate were derivatized quantitatively into fluorescent compounds by reacting with DAPS-Cl. The optimal conditions for the derivatization of GABA and glutamate with DAPS-Cl were estimated such as pH, reaction temperature and time, and the amount of DAPS-Cl. The derivatives were separated on a reverse phase column with a gradient elution using the 30 mM phosphate buffer and acetonitrile, and monitored by fluorescence detector. Calibration curves for GABA and glutamate exhibited good linearty over 1∼5 pmol. GABA and glutamate in hippocampus of rat brain were determined. After postmortem of rat brain, GABA increasing and glutamate decreasing in hippocampus were prevented 3-mercaptopropionic acid and microwave application.

The Teratogenicity Test of Radio-Irradiated Ginseng in Rats

Park Kui Lea,Kim Pan Gyi,Lee You Mie,Shin Jae Ho,Kwon Seok Chol,Kim Joo Il,Jang Seung Jae 한국실험동물학회 1995 Laboratory Animal Research Vol.11 No.1

Captafol이 혈액상 및 약물대사효소에 미치는 영향

박귀래(Kui Lea Park),홍사욱(Sa Uk Hong) 대한약학회 1989 약학회지 Vol.33 No.1

Examination of the subacute toxicity of captafol showed that. 1)In the captafol administered group, the body weight was significantly decreased but the amounts of AST, ALT, LDH, BUN, TG in serum were remarkably elevated in comparision to those of the control group. 2)In captafol treated animals, the amount of cytochrome P-450 and the activity of NADPH-cytochrome c reductase in liver and in kidney were decreased, but TAB value in serum and in liver and total ATPase activity in liver and in kideny were found to be remakably elevated. 3)When captafol administered with ethanol to the group, the group showed elevated serum levels of AST, ALT and BUN but the amount of cytochrome P-450 and the activity of NADPH-cytochrome c reductase in liver and in kidney were decreased as the group which was treated with captafol only.

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.

Sodium Alginate 가 Mouse 의 重金屬中毒에 미치는 影響에 關한冊究

朴貴禮(Kui Lea Park),金鐘五(Jong Oh Kim) 한국환경보건학회 1986 한국환경보건학회지 Vol.12 No.1

The purpose of the study is to determine the effects of sodium alginate on the suppression of organ accumulation of heavy metals were tested by mice. The seventy mice were divided into the control group and the experimental groups. The mice of cadmium group were subdivided into three groups by dose of 10 ppm cadmium group, adding 1 % sodium alginate to the diets contaminated with 10 ppm cadmium group and adding 10% sodium alginate to the diets contaminated with 10 ppm cadmium group. The mice of copper group were subdivided into three groups by dose of 10 ppm copper group, adding 1 % sodium a1ginate to the diets contaminated with 10 ppm copper group, and adding 10% sodium alginate to the diets contaminated with 10 ppm copper group. Mter the series of feeding of twenty-one days, the mice were killed and examined. Organs and feces were removed and analyzed for cadmium and copper amounts. The results obtained were as follows; 1. As for average body weight gains, those of control group mice were the highest than heavy metal group and those of adding 10% sodium alginate to the diets contaminated with 10 ppm copper group the lowest. 2. The amount of cadmium accumulated in liver and kidney was higher than blood. The amount of cadmium in organs was higher in cadmium group than adding sodium alginate to the diets contallÚnated with cadmium group. 3. The amount of copper in liver was the highest, and that of copper in blood was the lowest. 4. The excretion of heavy metals was promotioned by adding 10% sodium alginate to the diets contaminated with 10 ppm heavy metal. ( P < 0.05 ).

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.

학회참관기 : 제20회 일본동물대체시험법학회(JSAAE)를 다녀와서

박귀례 ( Kui Lea Park ) 한국동물실험대체법학회 2007 동물실험대체법학회지 Vol.1 No.1

퀴놀론 유도체인 Q-35 의 랫드에서의 주산 수유기시험 연구

박귀례(Kui Lea Park),한순영(Soon Young Han),김판기(Pan Gyi Kim),신재호(Jae Ho Shin),조인구(In Koo Cho),장성재(Seung Jae Jang) 한국응용약물학회 1998 Biomolecules & Therapeutics(구 응용약물학회지) Vol.6 No.1

Pregnant Sprague-Dawley rats were administered with Q-35 at the dose levels of 0, 30, 100 and 300 mg/kg/day by oral gavage from gestation day 17 to lactation period. Effects of the test chemical on general findings, reproductive performance of dams and development of F1 generation were examined. There were no treatment related changes in physical signs, body weight, necropsy findings, organ weights, delivery and nursing behavior. In 100 and 300 mg/kg/day treated groups, the food consumption of dams was decreased significantly during gestational day 19∼21. The gestation length of 300 mg/kg/day treated group was increased significantly compared to the control group (22.3 ±0.48 vs 22.0 ±0.39). Although the gestational length of all groups were in normal range of the rat, potential effect of the drug could not be ruled out. External anomaly of F1 fetus induced by Q-35 was not detected in any groups. There were no treatment related changes in physical development, reflex functions, sensory functions, locomotor activity and motor coordinating activity. Estrus cycle, fertility and reproductive performance of F1 were not changed in all treated groups. There was no external abnormality related to the drug administration on the examination of F2. These results suggest that Q-35 has no adverse effect on the peri- and postnatal period in rats except the reduction of food consumption at the beginning of drug administration, and the potential effect on the elongation of gestation length.

Retinoic acid와 dibutyryl cyclic AMP가 F9 embryonic carcinoma cell 분화 중 G1 Phase 관련 분자에 미치는 영향

박귀례(Kui Lea Park),김건홍(Kun Hong Kim),한순영(Soon Young Han),이유미(You Mie Lee),장성재(Seung Jea Jang) 대한약학회 1999 약학회지 Vol.43 No.3

Retinoic acid (RA) and dibutyryl cyclic AMP (dbcAMP) induce the differentiation of the multipotent embryonic carcinoma cell line, F9 cells, into parietal endoderm like cell. The F9 cells are highly proliferative doubling approximately 12 hours. S Phase is predominant, lasting 10 hours and G2/M phase occupies most of the remaining cycle (2 hours) and G1 phase is nearly non-existent. In this study, we showed the effect of RA and dbcAMP on the cell cycle associated molecules (especially around Gl phase) during F9 cell differentiation. Differentiation of F9 cells was induced by the combined addition of RA (10-7M) and dbcAMP (0.5mM), and cells were harvested daily up to 4 days. Flow cytometric analysis showed the prolongation of G1 phase around 30 hours after induction. Western blot analysis revealed that the amount of cyclin D1 and cdk2 were increased at day 4. However, histone H1 kinase activity of cdk2 was decreased. These data strongly suggest that RA and dbcAMP induce the growth arrest of F9 cells at G1 phase by decreasing the activity of cdk2, although they have increased the protein contents of cyclin Dl and cdk2. The reason for the discrepancy between the Hl kinase activity and protein contents are not clear yet.